1: Tavares N, Jarrett N, Wilkinson T, Hunt K. Clinician Perspectives on How to Hold Earlier Discussions About Palliative and End-of-Life Care With Chronic Obstructive Pulmonary Disease Patients: A Qualitative Study. J Hosp Palliat Nurs. 2022 Mar 24. doi: 10.1097/NJH.0000000000000858. Epub ahead of print. PMID: 35334479.
Chronic obstructive pulmonary disease is associated with progressive symptoms and increased treatment burden, especially at the end of life. However, most patients do not receive palliative care until late in their lives or discuss their end-of-life preferences with clinicians. This study explored clinicians’ perspectives on the timing and nature of palliative care discussions. Qualitative interviews were conducted with 7 physicians and 7 nurses working in primary and secondary care settings. Data were analyzed using a thematic analysis. Participants advocated for early, gradual, and informed palliative and future care discussions, because these discussions were thought to be less traumatic and better accepted by patients. Despite this, patient- and clinician-related barriers severely affected clinicians’ ability to start discussions at earlier stages. Participants felt many patients were not ready for these discussions and feared damaging hope if the subject was broached. Therefore, clinicians delayed discussions until patients approached the end of life. Stand-alone conversations about and near the end of life were described as current practice; however, clinicians believed these discussions reduced patients’ hope and were potentially upsetting. Instead, individualized early, regular, and gradual discussions about immediate and long-term care plans were thought to be less negative and be better accepted.

2: Phillips DB, Elbehairy AF, James MD, Vincent SG, Milne KM, de-Torres JP, Neder JA, Kirby M, Jensen D, Stickland MK, Guenette JA, Smith BM, Aaron SD, Tan WC, Bourbeau J, O’Donnell DE; CanCOLD Collaborative Research Group and the Canadian Respiratory Research Network. Impaired Ventilatory Efficiency, Dyspnea and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study. Am J Respir Crit Care Med. 2022 Mar 25. doi: 10.1164/rccm.202109-2171OC. Epub ahead of print. PMID: 35333135.
Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [V̇E/V̇CO2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD).
Objectives: To determine: 1) the association between high V̇E/V̇CO2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort.
Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing and chest computed tomography (CT). Impaired exercise ventilatory efficiency was defined by a nadir V̇E/V̇CO2 above the upper limit of normal (V̇E/V̇CO2>ULN), using population-based normative values.
Measurements and main results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with GOLD 1 COPD, and 200 with GOLD 2-4 COPD. Participants with V̇E/V̇CO2>ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale≥2, odds ratio=1.77[1.31-2.39]) and abnormally low peak oxygen uptake (V̇O2peak<LLN, odds ratio=4.58[3.06-6.86]). The carbon monoxide transfer coefficient (KCO) had a stronger correlation with nadir V̇E/V̇CO2 (r=-0.38, p<0.001) than other relevant lung function and CT metrics. The prevalence of V̇E/V̇CO2>ULN was 24% in COPD (similar in GOLD 1 and 2-4), which was greater than in never-smokers (13%) and ever-smokers (12%).
Conclusions: V̇E/V̇CO2>ULN was associated with greater dyspnea and low VO2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.

3: Li H, Chen J, Hu P. Diagnostic value of pulmonary ultrasound in acute exacerbation of chronic obstructive pulmonary disease: A pilot study. Med Clin (Barc). 2022 Mar 21:S0025-7753(22)00081-1. English, Spanish. doi: 10.1016/j.medcli.2022.01.022. Epub ahead of print. PMID: 35331547.
Background: To evaluate the value of the pulmonary ultrasound for the diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in emergency departments (EDs).
Materials and methods: Between January 2018 and December 2019, patients admitted to the ED of Shanxi Provincial People’s Hospital for suspected AECOPD were prospectively included in this study. Pulmonary ultrasound was performed using a linear transducer. The pulmonary ultrasound findings were evaluated for further discrimination for patients with AECOPD. Then, the diagnostic performance of pulmonary ultrasound was estimated and calculated. The clinical characteristics between groups with and without pneumonia were compared.
Results: A total of 53 patients with AECOPD were included in the final analysis. For diagnosis of AECOPD due to pneumonia, ultrasound findings, such as consolidation, slightly rough pleural line, or irregular and interrupted pleural line had a sensitivity of 92.3% and a specificity of 86.7%. For diagnosis of AECOPD complicating pulmonary fibrosis, fringed pleural line had a sensitivity of 100% and a specificity of 97.5%. In addition, patients with pleural effusion (n=19) or pneumothorax (n=1) were correctly identified and wavy or bulging pleural lines were common in patients with AECOPD (58.5%, 31/53).
Conclusion: Ultrasound findings could offer further discrimination for AECOPD complications and other pathological conditions, such as pneumonia, pulmonary fibrosis, pleural effusion, and pneumothorax in EDs.

4: Press VG, Randall K, Hanser A. Evaluation of COPD Chronic Care Management Collaborative to Reduce Emergency Department and Hospital Revisits Across U.S. Hospitals. Chronic Obstr Pulm Dis. 2022 Mar 23. doi: 10.15326/jcopdf.2022.0273. Epub ahead of print. PMID: 35322625.
Background: Chronic Obstructive Pulmonary Disease (COPD) is the third-leading cause of early readmissions. The Centers for Medicare and Medicaid instituted a financial penalty for excessive COPD readmissions galvanizing hospitals to implement effective strategies to reduce readmissions. We evaluated a 6-month COPD Chronic Care Management Collaborative to support hospitals to reduce preventable COPD-related revisits.
Methods: Sites were recruited among nearly 300 Vizient members. The Collaborative used performance improvement initiatives to assist with implementation of effective strategies. Participants submitted performance data for two outcome measures: emergency department (ED) and hospital revisits.
Results: Forty-seven members enrolled (Part I+II: n=33; Part I: n=3; Part II: n=11) of which 23 submitted data (n=23/47). The majority (n=19/23, 83%) reduced rates of COPD-related ED and/or hospital revisits. Among all 23 sites, the change in ED visits went from 11.05% to 10.87%; among 7 sites with reductions in ED visits, the reduction was 12.7% to 9%. Among all 23 sites, there were not reductions hospital readmissions (18.53% to 18.64%); among 7 sites with reductions, the readmission rate went from 20.1% to 15.6%. The mean reach across 17 hospitals reporting reach for their most successful measure at baseline was 35.2% (SD = 26.7%) and for the six reporting reach at follow-up was 73.8%% (SD = 18.3%); of note, only three sites submitted both baseline and follow-up data.
Conclusions: The Collaborative successfully supported the majority of sites to reduce COPD-related ED and/or hospital revisits using subject matter experts and coaching strategies to support hospitals’ implementation of COPD quality improvement interventions.

5: Rebordosa C, Farkas DK, Montonen J, Laugesen K, Voss F, Aguado J, Bothner U, Rothman KJ, Zint K, Mines D, Ehrenstein V. Cardiovascular Events and All-Cause Mortality in Patients With Chronic Obstructive Pulmonary Disease Using Olodaterol and Other Long-Acting Beta2-Agonists. Pharmacoepidemiol Drug Saf. 2022 Mar 23. doi: 10.1002/pds.5432. Epub ahead of print. PMID: 35320605.
Purpose: We examined the effect of olodaterol on the risk of myocardial ischaemia, cardiac arrhythmia, and all-cause mortality compared with use of other long-acting beta2-agonists (LABAs). Channelling bias was also explored.
Methods: This Danish population-based cohort study used data linked from registries of hospital diagnoses, outpatient dispensings, and deaths. It included patients (aged ≥40 years) with a diagnosis of chronic obstructive pulmonary disease (COPD) who initiated olodaterol or another LABA. Using matching and propensity score (PS) stratification, we calculated adjusted incidence rate ratios (IRRs) using Poisson regression, followed by several additional analyses to evaluate and control channelling bias.
Results: The IRRs of cardiac arrhythmias or myocardial ischaemia among users of olodaterol (n=14,239) compared to users of other LABA (n=51,167) ranged from 0.96 to 1.65 in various analyses, although some estimates had low precision. Initial analysis suggested an increased risk for death with olodaterol compared with other LABAs (IRR, 1.63; 95% CI, 1.44-1.84). Because olodaterol prescribing was associated with COPD severity, the mortality association was attenuated by using different methods of tighter confounding control: the IRRs were 1.26 (95% CI, 0.97-1.64) among LABA-naïve LABA/LAMA users without recent COPD hospitalisation; 1.27 (95% CI, 1.03-1.57) in a population with additional trimming from the tails of the PS distribution; and 1.32 (95% CI, 1.19-1.48) after applying overlap-weights analysis.
Conclusions: Olodaterol users had a similar risk for cardiac arrhythmias or myocardial ischaemia as other LABA users. The observed excess all-cause mortality associated with olodaterol use could be due to uncontrolled channelling bias.

