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13: Lee H, Sin DD. GETting to know the many causes and faces of COPD. Lancet Respir Med. 2022 May;10(5):426-428. doi: 10.1016/S2213-2600(22)00049-2. Epub 2022 Apr 12. PMID: 35427529.

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1: Olaguibel JM, Sastre J, Rodríguez JM, Del Pozo V. Eosinophilia induced by blocking the IL-4/IL-13 pathway. Potential mechanisms and clinical outcomes. J Investig Allergol Clin Immunol. 2022 May 6:0. doi: 10.18176/jiaci.0823. Epub ahead of print. PMID: 35522053.

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4: Tan HS, McAnally HM, Dummer J, Hancox RJ. Lifetime cannabis exposure and small airway function in a population-based cohort study. ERJ Open Res. 2022 May 3;8(2):00688-2021. doi: 10.1183/23120541.00688-2021. PMID: 35509440; PMCID: PMC9062301.

5: Martin M, Penque M, Wrotniak BH, Qiao H, Territo H. Single-Dose Dexamethasone Is Not Inferior to 2 Doses in Mild to Moderate Pediatric Asthma Exacerbations in the Emergency Department. Pediatr Emerg Care. 2022 May 3. doi: 10.1097/PEC.0000000000002727. Epub ahead of print. PMID: 35507383.

6: Domínguez-Ortega J, Luna-Porta JA, Olaguibel JM, Barranco E, Arismendi E, Barroso B, Betancor D, Bobolea I, Caballero ML, Cárdaba B, Cruz MJ, Curto E, González-Barcala FJ, Losantos-García I, Martínez-Rivera C, Mendez-Brea P, Mullol J, Muñoz X, Picado C, Plaza V, Del Pozo V, Rial MJ, Sastre J, Soto L, Valero A, Valverde-Monge M, Quirce S. Exacerbations among patients with asthma are largely dependent on the presence of multimorbidity. J Investig Allergol Clin Immunol. 2022 May 2:0. doi: 10.18176/jiaci.0816. Epub ahead of print. PMID: 35503227.

7: Hasan Arshad S. Does allergen Immunotherapy for allergic rhinitis prevent asthma? Ann Allergy Asthma Immunol. 2022 Apr 29:S1081-1206(22)00392-1. doi: 10.1016/j.anai.2022.04.028. Epub ahead of print. PMID: 35500864.

8: Matucci A, Nencini F, Maggiore G, Chiccoli F, Accinno M, Vivarelli E, Bruno C, Locatello LG, Palomba A, Nucci E, Mecheri V, Perlato M, Rossi O, Parronchi P, Maggi E, Gallo O, Vultaggio A. High proportion of inflammatory CD62L^low eosinophils in blood and nasal polyps of severe asthma patients. Clin Exp Allergy. 2022 May 1. doi: 10.1111/cea.14153. Epub ahead of print. PMID: 35490414.

9: Yamane M, Ohnishi H, Tsuji K, Anabuki K, Yokoyama A. Dupilumab-induced peripheral neuropathy in a patient with severe asthma. Ann Allergy Asthma Immunol. 2022 May;128(5):611. doi: 10.1016/j.anai.2022.01.028. PMID: 35489800.

10: Rabe KF, Pavord ID, Castro M, Wechsler ME, Daizadeh N, Kapoor U, Ortiz B, Radwan A, Johnson RR, Rowe PJ, Deniz Y, Jacob-Nara JA. Dupilumab efficacy and safety in patients with asthma and blood eosinophils ≥500 cells·µL^-1. Eur Respir J. 2022 Apr 29:2102577. doi: 10.1183/13993003.02577-2021. Epub ahead of print. PMID: 35487538.

11: van Meel ER, Mensink-Bout SM, den Dekker HT, Ahluwalia TS, Annesi-Maesano I, Arshad SH, Baïz N, Barros H, von Berg A, Bisgaard H, Bønnelykke K, Carlsson CJ, Casas M, Chatzi L, Chevrier C, Dalmeijer G, Dezateux C, Duchen K, Eggesbø M, van der Ent C, Fantini M, Flexeder C, Frey U, Forastiere F, Gehring U, Gori D, Granell R, Griffiths LJ, Inskip H, Jerzynska J, Karvonen AM, Keil T, Kelleher C, Kogevinas M, Koppen G, Kuehni CE, Lambrechts N, Lau S, Lehmann I, Ludvigsson J, Magnus MC, Mélen E, Mehegan J, Mommers M, Andersen AN, Nystad W, Pedersen ESL, Pekkanen J, Peltola V, Pike KC, de Moira AP, Pizzi C, Polanska K, Popovic M, Porta D, Roberts G, Santos AC, Schultz ES, Standl M, Sunyer J, Thijs C, Toivonen L, Uphoff E, Usemann J, Vafeidi M, Wright J, de Jongste JC, Jaddoe VWV, Duijts L. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children. Eur Respir J. 2022 Apr 29:2102395. doi: 10.1183/13993003.02395-2021. Epub ahead of print. PMID: 35487537.

12: Niessen NM, Fricker M, McDonald VM, Gibson PG. T2-low: What do we know? – Past, present, and future of biologic therapies in non-eosinophilic asthma. Ann Allergy Asthma Immunol. 2022 Apr 26:S1081-1206(22)00342-8. doi: 10.1016/j.anai.2022.04.020. Epub ahead of print. PMID: 35487388.

13: Hashimoto S, Kroes JA, Eger K, Mau-Asam P, Hofstee HB, Bendien SA, Braunstahl GJ, Broeders ME, Imming LM, Langeveld B, Maitland-van der Zee AH, Oud KT, Patberg KW, Smeenk FW, Petronella Romme EA, van Bezouw MJ, van de Ven MJ, van Veen A, van Velzen E, van Veen IH, Weersink EJ, Ten Brinke A, Sont JK, Bel EH; RAPSODI team. Real-World Effectiveness of Reslizumab in Patients with Severe Eosinophilic Asthma – “First Initiators” and “Switchers”. J Allergy Clin Immunol Pract. 2022 Apr 26:S2213-2198(22)00362-2. doi: 10.1016/j.jaip.2022.04.014. Epub ahead of print. PMID: 35487369.

14: Cazzola M, Rogliani P, Ora J, Calzetta L, Matera MG. Asthma and comorbidities: recent advances. Pol Arch Intern Med. 2022 Apr 28;132(4):16250. doi: 10.20452/pamw.16250. Epub 2022 Apr 28. PMID: 35485651.

15: Moitra S, Carsin AE, Abramson MJ, Accordini S, Amaral AFS, Anto J, Bono R, Casas Ruiz L, Cerveri I, Chatzi L, Demoly P, Dorado-Arenas S, Forsberg B, Gilliland F, Gislason T, Gullón JA, Heinrich J, Holm M, Janson C, Jogi R, Gómez Real F, Jarvis D, Leynaert B, Nowak D, Probst-Hensch N, Sánchez-Ramos JL, Raherison-Semjen C, Siroux V, Guerra S, Kogevinas M, Garcia-Aymerich J. Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS. Thorax. 2022 Apr 27:thoraxjnl-2021-217867. doi: 10.1136/thoraxjnl-2021-217867. Epub ahead of print. PMID: 35477559.

16: Verschakelen JA. Quantitative CT of the Lung to Study Asthma. Radiology. 2022 Apr 26:213091. doi: 10.1148/radiol.213091. Epub ahead of print. PMID: 35471116.

17: Trivedi AP, Hall C, Goss CW, Lew D, Krings JG, McGregor MC, Samant M, Sieren JP, Li H, Schechtman KB, Schirm J, McEleney S, Peterson S, Moore WC, Bleecker ER, Meyers DA, Israel E, Washko GR, Levy BD, Leader JK, Wenzel SE, Fahy JV, Schiebler ML, Fain SB, Jarjour NN, Mauger DT, Reinhardt JM, Newell JD Jr, Hoffman EA, Castro M, Sheshadri A; NHLBI Severe Asthma Research Program (SARP). Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts. Radiology. 2022 Apr 26:210363. doi: 10.1148/radiol.210363. Epub ahead of print. PMID: 35471111.

18: Rind DM, McQueen RB, Herron-Smith S, Herce-Hagiwara B, Gutierrez E, Campbell JD, Fluetsch N, Pearson SD. The effectiveness and value of tezepelumab for severe asthma. J Manag Care Spec Pharm. 2022 May;28(5):577-580. doi: 10.18553/jmcp.2022.28.5.577. PMID: 35471071.

19: Williams DM. The potential promise and challenge for tezepelumab as a biologic therapy for severe asthma. J Manag Care Spec Pharm. 2022 May;28(5):581-583. doi: 10.18553/jmcp.2022.28.5.581. PMID: 35471066.

20: Ali H, Brooks C, Tzeng YC, Crane J, Beasley R, Gibson P, Pattemore P, Stanley T, Pearce N, Douwes J. Heart rate variability as a marker of autonomic nervous system activity in young people with eosinophilic and non-eosinophilic asthma. J Asthma. 2022 May 5:1-9. doi: 10.1080/02770903.2022.2070763. Epub ahead of print. PMID: 35468039.

21: Torchio R, Gobbi A, Gulotta C, Antonelli A, Dellacà R, Pellegrino GM, Pellegrino R, Brusasco V. Role of hyperpnea in the relaxant effect of inspired CO₂ on methacholine-induced bronchoconstriction. J Appl Physiol (1985). 2022 May 1;132(5):1137-1144. doi: 10.1152/japplphysiol.00763.2021. Epub 2022 Mar 31. PMID: 35358399.

22: Korn S, Milger K, Skowasch D, Timmermann H, Taube C, Idzko M, Voß HW, Holtdirk A, Hamelmann E, Buhl R. Corrigendum to “The German severe asthma patient: Baseline characteristics of patients in the German Severe Asthma Registry, and relationship with exacerbations and control” [Respir. Med. 195 (2022) 106793]. Respir Med. 2022 May;196:106827. doi: 10.1016/j.rmed.2022.106827. Epub 2022 Mar 26. Erratum for: Respir Med. 2022 Feb26;195:106793. PMID: 35349956.

23: Barber CM, Cullinan P, Feary J, Fishwick D, Hoyle J, Mainman H, Walters GI. British Thoracic Society Clinical Statement on occupational asthma. Thorax. 2022 May;77(5):433-442. doi: 10.1136/thoraxjnl-2021-218597. Epub 2022 Mar 21. PMID: 35314486.

24: Niewodowski D, Langton D. Learning curve for bronchial thermoplasty. Respirology. 2022 May;27(5):366-369. doi: 10.1111/resp.14248. Epub 2022 Mar 16. PMID: 35293074.

25: Menzies-Gow A, Hoyte FL, Price DB, Cohen D, Barker P, Kreindler J, Jison M, Brooks CL, Papeleu P, Katial R. Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab. Adv Ther. 2022 May;39(5):2065-2084. doi: 10.1007/s12325-022-02098-1. Epub 2022 Mar 14. PMID: 35287231.

26: Singh D, Garcia G, Maneechotesuwan K, Daley-Yates P, Irusen E, Aggarwal B, Boucot I, Berend N. New Versus Old: The Impact of Changing Patterns of Inhaled Corticosteroid Prescribing and Dosing Regimens in Asthma Management. Adv Ther. 2022 May;39(5):1895-1914. doi: 10.1007/s12325-022-02092-7. Epub 2022 Mar 14. PMID: 35284999.

27: Svenningsen S, Nair P. Persistent Airway Plugs: A Call for Clinical Recognition and Novel Therapies. Am J Respir Crit Care Med. 2022 May 1;205(9):977-978. doi: 10.1164/rccm.202201-0147ED. PMID: 35259080.

28: McBride SC, McCarty K, Wong J, Baskin M, Currier D, Chiang VW. A pediatric hospital-wide asthma severity score: Reliability and effectiveness. Pediatr Pulmonol. 2022 May;57(5):1223-1228. doi: 10.1002/ppul.25861. Epub 2022 Mar 28. PMID: 35182050.

29: Charles D, Shanley J, Temple SN, Rattu A, Khaleva E, Roberts G. Real-world efficacy of treatment with benralizumab, dupilumab, mepolizumab and reslizumab for severe asthma: A systematic review and meta-analysis. Clin Exp Allergy. 2022 May;52(5):616-627. doi: 10.1111/cea.14112. Epub 2022 Mar 9. PMID: 35174566.

30: Tang M, Elicker BM, Henry T, Gierada DS, Schiebler ML, Huang BK, Peters MC, Castro M, Hoffman EA, Fain SB, Ash SY, Choi J, Hall C, Phillips BR, Mauger DT, Denlinger LC, Jarjour NN, Israel E, Phipatanakul W, Levy BD, Wenzel SE, Bleecker ER, Woodruff PG, Fahy JV, Dunican EM. Mucus Plugs Persist in Asthma, and Changes in Mucus Plugs Associate with Changes in Airflow over Time. Am J Respir Crit Care Med. 2022 May 1;205(9):1036-1045. doi: 10.1164/rccm.202110-2265OC. PMID: 35104436.

31: Stout S, Murphy H, Pandya A, Yeh HW, Portnoy J. The effect of coronavirus disease 2019 on asthma visits. Ann Allergy Asthma Immunol. 2022 May;128(5):594-595. doi: 10.1016/j.anai.2022.01.027. Epub 2022 Jan 31. PMID: 35101645; PMCID: PMC8801266.

32: Geng B, Dixon AE, Ko J, Janampally P, Haselkorn T, Holweg CTJ, Casale TB, Jarjour N. Impact of body mass index on omalizumab response in adults with moderate-to-severe allergic asthma. Ann Allergy Asthma Immunol. 2022 May;128(5):553-560. doi: 10.1016/j.anai.2022.01.025. Epub 2022 Jan 31. PMID: 35101644.

33: Wei Y, Qiu X, Sabath MB, Yazdi MD, Yin K, Li L, Peralta AA, Wang C, Koutrakis P, Zanobetti A, Dominici F, Schwartz JD. Air Pollutants and Asthma

Xia J, Gu S, Lei W, Zhang J, Wei H, Liu C, Zhang H, Lu R, Zhang L, Jiang M, Hu C, Cheng Z, Wei C, Chen Y, Lu F, Chen M, Bi H, Liu H, Yan C, Teng H, Yang Y, Liang C, Ge Y, Hou P, Liu J, Gao W, Zhang Y, Feng Y, Tao C, Huang X, Pan P, Luo H, Yun C, Zhan Q. High-flow nasal cannula versus conventional oxygen therapy in acute COPD exacerbation with mild hypercapnia: a multicenter randomized controlled trial. Crit Care. 2022 Apr 15;26(1):109. doi: 10.1186/s13054-022-03973-7. PMID: 35428349; PMCID: PMC9013098.
Background: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain.
Methods: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90.
Results: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups.
Conclusions: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups

1: Sánchez-García V, Pérez-Alcaraz L, Belinchón-Romero I, Ramos-Rincón JM. Comorbidities in Patients with Autoimmune Bullous Disorders: Hospital-Based Registry Study. Life (Basel).
2022 Apr 18;12(4):595. doi: 10.3390/life12040595. PMID: 35455086.
The incidence of autoimmune bullous disorders has increased over the years, especially in elderly patients with multiple comorbidities, which has stimulated research into their association with other diseases. We performed a retrospective observational study used the Minimum Basic Data Set of hospital discharges to review records of patients admitted to Spanish public hospitals between 2016 and 2019 with a diagnosis of any autoimmune bullous disorder. The objectives were to describe the comorbidity profile and the clinical-epidemiological characteristics of patients with pemphigus and pemphigoid, and analyze the evolution of the incidence of these diseases. The study included 1950 patients with pemphigus and 5424 patients with pemphigoid. Incidence increased from 2016 to 2019. The main comorbidities were hypertension (40.19%) and diabetes mellitus (28.57%). Compared to patients with pemphigoid, those with pemphigus had a higher prevalence of neoplasms, osteoporosis, solid metastases and malignant lymphoma, while the prevalence of hypertension, kidney disease, diabetes, heart failure, dementia, chronic obstructive pulmonary disease and Parkinson’s disease was higher in the pemphigoid group (p &lt; 0.05). Therefore, since autoimmune bullous disorders are associated with diverse comorbidities and their incidence has risen in recent years, the establishment of strategies to prevent the main comorbidities in these patients is justified.

2: Pépin JL, Degano B, Tamisier R, Viglino D. Remote Monitoring for Prediction and Management of Acute Exacerbations in Chronic Obstructive Pulmonary Disease (AECOPD). Life (Basel).
2022 Mar 29;12(4):499. doi: 10.3390/life12040499. PMID: 35454991.
The progression of chronic obstructive pulmonary disease (COPD) is characterized by episodes of acute exacerbation (AECOPD) of symptoms, decline in respiratory function, and reduction in quality-of-life increasing morbi-mortality and often requiring hospitalization. Exacerbations can be triggered by environmental exposures, changes in lifestyle, and/or physiological and psychological factors to greater or lesser extents depending on the individual’s COPD phenotype. The prediction and early detection of an exacerbation might allow patients and physicians to better manage the acute phase. We summarize the recent scientific data on remote telemonitoring (TM) for the prediction and management of acute exacerbations in COPD patients. We discuss the components of remote monitoring platforms, including the integration of environmental monitoring data; patient reported outcomes collected via interactive Smartphone apps, with data from wearable devices that monitor physical activity, heart rate, etc.; and data from medical devices such as connected non-invasive ventilators. We consider how telemonitoring and the deluge of data it potentially generates could be combined with electronic health records to provide personalized care and multi-disease management for COPD patients.

