20-27 March 2022

COPD

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.

ASTHMA

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.

RHINITIS-ALLERGY-ALLERGIC ASTHMA

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.

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