6: Baalbaki N, Giuliano C, Hartner CL, Kale-Pradhan P, Johnson L. Azithromycin Versus Beta-lactams in Hospitalized Patients with Acute Exacerbations of COPD. J Gen Intern Med. 2022 Mar 22:1–6. doi: 10.1007/s11606-022-07486-5. Epub ahead of print. PMID: 35316516; PMCID: PMC8939242.
Background: There is a lack of data comparing azithromycin to alternative antibiotic choices in managing COPD exacerbations, making appropriate antibiotic selection controversial.
Objective: To compare treatment failure in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) receiving azithromycin or beta-lactams.
Design: Retrospective, multicenter cohort study using logistic regression for multivariable analysis. Patients were included if they were at least 18 years old, admitted with AECOPD, and received at least two consecutive days of either a beta-lactam or azithromycin. Patients were excluded if they received concomitant azithromycin and beta-lactam antibiotics during the first 2 days, had a history of other severe underlying pulmonary diseases, pregnancy, COVID-19, alpha-1 antitrypsin deficiency, or received a corticosteroid for a diagnosis other than COPD.
Participants: Five hundred ninety-five patients were included, of which 428 (72%) received azithromycin and 167 patients (28%) received a beta-lactam.
Main measures: The primary endpoint was treatment failure rate in patients receiving azithromycin versus beta-lactams, which was a composite endpoint defined as in-hospital mortality, admission to intensive care, initiation of invasive mechanical ventilation, initiation of a new antibiotic, steroid therapy escalation, or readmission due to AECOPD within 30 days.
Key results: The composite primary outcome occurred in 84 patients (19.6%) in the azithromycin group and 54 (32.3%) in the beta-lactam group (p<0.01). The difference in the composite outcome was a result of higher rates of new antibiotics during admission (12.6% vs 4.2%; p<0.01) and higher readmission within 30 days (19.3% vs 12.4%; p=0.032). After controlling for potential confounders, beta-lactams continued to demonstrate a higher risk for treatment failure (OR, 2.30; 95% CI, 1.46-3.63). There was no difference in adverse effects between the groups.
Conclusion: Azithromycin was associated with less treatment failure in AECOPD which was driven by lower readmission rates and prescription of new antimicrobials.

7: Hyodo K, Masuko H, Oshima H, Shigemasa R, Kitazawa H, Kanazawa J, Iijima H, Ishikawa H, Kodama T, Nomura A, Kagohashi K, Satoh H, Saito T, Sakamoto T, Hizawa N. Common exacerbation-prone phenotypes across asthma and chronic obstructive pulmonary disease (COPD). PLoS One. 2022 Mar 21;17(3):e0264397. doi: 10.1371/journal.pone.0264397. PMID: 35312711; PMCID: PMC8936473.
Background and objectives: Chronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), are complex syndromes with diverse clinical symptoms due to multiple pathophysiological conditions. In this study, using common and shared risk factors for the exacerbation of asthma and COPD, we sought to clarify the exacerbation-prone phenotypes beyond disease labels, and to specifically investigate the role of the IL4RA gene polymorphism, which is related to type 2 inflammation, in these exacerbation-prone phenotypes.
Methods: The study population comprised patients with asthma (n = 117), asthma-COPD overlap (ACO; n = 37) or COPD (n = 48) and a history of exacerbation within the previous year. Cluster analyses were performed using factors associated with both asthma and COPD exacerbation. The association of the IL4RA gene polymorphism rs8832 with each exacerbation-prone phenotype was evaluated by multinomial logistic analyses using non-asthma non-COPD healthy adults as controls (n = 1,529). In addition, the genetic influence of rs8832 was also examined in asthma patients with allergic rhinitis and no history of exacerbation (n = 130).
Results: Two-step cluster analyses identified five clusters that did not necessarily correspond to the diagnostic disease labels. Cluster 1 was characterized by high eosinophil counts, cluster 2 was characterized by smokers with impaired lung function, cluster 3 was characterized by the presence of gastroesophageal reflux, cluster 4 was characterized by non-allergic females, and cluster 5 was characterized by allergic rhinitis and elevated total immunoglobulin E levels. A significant association with rs8832 was observed for cluster 5 (odds ratio, 3.88 (1.34-11.26), p = 0.013) and also for the type 2 exacerbation-prone phenotypes (clusters 1 and 5: odds ratio, 2.73 (1.45-5.15), p = 1.9 × 10-3).
Discussion: Our results indicated that the clinical heterogeneity of disease exacerbation may reflect the presence of common exacerbation-prone endotypes across asthma and COPD, and may support the use of the treatable traits approach for the prevention of exacerbations in patients with chronic inflammatory airway diseases.

1: McLaughlin K, Jensen M, Foureur M, Murphy VE. Are pregnant women with asthma receiving guideline-recommended antenatal asthma management? A survey of pregnant women receiving usual care in Australia. Women Birth. 2022 Mar 23:S1871-5192(22)00046-4. doi: 10.1016/j.wombi.2022.03.008. Epub ahead of print. PMID: 35339413.
Background: Asthma affects 12.7% of pregnant women in Australia. Key recommendations for asthma management during pregnancy include: 4-6 weekly review of lung function, medications, written asthma action plan, inhaler device technique, current asthma control and triggers; smoking cessation and vaccination advice. It is unknown if these key recommendations are provided to pregnant women with asthma in Australia.
Aim: To explore usual antenatal asthma management (usual care) in Australia and the inclusion of key recommendations.
Method: Pregnant women with asthma were invited to complete an online survey distributed in 2 antenatal clinics and via social media platforms from July 2017-Jan 2019.
Results: The survey was completed by 142 pregnant women with asthma. 87(61%) were enrolled in an asthma management clinical trial and were therefore not receiving ‘usual’ care. Data presented is from 55(39%) women receiving usual care at survey completion. Of these women, 36% did not have their asthma reviewed during their pregnancy, 31% had a written asthma action plan, 11% had lung function assessed, 38% had an asthma medication review and 35% had their inhaler technique reviewed. 65% were not questioned about their asthma symptoms, 85% were not asked about asthma triggers, 96% were not given information about vaccinations and 95% did not receive smoking cessation information.
Conclusions: Overall, the key recommendations for antenatal asthma management were not always provided for this sample of pregnant women receiving usual care. Improved knowledge and implementation of these key recommendations by health professionals may alter this situation and improve maternal and infant outcomes.

2: Li X, Zhang Y, Zhang R, Chen F, Shao L, Zhang L. Association Between E-Cigarettes and Asthma in Adolescents: A Systematic Review and Meta-Analysis. Am J Prev Med. 2022 Mar 22:S0749-3797(22)00098-8. doi: 10.1016/j.amepre.2022.01.015. Epub ahead of print. PMID: 35337694.
Introduction: Numerous studies have revealed the relationship between E-cigarettes and asthma but have shown inconsistent results. This study systematically evaluated the potential association between E-cigarette use and asthma in adolescents.
Methods: PubMed, Embase (Ovid), Cochrane Library, and the China Biological Medicine Database were searched for relevant articles published between database inception and February 28, 2021. The quality of included studies was evaluated using the Agency for Healthcare Research and Quality assessment, and a quantitative meta-analysis was conducted to pool outcomes of ORs with 95% CIs.
Results: A total of 10 cross-sectional studies incorporating a total of 483,948 participants were included. All the study participants were middle- and high-school students with a mean age of 15-16 years. The median prevalence of ever E-cigarette use was 11.2% (range=2.2%, 45%), and that of current use was 7.5% (range=2.7%, 25%). Overall, E-cigarette use was associated with significantly higher odds of having asthma (pooled OR=1.31, 95% CI=1.22, 1.42) than nonuse, and both current use (OR=1.36, 95% CI=1.26, 1.48) and ever use (OR=1.20, 95% CI=1.12, 1.28) showed similar associations.
Discussion: This study shows that both current and ever E-cigarette use have significant associations with asthma in adolescents. This knowledge might provide potential evidence for developing primary prevention strategies and serve as a reference for public health policy.