3: Eckhardt CM, Baccarelli AA, Wu H. Environmental Exposures and Extracellular Vesicles: Indicators of Systemic Effects and Human Disease. Curr Environ Health
Rep. 2022 Apr 21. doi: 10.1007/s40572-022-00357-5. Epub ahead of print. PMID: 35449498.
Purpose of review: Environmental pollutants contribute to the pathogenesis of numerous diseases including chronic cardiovascular, respiratory, and neurodegenerative diseases, among others. Emerging evidence suggests that extracellular vesicles (EVs) may mediate the association of environmental exposures with chronic diseases. The purpose of this review is to describe the impact of common environmental exposures on EVs and their role in linking environmental pollutants to the pathogenesis of chronic systemic diseases.
Recent findings: Common environmental pollutants including particulate matter, tobacco smoke, and chemical pollutants trigger the release of EVs from multiple systems in the body. Existing research has focused primarily on air pollutants, which alter EV production and release in the lungs and systemic circulation. Air pollutants also impact the selective loading of EV cargo including microRNA and proteins, which modify the cellular function in recipient cells. As a result, pollutant-induced EVs often contribute to a pro-inflammatory and pro-thrombotic milieu, which increases the risk of pollutant-related diseases including obstructive lung diseases, cardiovascular disease, neurodegenerative diseases, and lung cancer. Common environmental exposures are associated with multifaceted changes in EVs that lead to functional alterations in recipient cells and contribute to the pathogenesis of chronic systemic diseases. EVs may represent emerging targets for the prevention and treatment of diseases that stem from environmental exposures. However, novel research is required to expand our knowledge of the biological action of EV cargo, elucidate determinants of EV release, and fully understand the impact of environmental pollutants on human health

4: Ghosh AJ, Hobbs BD, Yun JH, Saferali A, Moll M, Xu Z, Chase RP, Morrow J, Ziniti J, Sciurba F, Barwick L, Limper AH, Flaherty K, Criner G, Brown KK, Wise R, Martinez FJ, McGoldrick D, Cho MH, DeMeo DL, Silverman EK, Castaldi PJ; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Hersh CP. Lung tissue shows divergent gene expression between chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Respir Res. 2022 Apr 21;23(1):97. doi: 10.1186/s12931-022-02013-w. PMID: 35449067.
Background: Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by shared exposures and clinical features, but distinct genetic and pathologic features exist. These features have not been well-studied using large-scale gene expression datasets. We hypothesized that there are divergent gene, pathway, and cellular signatures between COPD and IPF.
Methods: We performed RNA-sequencing on lung tissues from individuals with IPF (n = 231) and COPD (n = 377) compared to control (n = 267), defined as individuals with normal spirometry. We grouped the overlapping differential expression gene sets based on direction of expression and examined the resultant sets for genes of interest, pathway enrichment, and cell composition. Using gene set variation analysis, we validated the overlap group gene sets in independent COPD and IPF data sets.
Results: We found 5010 genes differentially expressed between COPD and control, and 11,454 genes differentially expressed between IPF and control (1% false discovery rate). 3846 genes overlapped between IPF and COPD. Several pathways were enriched for genes upregulated in COPD and downregulated in IPF; however, no pathways were enriched for genes downregulated in COPD and upregulated in IPF. There were many myeloid cell genes with increased expression in COPD but decreased in IPF. We found that the genes upregulated in COPD but downregulated in IPF were associated with lower lung function in the independent validation cohorts.
Conclusions: We identified a divergent gene expression signature between COPD and IPF, with increased expression in COPD and decreased in IPF. This signature is associated with worse lung function in both COPD and IPF.

5: Barrett NA, Hart N, Daly KJR, Marotti M, Kostakou E, Carlin C, Lua S, Singh S, Bentley A, Douiri A, Camporota L. A randomised controlled trial of non-invasive ventilation compared with extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease. Ann Intensive Care. 2022 Apr 21;12(1):36. doi: 10.1186/s13613-022-01006-8. PMID: 35445986; PMCID: PMC9021560.
Background: Patients presenting with acute hypercapnic respiratory failure due to exacerbations of chronic obstructive pulmonary disease (AECOPD) are typically managed with non-invasive ventilation (NIV). The impact of low-flow extracorporeal carbon dioxide removal (ECCO2R) on outcome in these patients has not been explored in randomised trials.
Methods: Open-label randomised trial comparing NIV (NIV arm) with ECCO2R (ECCO2R arm) in patients with AECOPD at high risk of NIV failure (pH < 7.30 after ≥ 1 h of NIV). The primary endpoint was time to cessation of NIV. Secondary outcomes included device tolerance and complications, changes in arterial blood gases, hospital survival.
Results: Eighteen patients (median age 67.5, IQR (61.5-71) years; median GOLD stage 3 were enrolled (nine in each arm). Time to NIV discontinuation was shorter with ECCO2R (7:00 (6:18-8:30) vs 24:30 (18:15-49:45) h, p = 0.004). Arterial pH was higher with ECCO2R at 4 h post-randomisation (7.35 (7.31-7.37) vs 7.25 (7.21-7.26), p < 0.001). Partial pressure of arterial CO2 (PaCO2) was significantly lower with ECCO2R at 4 h (6.8 (6.2-7.15) vs 8.3 (7.74-9.3) kPa; p = 0.024). Dyspnoea and comfort both rapidly improved with commencement of ECCO2R. There were no severe or life-threatening complications in the study population. There were no episodes of major bleeding or red blood cell transfusion in either group. ICU and hospital length of stay were longer with ECCO2R, and there was no difference in 90-day mortality or functional outcomes at follow-up.
Interpretation: There is evidence of benefit associated with ECCO2R with time to improvement in respiratory acidosis, in respiratory physiology and an immediate improvement in patient comfort and dyspnoea with commencement of ECCO2R. In addition, there was minimal clinically significant adverse events associated with ECCO2R use in patients with AECOPD at risk of failing or not tolerating NIV. However, the ICU and hospital lengths of stay were longer in the ECCO2R for similar outcomes. Trial registration The trial is prospectively registered on ClinicalTrials.gov: NCT02086084. Registered on 13th March 2014, https://clinicaltrials.gov/ct2/show/NCT02086084?cond=ecco2r&draw=2&rank=8.

6: Mk A, Gn N. Cardiac Troponin I in Acute Exacerbation of Chronic Obstructive Pulmonary Disease. J Assoc Physicians India. 2022 Apr;70(4):11-12. PMID: 35443477.
COPD is one of the leading causes of death worldwide and is very commonly associated with cardiovascular disorders and comorbidities. This study was carried out to assess the prognostic significance of cardiac troponin I when measured during an acute exacerbation of COPD.
Material: This is a cross-sectional study conducted for a period of 18 months among a total of 50 study subjects who presented with an acute exacerbation of COPD to the Medicine/Emergency Medicine/Pulmonary Medicine inpatient department after consideration of the inclusion and exclusion criteria. All the study subjects were tested for cardiac troponin I at admission and 24hrs later. Levels above 0.05 were considered positive. A detailed history, examination and relevant investigations were performed. All the categorical variables were expressed in proportions and continuous variables were expressed in means and standard deviation or medians and interquantile ranges. Chi square test was done to analyze the categorical variables. A p value of &lt;0.05 was considered statistically significant.
Observation: Among the 50 patients, 20 were females and 30 were males. cTnI was positive in 40% of patients. Patients with cTnI positive were included in group 1 and those with a negative cTnI were considered to be in group 2. Prevalence of comorbidities, the need for ICU admission and ventilatory support and in hospital mortality was higher in group 1 when compared to group 2.
Conclusion: Cardiac Troponin I is a strong and independent predictor of in hospital mortality in patients admitted with acute exacerbation of COPD. Patients with elevated Troponin I had longer duration of COPD and a higher incidence of IHD. Cardiac Troponin I elevation was associated with a greater need for ICU admission and ventilatory support.

7: Zhou J, Li X, Wang X, Yu N, Wang W. Accuracy of portable spirometers in the diagnosis of chronic obstructive pulmonary disease A meta-analysis. NPJ Prim Care Respir Med. 2022 Apr 19;32(1):15. doi: 10.1038/s41533-022-00275-x. PMID: 35440665.
Portable spirometers has been approved for diagnosing chronic obstructive pulmonary disease (COPD). However, their diagnostic accuracy has not been reviewed. Therefore, the purpose of this study was to systematically evaluate the diagnostic value of portable spirometers in detecting COPD. A comprehensive literature search for relevant studies was conducted in PubMed, Embase, CNKI, Wan Fang, and Web of Science databases. Pooled sensitivity, specificity, summary receiver operating characteristic (SROC), area under the curve (AUC), and other related indices were calculated using the bivariate mixed-effect model. Subgroup analysis was performed to explore the source of heterogeneity. Thirty one studies were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), SROC, and AUC of the SROC of portable spirometers were 0.85 (0.81-0.88), 0.85 (0.81-0.88), 5.6 (4.4-7.3), 0.18 (0.15-0.22), 31 (21-46) and 0.91 (0.89-0.94), respectively. Among the three commonly used types of portable spirometers, the accuracy of PIKO-6 was higher (0.95) than that of COPD-6 (0.91) and PEF (0.82). Subgroup analysis indicated that the accuracy of a multi-indices portable spirometer was higher than that of a single-index one (P < 0.05). In addition, portable spirometry performed by professional technicians in tertiary hospitals was more accurate than for those conducted by trained technicians in primary care facilities and communities (P < 0.05). Moreover, the accuracy of studies conducted in developing country was superior to developed country (P < 0.05). Portable spirometers have high accuracy in the diagnosis of COPD. Multi-index COPD-6 and PIKO-6 displayed higher accuracy than others. Standardized training of instrument operators should be considered to achieve reliable results.

8: Çolak Y, Nordestgaard BG, Lange P, Vestbo J, Afzal S. Prognosis of Patients with COPD Not Eligible for Major Clinical Trials. Am J Respir Crit Care Med. 2022 Apr 19. doi: 10.1164/rccm.202110-2441OC. Epub ahead of print. PMID:35438616.
Rationale: Randomised controlled trials only include a subset of patients with chronic obstructive pulmonary disease(COPD) fulfilling strict inclusion criteria. Thus, most patients with COPD in a real-world setting do not have the necessary evidence to support treatment effectiveness.
Objective: To test the hypotheses that most individuals with COPD in the general population are not represented in major clinical trials despite clinically significant disease with exacerbations and early death.
Methods: In 105,630 adults from a Danish contemporary population-based cohort, we defined COPD as age≥40 years, chronic respiratory symptoms, history of smoking exposure, and airflow limitation with forced expiratory volume in 1 second(FEV1)/forced vital capacity(FVC)<0.70. Outcomes included acute exacerbations and all-cause mortality. Symptomatic smokers without COPD were used as a reference group.
Measurements and main results: Of all, 7,516(7%) and 16,079(15%) were symptomatic smokers with and without COPD. Only 44% of those with COPD were eligible for major clinical trials when applying FEV1<80% predicted, smoking history≥10 pack-years, and no comorbid asthma as common inclusion criteria. During median 8.9 years follow-up, we observed 2,130 acute exacerbations and 3,973 deaths in symptomatic smokers. Compared to symptomatic smokers without COPD, multivariable adjusted hazard ratios(HRs) for exacerbations were 7.45(95% confidence interval:5.41-10.3) and 29.0(21.1-39.8) in those with COPD respectively excluded and eligible for clinical trials. Corresponding HRs for all-cause mortality were 1.21(1.11-1.31) and 1.67(1.54-1.81), respectively.
Conclusion: More than half of individuals with COPD in the general population are excluded from major clinical trials; however, these individuals have clinically significant disease with exacerbations and early death compared to symptomatic smokers without COPD.

9: Huang JT, Cant E, Keir HR, Barton AK, Kuzmanova E, Shuttleworth M, Pollock J, Finch S, Polverino E, Bottier M, Dicker AJ, Shoemark A, Chalmers JD. Endotyping COPD, Bronchiectasis and the ‘COPD-bronchiectasis Association’. Am J Respir Crit Care Med. 2022 Apr 18. doi: 10.1164/rccm.202108-1943OC. Epub ahead of print. PMID: 35436182.
Rationale Bronchiectasis and chronic obstructive pulmonary disease (COPD) are two disease entities with overlapped clinical features and co-diagnosis frequently occurs (termed as the ‘COPD-bronchiectasis association’). Objectives To investigate the sputum microbiome and proteome in patients with bronchiectasis, COPD, and the ‘COPD-bronchiectasis association’ with the aim of identifying endotypes that may inform treatment. Methods Sputum microbiome and protein profiling were carried out using 16S rRNA amplicon sequencing and a label-free proteomics workflow, respectively, in a cohort comprising patients with COPD (n=43), bronchiectasis (n=30) and the ‘COPD-bronchiectasis association’ (n=48). Results were validated in an independent cohort of 91 patients (n=28-31 each group) using targeted measurements of inflammatory markers, mucins and bacterial culture. Measurements and main results Principal component analysis of sputum microbiome and protein profiles showed a partial separation between the COPD and the ‘COPD-bronchiectasis association’ group. Further analyses revealed that patients with the ‘COPD-bronchiectasis association’ had a higher abundance of proteobacteria, higher expression of mucin-5AC and proteins from the “neutrophil degranulation” pathway compared to those with COPD. In contrast, COPD patients had an elevated expression of mucin-5B and several peptidase inhibitors, higher abundance of common commensal taxa, and a greater microbiome diversity. The profiles of ‘COPD-bronchiectasis association’ and bronchiectasis groups were largely overlapping. Five endotypes were proposed with differential inflammatory, mucin and microbiological features. The key features related to the ‘COPD-bronchiectasis association’ were validated in an independent cohort. Conclusion Neutrophilic inflammation, differential mucin expression and Gram-negative infection are dominant traits in patients with the ‘COPD-bronchiectasis association’.

10: Hirano T, Matsunaga K. Measurement of Blood Eosinophils in Asthma and Chronic Obstructive Pulmonary Disease. Intern Med. 2022 Apr 16. doi: 10.2169/internalmedicine.9339-22. Epub ahead of print. PMID: 35431305.
Eosinophils are important effector cells in airway inflammation, as pleiotropy and heterogeneity can be linked to various pathophysiologies in asthma and chronic obstructive pulmonary disease (COPD). Sputum eosinophils can reflect the heterogeneity of airway inflammation, and owing to their traits, blood eosinophils can be a surrogate and potential biomarker for managing both conditions. Blood eosinophils are activated via the stimulation of type 2 cytokines, such as interleukin (IL)-5, IL-4/13, granulocyte-macrophage colony-stimulating factor, IL-33, and thymic stromal lymphopoietin. There is sufficient evidence to support the relationship between the blood eosinophil count and clinical outcomes, including pulmonary function decline, exacerbations, all-cause mortality, and treatment response to inhaled corticosteroids and biologics. Thus, there is growing interest in the use of blood eosinophils for the management of these diseases. Compiling recent evidence, we herein review the significance of measuring blood eosinophils in asthma and COPD.

11: Mannino D, Bogart M, Wu B, Germain G, Laliberté F, MacKnight SD, Jung Y, Stiegler M, Duh MS. Adherence and persistence to once-daily single-inhaler versus multiple-inhaler triple therapy among patients with chronic obstructive pulmonary disease in the USA: A real-world study. Respir Med. 2022 Mar 18;197:106807. doi: 10.1016/j.rmed.2022.106807. Epub ahead of print. PMID: 35429764.
Background: Triple therapy comprising an inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2 agonist (ICS/LAMA/LABA) is recommended for chronic obstructive pulmonary disease (COPD) patients at risk of exacerbation. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence; however, these outcomes have not been evaluated for single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI).
Methods: This retrospective analysis of the IQVIA PharMetrics Plus claims database identified patients with COPD initiating triple therapy between 18 September 2017 and 30 June 2019. The first date of single-inhaler FF/UMEC/VI dispensing, or first day of overlapping ICS, LAMA, and LABA medications for MITT users, defined the index date. Patients were ≥40 years, had ≥12 months of continuous insurance coverage pre-index (baseline) and ≥6 months’ coverage post-index; those with MITT during baseline were excluded. Inverse probability weighting was used to balance baseline characteristics. Adherence was assessed using proportion of days covered (PDC) and was evaluated using linear and log-binomial models. Persistence (non-persistence identified as >30-day gap between fills) was evaluated using Cox models.
Results: 9942 patients (FF/UMEC/VI: 2782; MITT: 7160) were included. Adherence was significantly higher for FF/UMEC/VI versus MITT users (mean PDC, 0.66 vs. 0.48; p < 0.001), and FF/UMEC/VI users were twice as likely to be adherent (PDC ≥0.8) than MITT users (46.5% vs. 22.3%; risk ratio [95% CI]: 2.08 [1.85-2.30]; p < 0.001). After 12 months, significantly more FF/UMEC/VI users persisted on therapy than MITT users (35.7% vs. 13.9%; hazard ratio [95% CI]: 1.91 [1.81-2.01]; p < 0.001).
Conclusions: COPD patients initiating single-inhaler FF/UMEC/VI had significantly improved adherence and persistence compared with MITT.

Contoli M, Santus P, Menzella F, Rocchi C, Radovanovic D, Baraldi F, Martelli C, Casanova S, Barbetta C, Micheletto C, Scichilone N, Beghè B, Carpagnano E, Papi A. Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE). Clin Transl Allergy. 2022 Apr 7;12(4):e12143. doi: 10.1002/clt2.12143. PMID: 35423001; PMCID: PMC8988861.
Background: Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown.
Objectives: To evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels.
Methods: Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis.
Results: Three-month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (-35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig-E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control.
Conclusion: Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti-IL5-pathway treatments.

1: Buchheit KM, Sohail A, Hacker J, Maurer R, Gakpo D, Bensko JC, Taliaferro F, Ordovas-Montanes J, Laidlaw TM. Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2022 Apr 20:S0091-6749(22)00542-5. doi: 10.1016/j.jaci.2022.04.007. Epub ahead of print. PMID: 35460728.
Background: Dupilumab, a monoclonal antibody targeting IL-4Rα, improves upper and lower airway symptoms in patients with aspirin-exacerbated respiratory disease (AERD), but the mechanisms leading to clinical improvement are not fully elucidated.
Objective: To identify the mechanistic basis of clinical improvement in AERD patients treated with dupilumab.
Methods: Twenty-two patients with AERD were treated with dupilumab for 3 months for severe asthma and/or chronic rhinosinusitis with nasal polyps. Clinical outcomes were assessed at baseline and at one and three months after initiation of dupilumab. Nasal fluid, urine, blood, and inferior turbinate scrapings were collected at the three time points for mediator levels, cellular assays, and RNA-sequencing.
Results: Participants had rapid improvement in clinical measures including sense of smell, sinonasal symptoms, and lung function after 1 month of dupilumab, which were sustained after 3 months of dupilumab. Baseline severity of smell loss correlated with lower nasal prostaglandin E2 levels. Dupilumab increased nasal prostaglandin E2 and decreased levels of nasal albumin, nasal and urinary leukotriene E4, and serum and nasal IgE. Transcripts related to epithelial dysfunction and leukocyte activation and migration were downregulated in inferior turbinate tissue after treatment with dupilumab. There were no dupilumab-induced changes in nasal eosinophilia.
Conclusion: Inhibition of IL-4Rα in AERD led to rapid improvement in respiratory symptoms and smell, with a concomitant improvement in epithelial barrier function, a decrease in inflammatory eicosanoid levels, and an increase in the anti-inflammatory eicosanoid prostaglandin E2. The therapeutic effects of dupilumab are likely due to decreased IL-4Rα signaling on respiratory tissue granulocytes, epithelial cells, and B cells.