3: Menzella F, Fontana M, Ruggiero P, Livrieri F, Facciolongo N. Home-based treatment of biologics for asthma: who, what, where, when and why. Expert Rev Respir Med. 2022 Mar 24. doi: 10.1080/17476348.2022.2057301. Epub ahead of print. PMID: 35324362.
Introduction: The advent of biologic therapies for severe asthma has profoundly changed the management of this pathology. The introduction of home administration is therefore an important innovation to optimize the patients’ management, even if there are many aspects that need to be clarified and pointed out.
Areas covered: This review summarizes the path that led to the possibility of self-administration of biologics, and what the pandemic has changed in the management of these patients.
Expert opinion: The growing understanding of asthma phenotypes and endotypes is enabling the careful selection of patients suitable for biologics. In this context, the availability of reliable and simple self-injection devices is important in implementing self-administration. The transition to self-injection is also possible thanks to the high safety profile of biologics. With attention, most patients may potentially be suitable for self-administration. The transition process from hospital to home administration can therefore be carried out correctly by clinicians with adequate expertise in the field of severe asthma and biologic therapies, with the support of other health professionals, pharmacists, and general practitioners. Home administration is probably the best way to guarantee high adherence and high-level satisfaction of patients, even in the long term.

4: Aukstuolis K, Cooper JJ, Altman K, Lang A, Ayars AG. Hypereosinophilic syndrome presenting as coagulopathy. Allergy Asthma Clin Immunol. 2022 Mar 22;18(1):25. doi: 10.1186/s13223-022-00666-2. PMID: 35317854; PMCID: PMC8941788.
Background: Hypereosinophilic syndrome (HES) is an extremely uncommon group of disorders. It rarely presents with coagulopathy without cardiac involvement.
Case presentation: A 33-year-old previously healthy male with no history of atopic disease presented with abdominal pain, hematochezia, peripheral eosinophilia as high as 10,000 eos/µL, right and left portal vein, mesenteric, and splenic vein thrombi with ischemic colitis resulting in hemicolectomy and small bowel resection. Despite an extensive workup for primary and secondary etiologies of hypereosinophilia by hematology/oncology, infectious disease, rheumatology and allergy/immunology, no other clear causes were identified, and the patient was diagnosed with idiopathic HES. His eosinophilia was successfully treated with high-dose oral corticosteroids (OCS) and subsequently transitioned to anti-IL-5-receptor therapy with benralizumab. He has continued this treatment for over a year with no recurrence of eosinophilia or thrombosis while on benralizumab.
Conclusion: In patients with an unexplained coagulopathy and eosinophilia, eosinophilic disorders such as HES should be considered. Corticosteroid-sparing agents, such as benralizumab show promise for successfully treating these patients.

5: Kow CS, Ramachandram DS, Hasan SS. Early oxygen therapy may be beneficial to patients with COVID-19 and underlying pulmonary diseases. J Asthma. 2022 Mar 22:1-2. doi: 10.1080/02770903.2022.2056701. Epub ahead of print. PMID: 35315746.

6: Trischler J, von Blumroeder M, Donath H, Kluge S, Hutter M, Dreßler M, Zielen S. Antibiotic Use in Paediatric Patients Hospitalized with Acute Severe Asthma. Klin Padiatr. 2022 Mar 21. English. doi: 10.1055/a-1712-4225. Epub ahead of print. PMID: 35315003.
Background: Antibiotic use during asthma exacerbations in paediatric patients is not routinely recommended but common practise in out-patient and in-patient settings. Objective of this study was to analyse frequency of antibiotic use during acute severe asthma exacerbations, antibiotic classes utilized and clinical decision-making.
Methods: All in-patient admissions over 10 years in a single German Children’s University hospital due to acute severe asthma were included in this retrospective analysis. Age, length of stay, oxygen supplementation, treatment, laboratory parameters and chest x-rays of all patients ranging from 1 to 17 years were analysed.
Results: 580 hospital admissions were included in this study. Overall antibiotic use was high but decreased with age (1-5 years 69,6%, 6-11 years 57,6% and 12-17 years 39,7%, p<0.001). Analysis of antibiotic treatment without clear indication showed a consistently lower treatment rate of 28.3%, with macrolides being the most common antibiotic class. Younger age significantly decreased, whereas, increase of CrP value, use of oxygen supplementation and concomitant fever all significantly increased the odds ratio (OR 0.967; 4.366, 2.472 and 2.011 respectively) of receiving antibiotic treatment without clear indication.
Conclusion: Antibiotic treatment without clear indication during acute severe asthma is common in this German single-centre cohort. Clinical parameters of more severe disease affect clinician’s decision to administer antibiotics despite evidence of bacterial infection or improved outcome.

7: Kachroo P, Stewart ID, Kelly RS, Stav M, Mendez K, Dahlin A, Soeteman DI, Chu SH, Huang M, Cote M, Knilhtilä HM, Lee-Sarwar K, McGeachie M, Wang A, Wu AC, Virkud Y, Zhang P, Wareham NJ, Karlson EW, Wheelock CE, Clish C, Weiss ST, Langenberg C, Lasky-Su JA. Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma. Nat Med. 2022 Mar 21. doi: 10.1038/s41591-022-01714-5. Epub ahead of print. PMID: 35314841.
The application of large-scale metabolomic profiling provides new opportunities for realizing the potential of omics-based precision medicine for asthma. By leveraging data from over 14,000 individuals in four distinct cohorts, this study identifies and independently replicates 17 steroid metabolites whose levels were significantly reduced in individuals with prevalent asthma. Although steroid levels were reduced among all asthma cases regardless of medication use, the largest reductions were associated with inhaled corticosteroid (ICS) treatment, as confirmed in a 4-year low-dose ICS clinical trial. Effects of ICS treatment on steroid levels were dose dependent; however, significant reductions also occurred with low-dose ICS treatment. Using information from electronic medical records, we found that cortisol levels were substantially reduced throughout the entire 24-hour daily period in patients with asthma who were treated with ICS compared to those who were untreated and to patients without asthma. Moreover, patients with asthma who were treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS treatment. Adrenal suppression in patients with asthma treated with ICS might, therefore, represent a larger public health problem than previously recognized. Regular cortisol monitoring of patients with asthma treated with ICS is needed to provide the optimal balance between minimizing adverse effects of adrenal suppression while capitalizing on the established benefits of ICS treatment.

8: Barber CM, Cullinan P, Feary J, Fishwick D, Hoyle J, Mainman H, Walters GI. British Thoracic Society Clinical Statement on occupational asthma. Thorax. 2022 Mar 21:thoraxjnl-2021-218597. doi: 10.1136/thoraxjnl-2021-218597. Epub ahead of print. PMID: 35314486.

9: Proceedings of the Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2021. Allergy Asthma Clin Immunol. 2022 Mar 22;18(Suppl 1):11. doi: 10.1186/s13223-022-00647-5. PMID: 35313976; PMCID: PMC8938214.

10: Hoffmann C, Maglakelidze M, von Schneidemesser E, Witt C, Hoffmann P, Butler T. Asthma and COPD exacerbation in relation to outdoor air pollution in the metropolitan area of Berlin, Germany. Respir Res. 2022 Mar 20;23(1):64. doi: 10.1186/s12931-022-01983-1. PMID: 35307034; PMCID: PMC8935815.
Background: Ambient air pollution poses a major risk for the development and aggravation of respiratory diseases. Evidence suggests that even in low-level air pollution environments there is a risk for an increase in adverse respiratory symptoms. We examined whether variations in daily air pollution levels of nitrogen dioxide, ozone, or particulate matter in Berlin, Germany were associated with hospital admissions of chronic obstructive pulmonary disease (COPD) and asthma patients in a time series analysis.
Methods: We calculated single and multi-pollutant models, investigated possible lags in effect, and analysed the influence of meteorological variables on the results. Data from January 2005 through December 2015 were used to quantify the concentration-response.
Results: The risk ratio for asthma patients to be hospitalised on the same day of NO2 exposure was 1.101 per 10 µg/m3 NO2 increase (95% CI: 1.013 to 1.195), for COPD patients 1.123 (95% CI: 1.081 to 1.168). Neither the exposure to ozone (95% CI: 0.904 to 1.020), PM10 (95% CI: 0.990 to 1.127), nor PM2.5 (95% CI: 0.981 to 1.148) was associated with an increased risk ratio for asthma patients to be hospitalised. Risk ratios for the hospital admission of COPD patients were also not increased due to ozone (95% CI: 0.981 to 1.033), PM10 (95% CI: 0.988 to 1.032), or PM2.5 (95% CI: 0.966 to 1.019) exposure. The presented risk ratios and confidence intervals relate to the day of exposure. We found no increased hospitalisation risks with a delayed occurrence on subsequent days.
Conclusions: A quantifiable, statistically significant increase in risk for asthma and COPD exacerbations owing to NO2 exposure at levels well below European regulatory limit values was observed.