2: Ravi A, Chowdhury S, Dijkhuis A, Dierdorp BS, Dekker T, Kruize R, Sabogal Piñeros YS, Majoor CJ, Sterk PJ, Lutter R. Imprinting of bronchial epithelial cells upon <i>in vivo</i> rhinovirus infection in people with asthma. ERJ Open Res. 2022 Apr 19;8(2):00522-2021. doi: 10.1183/23120541.00522-2021. PMID: 35449758; PMCID: PMC9016171.
Background: Defective translocation of the translational repressor TIAR (T-cell internal antigen receptor) in bronchial epithelial cells (BECs) from asthma patients underlies epithelial hyperresponsiveness, reflected by an exaggerated production of a select panel of inflammatory cytokines such as CXCL-8, interleukin (IL)-6, granulocyte colony-stimulating factor, CXCL-10, upon exposure to tumour necrosis factor (TNF) and IL-17A. With this study we aimed to clarify whether epithelial hyperresponsiveness is a consistent finding, is changed upon in vivo exposure to rhinovirus (RV)-A16 and applies to the bronchoconstrictor endothelin-1.
Methods: BECs were obtained from asthma patients (n=18) and healthy individuals (n=11), 1 day before and 6 days post-RV-A16 exposure. BECs were cultured and stimulated with TNF and IL-17A and inflammatory mediators were analysed. The bronchoalveolar lavage fluid (BALF) was obtained in parallel with BECs to correlate differential cell counts and inflammatory mediators with epithelial hyperresponsiveness.
Results: Epithelial hyperresponsiveness was confirmed in sequential samples and even increased in BECs from asthma patients after RV-A16 exposure, but not in BECs from healthy individuals. Endothelin-1 tended to increase in BECs from asthma patients collected after RV-A16 exposure, but not in BECs from healthy individuals. In vitro CXCL-8 and endothelin-1 production correlated. In vivo relevance for in vitro CXCL-8 and endothelin-1 production was shown by correlations with forced expiratory volume in 1 s % predicted and CXCL-8 BALF levels.
Conclusion: Epithelial hyperresponsiveness is an intrinsic defect in BECs from asthma patients, which increases upon viral exposure, but not in BECs from healthy individuals. This epithelial hyperresponsiveness also applies to the bronchoconstrictor endothelin-1, which could be involved in airway obstruction.

3: Sicras-Mainar A, Gómez Rodríguez B, Traseira-Lugilde S, Fernández-Sánchez T, Velasco Garrido JL. Treatment persistence and exacerbations in patients with asthma initiating treatment with inhaled corticosteroids and beta-adrenergic agonists: retrospective cohort study. BMJ Open. 2022 Apr 20;12(4):e053964. doi: 10.1136/bmjopen-2021-053964. PMID: 35443946.
Objective: To determine treatment persistence and exacerbations in patients initiating inhaler treatment with fixed-dose combinations of inhaled corticosteroids/long-acting beta-2-adrenergic agonists (ICS/LABA) for the treatment of asthma.
Design: Retrospective observational study conducted by review of electronic medical records (database: Fundación RediSS).
Setting: Retrospective cohort study. The follow-up period was 1 year.
Participants: The study included patients aged ≥18 years who started treatment with ICS/LABA and met the inclusion/exclusion criteria.
Main outcomes and measures: The study groups were fluticasone propionate/salmeterol (FP/SAL), beclomethasone/formoterol (BDP/FORM), budesonide/formoterol (BUD/FORM), fluticasone furoate/vilanterol (FF/VI) and fluticasone propionate/formoterol (FP/FORM). The main measurements were persistence, medication possession ratio (MPR) and exacerbations. Statistical significance was established as p<0.05.
Results: In total, 3203 patients were recruited for the study. By groups, 31.1% FP/SAL, 28.6% BDP/FORM, 25.0% BUD/FORM, 8.2% FF/VI and 7.0% FP/FORM. The mean age was 52.2 years, 60.8% were female and 44.9% had persistent-moderate asthma. Treatment persistence was 61.7% (95% CI 60.0% to 63.4%) and by study group it was FP/SAL: 60.7%, BDP/FORM: 61.2%, BUD/FORM: 60.3%, FF/VI: 66.7% and FP/FORM: 67.6% (p=0.046). MPR by study group was FP/SAL: 74.3%, BDP/FORM: 73.8%, BUD/FORM: 74.6%, FF/VI: 79.4% and FP/FORM: 80.6% (p=0.028). The mortality rate was 2.9%. By treatment group, exacerbations were FP/SAL: 21.9% (95% CI 19.3% to 24.5%), BDP/FORM: 22.2% (95% CI 19.5% to 24.9%), BUD/FORM: 22.8% (95% CI 19.9% to 25.7%), FF/VI: 17.9% (95% CI 14.9% to 20.7%) and FP/FORM: 16.0% (95% CI 12.2% to 19.3%), p=0.036.
Conclusions: Patients undergoing treatment with FP/FORM and FF/VI versus FP/SAL, BDP/FORM and BUD/FORM were associated with greater treatment adherence (persistence, MPR) and lower rates of exacerbations. However, further studies will be needed to strengthen the consistency of the results.

4: van der Burg N, Stenberg H, Ekstedt S, Diamant Z, Bornesund D, Ankerst J, Georén SK, Cardell LO, Bjermer L, Erjefält J, Tufvesson E. Neutrophil phenotypes in bronchial airways differentiate single from dual responding allergic asthmatics. Clin Exp Allergy. 2022 Apr 19. doi: 10.1111/cea.14149. Epub ahead of print. PMID: 35437872.
Introduction: Allergic asthmatics with both an early (EAR) and a late allergic reaction (LAR) following allergen exposure are termed ‘dual responders’ (DR), while ‘single responders’ (SR) only have an EAR. Mechanisms that differentiate DR from SR are largely unknown, particularly regarding the role and phenotypes of neutrophils. Therefore, we aimed to study neutrophilsin DR and SR asthmatics.
Methods: Thirty-four allergic asthmatics underwent an inhaled allergen challenge, samples were collected before and up to 24 h post-challenge. Cell differentials were counted from bronchial lavage, alveolar lavage and blood; and tissue neutrophils were quantified in immune-stained bronchial biopsies. Lavage neutrophil nuclei lobe segmentation was used to classify active (1-4 lobes) from suppressive neutrophils (≥5 lobes). Levels of transmigration markers: soluble (s)CD62L and interleukin-1Ra, and activity markers: neutrophil elastase (NE), DNA-histone complex and dsDNA were measured in lavage fluid and plasma.
Results: Compared to SR at baseline, DR had more neutrophils in their bronchial airways at baseline, both in the lavage (p=0.0031) and biopsies (p=0.026) and elevated bronchial neutrophils correlated with less anti-transmigratory IL-1Ra levels (r=-0.64). DR airways had less suppressive neutrophils and more 3-lobed (active) neutrophils (p=0.029) that correlated with more bronchial lavage histone (p=0.020) and more plasma NE (p=0.0016). Post-challenge, DR released neutrophil extracellular trap factors in the blood earlier and had less pro-transmigratory sCD62L during the late phase (p=0.0076) than SR.
Conclusion: DR have a more active airway neutrophil phenotype at baseline and a distinct neutrophil response to allergen challenge that may contribute to the development of an LAR. Therefore, neutrophil activity should be considered during targeted diagnosis and bio-therapeutic development for DR.

5: Chung HL. Diagnosis and management of asthma in infants and preschoolers.
Clin Exp Pediatr. 2022 Apr 19. doi: 10.3345/cep.2021.01746. Epub ahead of print.
PMID: 35436814.
Asthma is one of the most common chronic disease affecting children, and it often starts in infancy and preschool years. In previous birth cohorts, frequent wheezing in early life was associated with the development of asthma in later childhood and reduced lung function persisting into adulthood. Preschool wheezing is considered an umbrella term for distinctive diseases with different clinical features (phenotypes), each of which may be related to different underlying pathophysiologic mechanisms (endotypes). The classification of phenotypes of early wheezing is needed to identify children at high risk for developing asthma later who might benefit from early intervention. However, diagnosis of asthma in infants and preschoolers is particularly difficult because objective lung function tests cannot be performed and definitive biomarkers are lacking. Moreover, management of early asthma is challenging because of its different phenotypic presentations. Many prediction models and asthma guidelines have been developed that provide useful information for physicians to assess young children with recurrent wheezing and present helpful approaches to manage them appropriately. Many recent studies have investigated the application of personalized medicine for early asthma by identifying specific phenotypes and biomarkers. Further researches, including genetic and molecular studies, are needed to establish a clear definition of asthma and develop more targeted therapeutic approaches in this age group

6: Extremera Ortega AM, Moreno Lozano L, González Jiménez OM, Borja Segade J, Joyanes Romo JB, Muñoz Rodríguez JR, Feo-Brito F, Galindo Bonilla PA. Findings in Chest High-Resolution Computed Tomography in Severe Asthma. J Investig Allergol Clin Immunol. 2022 Apr 19;32(2):146-147. doi: 10.18176/jiaci.0725. Epub 2021 Jul 2. PMID: 34213422.

7: Bobolea I, Bañas D, Melero C, de Andrés AI, Joksaite S, Sánchez-Herrero G.
Exacerbation Rate Reduction With Mepolizumab Stratified by Maintenance Oral Corticosteroids Use and Eosinophil Levels: A Post Hoc Analysis of the DREAM and MENSA Studies. J Investig Allergol Clin Immunol. 2022 Apr 19;32(2):148-150. doi: 10.18176/jiaci.0714. Epub 2021 Jun 4. PMID: 34085935
Background: Findings from previous studies showed that mepolizumab significantly reduces the rate of exacerbations in patients with severe eosinophilic asthma. To assess the relationship between baseline blood eosinophil counts and efficacy of mepolizumab we did a secondary analysis of data from two studies, stratifying patients by different baseline blood eosinophil thresholds.
Methods: We did a post-hoc analysis of data, which was completed on Sept 25, 2015, from two randomised, double-blind, placebo-controlled studies of at least 32 weeks duration (NCT01000506 [DREAM] and NCT01691521 [MENSA]) done between 2009 and 2014. In these studies, mepolizumab (
Dream: 75 mg, 250 mg, or 750 mg intravenously; MENSA: 75 mg intravenously or 100 mg subcutaneously) versus placebo was given at 4-week intervals in addition to standard care (high-dose inhaled corticosteroids plus ≥1 additional controller with or without daily oral corticosteroids) to patients aged 12 years or older with a clinical diagnosis of asthma, a history of at least two exacerbations in the previous year that required systemic corticosteroid treatment, and evidence of eosinophilic airway inflammation. The primary endpoint in both studies was the annual rate of clinically significant exacerbations (defined as worsening of asthma that required the use of systemic corticosteroids, or admission to hospital, or an emergency-room visit, or a combination of these occurrences). In our analysis, the primary outcome was the annualised rate of exacerbations in patients stratified by baseline eosinophil counts (≥150 cells per μL, ≥300 cells per μL, ≥400 cells per μL, and ≥500 cells per μL) and baseline blood eosinophil ranges (<150 cells per μL, ≥150 cells per μL to <300 cells per μL, ≥300 cells per μL to <500 cells per μL, and ≥500 cells per μL). We based our analysis on the intention-to-treat populations of the two original studies, and all mepolizumab doses were combined for analysis.
Findings: Of 1192 patients, 846 received mepolizumab and 346 received placebo. The overall rate of mean exacerbations per person per year was reduced from 1·91 with placebo to 1·01 with mepolizumab (47% reduction; rate ratio [RR] 0·53, 95% CI 0·44-0·62; p<0·0001). The exacerbation rate reduction with mepolizumab versus placebo increased progressively from 52%; 0·48, 0·39-0·58) in patients with a baseline blood eosinophil count of at least 150 cells per μL to 70%; 0·30, 0·23-0·40]) in patients with a baseline count of at least 500 cells per μL. At a baseline count less than 150 cells per μL, predicted efficacy of mepolizumab was reduced.
Interpretation: Our analysis has shown a close relationship between baseline blood eosinophil count and clinical efficacy of mepolizumab in patients with severe eosinophilic asthma and a history of exacerbations. We noted clinically relevant reductions in exacerbation frequency in patients with a count of 150 cells per μL or more at baseline. The use of this baseline biomarker will help to select patients who are likely to achieve important asthma outcomes with mepolizumab.

1: Soyyiğit S, Aydın Ö, Seçil D, Doğan C, Gökmen D, Sin BA, Mısırlıgil Z, Mungan
VD. Pre-seasonal immunotherapy is effective in both monosensitized and polysensitized patients with allergic rhinitis. Eur Ann Allergy Clin Immunol.
2022 Apr 22. doi: 10.23822/EurAnnACI.1764-1489.252. Epub ahead of print. PMID: 35448936.
Background. The effectiveness of pre-seasonal allergoid immunotherapy in polysensitized patients are not well-known. The aim of the present study was to compare the clinical efficacy and immunological changes of pre-seasonal allergoid immunotherapy in mono- and polysensitized patients with grass pollen allergy. Methods. Fourty six patients with seasonal allergic rhinitis undergoing pre-seasonal grass pollen immunotherapy and 28 cases followed by conventional drug treatment were included. These groups were divided into monosensitized and polysensitized ones. All patients were followed between March-September with symptom-medication scores, and visual analogue scale (VAS). The quality of life was assessed using the Mini-RQLQ questionnaire. Phleum pratense (Phl p) specific IgE and IgG4 (UNI-CAP 100, Phadia) measurements were performed before and after 7 weeks of immunotherapy. Results. In the immunotherapy group, 15th weekly symptom-medication scores and VAS scores between May and August were found to be significantly lower than those in the control group (p less than 0.05). Phl p specific IgE and IgG4 levels were significantly higher after immunotherapy compared to those before immunotherapy (p = 0.001). Furthermore, P

1: Xia J, Gu S, Lei W, Zhang J, Wei H, Liu C, Zhang H, Lu R, Zhang L, Jiang M,
Hu C, Cheng Z, Wei C, Chen Y, Lu F, Chen M, Bi H, Liu H, Yan C, Teng H, Yang Y,
Liang C, Ge Y, Hou P, Liu J, Gao W, Zhang Y, Feng Y, Tao C, Huang X, Pan P, Luo
H, Yun C, Zhan Q. High-flow nasal cannula versus conventional oxygen therapy in
acute COPD exacerbation with mild hypercapnia: a multicenter randomized
controlled trial. Crit Care. 2022 Apr 15;26(1):109. doi:
10.1186/s13054-022-03973-7. PMID: 35428349.
Background: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain.
Methods: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90.
Results: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups.
Conclusions: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups.

2: Cho MH, Hobbs BD, Silverman EK. Genetics of chronic obstructive pulmonary
disease: understanding the pathobiology and heterogeneity of a complex disorder.
Lancet Respir Med. 2022 Apr 12:S2213-2600(21)00510-5. doi:
10.1016/S2213-2600(21)00510-5. Epub ahead of print. PMID: 35427534.
Chronic obstructive pulmonary disease (COPD) is a deadly and highly morbid disease. Susceptibility to and heterogeneity of COPD are incompletely explained by environmental factors such as cigarette smoking. Family-based and population-based studies have shown that a substantial proportion of COPD risk is related to genetic variation. Genetic association studies have identified hundreds of genetic variants that affect risk for COPD, decreased lung function, and other COPD-related traits. These genetic variants are associated with other pulmonary and non-pulmonary traits, demonstrate a genetic basis for at least part of COPD heterogeneity, have a substantial effect on COPD risk in aggregate, implicate early-life events in COPD pathogenesis, and often involve genes not previously suspected to have a role in COPD. Additional progress will require larger genetic studies with more ancestral diversity, improved profiling of rare variants, and better statistical methods. Through integration of genetic data with other omics data and comprehensive COPD phenotypes, as well as functional description of causal mechanisms for genetic risk variants, COPD genetics will continue to inform novel approaches to understanding the pathobiology of COPD and developing new strategies for management and treatment.

3: Agustí A, Melén E, DeMeo DL, Breyer-Kohansal R, Faner R. Pathogenesis of
chronic obstructive pulmonary disease: understanding the contributions of gene-
environment interactions across the lifespan. Lancet Respir Med. 2022 Apr
12:S2213-2600(21)00555-5. doi: 10.1016/S2213-2600(21)00555-5. Epub ahead of
print. PMID: 35427533.
The traditional view of chronic obstructive pulmonary disease (COPD) as a self-inflicted disease caused by tobacco smoking in genetically susceptible individuals has been challenged by recent research findings. COPD can instead be understood as the potential end result of the accumulation of gene-environment interactions encountered by an individual over the life course. Integration of a time axis in pathogenic models of COPD is necessary because the biological responses to and clinical consequences of different exposures might vary according to both the age of an individual at which a given gene-environment interaction occurs and the cumulative history of previous gene-environment interactions. Future research should aim to understand the effects of dynamic interactions between genes (G) and the environment (E) by integrating information from basic omics (eg, genomics, epigenomics, proteomics) and clinical omics (eg, phenomics, physiomics, radiomics) with exposures (the exposome) over time (T)-an approach that we refer to as GETomics. In the context of this approach, we argue that COPD should be viewed not as a single disease, but as a clinical syndrome characterised by a recognisable pattern of chronic symptoms and structural or functional impairments due to gene-environment interactions across the lifespan that influence normal lung development and ageing.

4: Yang IA, Jenkins CR, Salvi SS. Chronic obstructive pulmonary disease in
never-smokers: risk factors, pathogenesis, and implications for prevention and
treatment. Lancet Respir Med. 2022 Apr 12:S2213-2600(21)00506-3. doi:
10.1016/S2213-2600(21)00506-3. Epub ahead of print. PMID: 35427530.
Chronic obstructive pulmonary disease (COPD) was traditionally thought to be caused by tobacco smoking. However, recognition of the importance of non-smoking-related risk factors for COPD has increased over the past decade, with evidence on the burden, risk factors, and clinical presentations of COPD in never-smokers. About half of all COPD cases worldwide are due to non-tobacco-related risk factors, which vary by geographical region. These factors include air pollution, occupational exposures, poorly controlled asthma, environmental tobacco smoke, infectious diseases, and low socioeconomic status. Impaired lung growth during childhood, caused by a range of early-life exposures, is associated with an increased risk of COPD. Potential mechanisms for the pathogenesis of COPD in never-smokers include inflammation, oxidative stress, airway remodelling, and accelerated lung ageing. Compared with smokers who develop COPD, never-smokers with COPD have relatively mild chronic respiratory symptoms, little or no emphysema, milder airflow limitation, and fewer comorbidities; however, exacerbations can still be frequent. Further research-including epidemiological, translational, clinical, and implementation studies-is needed to address gaps in understanding and to advance potential solutions to reduce the burden of COPD in never-smokers.