11: Zhu Y, Yang T, Huang S, Li H, Lei J, Xue X, Gao Y, Jiang Y, Liu C, Kan H, Chen R. Cold temperature and sudden temperature drop as novel risk factors of asthma exacerbation: a longitudinal study in 18 Chinese cities. Sci Total Environ. 2022 Mar 25;814:151959. doi: 10.1016/j.scitotenv.2021.151959. Epub 2021 Nov 27. PMID: 34843761.
Background: Few studies have explored the role of ambient temperature in asthma exacerbation.
Objective: We aimed to explore the association of temperature with diurnal peak expiratory flow (PEF) variation and asthma exacerbation.
Method: We developed a longitudinal study among asthmatic adults in 18 Chinese cities. Subjects recorded PEF in dynamic pulmonary function monitoring from 2017 to 2020. Linear mixed-effect model and generalized additive model with distributed non-linear models were used to assess the effect of temperature and temperature change between neighboring days (TCN) on diurnal PEF variation and the risk of asthma exacerbation.
Result: We evaluated a total of 79,217 daily PEF monitoring records from 4467 adult asthmatic patients. There were significant increase of diurnal PEF variation and higher risk of asthma exacerbation with cold and sudden temperature drop. Compared with the referent temperature (99th percentile, 32 °C), exposure to moderate cold (25th percentile, 3 °C) and extreme cold (2.5th percentile, -7 °C) was associated with elevations of 1.28% and 1.16% in diurnal PEF variation over lag 0-2 days, respectively. The odds ratios of asthma exacerbation (determined by diurnal PEF variation >20%) at the two temperature cutoffs were 1.68 and 1.73. A sudden temperature drop (2.5th percentile of TCN, -5 °C) was associated with 1.13% elevation in diurnal PEF variation, and with increased risk of asthma exacerbation (odd ratio = 1.50) over lag 0-4 days.
Conclusion: This large multicenter study provided the first-hand empirical evidence that cold temperature and a temperature drop may increase the risk of asthma exacerbation.

1: Testera-Montes A, Palomares F, Jurado-Escobar R, Fernandez-Santamaria R, Ariza A, Verge J, Salas M, Campo P, Mayorga C, Torres MJ, Rondon C, Eguiluz- Gracia I. Sequential class switch recombination to IgE and allergen-induced accumulation of IgE+ plasmablasts occur in the nasal mucosa of local allergic rhinitis patients. Allergy. 2022 Mar 27. doi: 10.1111/all.15292. Epub ahead of print. PMID: 35340036.
Background: the involvement of allergen-specific (s)IgE in local allergic rhinitis (LAR) has been debated. Here, we investigate the effect of nasal allergen challenge with Dermatophagoides pteronyssinus (NAC-DP) in mucosal and peripheral B-cell subpopulations in LAR patients.
Methods: Nine LAR, 5 allergic rhinitis (AR) and 5 non-atopic healthy-control (HC) individuals were subjected to a 3-day NAC-DP protocol, and nasal biopsies and blood samples were collected before and after provocation. Nasal biopsies were used for immunohistochemistry and gene expression studies, whereas the frequency of lymphocyte subsets and basophil activation test (BAT) were analyzed in blood samples by flow cytometry. sIgG was measured in sera.
Results: NAC-DP induced an increase of IgE+ CD38+ plasmablasts in the nasal mucosa of LAR patients, but not in AR or HC individuals. Markers of sequential recombination to IgE (εCSR) (from IgG) were observed in 33% of LAR, 20% of AR and 0% of HC subjects. NAC-DP increased the proportion of peripheral CD19+ CD20+ CD38+ plasmablastsin AR and LAR patients, but not in HC. Expression of the mucosal homing receptor CXCR3 in peripheral CD19+ CD20+ CD38+ plasmablasts from LAR, AR and HC individuals was 7%, 5% and 0.5%, respectively. In vitro DP stimulation increased proliferating CD19+ CD20+ CD38+ plasmablasts in LAR and AR patients, but not in HC. Serum DP-sIgG was higher in LAR and AR patients as compared to HC. BAT was positive in 38%, 100% and 0% of LAR, AR and HC subjects, respectively.
Conclusion: These results suggest that allergen exposure induces the sequential εCSR of IgG+ CD19+ CD20+ CD38+ plasmablasts in the nasal mucosa of LAR patients

2: Ahlbeck L, Ahlberg E, Björkander J, Aldén C, Papapavlou G, Palmberg L, Nyström U, Retsas P, Nordenfelt P, Togö T, Johansen P, Rolander B, Duchén K, Jenmalm MC. Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen. Clin Exp Allergy. 2022 Mar 25. doi: 10.1111/cea.14138. Epub ahead of print. PMID: 35332591.
Introduction: There is need for a fast, efficient, and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.
Methods: Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abelló), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis Total Symptom Score, Medication Score and Rhinoconjunctivitis Quality of Life Questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analyzed by flow cytometry and Luminex.
Results: The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased three years after treatment.
Conclusions: Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective, and may be associated with bystander immune modulatory responses.
Keywords: Allergy; Hypersensitivity; Intralymphatic; Intralymphatic immunotherapy; Rhinoconjunctivitis Immunotheraphy.

3: Han J, Wang W, Zhu Z, Wang L, Chen Y, Wang R, Guan K, Lv W. Profile of Tissue Immunoglobulin E in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps. Int Arch Allergy Immunol. 2022 Mar 21:1-8. doi: 10.1159/000522624. Epub ahead of print. PMID: 35313318.
Introduction: Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) exhibits a poorer prognosis than noneCRSwNP. The aim of this study was to analyze the potential of total immunoglobulin E (tIgE) and specific IgE (sIgE) levels in tissues for distinguishing and assessing eCRSwNP.
Methods: We enrolled 10 control and 88 CRSwNP patients. The clinical data of patients were collected before surgery. Nasal mucosa tissues were taken during surgery for measurements of tIgE, sIgE (weed pollen, epidermal and animal protein, mold, house dust, tree pollen), and subepithelial eosinophil (EOS) counts. The predictive significance of the potential predictors for eCRSwNP was assessed with receiver operating characteristic (ROC) curves.
Results: Nasal polyps tIgE and mold-sIgE were positively correlated with blood and tissue EOSs, comorbid allergic rhinitis and asthma, ethmoid score/total maxillary score ratio, visual analog scale, and CT score. The ROC curve analysis showed that tissue tIgE (p = 0.0004), mold-sIgE (p = 0.0030), blood EOS percentage (p = 0.0003), and absolute blood EOS count (p = 0.0010) acted as predictive factors for eCRSwNP. According to the cutoff value of tissue tIgE of 34.55 ku/L, patients with a high level were more likely to suffer from asthma (p = 0.016) and showed a significantly higher EOS count (p = 0.022), EOS percentage (p = 0.029), and tIgE (p = 0.002) in blood.
Conclusion: Tissue tIgE and mold-sIgE had a significant relationship with the clinical and pathological characteristics of CRSwNP patients and might be reliable for distinguishing and assessing eCRSwNP.

Tang et al. Mucus Plugs Persist in Asthma and Changes in Mucus Plugs Associate with Changes in Airflow Over Time. AJRCCM 2022, March. On line + Editorial
Objectives: To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function.
Methods: In a longitudinal analysis of baseline and year 3 CT lung scans in SARP-3 participants, radiologists generated mucus plug scores to assess mucus plug persistence over time. Changes in mucus plug score were analyzed in relation to changes in lung function and CT air trapping measures.
Measurements and Main Results: In 164 participants, the mean (range) mucus plug score was similar at baseline and year 3 (3.4 [0-20] vs 3.8 [0-20]). Participants and bronchopulmonary segments with a baseline plug were more likely to have plugs at year 3 than those without baseline plugs (RR 2.8, 95% CI 2.0-4.1, p<0.001 and RR 5.0, 95% CI 4.5-5.6, p<0.001, respectively). The change in mucus plug score from baseline to year 3 was significantly negatively correlated with change in FEV1% predicted (rp = – 0.35, p<0.001) and with changes in CT air trapping measures (all p values < 0.05).
Conclusions: Mucus plugs identify a persistent asthma phenotype and susceptibility to mucus plugs occurs at the subject and the bronchopulmonary segment level. The association between change in mucus plug score and change in airflow over time supports a causal role for mucus plugs in mechanisms of airflow obstruction in asthma.

Gelbman BD, Reed CR. An Integrated, Multimodal, Digital Health Solution for Chronic Obstructive Pulmonary Disease: Prospective Observational Pilot Study. JMIR Form Res. 2022 Mar 17;6(3):e34758. doi: 10.2196/34758. PMID: 35142291.

Dransfield M, Rowe S, Vogelmeier CF, Wedzicha J, Criner GJ, Han MK, Martinez FJ, Calverley P. Cystic Fibrosis Transmembrane Conductance Regulator: Roles in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2022 Mar 15;205(6):631-640. doi: 10.1164/rccm.202109-2064TR. PMID: 34982651.

Mannino D, Bogart M, Germain G, Huang SP, Ismaila AS, Laliberté F, Jung Y, MacKnight SD, Stiegler MA, Duh MS. Benefit of Prompt versus Delayed Use of Single-Inhaler FluticasoneFuroate/Umeclidinium /Vilanterol (FF/UMEC/VI) Following a COPD Exacerbation. Int J Chron Obstruct Pulmon Dis. 2022 Mar 5;17:491-504. doi: 10.2147/COPD.S337668. PMID: 35281476; PMCID: PMC8906822.

Lei J, Yang T, Liang C, Huang K, Wu S, Wang C. Comparison of Clinical Characteristics and Short-Term Prognoses Within Hospitalized Chronic Obstructive Pulmonary Disease Patients Comorbid With Asthma, Bronchiectasis, and Their Overlaps: Findings From the ACURE Registry. Front Med (Lausanne). 2022 Feb 25;9:817048. doi: 10.3389/fmed.2022.817048. PMID: 35280888; PMCID: PMC8914031.

Niewodowski D, Langton D. Learning curve for bronchial thermoplasty. Respirology. 2022 Mar 16. doi: 10.1111/resp.14248. Epub ahead of print. PMID: 35293074.

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 Mar 14. doi: 10.1007/s12325-022-02098-1. Epub ahead of print. PMID: 35287231.
ABSTRACT
Introduction: Consensus definitions for clinical remission and super-response were recently established for severe asthma. Benralizumab is an interleukin-5 (IL-5) receptor α-directed monoclonal antibody for severe, uncontrolled asthma; efficacy and safety were demonstrated in previous pivotal phase 3 trials (SIROCCO, CALIMA, ZONDA). This analysis applied a composite remission definition to characterize individual responses to benralizumab after 6 and 12 months.
Methods: In previous phase 3 studies, eligible patients were those with severe, uncontrolled asthma receiving medium- or high-dosage inhaled corticosteroids plus long-acting β2-agonists. This post hoc analysis included patients randomized to the approved benralizumab dose and not receiving oral corticosteroids (OCS) at baseline (SIROCCO/CALIMA) or OCS ≤ 12.5 mg per day (ZONDA). Individual remission components were zero exacerbations; zero OCS use; Asthma Control Questionnaire-6 (ACQ-6) score < 1.5 or ≤ 0.75; and pre-bronchodilator forced expiratory volume in 1 s (FEV1) increase ≥ 100 mL; clinical remission incorporated zero exacerbations, zero OCS use, ACQ-6 score ≤ 0.75, and pre-bronchodilator FEV1 increase ≥ 100 mL after 6 or 12 months.
Results: Overall, 609 patients (N = 301 and N = 308) and 586 patients (N = 293 and N = 293) receiving benralizumab in SIROCCO and CALIMA were included at 6 and 12 months, respectively; 40 ZONDA patients were included after 6 months. In SIROCCO/CALIMA, similar to 6-month findings, approx. 83% and approx. 49% receiving benralizumab, and 77% and 37% on placebo achieved ≥ 2 and ≥ 3 remission components after 12 months; 14.5% (85/586) on benralizumab and 7.7% (48/620) on placebo achieved clinical remission at 12 months. Among ZONDA patients, 75% and approx. 48% on benralizumab and 35% and 20% on placebo achieved ≥ 2 and ≥ 3 remission components at 6 months, respectively; 22.5% (9/40) on benralizumab and 7.5% on placebo achieved clinical remission.
Conclusions: This analysis demonstrates clinical remission is achievable by targeting the underlying drivers of inflammation. Precision medicines can help shift treatment paradigms toward treat-to-target, with clinical remission as the ultimate therapeutic goal in severe asthma.

Kum E, Guyatt GH, Munoz C, Beaudin S, Li SA, Abdulqawi R, Badri H, Boulet LP, Chen R, Dicpinigaitis P, Dupont L, Field SK, French CL, Gibson PG, Irwin RS, Marsden P, McGarvey L, Smith JA, Song WJ, O’Byrne PM, Satia I. Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel. ERJ Open Res. 2022 Mar 14;8(1):00667-2021. doi: 10.1183/23120541.00667-2021. PMID: 35295233; PMCID: PMC8918938.

Badri H, Gibbard C, Denton D, Satia I, Al-Sheklly B, Dockry RJ, Holt K, McGuiness K, Treadway S, Whorwell P, Houghton L, Lee A, Escott KJ, Lee T, Wilkinson G, Holt A, Canning BJ, Smith JA. A double-blind randomised placebo-controlled trial investigating the effects of lesogaberan on the objective cough frequency and capsaicin-evoked coughs in patients with refractory chronic cough. ERJ Open Res. 2022 Mar 14;8(1):00546-2021. doi: 10.1183/23120541.00546-2021. PMID: 35295236; PMCID: PMC8918934.

Van Hulst G, Jorssen J, Jacobs N, Henket M, Louis R, Schleich F, Bureau F, Desmet CJ. Anti-IL5 mepolizumab minimally influences residual blood eosinophils in severe asthma. Eur Respir J. 2022 Mar 17;59(3):2100935. doi: 10.1183/13993003.00935-2021. PMID: 34475229.
ABSTRACT
Neutralising antibodies against the cytokine interleukin (IL)5 have become widely used for the control of severe eosinophilic asthma. Remarkably, patients receiving neutralising anti-IL5 biological therapies retain a very stable population of residual blood eosinophils. Whether these residual eosinophils are endowed with particular biological activity has not yet been studied, but is of importance in predicting potential long-term effects of IL5 neutralisation in patients. To tackle the effect of IL5 depletion on residual eosinophils, we used a comparative RNA-sequencing approach and compared the gene expression programme of eosinophils arising in IL5-depleted or IL5-replete human or murine hosts, at steady-state in vivo and following in vitro stimulation with the eosinophil-activating alarmin IL33. We compared blood eosinophils from patients with severe allergic eosinophilic asthma treated with anti-IL5 mepolizumab therapy to those of healthy controls and matched asthma patients receiving anti-IgE omalizumab therapy. We made similar comparisons on bone marrow eosinophils from mice genetically deficient or not for IL5. We report that restriction of IL5 availability did not elicit any detectable transcriptional response in steady-state residual eosinophils in mepolizumab-treated patients or IL5-deficient mice, and influenced only a handful of genes in their response to IL33. Together, these results support the notion that treatment with IL5 neutralising antibodies spares a pool of circulating residual eosinophils largely resembling those of healthy individuals.