5: Cotton S, Devereux G, Abbas H, Briggs A, Campbell K, Chaudhuri R, Choudhury
G, Dawson D, De Soyza A, Fielding S, Gompertz S, Haughney J, Lang CC, Lee AJ,
MacLennan G, MacNee W, McCormack K, McMeekin N, Mills NL, Morice A, Norrie J,
Petrie MC, Price D, Short P, Vestbo J, Walker P, Wedzicha J, Wilson A, Lipworth
BJ. Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation
in people with chronic obstructive pulmonary disease (COPD): a randomised
controlled trial (BICS). Trials. 2022 Apr 14;23(1):307. doi:
10.1186/s13063-022-06226-8. PMID: 35422024.
Background: Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.
Methods: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1 < 80% predicted, FEV1/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4-7 weeks depending on tolerance to up-dosing of bisoprolol/placebo-these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and measurement of blood biomarkers.
Discussion: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally.

6: Congleton J. Urgent! A call to put the ‘O’ back in COPD. Drug Ther Bull. 2022
Apr 12:dtb-2021-000068. doi: 10.1136/dtb.2021.000068. Epub ahead of print. PMID:
35414593.
Chronic obstructive pulmonary disease (COPD) is the second most common long-term respiratory condition and it is estimated that exacerbations of COPD lead to over a million bed-days per year.1–3 In 2020/2021, the Quality and Outcomes Framework (QOF) data recorded 1.2 million people in England with a diagnosis of COPD and it is thought that an additional 2 million cases may be undiagnosed.1 2 The cause of COPD is inhalation of toxins, primarily cigarette smoke, which results in mucus hypersecretion and anatomical distortion in the large airways, fibrosis and obliteration of small airways and destruction of the parenchyma (emphysema). All three processes lead to ‘airflow obstruction’, that is, limitation of flow in expiration, particularly apparent when increased flow is required on exertion, leading to breathlessness and exercise limitation. The degree of airflow obstruction is an important predictor of complications such as exacerbations, respiratory failure and death …..
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7: Choi N, Jang S, Yoo KH, Rhee CK, Kim Y. The Effectiveness and Harms of
Screening for Chronic Obstructive Pulmonary Disease: An Updated Systematic
Review and Meta-Analysis. J Korean Med Sci. 2022 Apr 11;37(14):e117. doi:
10.3346/jkms.2022.37.e117. PMID: 35411733.
Background: This study aimed to perform meta-analyses to update a previous systematic review (SR) conducted by the US Preventive Services Task Force (USPSTF) to evaluate the benefits and harms of screening for chronic obstructive pulmonary disease (COPD) in asymptomatic adults.
Methods: MEDLINE, EMBASE, Cochrane Library, and regional databases were searched from their inception to January 2020. Studies for diagnostic accuracy, preventive services effect, treatment efficacy, and treatment harms were included.
Results: Eighteen studies were included, and twelve of these were newly added in this update. In meta-analyses, the pooled sensitivity and specificity for COPD diagnosis using spirometry were 73.4% and 89.0%, respectively. The relative effect of smoking cessation intervention with screening spirometry, presented as abstinence rate, was not statistically significant (risk ratio [RR], 1.21; 95% confidence interval [CI], 0.87-1.67) when all selected studies were pooled, but screening on smoking cessation was effective (RR, 1.58; 95% CI, 1.14-2.19) when limited to studies with smoking cessation programs that provided smoking cessation medicines or intensive counseling at public health centers or medical institutions.
Conclusion: In this study, no direct evidence for the impact on health outcomes of screening asymptomatic adults for COPD was identified similar to the previous SR. Further research is necessary to confirm the benefits of COPD screening.

8: Singanayagam A, Footitt J, Marczynski M, Radicioni G, Cross MT, Finney LJ,
Trujillo-Torralbo MB, Calderazzo M, Zhu J, Aniscenko J, Clarke TB, Molyneaux PL,
Bartlett NW, Moffatt MF, Cookson WO, Wedzicha J, Evans CM, Boucher RC, Kesimer
M, Lieleg O, Mallia P, Johnston SL. Airway mucins promote immunopathology in
virus-exacerbated chronic obstructive pulmonary disease. J Clin Invest. 2022 Apr
15;132(8):e120901. doi: 10.1172/JCI120901. PMID: 35239513.
The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases, but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway mucin 5AC (MUC5AC) and MUC5B concentrations during spontaneous and experimentally induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with viral load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation, as Muc5ac-deficient (Muc5ac-/-) mice had attenuated RV-induced (RV-induced) airway inflammation, and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased the release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of RV-induced inflammation in mice. Therapeutic suppression of mucin production using an EGFR antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B expression suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identified a proinflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.

1: Holmes J, Heaney LG, McGarvey LPA. Objective and Subjective Measurement of
Cough in Asthma: A Systematic Review of the Literature. Lung. 2022 Apr 13. doi:
10.1007/s00408-022-00527-0. Epub ahead of print. PMID: 35416544.
Background: The extent to which objective and subjective tools has been used to measure the characteristics and burden of cough in patients with asthma has not been reported.
Objective: To review the large and extensive body of literature in asthma with the specific hypothesis that the characteristics of cough and clinical impact in this disease has only occasionally been studied.
Methods: For this systematic review, we searched EMBASE and MEDLINE databases using a combination of MeSH terms for “cough” and “asthma” for studies published up to and including end of August 2021. Studies included for analysis were confined to those undertaken in adult patients (≥ 18 years) with asthma of any severity where any tool or method to specifically measure cough was employed.
Results: Of 12,090 citations identified after our initial search, 112 full-text articles met criteria for inclusion in our analysis. We found that a broad range of objective and subjective measures have been used albeit with a lack of consistency between studies. Clinically important levels of cough associated with impaired health status were identified in patients with asthma.
Conclusion: Although cough is a common symptom in asthma, the clinical features and accompanying healthcare burden have been studied infrequently. In studies where cough was measured, the methods employed varied considerably. A more consistent use of cough-specific measurement tools is required to better determine the nature and burden of cough in asthma.

2: Duijts L, Fleming LJ, Bacharier LB, Pitrez PM, Reddel HK. Reply to Baraldi
and Piacentini: Global Initiative for Asthma 2021: Asthma in Preschool Children
and Short-Acting β₂-Agonist-Only Treatment. Am J Respir Crit Care
Med. 2022 Apr 15;205(8):972-973. doi: 10.1164/rccm.202112-2788LE. PMID:
35202561.

3: Baraldi E, Piacentini G. Global Initiative for Asthma 2021: Asthma in
Preschool Children and Short-Acting β₂-Agonist-Only Treatment. Am J
Respir Crit Care Med. 2022 Apr 15;205(8):971-972. doi:
10.1164/rccm.202111-2465LE. PMID: 35202554.

1: Chu NN, Huang K, Que LL, Ding Y, Gu XH, Zhang L, Wang JK, Chen XP, Sun ZG, He
Q. Safety, Tolerability, and Pharmacokinetic Study of 101BHG-D01 Nasal Spray, a
Novel Long-Acting and Selective Cholinergic M Receptor Antagonist, in Healthy
Chinese Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Single-Dose
Escalation, First-In-Human Study. Eur J Drug Metab Pharmacokinet. 2022 Apr 16.
doi: 10.1007/s13318-022-00769-6. Epub ahead of print. PMID: 35429285.
Background and objective: 101BHG-D01 nasal spray is the first novel long-acting cholinergic M receptor antagonist under development to treat rhinorrhea in rhinitis. This first-in-human study aimed to evaluate the safety, tolerability, and pharmacokinetics of 101BHG-D01 nasal spray following single intranasal doses in healthy Chinese subjects.
Methods: A randomized, double-blind, placebo-controlled, single-dose escalation study was conducted in healthy Chinese volunteers after intranasal doses of 101BHG-D01 nasal spray or placebo ranging from 40 µg to 960 µg (total of six doses). Blood samples were collected at scheduled time points, and plasma concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental method was used to calculate the main pharmacokinetic parameters, including the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t), the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), the maximum plasma concentration (Cmax), the time to maximum plasma concentration (Tmax), and the elimination half-life (t1/2). Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations, 12-lead electrocardiograms (ECGs), anterior rhinoscopy, ophthalmic examination, and ambulatory ECG monitoring.
Results: Following single intranasal dosing, 101BHG-D01 was rapidly absorbed with a median Tmax of 0.34-0.50 h and eliminated slowly with a mean t1/2 ranging from 4.29 to 46.76 h for different dose groups. The Cmax and AUC of 101BHG-D01 increased linearly across the examined dose range of 40-960 µg. 101BHG-D01 nasal spray was well tolerated, all AEs were mild, and no serious adverse events occurred during the study.
Conclusions: 101BHG-D01 nasal spray was safe and well tolerated in healthy Chinese subjects when administered intranasally in single escalating doses. The mean Cmax and AUC increased proportionally to the studied dose. The pharmacokinetic, safety, and tolerability profiles of 101BHG-D01 nasal spray indicate that it is a good candidate for further development as a treatment for rhinorrhea in rhinitis.

Vestergaard AHS, Christiansen CF, Neergaard MA, Valentin JB, Johnsen SP. Healthcare utilisation trajectories in patients dying from chronic obstructive pulmonary disease, heart failure or cancer: a nationwide register-based cohort study. BMJ Open. 2021 Nov 24;11(11):e049661. doi: 10.1136/bmjopen-2021-049661. PMID: 34819282; PMCID: PMC8614146.
Objectives: To investigate illness trajectories as reflected by healthcare utilisation, including hospital and intensive care unit admissions, consultations in general practice and home care provision, before death comparing people dying from chronic obstructive pulmonary disease (COPD), heart failure and cancer.
Design: Nationwide register-based cohort study.
Setting: Data on all hospital admissions, including intensive care unit admissions, consultations in general practice and home care provision were obtained from nationwide Danish registries.
Participants: All adult decedents in Denmark dying from COPD, heart failure or cancer between 2006 and 2016.
Outcome measures: For each day within 5 years before death, we computed a daily prevalence proportion (PP) of being admitted to hospital or consulting a general practitioner. For each day within 6 months before death, we computed PPs of being admitted to intensive care or receiving home care. The PPs were plotted and compared by regression analyses adjusting for age, gender, comorbidity level, marital/cohabitation status, municipality and income level.
Results: Among 1 74 086 patients dying from COPD (n=22 648), heart failure (n=11 498) or cancer (n=139 940), the PPs of being admitted to hospital or consulting a general practitioner showed similar steady progression and steep increase in the last year of life for all patient populations. The PP of being admitted to intensive care showed modest increase during the last 6 months of life, accelerating in the last month, for all patient populations. For patients with COPD and heart failure, the PP of receiving home care remained stable during the last 6 months of life but increased steadily for patients with cancer.
Conclusion: We found limited differences in healthcare resource utilisation at the end of life for people with COPD, heart failure or cancer, indicating comparable illness trajectories.This supports the need to reconsider efforts in achieving equal access to palliative care interventions, which is still mainly offered to patients with cancer.

Whittaker H, Rubino A, Müllerová H, Morris T, Varghese P, Xu Y, De Nigris E, Quint JK. Frequency and Severity of Exacerbations of COPD Associated with Future Risk of Exacerbations and Mortality: A UK Routine Health Care Data Study. Int J Chron Obstruct Pulmon Dis. 2022 Mar 3;17:427-437. doi: 10.2147/COPD.S346591. PMID: 35264849; PMCID: PMC8901192.
Background: Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes.
Objective: To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort.
Methods: Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up.
Results: Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66-1.74), 2.31 (95% CI 2.24-2.37), and 3.52 (95% CI 3.43-3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion.
Conclusion: Increasing number and severity of exacerbations were associated with increasing risk of subsequent exacerbations, all-cause mortality and COPD-related mortality. Even a single moderate event increases the risk of future events, illustrating that every exacerbation counts.

Wollsching-Strobel M, Schwarz SB, Mathes T, Majorski DS, Heidari P, Kroppen D, Magnet FS, Windisch W. Anemia Severely Reduces Health-Related Quality of Life in COPD Patients Receiving Long-Term Home Non-Invasive Ventilation. Int J Chron Obstruct Pulmon Dis. 2021 Oct 28;16:2963-2971. doi: 10.2147/COPD.S328404. PMID: 34737561; PMCID: PMC8560082.
Purpose: To assess the influence of anemia on health-related quality of life (HRQL) in COPD patients receiving long-term non-invasive ventilation (NIV).
Patients and methods: In this prospective single-center cohort study, COPD patients on long-term NIV were analyzed between June 2015 and May 2020. Linear multiple regression analyses were performed using the results of the Severe Respiratory Insufficiency Questionnaire (SRI) along with the following variables: sex, age, body mass index, duration of NIV, exacerbation history (≤1 versus >1 in the previous year), the updated Charlson comorbidity index, hemoglobin levels and anemia (WHO criteria).
Results: Anemia was identified in 32.8% (N=128). Anemia (mean difference -8.4, 95% CI -2.0/-14.9 SRI points, P=0.011) and exacerbations (mean difference -9.9, 95% CI -4.3/-15.5 SRI points, P=0.001) each had a negative impact on SRI summary scores. Exacerbations were negatively associated with six out of seven SRI subscale scores, while anemia was negatively associated with four out of seven. SRI summary scores dropped by 1.5 points for every g/dl of hemoglobin (P=0.08). No other variables had an influence on the SRI scores.
Conclusion: The present study has shown that within a cohort of COPD patients undergoing long-term NIV, one-third were identified as anemic. Furthermore, anemia, like exacerbation history, was found to have a considerable negative impact on HRQL that is specific to patients with chronic respiratory failure.

You L, Niu H, Huang K, Dong F, Yang T, Wang C. Clinical Features and Outcomes of Acute Exacerbation in Chronic Obstructive Pulmonary Disease Patients with Pulmonary Heart Disease: A Multicenter Observational Study. Int J Chron Obstruct Pulmon Dis. 2021 Oct 22;16:2901-2910. doi: 10.2147/COPD.S325925. PMID: 34712043; PMCID: PMC8547596.
Purpose: To identify clinical features and outcomes associated with pulmonary heart disease among patients with chronic obstructive pulmonary disease exacerbation (COPD), which may help reduce economic burden accrued over hospital stay and shorten length of stay (LOS).
Patients and methods: Totally, 4386 patients with acute exacerbation of COPD (AECOPD) classified into pulmonary heart disease (PHD) group and non-pulmonary heart disease group, were included from the ACURE registry, a prospective multicenter patient registry study. Clinical features and outcomes were compared between groups.
Results: PHD patients had a more severe profile, including having higher scores of COPD assessment test and modified British Medical Research Council, worse lung function, more patients hospitalized more than once in the past year due to acute exacerbation of COPD, and more comorbidities. Furthermore, drug cost was higher and length of stay was longer in AECOPD patients with PHD.
Conclusion: AECOPD patients with PHD had a more severe profile and worse clinical outcomes, including higher drug cost and longer LOS. PHD is an independent risk factor of drug cost and LOS. Complicated with PHD in COPD/AECOPD patients with PHD means heavier disease burden and worse prognosis. It merits further study to focus on PHD management in COPD/AECOPD patients.

Zhou T, Liu P, Dhruva SS, Shah ND, Ramachandran R, Berg KM, Ross JS. Assessment of Hypothetical Out-of-Pocket Costs of Guideline-Recommended Medications for the Treatment of Older Adults With Multiple Chronic Conditions, 2009 and 2019. JAMA Intern Med. 2022 Feb 1;182(2):185-195. doi: 10.1001/jamainternmed.2021.7457. PMID: 34982097; PMCID: PMC8728660.
Importance: Most adults 65 years or older have multiple chronic conditions. Managing these conditions with prescription drugs can be costly, particularly for older adults with limited incomes.
Objective: To estimate hypothetical out-of-pocket costs associated with guideline-recommended outpatient medications for the initial treatment of 8 common chronic diseases among older adults with Medicare prescription drug plans (PDPs).
Design, setting, and participants: This retrospective cross-sectional study used 2009 and 2019 Medicare prescription drug plan formulary files to estimate annual out-of-pocket costs among hypothetical patients enrolled in Medicare Advantage or stand-alone Medicare Part D plans. A total of 3599 PDPs in 2009 and 3618 PDPs in 2019 were included after inclusion and exclusion criteria were applied. Costs associated with guideline-recommended medications for 8 of the most common chronic diseases (atrial fibrillation, chronic obstructive pulmonary disease [COPD], heart failure with reduced ejection fraction, hypercholesterolemia, hypertension, osteoarthritis, osteoporosis, and type 2 diabetes), alone and in 2 clusters of commonly comorbid conditions, were examined.
Main outcomes and measures: Annual out-of-pocket costs for each chronic condition, inflation adjusted to 2019 dollars.
Results: Among 3599 Medicare PDPs in 2009, 1998 were Medicare Advantage plans and 1601 were stand-alone plans; among 3618 Medicare PDPs in 2019, 2719 were Medicare Advantage plans and 899 were stand-alone plans. For an older adult enrolled in any Medicare PDP in 2019, the median annual out-of-pocket costs for individual conditions varied, from a minimum of $32 (IQR, $6-$48) for guideline-recommended management of osteoporosis (a decrease from $128 [IQR, $102-$183] in 2009) to a maximum of $1579 (IQR, $1524-$2229) for guideline-recommended management of atrial fibrillation (an increase from $91 [IQR, $73-$124] in 2009). For an older adult with a cluster of 5 commonly comorbid conditions (COPD, hypertension, osteoarthritis, osteoporosis, and type 2 diabetes) enrolled in any PDP, the median out-of-pocket cost in 2019 was $1999 (IQR, $1630-$2564), a 12% decrease from $2284 (IQR, $1920-$3107) in 2009. For an older adult with all 8 chronic conditions (atrial fibrillation, COPD, diabetes, hypercholesterolemia, heart failure, hypertension, osteoarthritis, and osteoporosis) enrolled in any PDP, the median out-of-pocket cost in 2019 was $3630 (IQR, $3234-$5197), a 41% increase from $2571 (IQR, $2185-$3719) in 2009.
Conclusions and relevance: In this cross-sectional study, out-of-pocket costs for guideline-recommended outpatient medications for the initial treatment of 8 common chronic diseases varied by condition. Although costs generally decreased between 2009 and 2019, particularly with regard to conditions for which generic drugs were available, out-of-pocket costs remained high and may have presented a substantial financial burden for Medicare beneficiaries, especially older adults with conditions for which brand-name drugs were guideline recommended.