Sharma V, Ricketts HC, Steffensen F, Goodfellow A, Cowan DC. Obesity affects type 2 biomarker levels in asthma. J Asthma. 2022 Mar 17:1-8. doi: 10.1080/02770903.2022.2051548. Epub ahead of print. PMID: 35260034.
ABSTRACT
Objective: Type 2 (T2) inflammation offers a therapeutic target for biologics. Previous trials suggest obesity influences T2-biomarker levels in asthma, though have not accounted for key variables, e.g. inhaled (ICS)/oral corticosteroid (OCS) use. We hypothesized that body mass index (BMI) would affect T2-biomarker levels, after adjusting for covariates.
Methods: A retrospective analysis of data from two recent local trials of 153 participants with asthma (102 difficult-to-treat, 51 mild). Measurements included BMI, fractional exhaled nitric oxide (FeNO) and eosinophils. Correlation and regression analysis were performed for each biomarker to describe their relationship with BMI. Data was analyzed overall, and by asthma severity, T2-status and BMI tertile.
Results: Increasing BMI was associated with reduction in FeNO when stratified by BMI tertile (25 ppb lowest tertile, 18 ppb highest tertile; p = 0.014). Spearmans rank showed a negative correlation between BMI and FeNO in difficult-to-treat asthma (ρ= -0.309, p = 0.002). Linear regression adjusting for sex, age, smoking, atopy, allergic/perennial rhinitis, ICS and OCS confirmed BMI as a predictor of FeNO overall (β= -2.848, p = 0.019). Eosinophils were reduced in the highest BMI tertile versus lowest in difficult-to-treat asthma (0.2×109/L, 0.3×109/L respectively; p = 0.02).
Conclusions: Increasing BMI is associated with lower FeNO in asthma when adjusted for relevant covariates, including steroid use. There also appears to be an effect on eosinophil levels. Obesity, therefore, affects T2 biomarker levels with implications for disease endotyping and determination of eligibility for biologic therapy. Whether this is due to masking of underlying T2-high status or development of a truly T2-low endotype requires further research.

Casselbrant A, Fedorowski A, Frantz S, Engström G, Wollmer P, Hamrefors V. Common physiologic and proteomic biomarkers in pulmonary and coronary artery disease. PLoS One. 2022 Mar 9;17(3):e0264376. doi: 10.1371/journal.pone.0264376. PMID: 35263363

Kor CT, Li YR, Lin PR, Lin SH, Wang BY, Lin CH. Explainable Machine Learning Model for Predicting First-Time Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease. J Pers Med. 2022 Feb 7;12(2):228. doi: 10.3390/jpm12020228. PMID: 35207716; PMCID: PMC8879653.

Liang H, Zhi H, Ye W, Wang Z, Liang J, Yi F, Kong X, Jiang M, Chen R, Lai K. Risk factors of chronic cough in China: a systematic review and meta-analysis. Expert Rev Respir Med. 2022 Mar 10. doi: 10.1080/17476348.2022.2049759. Epub ahead of print. PMID: 35271782.
Objectives: Risk factors of chronic cough in China have not been systematically analyzed and we hypothesized that risk factors of chronic cough might have distinct characteristics in China. Hence, we performed this meta-analysis focusing on the potential risk factors of chronic cough in China.
Methods: We searched 7 databases for studies published before May 8, 2021. This systematic review was performed in accordance with the PRISMA checklist.
Results: A total of 33 eligible articles were identified and included in this systematic review, and 28 studies were included in the meta-analysis. Our results showed that allergy (OR: 3.72; 95% CI: 1.85-7.47), nasal/sinusitis diseases (OR: 3.56; 95% CI: 2.02-6.29), family history of allergy (OR = 1.74; 95% CI: 1.59-1.90), family history of chronic respiratory diseases (OR = 1.67; 95% CI: 1.47-1.91), exposure to pollutants (OR = 1.60; 95% CI: 1.26-2.04), passive smoking (OR = 1.44; 95% CI: 1.32-1.57), and exposure to pets (OR = 1.37; 95% CI: 1.18-1.58) were risk factors for chronic cough in China.
Conclusions: Our study indicated some potential risk factors of chronic cough in China, which provides useful epidemiological information for managing chronic cough in China and is worthy as a reference for future global investigations

Xiao T, Wijnant SRA, van der Velpen I, Terzikhan N, Lahousse L, Ikram MK, Vernooij MW, Brusselle GG, Ikram MA. Lung function impairment in relation to cognition and vascular brain lesions: the Rotterdam Study. J Neurol. 2022 Mar 10. doi: 10.1007/s00415-022-11027-9. Epub ahead of print. PMID: 35267082.
Objective: To investigate the association of chronic obstructive pulmonary disease (COPD) and Preserved Ratio Impaired Spirometry (PRISm) with cognitive performance and presence of vascular brain lesions (VBL).
Methods: We determined both cross-sectional and longitudinal association of lung function impairment with cognition, as well as cross-sectional association of lung function impairment with VBL, in the general population. Between 2009 and 2014 we included 3,941 participants from the Rotterdam Study with spirometry tests, brain MRI scans and cognition tests, of whom 1815 had follow-up data on cognition.
Results: Our finding indicated that cross-sectionally, participants with PRISm or COPD GOLD2-4 had a worse global cognitive performance. We did not find differences in cognition over time between those with normal spirometry versus those with lung function impairment. In addition, PRISm and COPD GOLD2-4 were associated with a higher prevalence of lacunar infarcts compared to normal spirometry.
Conclusions: This study suggests that persons with COPD GOLD2-4 or restrictive lung function, defined as PRISm, are characterized by poorer global cognitive function and a higher prevalence of lacunar infarcts.

Antwi GO, Rhodes DL. Association between E-cigarette use and chronic obstructive pulmonary disease in non-asthmatic adults in the USA. J Public Health (Oxf). 2022 Mar 7;44(1):158-164. doi: 10.1093/pubmed/fdaa229. PMID: 33348361.
Background: Concern about the health impacts of e-cigarette use is growing; however, limited research exists regarding potential long-term health effects of this behavior. This study explored the relationship between e-cigarette use and COPD in a sample of US adults.
Methods: A secondary data analysis using data from the 2018 Behavioral Risk Factor Surveillance Survey in the USA was computed to examine associations between e-cigarette use and COPD controlling for conventional cigarette smoking status, past month leisure physical activity and demographic characteristics including age, sex, education, race, marital status and body mass index.
Results: Significant associations between e-cigarette use and COPD among former combustible cigarette smokers and those who reported never using combustible cigarettes were found. Compared with never e-cigarette users, the odds of having COPD were significantly greater for daily e-cigarette users (OR = 1.53; 95% CI: 1.11-2.03), occasional users (OR = 1.43, 95% CI: 1.13-1.80) and former users (OR = 1.46 95% CI: 1.28-1.67).
Conclusions: Findings from this study indicate a potential link between e-cigarette use and COPD. Further research to explore the potential effects of e-cigarette on COPD is recommended.

Ian R Reid, Emma O Billington Drug therapy for osteoporosis in older adults. Lancet 2022; 399: 1080–92
The goal of osteoporosis management is to prevent fractures. Several pharmacological agents are available to lower fracture risk, either by reducing bone resorption or by stimulating bone formation. Bisphosphonates are the most widely used anti-resorptives, reducing bone turnover markers to low premenopausal concentrations and reducing fracture rates (vertebral by 50–70%, non-vertebral by 20–30%, and hip by ~40%). Bisphosphonates bind avidly to bone mineral and have an offset of effect measured in months to years. Long term, continuous use of oral bisphosphonates is usually interspersed with drug holidays of 1–2 years, to minimise the risk of atypical femoral fractures. Denosumab is a monoclonal antibody against RANKL that potently inhibits osteoclast development and activity. Denosumab is administered by subcutaneous injection every 6 months. Anti-fracture effects of denosumab are similar to those of the bisphosphonates, but there is a pronounced loss of anti-resorptive effect from 7 months after the last injection, which can result in clusters of rebound vertebral fractures. Two classes of anabolic drugs are now available to stimulate bone formation. Teriparatide and abaloparatide both target the parathyroid hormone-1 receptor, and are given by daily subcutaneous injection for up to 2 years. Romosozumab is an anti-sclerostin monoclonal antibody that stimulates bone formation and inhibits resorption. Romosozumab is given as monthly subcutaneous injections for 1 year. Head-to-head studies suggest that anabolic agents have greater anti-fracture efficacy and produce larger increases in bone density than anti-resorptive drugs. The effects of anabolic agents are transient, so transition to anti-resorptive drugs is required. The optimal strategy for cycling anabolics, anti-resorptives, and off-treatment periods remains to be determined.

Helen K. Reddel, MB, BS, PhDa,*, Eric D. Bateman, MB, ChB, MDb,*, Michael Schatz, MD, MSc, Jerry A. Krishnan, MD, PhDd, and Michelle M. Cloutier, MDe A Practical Guide to Implementing SMART in Asthma Management. J Allergy Clin Immunol Pract 2022;10:S31-S8)

Achten NB, van Rossum AMC, Bacharier LB, Fitzpatrick AM, Hartert TV. Long-Term Respiratory Consequences of Early-Life Respiratory Viral Infections: A Pragmatic Approach to Fundamental Questions. J Allergy Clin Immunol Pract. 2021 Dec 20:S2213-2198(21)01367-2. doi: 10.1016/j.jaip.2021.12.005. Epub ahead of print. PMID: 34942383.

Jackson DJ. Rhinovirus Infections and Their Roles in Asthma: Etiology and Exacerbations. (J Allergy Clin Immunol Pract 2022;10:673-81

Fizpatrick A AND Busse WW. Perspectives in Respiratory Infections and the Lung. J Allergy Clin Immunol Pract 2022;10:694-6.

Griesel M, Wagner C, Mikolajewska A, Stegemann M, Fichtner F, Metzendorf MI, Nair AA, Daniel J, Fischer AL, Skoetz N. Inhaled corticosteroids for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Mar 9;3:CD015125. doi: 10.1002/14651858.CD015125. PMID: 35262185.
Background: Inhaled corticosteroids are well established for the long-term treatment of inflammatory respiratory diseases such as asthma or chronic obstructive pulmonary disease. They have been investigated for the treatment of coronavirus disease 2019 (COVID-19). The anti-inflammatory action of inhaled corticosteroids might have the potential to reduce the risk of severe illness resulting from hyperinflammation in COVID-19.
Objectives: To assess whether inhaled corticosteroids are effective and safe in the treatment of COVID-19; and to maintain the currency of the evidence, using a living systematic review approach.
Search methods: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 7 October 2021.
Selection criteria: We included randomised controlled trials (RCTs) evaluating inhaled corticosteroids for COVID-19, irrespective of disease severity, age, sex, or ethnicity. We included the following interventions: any type or dose of inhaled corticosteroids. We included the following comparison: inhaled corticosteroids plus standard care versus standard care (with or without placebo). We excluded studies examining nasal or topical steroids.
Data collection and analysis: We followed standard Cochrane methodology. For risk of bias assessment, we used the Cochrane RoB 2 tool. We rated the certainty of evidence using the GRADE approach for the outcomes of mortality, admission to hospital or death, symptom resolution, time to symptom resolution, serious adverse events, adverse events, and infections.
Main results: Inhaled corticosteroids plus standard care versus standard care (with/without placebo) People with a confirmed diagnosis of moderate-to-severe COVID-19 We found no studies that included people with a confirmed diagnosis of moderate-to-severe COVID-19. People with a confirmed diagnosis of asymptomatic SARS-CoV-2 infection or mild COVID-19 We included three RCTs allocating 3607 participants, of whom 2490 had confirmed mild COVID-19. We analysed a subset of the total number of participants recruited to the studies (2171, 52% female) as some trials had a platform design where not all participants were allocated to treatment groups simultaneously. The included studies were community-based, recruiting people who were able to use inhaler devices to deliver steroids and relied on remote assessment and self-reporting of outcomes. Most people were older than 50 years and had co-morbidities such as hypertension, lung disease, or diabetes. The studies were conducted in high-income countries prior to wide-scale vaccination programmes. A total of 1057 participants were analysed in the inhaled corticosteroid arm (budesonide: 860 participants; ciclesonide: 197 participants), and 1075 participants in the control arm. No studies included people with asymptomatic SARS-CoV-2 infection. With respect to the following outcomes, inhaled corticosteroids compared to standard care: – may result in little to no difference in all-cause mortality (at up to day 30) (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.22 to 1.67; 2132 participants; low-certainty evidence). In absolute terms, this means that for every nine deaths per 1000 people not receiving inhaled corticosteroids, there were six deaths per 1000 people who did receive the intervention (95% CI 2 to 16 per 1000 people); – probably reduces admission to hospital or death (at up to 30 days) (RR 0.72, 95% CI 0.51 to 0.99; 2025 participants; moderate-certainty evidence); – probably increases resolution of all initial symptoms at day 14 (RR 1.19, 95% CI 1.09 to 1.30; 1986 participants; moderate-certainty evidence); – may reduce the duration to symptom resolution (at up to day 30) (by -4.00 days, 95% CI -6.22 to -1.78 less than control group rate of 12 days; 139 participants; low-certainty evidence); – the evidence is very uncertain about the effect on serious adverse events (during study period) (RR 0.51, 95% CI 0.09 to 2.76; 1586 participants; very low-certainty evidence); – may result in little to no difference in adverse events (at up to day 30) (RR 0.78, 95% CI 0.47 to 1.31; 400 participants; low-certainty evidence); – may result in little to no difference in infections (during study period) (RR 0.88, 95% CI 0.30 to 2.58; 400 participants; low-certainty evidence). As studies did not report outcomes for subgroups (e.g. age, ethnicity, sex), we did not perform subgroup analyses.
Authors’ conclusions: In people with confirmed COVID-19 and mild symptoms who are able to use inhaler devices, we found moderate-certainty evidence that inhaled corticosteroids probably reduce the combined endpoint of admission to hospital or death and increase the resolution of all initial symptoms at day 14. Low-certainty evidence suggests that corticosteroids make little to no difference in all-cause mortality up to day 30 and may decrease the duration to symptom resolution. We do not know whether inhaled corticosteroids increase or decrease serious adverse events due to heterogeneity in the way they were reported across the studies. There is low-certainty evidence that inhaled corticosteroids may decrease infections. The evidence we identified came from studies in high-income settings using budesonide and ciclesonide prior to vaccination roll-outs. We identified a lack of evidence concerning quality of life assessments, serious adverse events, and people with asymptomatic infection or with moderate-to-severe COVID-19. The 10 ongoing and four completed, unpublished RCTs that we identified in trial registries address similar settings and research questions as in the current body of evidence. We expect to incorporate the findings of these studies in future versions of this review. We monitor newly published results of RCTs on inhaled corticosteroids on a weekly basis and will update the review when the evidence or our certainty in the evidence changes

Molina MF, Okoniewski W, Puranik S, Aujla S, Celedón JC, Larkin A, Forno E. Severe asthma in children: description of a large multidisciplinary clinical cohort. Pediatr Pulmonol. 2022 Mar 9. doi: 10.1002/ppul.25887. Epub ahead of print. PMID: 35261210.
Background: Children with severe asthma have substantial morbidity and healthcare utilization. Pediatric severe asthma is a heterogeneous disease, and a multidisciplinary approach can improve the diagnosis and management of these children.
Methods: We reviewed the electronic health records for patients seen in the Severe Asthma Clinic (SAC) at UPMC Children’s Hospital of Pittsburgh between August 2012 and October 2019.
Results: Of the 110 patients in whom we extracted data, 46% were female, 48% were Black/African American, and 41% had ≥1 admission to the pediatric intensive care unit (PICU) for asthma. Compared to patients without a PICU admission, those with ≥1 PICU admission were more likely to be non-White (64.4% vs 41.5%, P=0.031) and more atopic (eosinophil count geometric mean= 673 vs 319 cells/mm3 , P=0.002; total IgE geometric mean=754 vs 303 KU/L, P=0.003), and to have lower pre-bronchodilator FEV1 (58.6% [±18.1%] vs 69.9% [±18.7%], P=0.002) and elevated FeNO (60% vs 22%, P=0.02). In this cohort, 84% of patients were prescribed high-dose ICS/LABA and 36% were on biologics. Following enrollment in the SAC, severe exacerbations decreased from 3.2/year to 2.2/year (P<0.0001); compared to the year prior to joining the SAC, in the following year the group had 106 fewer severe exacerbations.
Conclusions: This large cohort of children with severe asthma had a high level of morbidity and healthcare utilization. Patients with a history of PICU admissions for asthma were more likely to be non-White and highly atopic, and to have lower lung function. Our data supports a positive impact of a multidisciplinary clinic on patients with severe childhood asthma. This article is protected by copyright. All rights reserved

Antonio Buendía J, Patiño DG. Fluticasone furoate plus vilanterol in patients with moderate persistent asthma: a cost-utility analysis. J Asthma. 2022 Mar 9:1-9. doi: 10.1080/02770903.2022.2051547. Epub ahead of print. PMID: 35261332.
Background: In recent years, the combination of fluticasone furoate and vilanterol (FF/VI) has emerged as an alternative therapy, since it is administered every 24 h, in contrast to other ICS/LABAs such as fluticasone propionate plus salmeterol (FP/Salm), which requires administration every 12 hrs. Concerns have arisen over whether the benefit generated by FF/VI justifies the additional costs it involves over FP/Salm. This study aimed at assessing the health and economic consequences of FF/VI in patients with moderate-severe persistent asthma.
Methods: A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with persistent asthma. Total costs and QALYs for FF/VI and FP/Salm were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.
Results: We estimated a gain of 16.8 and 10.7 QALYs per patient per year on FF/VI and FP/Salm, respectively. At the same time, we observed a difference of US$216 in total discounted cost per person-year on FF/VI with respect to FP/Salm. The incremental cost-effectiveness ratio (ICER) of FF/VI was USD $70 per QALY with respect to FP/Salm. In the deterministic and probabilistic sensitivity analyses, our base-case results were robust to variations in all assumptions and parameters.
Conclusion: FF/VI is more cost-effective than FP/Salm. The evidence supports using FF/VI therapy in Colombia, and the study should be replicated in other middle-income countries.