Gomez N, James V, Onion D, Fairclough LC. Extracellular vesicles and chronic obstructive pulmonary disease (COPD): a systematic review. Respir Res. 2022 Apr 5;23(1):82. doi: 10.1186/s12931-022-01984-0. PMID: 35382831.
Background: Chronic Obstructive Pulmonary Disease (COPD) is a common inflammatory disease of the airways characterized by irreversible airflow limitation, ranking the third highest cause of death worldwide. Extracellular vesicles (EVs) are important intercellular communication mediators released by cells into their extracellular environment with the capacity to transfer biological signals. EVs involved in COPD hold great potential to understand disease pathogenesis and identify important biomarkers. This systematic review aims to examine all available research on EVs in the pathogenesis and diagnosis of COPD to identify existing knowledge and support further research within the field.
Methods: Publications were searched using PubMed and EMBASE with the search terms (Exosomes or extracellular vesicles or microvesicles or microparticles or ectosomes) AND (chronic obstructive pulmonary disease or COPD or emphysema or bronchitis).
Results: Initial search yielded 512 papers of which 142 were manually selected for review and 43 were eligible for analyses. The studies were divided into groups according to the role of EVs in pathogenesis, EV origin and cargo, their role in COPD exacerbations and their diagnostic utility. EVs were found to be involved in the mechanism of pathogenesis of COPD, derived from various cell types, as well as containing modified levels of miRNAs. EVs also varied according to the pathophysiological status of disease, therefore presenting a possible method for COPD diagnosis and progress monitoring.
Conclusion: The current findings show the limited but good quality research looking at the role of EVs in COPD, demonstrating the need for more studies to better define and provide further insight into the functional characteristics of EV in COPD pathogenesis

Owusuaa C, Dijkland SA, Nieboer D, van der Rijt CCD, van der Heide A. Predictors of mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis. BMC Pulm Med. 2022 Apr 4;22(1):125. doi: 10.1186/s12890-022-01911-5. PMID: 35379214; PMCID: PMC8978392.
Background: Better insight in patients’ prognosis can help physicians to timely initiate advance care planning (ACP) discussions with patients with chronic obstructive pulmonary disease (COPD). We aimed to identify predictors of mortality.
Methods: We systematically searched databases Embase, PubMed, MEDLINE, Web of Science, and Cochrane Central in April 2020. Papers reporting on predictors or prognostic models for mortality at 3 months and up to 24 months were assessed on risk-of-bias. We performed a meta-analysis with a fixed or random-effects model, and evaluated the discriminative ability of multivariable prognostic models.
Results: We included 42 studies (49-418,251 patients); 18 studies were included in the meta-analysis. Significant predictors of mortality within 3-24 months in the random-effects model were: previous hospitalization for acute exacerbation (hazard ratio [HR] 1.97; 95% confidence interval [CI] 1.32-2.95), hospital readmission within 30 days (HR 5.01; 95% CI 2.16-11.63), cardiovascular comorbidity (HR 1.89; 95% CI 1.25-2.87), age (HR 1.48; 95% CI 1.38-1.59), male sex (HR 1.68; 95% CI 1.38-1.59), and long-term oxygen therapy (HR 1.74; 95% CI 1.10-2.73). Nineteen previously developed multicomponent prognostic models, as examined in 11 studies, mostly had moderate discriminate ability.
Conclusion: Identified predictors of mortality may aid physicians in selecting COPD patients who may benefit from ACP. However, better discriminative ability of prognostic models or development of a new prognostic model is needed for further large-scale implementation.

1: Domingo C, Maspero JF, Castro M, Hanania NA, Ford LB, Halpin DMG, Jackson DJ,
Daizadeh N, Djandji M, Mitchell CP, Crikelair N, Jacob-Nara JA, Deniz Y, Rowe
PJ, Ortiz B. Dupilumab Efficacy in Steroid-Dependent Severe Asthma by Baseline
Oral Corticosteroid Dose. J Allergy Clin Immunol Pract. 2022 Apr
7:S2213-2198(22)00332-4. doi: 10.1016/j.jaip.2022.03.020. Epub ahead of print.
PMID: 35398549.
Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in multiple diseases. In phase 3 VENTURE study (NCT02528214), dupilumab vs placebo reduced oral corticosteroid (OCS) dose and improved clinical outcomes in patients with OCS-dependent severe asthma. Dupilumab efficacy in patients with varying disease burden (defined by baseline OCS dose) has not been assessed.
Objective: This post hoc analysis of VENTURE evaluated dupilumab efficacy across subgroups defined by baseline OCS dose.
Methods: OCS dose, proportion no longer needing OCS at week 24, annualized severe exacerbation rate, and least squares mean change from baseline in pre- and post-bronchodilator FEV1 at week 24 were evaluated in VENTURE patients with OCS-dependent severe asthma receiving dupilumab 300 mg every 2 weeks vs placebo, categorized by baseline OCS dose <10 or ≥10 mg/day.
Results: Dupilumab reduced daily OCS dose from baseline at week 24 in both dose groups. In dupilumab-/placebo-treated patients with a baseline OCS dose <10 and ≥10 mg/day, 72%/42% and 37%/23% stopped OCS by week 24 (P < .01/P < .05), respectively. Dupilumab significantly reduced the annualized severe exacerbation rate by 71% and 48% (P < .01/P < .05). At week 24, dupilumab improved pre- and post-bronchodilator FEV1 in patients in both dose groups.
Conclusions: In patients with OCS-dependent severe asthma receiving lower or higher baseline OCS doses, dupilumab significantly reduced the OCS dose and improved the likelihood of no longer requiring OCS, while also reducing exacerbations and improving lung function.

2: Park HJ, Huh JY, Lee JS, Lee JS, Oh YM, Lee SW. Comparative efficacy of
inhalers in mild-to-moderate asthma: systematic review and network meta-
analysis. Sci Rep. 2022 Apr 8;12(1):5949. doi: 10.1038/s41598-022-09941-z. PMID:
35396495.
The comparative effectiveness of different inhaler therapies in mild-to-moderate asthma remains unclear. To assess this, we performed a systematic review and network meta-analysis of randomized controlled trials on the use of inhalers for mild-to-moderate asthma by searching PubMed, Cochrane, and Embase. A total of 29 trials including 43,515 patients and 12 types of inhaler therapies were included. For the prevention of severe and moderate-to-severe exacerbations, inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) as maintenance and reliever (SMART) showed the highest rank for effectiveness. As-needed ICS/LABA or short-acting β2-agonist (SABA) was similar to low-dose ICS and superior to as-needed SABA or LABA for the prevention of severe and moderate-severe exacerbations. As for lung function (FEV1), low-dose ICS/LABA had the highest rank; as-needed ICS/LABA was inferior to regular low-dose ICS but superior to placebo. Higher-dose ICS had a superior effect on the Asthma Control Questionnaire (ACQ) scores, and as-needed ICS/LABA and as-needed SABA or LABA had lower ranks in p-rankogram than did the regular use of low-dose ICS. As-needed ICS with LABA or SABA was more effective than a similar dose of regular ICS for preventing exacerbation in mild-to-moderate asthma. As-needed ICS showed some weakness in improving lung function and controlling asthma symptoms.

3: Cropper KJ, Davis BE, Cockcroft DW. Effect of daily tiotropium on allergen-
induced early asthmatic responses and airway inflammation. Ann Allergy Asthma
Immunol. 2022 Apr 5:S1081-1206(22)00296-4. doi: 10.1016/j.anai.2022.04.001. Epub
ahead of print. PMID: 35395397.
NO ABSTRACT

4: Harper V, Trayer J. Breathing exercises for adults with asthma. Clin Exp
Allergy. 2022 Apr 6. doi: 10.1111/cea.14141. Epub ahead of print. PMID:
35388565.
NO ABSTRACT

5: Vesper SJ, Wymer L, Coull BA, Koutrakis P, Cunningham A, Petty CR, Metwali N,
Sheehan WJ, Gaffin JM, Permaul P, Lai PS, Bartnikas LM, Hauptman M, Gold DR,
Baxi SM, Phipatanakul W. HEPA filtration intervention in classrooms may improve
some students’ asthma. J Asthma. 2022 Apr 10:1-8. doi:
10.1080/02770903.2022.2059672. Epub ahead of print. PMID: 35341426.
Objective: The School Inner-City Asthma Intervention Study 2 (SICAS 2) tested interventions to reduce exposures in classrooms of students with asthma. The objective of this post-hoc analysis was limited to evaluating the effect of high-efficiency particulate (HEPA) filtration interventions on mold levels as quantified using the Environmental Relative Moldiness Index (ERMI) and the possible improvement in the students’ asthma, as quantified by spirometry testing.
Methods: Pre-intervention dust samples were collected at the beginning of the school year from classrooms and corresponding homes of students with asthma (n = 150). Follow-up dust samples were collected in the classrooms at the end of the HEPA or Sham intervention. For each dust sample, ERMI values and the Group 1 and Group 2 mold levels (components of the ERMI metric) were quantified. In addition, each student’s lung function was evaluated by spirometry testing, specifically the percentage predicted forced expiratory volume at 1 sec (FEV1%), before and at the end of the intervention.
Results: For those students with a higher Group 1 mold level in their pre-intervention classroom than home (n = 94), the FEV1% results for those students was significantly (p < 0.05) inversely correlated with the Group 1 level in their classrooms. After the HEPA intervention, the average Group 1 and ERMI values were significantly lowered, and the average FEV1% test results significantly increased by an average of 4.22% for students in HEPA compared to Sham classrooms.
Conclusions: HEPA intervention in classrooms reduced Group 1 and ERMI values, which corresponded to improvements in the students’ FEV1% test results.

1: Sweiss K, Naser AY, Alrawashdeh HM, Alharazneh A. Hospital admissions due to
vasomotor and allergic rhinitis in England and Wales between 1999 and 2019: an
ecological study. Ir J Med Sci. 2022 Apr 7. doi: 10.1007/s11845-022-02996-x.
Epub ahead of print. PMID: 35391654.
Background: Allergic rhinitis is among the most prevalent chronic disorders in high-income countries. Its estimated cost is €30-€50 billion annually in the European Union and in the UK, it is approximately €1.8 billion per year.
Aim: To study hospital admissions for vasomotor and allergic rhinitis in England and Wales during the past 20 years.
Method: This was an ecological study using publicly available data extracted from the Hospital Episode Statistics (HES) database in England and the Patient Episode Database for Wales (PEDW). The trend in hospital admissions was assessed using a Poisson model.
Results: Admission rate increased by 2.14-fold [from 2.59 (95% CI 2.46-2.73) in 1999 to 8.16 (95% CI 7.93-8.39) in 2020 per 100,000 persons, trend test, p < 001]. The most prevalent hospital admission reasons were allergic rhinitis due to pollen, other allergic rhinitis, and unspecified allergic rhinitis, which accounted for 56.4%, 22.3%, and 15.7%, respectively. The age group 15-59 years accounted for 69.5% of the total number of admissions. Admission rate between males increased by 2.25-fold. Admission rate between females increased by 2.02-fold.
Conclusion: Vasomotor and allergic rhinitis are common cause of hospital admissions in England and Wales that showed a clear increase in the rate of their admissions in the past 20 years. Allergic rhinitis due to pollen was the most dominant cause of admission, which warrants further investigation to identify its preventable risk factors and decrease the probability of the exacerbation of patients’ cases and the need for hospitalization.

2: Chen Z, Ke X, Wang X, Kang H, Hong S. LncRNA JPX contributes to Treg/Th17
imbalance in allergic rhinitis <i>via</i> targeting the miR-378g/CCL5 axis.
Immunopharmacol Immunotoxicol. 2022 Apr 6:1-6. doi:
10.1080/08923973.2022.2055566. Epub ahead of print. PMID: 35387544.
Aim: T-regulatory (Treg)/T-helper (Th) 17 imbalance contributes to the pathogenesis of allergic rhinitis (AR). Long non-coding RNAs (lncRNAs) participate in the progression of AR. Herein, the effect of lncRNA JP X on Treg/Th17 balance in AR was explored.Methods: CD4+ T cells were isolated from patients with AR and healthy control. The percentage of Treg and Th17 cells were examined by flow cytometry. The levels of JP X, miR-378g, CCL5, T GF-β, and IL-17A were tested using qRT-P CR. The protein expression of Foxp3 and RORγt was measured by western blot.Results: The data showed that an imbalance of Treg/Th17 was associated with AR. Upregulation of JP X was found in AR, and knockdown of which improved the imbalance of Treg/Th17. Furthermore, JP X functioned as a sponge of miR-378g to upregulate CCL5. Inhibition of miR-378g reversed the effects on Treg/Th17 induced by silencing of JP X. Moreover, overexpression of CCL5 reversed miR-378g-induced effects.Conclusion: In conclusion, depletion of JP X promoted Treg/Th17 balance in AR via regulating the miR-378g/CCL5 axis. The findings provided a novel therapeutic insight for AR.

3: Hoang MP, Chitsuthipakorn W, Seresirikachorn K, Snidvongs K. As-needed
intranasal corticosteroid spray for allergic rhinitis: a systematic review and
meta-analysis. Rhinology. 2022 Apr 5. doi: 10.4193/Rhin21.355. Epub ahead of
print. PMID: 35379997.
ackground: As-needed intranasal corticosteroid spray (INCS) is commonly used by patients with allergic rhinitis (AR) who have suboptimal symptom control. This systematic review aimed to assess the effectiveness of as-needed INCS for treating AR.
Methodology: Systematic searches for randomized controlled trials studying the effects of as-needed INCS compared to regular INCS, as-needed antihistamine, or placebo were performed. Primary outcomes were total nasal symptom score (TNSS) and disease-specific quality of life (DSQoL).
Results: Eight studies (882 participants) met the criteria. Regular use of INCS showed greater improvements than as-needed INCS in TNSS, DSQoL, nasal peak inspiratory flow, sneezing, and nasal congestion scores with small effect sizes. There were no differences between regular and as-needed INCS usage for ocular symptoms, symptom-free days, nasal itching, and rhinorrhea scores. As-needed INCS was superior to as-needed antihistamine and placebo with medium effect sizes. There were no differences in risk of adverse events between the groups in all three comparisons.
Conclusions: Regular use of INCS improved total nasal symptoms score and DSQoL better than as-needed INCS. However, as-needed INCS improved TNSS better than as-needed antihistamine and placebo. The effects of as-needed INCS were closer to regular INCS usage than to placebo or as-needed AH usage.

1: Leuppi J, Guggisberg P, Koch D, Favre-Bulle A, Fabiani M, Heinz S, Zeller A.
Understanding the knowledge and perception of chronic cough from a physician’s
perspective in Switzerland. Curr Med Res Opin. 2022 Apr 4:1-18. doi:
10.1080/03007995.2022.2057154. Epub ahead of print. PMID: 35369836.
Background: Cough is one of the most common health issues for which medical attention is sought. A chronic cough (CC) is understood as a cough that lasts longer than 8 weeks. CC encompasses two subsets referred to as refractory chronic cough (RCC) and unexplained chronic cough (UCC). This study aims to assess the current understanding and perceptions of a RCC and UCC, from a physician’s perspective in Switzerland and how this understanding and practical work leads to the relevant diagnosis and treatment.
Methods: In October 2020, 549 GPs and 338 pulmonologists in Switzerland, received an invite to participate in the online-based quantitative survey. Data collection was carried out through a 25-minute online survey. The questionnaire was based on structured questions, and conducted on a randomized sample of doctors (general practitioners -GPs and pulmonologists) in the German- and French-speaking part of Switzerland.
Results: Overall, 33 pulmonologists and 52 GPs participated in the online survey. Only 38% of GPs, but 73% of pulmonologists, defined chronic cough as a cough lasting 8 weeks or longer. The majority of physicians (72%), especially pulmonologists (88%), perceived a clinical gap regarding the treatment of persistent cough. 74% of the sampled physicians agreed that persistent cough is a high burden of disease for patients. Based on the answers, the annual number of new patients with RCC and UCC in Switzerland is estimated at 9,322 patients.
Conclusions: Results of this study have highlighted differences in the terminology used to describe CC (RCC and UCC), in the diagnostic tests used and, in the treatments used between GPs and pulmonologists. These findings suggest the need to align the current language regarding the disease to facilitate a standardised approach for diagnosis and treatment and towards improving patient care and reduce burden of disease for CC (RCC and UCC) patients.

1. Ann Am Thorac Soc. 2022 Apr 1. doi: 10.1513/AnnalsATS.202109-1042OC. Online ahead of print.
Lung Function and the Risk of Exacerbation in the BLOCK COPD (beta-blocker) TrialParekh TM(1), Helgeson ES(2), Connett J(3), Voelker H(4), Ling SX(5), Lazarus SC(6), Bhatt SP(7), MacDonald DM(8), Mkorombindo T(9), Kunisaki KM(10)(11), Fortis S(12), Kaminsky D(13), Dransfield MT(14).
RATIONALE: The Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK COPD) study found that metoprolol was associated with a higher risk of severe exacerbation.
OBJECTIVES: To determine the mechanism underlying these results, we compared changes in lung function over the course of the study between treatment groups and evaluated whether baseline bronchodilator response or early reduction in FEV1 or FVC was associated with exacerbation risk.
METHODS: We compared changes in lung function (FEV1 and FVC) over the treatment period between treatment groups using linear mixed-effect models. Cox proportional hazards models were used to evaluate the association between baseline bronchodilator responsiveness (FEV1, FVC, and combined FEV1 and FVC), early post-randomization (14 day) change in lung function, and the interaction between treatment assignment and these measures with risk of any or severe/very severe exacerbations. Negative binomial models were used to evaluate the relationship between bronchodilator responsiveness, the interaction between bronchodilator responsiveness and treatment assignment, and exacerbation rate.
RESULTS: Over the 336 day treatment period, individuals in the metoprolol group had a significantly greater decrease in log-FEV1, from baseline to visit day 28 compared to individuals in the placebo group. Individuals in the metoprolol group had a significantly greater decrease in FVC from baseline to visit day 14 and 28 and additionally a significantly greater decrease in log FVC from baseline to visits 42 and 112 than individuals in the placebo group. There were no associations between early lung function reduction, or interactions between lung function reduction and treatment assignment, and time to any or severe/very severe exacerbations. There were no interactions between treatment arm and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. However, those with baseline FVC bronchodilator responsiveness had a higher rate of severe/very severe exacerbations (adjusted RR = 1.62, 95% CI, 1.04-2.48).
CONCLUSION: Metoprolol was associated with reduced lung function during the early part of the treatment period, but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe/very severe exacerbations.

2. Am J Respir Crit Care Med. 2022 Apr 1. doi: 10.1164/rccm.202111-2630OC. Online ahead of print.
International Differences in the Frequency of COPD Exacerbations Reported in Three Clinical Trials.
Calverley PMA(1), Martinez FJ(2), Vestbo J(3)(4), Jenkins CR(5), Wise R(6), Lipson DA(7), Cowans NJ(8), Yates J(9), Crim C(10)(11), Celli BR(12).
RATIONALE: Exacerbations of chronic obstructive pulmonary disease are an important endpoint in multinational clinical treatment trials, but the observed event rate is often lower than anticipated and appears to vary between countries.
OBJECTIVES: We investigated whether systematic differences in national exacerbation rates might explain this observed variation.
METHODS: We reviewed data from three large multicenter international randomized trials conducted over an 18-year period with different designs and clinical severities of chronic obstructive pulmonary disease, comparing bronchodilator and/or inhaled corticosteroids with bronchodilators alone and/or placebo. Exacerbations were defined by antibiotic and/or oral corticosteroid use (moderate) or need for hospitalization (severe). We calculated crude exacerbation rates in the 30 countries contributing 30 or more patients to at least two trials. We grouped data by exacerbation rate based on their first study contribution.
MEASUREMENTS AND MAIN RESULTS: For the 29,756 patients in 41 countries analyzed, the mean exacerbation rate was 2-3-fold different between the highest and lowest tertiles of the recruiting nations. These differences were not explained by demographic features, study protocol, or reported exacerbation history at enrolment. Of the 18 countries contributing to all studies, half of those in the highest and half in the lowest tertiles of exacerbation history remained in these groups across studies. Severe exacerbations showed a different rank order internationally.
CONCLUSIONS: Countries contributing to chronic obstructive pulmonary disease trials differ consistently in their reporting of health care-defined exacerbations. These differences help explain why large studies have been needed to show differences between treatments that decrease exacerbation risk.
DOI: 10.1164/rccm.202111-2630OC
PMID: 35363593

3. Nature. 2022 Mar 30. doi: 10.1038/s41586-022-04552-0. Online ahead of print.
Human distal airways contain a multipotent secretory cell that can regenerate alveoli.
Basil MC(#)(1)(2), Cardenas-Diaz FL(#)(1)(2), Kathiriya JJ(3), Morley MP(1)(2)(4), Carl J(1)(2), Brumwell AN(3), Katzen J(1)(2), Slovik KJ(1)(2)(4), Babu A(1)(2)(4), Zhou S(1)(2), Kremp MM(1)(2), McCauley KB(5), Li S(1)(2), Planer JD(1)(2), Hussain SS(6), Liu X(7), Windmueller R(2)(8), Ying Y(1)(2), Stewart KM(1)(2), Oyster M(1), Christie JD(1)(2), Diamond JM(1), Engelhardt JF(7), Cantu E(2)(9), Rowe SM(6), Kotton DN(5)(10), Chapman HA(3)(11), Morrisey EE(12)(13)(14).
The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
DOI: 10.1038/s41586-022-04552-0
PMID: 35355013

4. Lung. 2022 Mar 29. doi: 10.1007/s00408-022-00521-6. Online ahead of print.
Identifying Patients with Group 3 Pulmonary Hypertension Associated with COPD or ILD Using an Administrative Claims Database.Heresi GA(1), Dean BB(2), Castillo H(3), Lee HF(4), Classi P(3), Stafkey-Mailey D(4), Kantorovich A(3), Morland K(3), Sketch MR(3), Wu BS(3), King CS(5).
BACKGROUND: Group 3 pulmonary hypertension (PH) describes a subpopulation of patients with PH due to chronic lung disease and/or hypoxia, with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) being two large subgroups. Claims database studies provide insights into the real-world treatment patterns and outcomes among these patients. However, claims data do not provide sufficient detail to assign the clinical subtype of PH required for identifying these patients.
METHODS: A panel of PH clinical experts and researchers was convened to discuss methodologies to identify patients with Group 3 PH associated with COPD or ILD in retrospective claims databases. To inform the discussion, a literature review was conducted to identify claims-based studies of Group 3 PH associated with COPD or ILD published from 2010 through June 2020.
RESULTS: Targeted title and abstract review identified 11 claims-based studies and two conference abstracts (eight based in the United States [US] and five conducted outside the US) that met search criteria. Based on insights from the panel and literature review, the following components were detailed across studies in the identification of Group 3 PH associated with COPD and ILD: (a) COPD or ILD identification, (b) PH identification, (c) defining the sequence between COPD/ILD and PH, and (d) other PH Group and Group 3 PH exclusions.
CONCLUSION: This article provides recommended approaches and considerations for identifying and studying patients with Group 3 PH associated with COPD or ILD using administrative claims data that provide the foundation for future validation studies.
© 2022. The Author(s).
DOI: 10.1007/s00408-022-00521-6
PMID: 35348836

5. BMC Health Serv Res. 2022 Mar 28;22(1):408. doi: 10.1186/s12913-022-07778-w.
Healthcare costs of patients with chronic obstructive pulmonary disease in Denmark – specialist care versus GP care only.
Lykkegaard J(1), Nielsen JB(2), Storsveen MM(2), Jarbøl DE(2), Søndergaard J(2).
BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD) are treated in general practice only and have never received specialist care for COPD. They are seldom included in COPD cost studies but may account for a substantial proportion of the total costs.
OBJECTIVE: To estimate and specify the total healthcare costs of patients who are treated for COPD in Denmark comparing those who have- and have not had specialist care for COPD.
SETTING: Denmark, population 5.7 million citizens.
METHODS: Via national registers, we specified the total healthcare costs of all + 30-years-old current users of respiratory pharmaceuticals. We identified the patients with COPD and compared those with at least one episode of pulmonary specialist care to those with GP care only.
RESULTS: Among totally 329,428 users of respiratory drugs, we identified 46,084 with specialist-care- and 68,471 with GP-care-only COPD. GP-care-only accounted for 40% of the two populations’ total healthcare costs. The age- and gender-adjusted coefficient relating the individual total costs specialist-care versus GP-care-only was 2.19. The individual costs ranged widely and overlapped considerably (p25-75: specialist-care €2,175-€12,625, GP-care-only €1,110-€4,350). Hospital treatment accounted for most of the total cost (specialist-care 78%, GP-care-only 62%; coefficient 2.81), pharmaceuticals (specialist-care 16%, GP-care-only 27%; coefficient 1.28), and primary care costs (specialist-care 6%, GP-care-only 11%; coefficient 1.13). The total costs of primary care pulmonary specialists were negligible.
CONCLUSION: Healthcare policy makers should consider the substantial volume of patients who are treated for COPD in general practice only and do not appear in specialist statistics.

6. Clin Sci (Lond). 2022 Mar 31;136(6):405-423. doi: 10.1042/CS20210835.
Chronic obstructive pulmonary disease and atherosclerosis: common mechanisms and novel therapeutics.
Brassington K(1), Selemidis S(1), Bozinovski S(1), Vlahos R(1).
Chronic obstructive pulmonary disease (COPD) and atherosclerosis are chronic irreversible diseases, that share a number of common causative factors including cigarette smoking. Atherosclerosis drastically impairs blood flow and oxygen availability to tissues, leading to life-threatening outcomes including myocardial infarction (MI) and stroke. Patients with COPD are most likely to die as a result of a cardiovascular event, with 30% of all COPD-related deaths being attributed to cardiovascular disease (CVD). Both atherosclerosis and COPD involve significant local (i.e. lung, vasculature) and systemic inflammation and oxidative stress, of which current pharmacological treatments have limited efficacy, hence the urgency for the development of novel life-saving therapeutics. Currently these diseases must be treated individually, with no therapies available that can effectively reduce the likelihood of comorbid CVD other than cessation of cigarette smoking. In this review, the important mechanisms that drive atherosclerosis and CVD in people with COPD are explained and we propose that modulation of both the oxidative stress and the inflammatory burden will provide a novel therapeutic strategy to treat both the pulmonary and systemic manifestations related to these diseases.

7. Respir Med. 2022 Apr-May;195:106774. doi: 10.1016/j.rmed.2022.106774. Epub 2022 Feb 22.
Nasal and systemic inflammation in Chronic Obstructive Pulmonary Disease (COPD).
Obling N(1), Backer V(2), Hurst JR(3), Bodtger U(4).
Systemic inflammation is a well-established feature of Chronic Obstructive Pulmonary Disease, COPD, but less is known about inflammation in the upper airways in the disease. In the current study, we investigated the inflammatory profile in the upper airway and in serum in a cohort of patients with COPD. Patients were examined with inflammatory profiles measured on material from the upper airway and in serum using a 14-plex Bioplex multiplex immunoassay containing the following cytokines: IL-1-beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-18, Interferon-gamma, Tumour Necrosis Factor-alpha, Tumour Necrosis Factor beta, and GM-CSF. We evaluated COPD disease burden using the CAT questionnaire and symptoms from the upper airways with the nasal domain of the 22 items Sino Nasal Outcome Test (SNOT22nasal). We included 180 patients (female 55%, age 67 (±8) years, FEV1% 52.4 (±16.6). Using a SNOT22nasal threshold of ≥6, we divided patients into high upper airways symptoms (high UAS), n = 74 (41%) and low upper airway symptoms (low UAS), n = 106 (59%). High UAS was significantly associated with higher levels of IL-1 beta and IL-3 in nasal samples (p = 0.016 and 0.02, respectively) and higher serum levels of IL-1 beta (p = 0.003). Upper airway scores correlated positively with nasal levels of IL-3 (rho = 0.195, p = 0.01) and serum levels of IL-1 beta (rho = 0.226, p = 0.005). Patients with COPD and high upper airway symptoms displayed signs of eosinophilic and neutrophilic inflammation with elevated levels of IL-1 beta and IL-3 in the nose and elevated IL-1 beta in serum.

8. Respirology. 2022 Apr;27(4):258-259. doi: 10.1111/resp.14233. Epub 2022 Feb 23.
CT in COPD: To be or not to be.
Agusti A(1)(2)(3)(4), Faner R(2)(3)(4).
DOI: 10.1111/resp.14233
PMID: 35199426

9. Respirology. 2022 Apr;27(4):277-285. doi: 10.1111/resp.14222. Epub 2022 Feb 10.
The HUNT study: Association of comorbidity clusters with long-term survival and incidence of exacerbation in a population-based Norwegian COPD cohort.
Vikjord SAA(1)(2), Brumpton BM(3)(4)(5), Mai XM(6), Romundstad S(2)(7), Langhammer A(1)(2), Vanfleteren L(8).
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease often viewed as part of a multimorbidity complex. There is a need for better phenotyping of the disease, characterization of its interplay with other comorbidities and its association with long-term outcomes. This study aims to examine how clusters of comorbidities are associated with severe exacerbations and mortality in COPD.
METHODS: Participants with potential COPD were recruited from the second (1995-1997) and third (2006-2008) survey of the HUNT Study and followed up until April 2020. Ten objectively identified comorbidities were clustered using self-organizing maps. Severe COPD exacerbations requiring hospitalization were assessed using hospital data. All-cause mortality was collected from national registries. Multivariable Cox regression was used to calculate hazard ratios (HRs) with 95% CIs for the association between comorbidity clusters and all-cause mortality. Poisson regression was used to calculate incidence rate ratios (IRRs) with 95% CI for the cumulative number of severe exacerbations for each cluster.
RESULTS: Five distinct clusters were identified, including ‘less comorbidity’, ‘psychological’, ‘cardiovascular’, ‘metabolic’ and ‘cachectic’ clusters. Using the less comorbidity cluster as reference, the psychological and cachectic clusters were associated with all-cause mortality (HR 1.23 [1.04-1.45] and HR 1.83 [1.52-2.20], adjusted for age and sex). The same clusters also had increased risk of exacerbations (unadjusted IRR of 1.24 [95% CI 1.04-1.48] and 1.50 [95% CI 1.23-1.83], respectively).
CONCLUSION: During 25 years of follow-up, individuals in the psychological and cachectic clusters had increased mortality. Furthermore, these clusters were associated with increased risk of severe COPD exacerbations.
DOI: 10.1111/resp.14222
PMID: 35144315

10. Respirology. 2022 Apr;27(4):286-293. doi: 10.1111/resp.14223. Epub 2022 Feb 7.
Chest CT-assessed comorbidities and all-cause mortality risk in COPD patients in the BODE cohort.
Ezponda A(1), Casanova C(2)(3), Divo M(4), Marín-Oto M(5), Cabrera C(6), Marín JM(7), Bastarrika G(1), Pinto-Plata V(8), Martin-Palmero Á(9), Polverino F(10), Celli BR(4), de Torres JP(5)(9)(11).
BACKGROUND AND OBJECTIVE: The availability of chest computed tomography (CT) imaging can help diagnose comorbidities associated with chronic obstructive pulmonary disease (COPD). Their systematic identification and relationship with all-cause mortality have not been explored. Furthermore, whether their CT-detected prevalence differs from clinical diagnosis is unknown.
METHODS: The prevalence of 10 CT-assessed comorbidities was retrospectively determined at baseline in 379 patients (71% men) with mild to severe COPD attending pulmonary clinics. Anthropometrics, smoking history, dyspnoea, lung function, exercise capacity, BODE (BMI, Obstruction, Dyspnoea and Exercise capacity) index and exacerbations rate were recorded. The prevalence of CT-determined comorbidities was compared with that recorded clinically. Over a median of 78 months of observation, the independent association with all-cause mortality was analysed. A ‘CT-comorbidome’ graphically expressed the strength of their association with mortality risk.
RESULTS: Coronary artery calcification, emphysema and bronchiectasis were the most prevalent comorbidities (79.8%, 62.7% and 33.9%, respectively). All were underdiagnosed before CT. Coronary artery calcium (hazard ratio [HR] 2.09; 95% CI 1.03-4.26, p = 0.042), bronchiectasis (HR 2.12; 95% CI 1.05-4.26, p = 0.036) and low psoas muscle density (HR 2.61; 95% CI 1.23-5.57, p = 0.010) were independently associated with all-cause mortality and helped define the ‘CT-comorbidome’.
CONCLUSION: This study of COPD patients shows that systematic detection of 10 CT-diagnosed comorbidities, most of which were not detected clinically, provides information of potential use to patients and clinicians caring for them.
DOI: 10.1111/resp.14223
PMID: 35132732

11. Life Sci. 2022 Apr 1;294:120374. doi: 10.1016/j.lfs.2022.120374. Epub 2022 Feb 4.
Impact of chronic obstructive pulmonary disease, lung infection, and/or inhaled corticosteroids use on potential risk of lung cancer.
Patel B(1), Priefer R(2).
Chronic obstructive pulmonary disease is the 3rd leading cause of death worldwide. It not only affects current and former smokers, but non-smokers as well. Chronic inflammatory response in this disease state leads to the production of genotoxic free radicals and reactive oxygen species that could result in tumorigenesis. Inhaled corticosteroids are used for the management of inflammation in patients experiencing frequent exacerbation and/or have a high eosinophil count. However, these steroids are often prescribed off-label for symptom management. Using inhaled corticosteroids to combat inflammation in chronic obstructive pulmonary disease patients is suggested to be protective against lung cancer. However, immunomodulatory effects of these medications can pre-dispose patients to develop respiratory infections such as tuberculosis or pneumonia. These lung infections have shown to also increase the risk of developing lung cancer. Since chronic obstructive pulmonary disease is an independent risk factor for developing lung cancer, a subsequent infection could have an additive effect. Additionally, the aforementioned chemo-preventive effects of inhaled corticosteroids are inconsistent due to there being limited data on the long term effects of using inhaled corticosteroids in patients who do not meet the treatment recommendation guidelines. Hence, it is necessary to recognize the indirect connection between inhaled corticosteroids and lung cancer possibly via lung infections in chronic obstructive pulmonary disease patients. The rationale behind this review is to better understand the mechanistic links that connect these multiple disease states which could aid in guiding treatment with inhaled corticosteroids in specific sub-groups. This review discusses possible pathways that could lead to the lung carcinogenesis and the cumulative impact of chronic obstructive pulmonary disease, inhaled corticosteroids use, and pulmonary infections on the risk of lung cancer.
DOI: 10.1016/j.lfs.2022.120374
PMID: 35131234 [Indexed for MEDLINE]

12. Curr Opin Allergy Clin Immunol. 2022 Apr 1;22(2):73-79. doi: 10.1097/ACI.0000000000000817.
Occupational causes of chronic obstructive pulmonary disease: an update.
De Matteis S(1).
PURPOSE OF REVIEW: This brief narrative review aims to highlight relevant recent updates on occupational causes of chronic obstructive pulmonary disease (COPD).
RECENT FINDINGS: The most recent literature has been searched for any new relevant association between occupational exposures and COPD. Only large epidemiological studies of high quality have been included. Beyond the more traditional exposures, such as mineral or organic dusts, new chemicals have emerged as potential occupational causal agents for COPD. In particular, pesticides and cleaning products, including disinfectants, that have shown also positive exposure-response trends. For cleaning products, some specific chemicals have been identified, but for pesticides the identification of specific causal compounds is more challenging. The biological underlying mechanisms are still under study.
SUMMARY: In the recent literature, occupational exposure to pesticides and cleaning products has emerged as potential cause of COPD. Awareness on occupational causes of COPD should increase among all stakeholders, from health professionals to public to prevent the associated public health burden. More studies on identifying the specific causal agents and mechanisms are needed to focus preventive strategies.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/ACI.0000000000000817
PMID: 35125392