Phinyo P, Wongsa C, Sompornrattanaphan M, Thongngarm T. As-needed versus regular intranasal corticosteroid for allergic rhinitis: A systematic review and meta-analysis. Asian Pac J Allergy Immunol. 2022 Mar 12. doi: 10.12932/AP-091121-1269. Epub ahead of print. PMID: 35278059.
Background: Daily intranasal corticosteroid (INCS) is recommended for treating allergic rhinitis (AR). Nevertheless, patients are generally not adherent and use it on-demand. The data on the efficacy of as-needed INCS was insufficient.
Objective: We conducted a systematic review and meta-analysis to assess the efficacy of as-needed INCS compared with regular use for AR.
Methods: We searched PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) until May 2021. A pairwise meta-analysis used a random-effects model to estimate the pooled standardized mean difference (SMD). The primary outcome was the total nasal symptom score (TNSS) changes from baseline at 4 and 6 weeks. Secondary outcomes were the changes of individual nasal symptom score and quality-of-life (QoL) score.
Results: We identified five eligible RCTs with a total of 436 patients with AR. Only four studies had adequate data for quantitative synthesis. The TNSS changes of as-needed INCS were not significantly different from the regular use at both 4 (SMD 0.23 [95%CI: -0.14 to 0.60], p = 0.230) and 6 weeks (SMD 0.21 [95%CI: -0.02 to 0.44], p = 0.080). Most of the changes of individual nasal symptom scores and QoL scores were not significantly different between the two regimens. At 50% or more INCS dose of regular use, as-needed and regular INCS provided a similar efficacy. The treatment effect was, however, less sustained with as-needed INCS.

Ilaria Baiardini, PhDa,b, Salvatore Fasola, PhDc, Stefania La Grutta, MDc, Elisa Trucco, MDa, Giorgio Walter Canonica, MDb,d, and Fulvio Braido, MDaRhinitis and Asthma Patient Perspective (RAPP): Clinical Utility and Predictive Value. (J Allergy Clin Immunol Pract 2022;10:846-52)

Rodrigues Sousa S, Tenda A, Farinha I, Carvalho A, Chaves Loureiro C. Home administration of biological treatment in severe asthma in real-life experience: impact on asthma control and quality of life. Eur Ann Allergy Clin Immunol. 2022 Mar 10. doi: 10.23822/EurAnnACI.1764-1489.248. Epub ahead of print. PMID: 35261225.
Introduction. Several biological agents for the treatment of severe asthma have been approved for self-administration on an outpatient basis in the last years. However, data on the impact of home administration in outcomes such as asthma control and quality of life in real-life settings are sparse. Being this knowledge crucial for clinical practice, this study aimed to assess asthma control and quality of life in patients who transitioned from day hospital administration of biological therapy to home administration. Methods. A single-center prospective analysis of 33 patients treated with biologics for severe asthma, who switched from hospital to home treatment was performed. Asthma Control Test (ACT), Control of Allergic Rhinitis and Asthma Test (CARAT), Asthma Life Quality (ALQ) and the number of exacerbations were assessed 3 months before and 3 and 6 months after of home-use. Results. ACT and CARAT did not show statistical differences comparing to the baseline values (21.8 ± 2.7 and 23.8 ± 5.5) within 3 months (22.1 ± 2.4, p = 0.609; 23.2 ± 5.3, p = 0.572) or 6 months (23.4 ± 0.9, p = 0.553; 23.7 ± 6.2, p = 0.149) of home administration. Also, ALQ score did not show meaningful variations between baseline (9.5 ± 3.2) and after 3 months (11.2 ± 4.4, p = 0.275) and 6 months (10.3 ± 3.8, p = 0.209) of home-use. Regarding asthma exacerbations, we did not record a significant difference comparing to the baseline values of 3 months/patient exacerbations (0.2 ± 0.4) and after 3 months (0.2 ± 0.5, p = 0.786) or 6 months (0.2 ± 0.4, p = 1.000) of change in modality treatment. There was no cases of anaphylaxis or other serious adverse effects in those patients treated at home. Conclusions. Transition of day hospital administration of biologic treatment for severe asthma to home administration did not lead to any deterioration of asthma control or quality of life. Our results emphasized the efficacy and safety of home administration of biologic treatment and provide support on changing the paradigm of the administration of biological treatment in severe asthma.

Eide JG, Wu J, Stevens WW, Bai J, Hou S, Huang J, Rosenberg J, Utz P, Shintani-Smith S, Conley D, Welch K, Kern R, Hulse KE, Peters AT, Grammer LC, Zhao M, Lindholm P, Schleimer R, Tan BK. Antiphospholipid Antibodies are Elevated and Functionally Active in Chronic Rhinosinusitis with Nasal Polyps. Clin Exp Allergy. 2022 Mar 6. doi: 10.1111/cea.14120. Epub ahead of print. PMID: 35253284.
Background: Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells, and fibrin deposition. Anti-phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS).
Objective: To compare APA levels (anti-cardiolipin, anti-phosphatidylethanolamine (anti-PE), and anti-β2 -glycoprotein (anti-B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti-dsDNA IgG and markers of coagulation.
Methods: Patient specimens were assayed for APA IgG, anti-dsDNA IgG, and thrombin-anti-thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical-mechanical coagulometer.
Results: Anti-cardiolipin IgG in NP was 5-fold higher than control tissue (p<0.0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 μg/mL (36.7 sec vs 33.8 sec, p=0.024) and 600 μg/mL (40.9 sec vs 34.7 sec, p=0.0037). Anti-PE IgG antibodies were increased in NP (p=0.027), but anti-B2GP IgG was not significantly higher (p=0.084). All APAs correlated with anti-dsDNA IgG levels, which were also elevated (R=0.77, 0.71, and 0.54, respectively, for anti-cardiolipin, anti-PE, and anti-B2GP; all p<0.001), but only anti-cardiolipin (R=0.50, p=0.0185) and anti-PE (R=0.45, p=0.037) correlated with TaT complex levels.
Conclusions: APA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti-coagulant activity similar to those observed in anti-phospholipid syndrome, suggesting that they may have pro-coagulant effects in polyp tissue.

Rossi CM et al. Adult anaphylaxis: A state-of-the-art review. Eur J Intern Med 2022, March 8 , in press.
Anaphylaxis is the most severe among acute allergic diseases and potentially life threatening. Despite its increasing frequency and related burden, it remains often underdiagnosed and improperly managed. Its multisystemic involvement, protean clinical manifestations and its rapid onset are contributory factors. In recent years new acquisitions have shed light into its pathogenesis pathways (and related biomarkers), triggers, factors increasing its severity, along with peculiar clinical manifestations. These breakthrough discoveries have contributed to phenotyping and endotyping this disease, possibly paving the way to a personalized approach which is not available at present. Moreover, to disseminate awareness and standardize diagnostic criteria and management practices, several guidelines and consensus reports, albeit mainly intended for specialist care, have been issued. We here discuss the latest issues in the field of anaphylaxis from the perspective of the emergency and/or internal medicine physician, so to improve its early recognition and treatment in the acute setting and favor allergology referral to implement therapeutical and preventive strategies, such as allergen identification in unclear cases and desensitizing t