13. Am J Prev Med. 2022 Apr;62(4):492-502. doi: 10.1016/j.amepre.2021.12.001. Epub 2022 Feb 2.
Smoking Cessation Among U.S. Adult Smokers With and Without Chronic Obstructive Pulmonary Disease, 2018.
Liu Y(1), Greenlund KJ(2), VanFrank B(3), Xu F(2), Lu H(2), Croft JB(2).
INTRODUCTION: More than 3 of 5 U.S. adults who have ever smoked cigarettes have quit. This study assesses the latest estimates of smoking cessation among U.S. adults with and without chronic obstructive pulmonary disease who have ever smoked cigarettes (ever smokers).METHODS: Data from 161,233 ever smokers (12.8% with chronic obstructive pulmonary disease) in the 2018 Behavioral Risk Factor Surveillance System were analyzed in 2020. Weighted percentages of quit ratios (percentage of ever smokers who quit smoking), past-year quit attempts (≥1 day), and recent successful cessation (quit ≥6 months ago) by self-reported physician-diagnosed chronic obstructive pulmonary disease status were obtained from multivariable logistic regression analyses, with adjustment for sociodemographic characteristics, health risk behaviors, depression, and asthma.
RESULTS: Adults with chronic obstructive pulmonary disease who smoked had greater age-adjusted past-year quit attempts (68.8% vs 64.3%) but lower recent successful cessation (4.5% vs 5.8%) and quit ratio (53.2% vs 63.9%) than those without chronic obstructive pulmonary disease. After adjusting for covariates, adults with chronic obstructive pulmonary disease who smoked had a significantly higher percentage of past-year quit attempts but similar recent successful cessation and a significantly lower lifetime quit ratio than their counterparts without chronic obstructive pulmonary disease.
CONCLUSIONS: These findings suggest that individuals with chronic obstructive pulmonary disease who try to quit smoking may be less likely to succeed than those without chronic obstructive pulmonary disease. Evidence-based treatments for smoking cessation remain an important component of a comprehensive approach to helping all adults to quit and are a particularly important element of chronic obstructive pulmonary disease management and care.
DOI: 10.1016/j.amepre.2021.12.001
PMID: 35120768 [Indexed for MEDLINE]

14. ESC Heart Fail. 2022 Apr;9(2):1351-1359. doi: 10.1002/ehf2.13824. Epub 2022 Jan 27.
Inaccurate recognition of own comorbidities is associated with poor prognosis in elderly patients with heart failure.
Maeda D(1)(2), Matsue Y(1)(3), Kagiyama N(4)(5)(6), Jujo K(7), Saito K(8), Kamiya K(9), Saito H(1)(10), Ogasahara Y(11), Maekawa E(12), Konishi M(13), Kitai T(14)(15), Iwata K(15), Wada H(16), Hiki M(1), Dotare T(1), Sunayama T(1), Kasai T(1)(3), Nagamatsu H(17), Ozawa T(18), Izawa K(19), Yamamoto S(20), Aizawa N(21), Yonezawa R(22), Oka K(23), Momomura SI(24), Minamino T(1)(25).
AIMS: A patient’s understanding of his or her own comorbidities is part of the recommended patient education for those with heart failure. The accuracy of patients’ understanding of their comorbidities and its prognostic impact have not been reported.
METHODS AND RESULTS: Patients hospitalized for heart failure (n = 1234) aged ≥65 years (mean age: 80.1 ± 7.7 years; 531 females) completed a questionnaire regarding their diagnoses of diabetes, malignancy, stroke, hypertension, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD). The patients were categorized into three groups based on the number of agreements between self-reported comorbidities and provider-reported comorbidities: low (1-2, n = 19); fair (3-4, n = 376); and high (5-6, n = 839) agreement groups. The primary outcome was a composite of all-cause mortality or heart failure rehospitalization at 1 year. The low agreement group had more comorbidities and a higher prevalence of a history of heart failure. The agreement was good for diabetes (κ = 0.73), moderate for malignancy (κ = 0.56) and stroke (κ = 0.50), and poor-to-fair for hypertension (κ = 0.33), COPD (κ = 0.25), and CAD (κ = 0.30). The fair and low agreement groups had poorer outcomes than the good agreement group [fair agreement group: hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.01-1.56; P = 0.041; low agreement group: HR: 2.74: 95% CI: 1.40-5.35; P = 0.003].
CONCLUSIONS: The ability to recognize their own comorbidities among older patients with heart failure was low. Patients with less accurate recognition of their comorbidities may be at higher risk for a composite of all-cause mortality or heart failure rehospitalization.
DOI: 10.1002/ehf2.13824
PMCID: PMC8934983
PMID: 35088546 [Indexed for MEDLINE]

15. Eur Respir Rev. 2022 Jan 25;31(163):210150. doi: 10.1183/16000617.0150-2021. Print 2022 Mar 31.
Eosinophils and eosinophilic immune dysfunction in health and disease.
Jackson DJ(1)(2), Akuthota P(3), Roufosse F(4).
The functions ascribed to eosinophils have classically been limited to host defence against certain parasitic infections and potentially deleterious effects in the setting of specific diseases that are associated with elevated eosinophil counts in blood and/or tissue. The ability to induce eosinophil depletion either experimentally in animal models or through targeted therapies in humans has extended our understanding of the roles played by eosinophils in health and homeostasis as well as in disease pathogenesis. When associated with human disease aetiology, the eosinophil takes on a pathogenic rather than a protective role. This maladaptive response, called “eosinophilic immune dysfunction” herein, appears central to exacerbation pathogenesis and disease control in severe asthma and may be involved in the aetiology of other eosinophil-related conditions ranging from organ-system-limited diseases such as phenotypic subsets of chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyposis to more broadly systemic diseases such as eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. In this review, we describe the evidence supporting eosinophilic functions related to health and homeostasis and explore the contribution of eosinophilic immune dysfunction to human disease.
DOI: 10.1183/16000617.0150-2021
PMID: 35082127 [Indexed for MEDLINE]

16. Br J Radiol. 2022 Apr 1;95(1132):20201005. doi: 10.1259/bjr.20201005. Epub 2021 Sep 19.
Functional imaging of COPD by CT and MRI.
Lynch DA(1).
This commentary reviews the contribution of imaging by CT and MRI to functional assessment in chronic obstructive pulmonary disease (COPD). CT can help individualize the assessment of COPD by quantifying emphysema, air trapping and airway wall thickening, potentially leading to more specific treatments for these distinct components of COPD. Longitudinal changes in these metrics can help assess progression or improvement. On hyperpolarized gas MRI, the apparent diffusion coefficient of provides an index of airspace enlargement reflecting emphysema. Perfusion imaging and measurement of pulmonary vascular volume on non-contrast CT provide insight into the contribution of pulmonary vascular disease to pulmonary impairment. Functional imaging is particularly valuable in detecting early lung dysfunction in subjects with inhalational exposures.
DOI: 10.1259/bjr.20201005
PMID: 34541865 [Indexed for MEDLINE]

17. Postgrad Med J. 2022 Apr;98(1158):258-263. doi: 10.1136/postgradmedj-2020-139341. Epub 2021 Jan 12.
Short-term and long-term impact of diagnosed and undiagnosed chronic obstructive pulmonary disease on coronary artery bypass grafting surgery.
Gatta F(1), Haqzad Y(2), Loubani M(3).
OBJECTIVES: This study sought to compare clinical outcomes between three categories of patients: non-chronic obstructive pulmonary disease (COPD), diagnosed COPD and undiagnosed COPD in coronary artery bypass grafting surgery.
METHODS: A single-centred retrospective study from January 2010 to December 2019. Primary outcomes were postoperative complications, length of ITU admission and in-hospital staying. Secondary outcomes were reintervention rate, in-hospital and long-term mortality.
RESULTS: A total of 4020 patients were analysed and divided into three cohorts: non-COPD (group A) (74.55%, n=2997), diagnosed COPD (group B) (14.78%, n=594) and undiagnosed COPD (group C) (10.67%, n=429). The rate of respiratory complications was noted in this order: group B>group C>group A (p 0.00000002). Periooperative acute kidney injury and wound complications were higher in group B (p 0.0004 and p 0.03, respectively). Prolonged in-hospital staying (days) resulted in group B (p 0.0009). Finally, long-term mortality was statistically higher in group B and C compared with group A (p 0.0004). No difference in long-term mortality was noted in relation to the expected FEV1% in group B (p 0.29) and group C (p 0.82).
CONCLUSIONS: In CABG surgery, COPD is a well-known independent risk factor for morbidity. Patients with preoperative spirometry results indicative of COPD result in the same outcomes of known patients with COPD. As a result of that, greater value should be given to the preoperative spirometry in the EuroSCORE. Finally, the expected FEV1% appears not be a predictor for long-term survival.
DOI: 10.1136/postgradmedj-2020-139341
PMID: 33436479 [Indexed for MEDLINE]
Conflict of interest statement: Competing interests: None declared.

1: Couillard S, Steyerberg E, Beasley R, Pavord I. Blood eosinophils, fractionalexhaled nitric oxide and the risk of asthma attacks in randomised controlledtrials: protocol for a systemic review and control arm patient-level meta-analysis for clinical prediction modelling. BMJ Open. 2022 Apr 1;12(4):e058215.doi: 10.1136/bmjopen-2021-058215. PMID: 35365539.
Introduction: The reduction of the risk of asthma attacks is a major goal of guidelines. The fact that type-2 inflammatory biomarkers identify a higher risk, anti-inflammatory responsive phenotype is potentially relevant to this goal. We aim to quantify the relation between blood eosinophils, exhaled nitric oxide (FeNO) and the risk of severe asthma attacks.
Methods and analysis: A systematic review of randomised controlled trials (RCTs) will be conducted by searching MEDLINE from January 1993 to April 2021. We will include RCTs that investigated the effect of fixed treatment(s) regimen(s) on severe asthma exacerbation rates over at least 24 weeks and reported a baseline value for blood eosinophils and FeNO. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the methodological appraisal of the studies will be assessed by the Cochrane Risk-of-Bias Tool for RCTs. Study authors will be contacted to request anonymised individual participant data (IPD) for patients randomised to the trial’s control arm. An IPD meta-analysis will be performed for multivariable prognostic modelling with performance assessment (calibration plots and the c-statistic) in a cross-validation by study procedure. The outcome to predict is the absolute number of severe asthma attacks to occur in the following 12 months if anti-inflammatory therapy is not changed (ie, annualised number of attacks requiring ≥3 days of systemic corticosteroids and/or hospitalisation if the patient was randomised to the control arm of an RCT). A summary prognostic equation and risk stratification chart will be reported as a basis for further analyses of individualised treatment benefit.

2: Oppenheimer J, Leung DYM. Asthma 2022-moving toward precision medicine. AnnAllergy Asthma Immunol. 2022 Apr;128(4):343. doi: 10.1016/j.anai.2022.01.011.
PMID: 35365251.

3: Quint JK, Arnetorp S, Kocks JWH, Kupczyk M, Nuevo J, Plaza V, Cabrera C,Raherison-Semjen C, Walker B, Penz E, Gilbert I, Lugogo NL, van der Valk RJP;SABINA North American and European Study contributors. Short-actingβ₂-agonist exposure and severe asthma exacerbations: SABINA findingsfrom Europe and North America. J Allergy Clin Immunol Pract. 2022 Mar29:S2213-2198(22)00285-9. doi: 10.1016/j.jaip.2022.02.047. Epub ahead of print.
PMID: 35364341.
Background: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting β2-agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists.
Objective: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe.
Methods: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 years) from Canada, France, the Netherlands, Poland, Spain, United Kingdom (UK), and United States (US). Negative binomial models (incidence rate-ratio [95% confidence interval]) adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations.
Results: Across severities, 40.2% of patients were prescribed/possessed ≥3 SABA canisters/year. Per GINA-2018 definitions, step 3‒5-treated patients prescribed/possessing ≥3 vs. 1‒2 SABA experienced more severe exacerbations (between 1.08 [1.04‒1.13], US-Medicare; 2.11 [1.96‒2.27], Poland). This association was not observed in all step 1‒2-treated patients (the Netherlands 1.25 [0.91‒1.71]; US-commercial 0.92 [0.91‒0.93]; US-Medicare 0.74 [0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the US datasets was attributable to the large patient population possessing <3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face healthcare provider encounters. In US SABA monotherapy-treated patients, ≥3 SABA was associated with more emergency/outpatient visits and hospitalizations (1.31 [1.29‒1.34]). Most GINA 2‒5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of ≥3 SABA and severe exacerbations persisted (1.32 [1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when UK SABA data was analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications.
Conclusions: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

4: Wechsler ME, Menzies-Gow A, Brightling CE, Kuna P, Korn S, Welte T, GriffithsJM, Sałapa K, Hellqvist Å, Almqvist G, Lal H, Kaur P, Skärby T, Colice G; SOURCE
study group. Evaluation of the oral corticosteroid-sparing effect of tezepelumabin adults with oral corticosteroid-dependent asthma (SOURCE): a randomised,
placebo-controlled, phase 3 study. Lancet Respir Med. 2022 Mar
29:S2213-2600(21)00537-3. doi: 10.1016/S2213-2600(21)00537-3. Epub ahead of
print. PMID: 35364018.
Background: Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. SOURCE evaluated the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma.
Methods: We conducted this phase 3, multicentre, randomised, double-blind, placebo-controlled study across 60 sites in seven countries. Participants aged 18-80 years with physician-diagnosed asthma, who had been receiving medium-dose or high-dose inhaled corticosteroids and had at least one asthma exacerbation in the 12 months before screening were eligible. Patients who were receiving medium-dose inhaled corticosteroids must have had their dose increased to a high dose for at least 3 months before screening. After an oral corticosteroid optimisation phase of up to 8 weeks, participants were randomly assigned according to a computer-generated fixed block randomisation sequence to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks during a 48 week treatment period (4 week induction phase, 36 week oral corticosteroid reduction phase, and 8 week maintenance phase). Randomisation was stratified by region. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoint was the categorised percentage reduction from baseline in daily oral corticosteroid dose at week 48 without the loss of asthma control. Efficacy and safety endpoints were assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03406078.
Findings: Between March 5, 2018, and Sept 27, 2019, 150 participants were randomly assigned to receive tezepelumab 210 mg (n=74) or placebo (n=76). The cumulative odds of achieving a category of greater percentage reduction in an oral corticosteroid dose for daily maintenance at week 48 were similar with tezepelumab or placebo in the overall population (odds ratio [OR] 1·28 [95% CI 0·69-2·35], p=0·43; the primary endpoint was not met). The cumulative odds were higher with tezepelumab than with placebo in participants with baseline blood eosinophil counts of at least 150 cells per μL (2·58 [1·16-5·75]), but not in participants with counts below 150 cells per μL (0·40 [0·14-1·13]). Tezepelumab was well tolerated, with no safety concerns identified. 53 (72%) of 74 tezepelumab-assigned participants and 65 (86%) of 76 placebo-assigned participants reported an adverse event. Serious adverse events were reported in 12 (16%) participants in the tezepelumab group and 16 (21%) participants in the placebo group.
Interpretation: We did not observe a significant improvement in oral corticosteroid dose reduction with tezepelumab versus placebo in the overall population of this oral corticosteroid-sparing study, although an improvement was observed in participants with baseline blood eosinophil counts of at least 150 cells per μL.

5: Bapat SP, Whitty C, Mowery CT, Liang Y, Yoo A, Jiang Z, Peters MC, Zhang LJ,
Vogel I, Zhou C, Nguyen VQ, Li Z, Chang C, Zhu WS, Hastie AT, He H, Ren X, Qiu
W, Gayer SG, Liu C, Choi EJ, Fassett M, Cohen JN, Sturgill JL, Crotty Alexander
LE, Suh JM, Liddle C, Atkins AR, Yu RT, Downes M, Liu S, Nikolajczyk BS, Lee IK,
Guttman-Yassky E, Ansel KM, Woodruff PG, Fahy JV, Sheppard D, Gallo RL, Ye CJ,
Evans RM, Zheng Y, Marson A. Obesity alters pathology and treatment response in
inflammatory disease. Nature. 2022 Mar 30. doi: 10.1038/s41586-022-04536-0. Epub
ahead of print. PMID: 35355021.
Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation. We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.

6: Coker RK, Armstrong A, Church AC, Holmes S, Naylor J, Pike K, Saunders P,
Spurling KJ, Vaughn P. BTS Clinical Statement on air travel for passengers with
respiratory disease. Thorax. 2022 Apr;77(4):329-350. doi:
10.1136/thoraxjnl-2021-218110. Epub 2022 Feb 28. PMID: 35228307.

7: Abrams EM. Coronavirus disease 2019 and pediatric asthma: friend or foe? Curr
Opin Allergy Clin Immunol. 2022 Apr 1;22(2):95-100. doi:
10.1097/ACI.0000000000000809. PMID: 35197430.
Purpose of review: The interplay of asthma and coronavirus disease 2019 (COVID-19) in children is yet unknown. The purpose of this review is to determine the interplay of asthma and asthma therapeutics and COVID-19.
Recent findings: There is no evidence to date that asthma is a risk factor for more severe COVID-19 outcomes, especially in children. There is actually some basis to suggest that children with atopic asthma may be at reduced risk of asthma exacerbations during COVID-19. The impact of asthma therapeutics on COVID-19 outcomes is unclear, but guidance is relatively uniform in recommending that those with asthma remain on current asthma medications. A focus on social determinants of health may be increasingly important during the pandemic and beyond.
Summary: Asthma in children appears to be more friend, than foe, during COVID-19.

8: Al-Ahmad M, Webb D. A prospective study of switching asthma patients from a
Fixed-Dose Combination (FDC) Inhaled Corticosteroid [ICS]/Long-Acting Beta
Agonist [LABA] therapy delivered by Dry Powder Inhaler (DPI) to ICS/LABA
delivered by pressurised Metered Dose Inhaler (pMDI). Respir Med. 2022
Apr;194:106771. doi: 10.1016/j.rmed.2022.106771. Epub 2022 Feb 12. PMID:
35180515.
Background: Previous real-world studies have suggested that in comparison to a dry powder inhaler (DPI), the rate of critical errors is lower with a pressurised metered dose inhaler (pMDI), and inhaled corticosteroid/long-acting bronchodilator (ICS/LABA) delivered by pMDI is more likely to achieve asthma control.
Objectives: To evaluate the acceptability, efficacy, safety and cost-effectiveness of switching asthma patients from an ICS/LABA DPI to an ICS/LABA pMDI in a real-world population in Kuwait.
Methods: This was a 12-month, observational, nonblinded, prospective, real world study. Patients with asthma for ≥1 year with 2 or more asthma exacerbations in the last year were assigned to either switch to ICS/LABA pMDI, or to continue with ICS/LABA DPI.
Results: A total of 239 patients were treated with either ICS/LABA pMDI (Switch cohort; n = 119) or ICS/LABA DPI (Maintenance cohort; n = 120). The majority of patients (99/119; 83.2%) in the Switch cohort remained on ICS/LABA pMDI over 12 months of follow-up. Both cohorts experienced an improvement in their FEV1 levels, with mean values in the Switch group reaching normal levels (>80% predicted). On average, at 3 and 12 months, the Switch cohort had significantly better FEV1 values than patients in the Maintenance cohort (p = 0.001). At 12 months, the proportion of patients with controlled asthma increased in the Switch group, but did not change significantly in the Maintenance group.
Conclusions: In patients with asthma symptoms that are not well controlled with an ICS/LABA DPI, switching to an ICS/LABA pMDI provides an alternative choice that may improve asthma control.

9: Persaud YK. Using Telemedicine to Care for the Asthma Patient. Curr Allergy
Asthma Rep. 2022 Apr;22(4):43-52. doi: 10.1007/s11882-022-01030-5. Epub 2022 Feb
2. PMID: 35107807; PMCID: PMC8807679.
Purpose of review: To review the data supporting the use of telemedicine (TM) and to provide practical guidance for practitioners to optimize the care of their asthmatic patients.
Recent findings: Previous to the pandemic, TM was little used in various aspects of asthma care. Since the pandemic, TM has been increasingly used in new ways to care for asthma patients at various locations. In addition to direct-to-consumer visits for asthma care, other forms of telehealth visits have been increasing such as facilitated visits, asynchronous, remote patient monitoring, e-consults, and mHealth. Moreover, patient and provider satisfaction with the use of TM has been increasing and is comparable at times with face-to-face visits. In this review, best practices for starting a telemedicine asthma service with patients at home, distant clinic sites, and various other locations, including school-based asthma programs, are reviewed. TM is a valuable adjunct to face-to-face visits for asthma care. Following the recommended best practices can strengthen the implementation of a telemedicine asthma program (TMAP) into clinical practice. Providers must be vigilant in keeping current with the various nuances required for asthma telemedicine care in preparation for the post-pandemic environment.

10: Wang E, Wechsler ME. A rational approach to compare and select biologic
therapeutics in asthma. Ann Allergy Asthma Immunol. 2022 Apr;128(4):379-389.
doi: 10.1016/j.anai.2022.01.024. Epub 2022 Jan 31. PMID: 35093555.
Objective: To review key literature on asthma biologic therapeutics-currently available and under investigation-to inform a rational approach to select biologics for the management of people with severe asthma by precision medicine.
Data sources: We used the PubMed database to review literature on biologic therapeutics in asthma.
Study selections: We included published randomized control trials and real-world studies on biologic therapeutics, available in English, through September 2021.
Results: Increased understanding of asthma endotypes and the roles of various inflammatory mechanisms has led to therapeutic agents that inhibit specific cytokines or immune pathways. Currently available biologic therapeutics target type 2-high asthma. Grouped by mechanisms of action, there are the following 3 types: (1) anti-immunoglobulin E, (2) anti-interleukin (IL)-5 or IL-5 receptor, and (3) anti-IL-4 receptor α. There are also various potential future biologic therapeutics currently under investigation. Although there remains a paucity of data regarding prospective direct head-to-head comparisons of biologic therapeutics in asthma, there are some retrospective and indirect comparison data available.
Conclusion: Precision medicine guides selection of biologic therapeutics along with shared decision-making. Biomarkers, although not comprehensive, allow approximations of likely mechanisms. Use of biomarkers, to include historical levels and trends, in addition to consideration of key clinical characteristics and comorbidities can greatly help guide biologic selection. Efficacy, safety, potential adverse effects, indications for other key comorbidities, and logistics should also be considered.

11: Busse WW, Kraft M. Current unmet needs and potential solutions to
uncontrolled asthma. Eur Respir Rev. 2022 Jan 25;31(163):210176. doi:
10.1183/16000617.0176-2021. PMID: 35082128.
Despite the availability of effective inhaled therapies, many patients with asthma have poor asthma control. Uncontrolled asthma presents a significant burden on the patient and society, and, for many, remains largely preventable. There are numerous reasons why a patient may remain uncontrolled despite access to therapies, including incorrect inhaler technique, poor adherence to treatment, oversight of triggers and suboptimal medical care. Shared decision-making, good patient-clinician communication, supported self-management, multidisciplinary patient education, new technology and risk stratification may all provide solutions to this major unmet need in asthma. Novel treatments such as biologics could benefit patients’ lives, while the investigations into biomarkers, non-Type 2 asthma, treatable traits and disease modification give an exciting glimpse into the future of asthma care.
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12: Mummy DG, Dunican EM, Carey KJ, Evans MD, Elicker BM, Newell JD Jr, Gierada
DS, Nagle SK, Schiebler ML, Sorkness RL, Jarjour NN, Denlinger LC, Fahy JV, Fain
SB. Mucus Plugs in Asthma at CT Associated with Regional Ventilation Defects at
³He MRI. Radiology. 2022 Apr;303(1):184-190. doi:
10.1148/radiol.2021204616. Epub 2021 Dec 21. PMID: 34931858.
Background Airway mucus plugs in asthma are associated with exacerbation frequency, increased eosinophilia, and reduced lung function. The relationship between mucus plugs and spatially overlapping ventilation abnormalities observed at hyperpolarized gas MRI has not been assessed quantitatively. Purpose To assess regional associations between CT mucus plugs scored by individual bronchopulmonary segment and corresponding measurements of segmental ventilation defect percentage (VDP) at hyperpolarized helium 3 (3He) MRI. Materials and Methods In this secondary analysis of a Health Insurance Portability and Accountability Act-compliant prospective observational cohort, participants in the Severe Asthma Research Program (SARP) III (NCT01760915) between December 2012 and August 2015 underwent hyperpolarized 3He MRI to determine segmental VDP. Segmental mucus plugs at CT were scored by two readers, with segments scored as plugged only if both readers agreed independently. A linear mixed-effects model controlling for interpatient variability was then used to assess differences in VDP in plugged versus plug-free segments. Results Forty-four participants with asthma were assessed (mean age ± standard deviation, 47 years ± 15; 29 women): 19 with mild-to-moderate asthma and 25 with severe asthma. Mucus plugs were observed in 49 total bronchopulmonary segments across eight of 44 patients. Segments containing mucus plugs had a median segmental VDP of 25.9% (25th-75th percentile, 7.3%-38.3%) versus 1.4% (25th-75th percentile, 0.1%-5.2%; P < .001) in plug-free segments. Similarly, the model estimated a segmental VDP of 18.9% (95% CI: 15.7, 22.2) for mucus-plugged segments versus 5.1% (95% CI: 3.3, 7.0) for plug-free segments (P < .001). Participants with one or more mucus plugs had a median whole-lung VDP of 11.1% (25th-75th percentile, 7.1%-18.9%) versus 3.1% (25th-75th percentile, 1.1%-4.4%) in those without plugs (P < .001). Conclusion Airway mucus plugging at CT was associated with reduced ventilation in the same bronchopulmonary segment at hyperpolarized helium 3 MRI, suggesting that mucus plugging may be an important cause of ventilation defects in asthma. © RSNA, 2021 Online supplemental material is available for this article.

13: Agusti A, Fabbri L, Lahousse L, Singh D, Papi A. Single inhaler triple
therapy (SITT) in asthma: Systematic review and practice implications. Allergy.
2022 Apr;77(4):1105-1113. doi: 10.1111/all.15076. Epub 2021 Sep 15. PMID:
34478578.
A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long-acting β2 adrenergic bronchodilators (LABA). The addition of long-acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single-inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS-LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.

14: Krings JG, Wenzel SE, Castro M. The emerging role of quantitative imaging in
asthma. Br J Radiol. 2022 Apr 1;95(1132):20201133. doi: 10.1259/bjr.20201133.
Epub 2020 Dec 3. PMID: 33242252.
Quantitative imaging of the lung has proved to be a valuable tool that has improved our understanding of asthma. CT, MRI, and positron emission tomography have all been utilized in asthma with each modality having its own distinct advantages and disadvantages. Research has now demonstrated that quantitative imaging plays a valuable role in characterizing asthma phenotypes and endotypes, as well as potentially predicting future asthma morbidity. Nonetheless, future research is needed in order to minimize radiation exposure, standardize reporting, and further delineate how imaging can predict longitudinal outcomes. With future work, quantitative imaging may make its way into the clinical care of asthma and change our practice

1: Son DS, Cho MS, Kim DK. Chronic Rhinosinusitis and the Increased Incidence of
Atopic Dermatitis. Am J Rhinol Allergy. 2022 Mar 29:19458924221090050. doi:
10.1177/19458924221090050. Epub ahead of print. PMID: 35345892.
Background: Chronic rhinosinusitis (CRS) is often associated with other comorbidities due to chronic inflammation. However, no population-based, longitudinal study has investigated the relationship between CRS and chronic skin inflammation.
Objective: To investigate the potential relationship between CRS and chronic skin inflammatory diseases, such as atopic dermatitis (AD), vitiligo, and psoriasis.
Methods: A total of 5638 patients with CRS and 11 276 without CRS as a comparison group, were included from the Korean National Health Insurance Service database from 2002-2013. A propensity score matching (1:2) was performed using the nearest neighbor matching method, sociodemographic factors, and enrollment year. The Cox proportional hazards model was used to analyze the hazard ratio of CRS for AD, vitiligo, and psoriasis.
Results: Results from this study showed that patients with CRS had no significant risk of the subsequent development of vitiligo or psoriasis compared to patients without CRS. However, we found a significantly higher incidence of AD in CRS patients than in those without CRS. The incidence of AD was 63.59 per 1000 person-years in the CRS group and 45.38 per 1000 person-years in the comparison group. Additionally, young and middle-aged CRS patients were independently associated with a higher incidence of subsequent AD events, but we could not find a significantly higher incidence of AD events in the elderly group.
Conclusions: Our findings suggest there are no significant differences in the overall risk of vitiligo and psoriasis events in patients with CRS; however, we detected a higher risk of AD in young and middle-aged CRS patients. Therefore, clinicians should consider the risk of developing AD in specific patients who are newly diagnosed with CRS.

2: Farraia M, Paciência I, Castro Mendes F, Cavaleiro Rufo J, Shamji M, Agache
I, Moreira A. Allergen immunotherapy for asthma prevention: A systematic review
and meta-analysis of randomized and non-randomized controlled studies. Allergy.
2022 Mar 28. doi: 10.1111/all.15295. Epub ahead of print. PMID: 35342949.
Background: Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated diseases. Randomized controlled trials (RCTs) support AIT’s potential role in asthma prevention but evidence from non-randomized studies of interventions (NRSI) and longitudinal observational studies has been poorly addressed. Therefore, we aimed to conduct a systematic review and meta-analysis to assess clinical data from all study types to evaluate quantitatively the preventive role of AIT in asthma onset.
Methods: We search three databases. Studies were screened, selected and evaluated for quality using risk-of-bias (ROB) tools. Data were descriptively summarized and meta-analysed using random effects. We performed a sensitivity, influence and subgroup analyses. Publication bias and heterogeneity were assessed.
Results: From the 4549 identified studies, 24 (12 RCTs and 12 NRSI) were included in the qualitative synthesis and 18 underwent meta-analysis. One study was at low ROB, seven had moderate ROB, and 15 were proven of high ROB. Random-effects analysis showed a significant decrease in the risk of developing asthma following AIT by 25% (RR, 95% CI: 0.75, 0.64-0.88). This effect was not significant in the sensitivity analysis. Publication bias raised concerns, together with the moderate heterogeneity between studies (I2 = 58%). Subgroup analysis showed a remarkable preventive effect of AIT in children (RR, 95% CI: 0.71, 0.53-0.96), when completing 3 years of therapy (RR, 95% CI: 0.64, 0.47-0.88), and in mono-sensitized patients (RR, 95% CI: 0.49, 0.39-0.61).
Conclusions: Our findings support a possible preventive effect of AIT in asthma onset and suggest an enhanced effect when administered in children, mono-sensitized, and for at least 3 years, independently of allergen type.

3: De Corso E, Seccia V, Ottaviano G, Cantone E, Lucidi D, Settimi S, Di Cesare
T, Galli J. Clinical Evidence of Type 2 Inflammation in Non-allergic Rhinitis
with Eosinophilia Syndrome: a Systematic Review. Curr Allergy Asthma Rep. 2022
Apr;22(4):29-42. doi: 10.1007/s11882-022-01027-0. Epub 2022 Feb 9. PMID:
35141844.
Purpose of review: Non-allergic rhinitis (NAR) includes different subtypes, among which NAR with eosinophilia syndrome (NARES) is the most important because of severity of symptoms and the high risk of comorbidities. Its pathophysiology is still object of debate, but a crucial role of chronic eosinophilic inflammation has been recognized. The aim of this review is to critically analyze the current evidence regarding the hypothesis that NARES may be considered a type 2 inflammatory disorder.
Recent findings: The definition and diagnostic criteria for NARES are not universally shared and adopted, thus generating difficulties in reproducing the results. At present, there is extreme heterogeneity in sampling methods and disagreement in the cut-off of local eosinophilic count to determine a diagnosis of NARES. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was applied to identify English-language experimental and clinical articles regarding NARES. The search was performed in April 2021. Twenty-six articles were included. Our data suggest a particular heterogeneity regarding sampling and specific cut-offs adopted for diagnosis of NARES and consensus should be reached. We suggest that eosinophil count should be reported as an absolute value for at least 10 observed rich fields in order to increase the level of standardization. Consensus among authors on this topic should be reached with particular attention to the cut-off for diagnosis. In the future, this limitation may be overcome by the identification of repeatable biomarkers to refine diagnosis and prognosis of NARES. Furthermore, our data strongly suggest that NARES have numerous similarities with clinical features of the most common type 2 diseases such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP): late onset, association with type 2 comorbidities, selective eosinophilic tissue infiltration, remarkable response to oral and intranasal corticosteroids, and progression in a type 2 CRSwNP.

4: Li S, Wu W, Wang G, Zhang X, Guo Q, Wang B, Cao S, Yan M, Pan X, Xue T, Gong
J, Duan X. Association between exposure to air pollution and risk of allergic
rhinitis: A systematic review and meta-analysis. Environ Res. 2022 Apr
1;205:112472. doi: 10.1016/j.envres.2021.112472. Epub 2021 Dec 1. PMID:
34863689.
Background: Allergic rhinitis (AR) is one of the most common allergic diseases in the world, and usually persists throughout the activity. Epidemiological studies have shown a positive association between air pollution and allergic rhinitis. However, we could not find any meta-analysis of the risk of air pollutants (PM2.5, PM10, NO2, SO2, O3 and CO) on the prevalence of AR in people of all ages.
Objectives: Carry out a meta-analysis on the results of recent studies (up to 2020) to present valid information about exposure to air pollution and risk of prevalence of AR.
Methods: We systematically searched three databases for studies up to December 17, 2020, including air pollution and AR. Random effect models were conducted to estimate the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Subgroup analysis, funnel plot, Egger’s test, and the trim-and-fill method were also conducted.
Results: Thirty-five studies across 12 countries, including a total of 453,470 participants, were included. The OR per 10 μg/m3 increase of pollutants was 1.13 (1.04-1.22) for PM10 and 1.12 (1.05-1.20) for PM2.5. The OR per 10 μg/m3 increment of gaseous pollutants were 1.13 (1.07-1.20) for NO2, 1.13 (1.04-1.22) for SO2 and 1.07 (1.01-1.12) for O3. No significant association was observed between CO and AR. Children or adolescents are more sensitive to air pollution than adults. The effects of PM10 and SO2 were significantly stronger in Europe than Asia. The effects of air pollutants were more significant and higher in developing countries than in developed countries, except for PM10. A significant difference of subgroup test was found between developed and developing countries of NO2.
Conclusion: This meta-analysis showed a positive association between air pollution and the prevalence of allergic rhinitis, and identified geographic area and economic level as the potential modifiers for the association.

5: Chen R, Zheng D, Zhang Y, Sima G. Efficacy and safety of twice-daily
olopatadine-mometasone combination nasal spray (GSP301) in the treatment of
allergic rhinitis: a systematic review and meta-analysis. Eur Arch
Otorhinolaryngol. 2022 Apr;279(4):1691-1699. doi: 10.1007/s00405-021-07085-w.
Epub 2021 Sep 30. PMID: 34591150.
Purpose: GSP301 is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). This meta-analysis aims to evaluate the efficacy and safety of GSP301 in the treatment of allergic rhinitis.
Methods: A systematic review and meta-analysis were conducted. The data were collected from PubMed, Cochrane Central Register of Controlled Trials and Embase databases till June 2021. In patients with AR, short-term (2/6 weeks) and long-term (52 weeks) effects of GSP301 were assessed. Average morning and evening 12-h reflective total nasal symptom score (rTNSS), instantaneous total nasal symptom score (iTNSS), reflective total ocular symptom score (rTOSS), instantaneous total ocular symptom score(iTOSS), Physician-assessed nasal symptom score (PNSS), rhinoconjunctivitis quality of life (RQLQ), rhinitis control assessment test (RCAT) and adverse events (AEs) were measured.
Results: Five randomized controlled trials were included. GSP301 showed greatly improvement in rTNSS (MD = – 0.99; [95% CI – 1.19 to – 0.79]; P < 0.01; I2 = 0), iTNSS (MD = – 1.05; [95% CI – 1.44 to – 0.67]; P < 0.01; I2 > 50%), rTOSS (MD = – 0.50; [95% CI – 0.72 to – 0.29]; P < 0.01; I2 = 0), iTOSS (MD = – 0.64; [95% CI – 1.02 to – 0.26]; P < 0.01; I2 > 50%), PNSS (MD = – 1.01; [95% CI – 1.32 to – 0.69]; P < 0.01; I2 = 22.13%), RQLQ (MD = – 0.43; [95% CI – 0.57 to – 0.30]; P < 0.01; I2 = 0%) and RCAT (MD = 1.94; [95% CI 1.43-2.45]; P < 0.01; I2 = 0%) in the short term. No statistical difference was observed in the outcome of long-term PNSS, RQLQ and RCAT.
Conclusion: GSP301 is a safe and well-tolerated medication. It showed short-term benefits for seasonal and perennial AR, but may not help to improve patients’ quality of life and rhinitis control in the long run