The Association between Bronchiectasis and Chronic Obstructive Pulmonary Disease: Data from the European Bronchiectasis Registry (EMBARC).

Rationale: COPD and bronchiectasis are commonly reported together. Studies report varying impacts of co-diagnosis on outcomes, which may be related to different definitions of disease used across studies. Objectives: To investigate the prevalence of chronic obstructive pulmonary disease (COPD) associated with bronchiectasis and its relationship with clinical outcomes. We further investigated the impact of implementing the standardized ROSE criteria (radiological bronchiectasis [R], obstruction [FEV1/FVC ratio <0.7; O], symptoms [S], and exposure [⩾10 pack-years of smoking; E]), an objective definition of the association of bronchiectasis with COPD. Methods: Analysis of the EMBARC (European Bronchiectasis Registry), a prospective observational study of patients with computed tomography-confirmed bronchiectasis from 28 countries. The ROSE criteria were used to objectively define the association of bronchiectasis with COPD. Key outcomes during a maximum of 5 years of follow-up were exacerbations, hospitalization, and mortality. Measurements and Main Results: A total of 16,730 patients with bronchiectasis were included; 4,336 had a clinician-assigned codiagnosis of COPD, and these patients had more exacerbations, worse quality of life, and higher severity scores. We observed marked overdiagnosis of COPD: 22.2% of patients with a diagnosis of COPD did not have airflow obstruction and 31.9% did not have a history of ⩾10 pack-years of smoking. Therefore, 2,157 patients (55.4%) met the ROSE criteria for COPD. Compared with patients without COPD, patients who met the ROSE criteria had increased risks of exacerbations and exacerbations resulting in hospitalization during follow-up (incidence rate ratio, 1.25; 95% confidence interval, 1.15-1.35; vs. incidence rate ratio, 1.69; 95% confidence interval, 1.51-1.90, respectively). Conclusions: The label of COPD is often applied to patients with bronchiectasis who do not have objective evidence of airflow obstruction or a smoking history. Patients with a clinical label of COPD have worse clinical outcomes.

Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. OBJECTIVE: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. METHODS: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography-confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. RESULTS: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. CONCLUSIONS: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A.

Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. METHODS: We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. RESULTS: 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence. CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use. METHODS: This was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs. RESULTS: 16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67 years (interquartile range 57-74 years, range 18-100 years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51-53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe. CONCLUSIONS: Only a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

Occupational exposure to vapors, gasses, dusts, and fumes in relation to causes of death during 24 years in Helsinki, Finland.

PURPOSE: Environmental particulate matter (PM) exposure has been shown to cause excess all-cause and disease-specific mortality. Our aim was to compare disease-specific mortality by estimated occupational exposure to vapors, gasses, dusts, and fumes (VGDF). METHODS: The data source is the Helsinki part of the population-based FinEsS study on chronic obstructive pulmonary diseases including information on age, education level, main occupation, sex, and tobacco smoking combined with death registry information. We compared estimated VGDF exposure to mortality using adjusted competing-risks regression for disease-specific survival analysis for a 24-year follow-up. RESULTS: Compared to the no-exposure group, the high occupational VGDF exposure group had sub-hazard ratios (sHR) of 1.7 (95% CI 1.3-2.2) for all cardiovascular-related and sHR 2.1 (1.5-3.9) for just coronary artery-related mortality. It also had sHR 1.7 (1.0-2.8) for Alzheimer's or vascular dementia-related mortality and sHR 1.7(1.2-2.4) for all respiratory disease-related mortality. CONCLUSION: Long-term occupational exposure to VGDF increased the hazard of mortality- to cardiovascular-, respiratory-, and dementia-related causes. This emphasizes the need for minimizing occupational long-term respiratory exposure to dust, gasses, and fumes.

Severe asthma trajectories in adults: findings from the NORDSTAR cohort.

BACKGROUND: There is limited evidence on the pathways leading to severe asthma and we are presently unable to effectively predict the progression of the disease. We aimed to describe the longitudinal trajectories leading to severe asthma and to describe clinical events preceding disease progression in a nationwide population of patients with severe asthma. METHODS: We conducted an observational study based on Swedish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. We identified adult patients with severe asthma in 2018 according to the European Respiratory Society/American Thoracic Society definition and used latent class analysis to identify trajectories of asthma severity over a 10-year retrospective period from 2018. RESULTS: Among 169 128 asthma patients, we identified 4543 severe asthma patients. We identified four trajectories of severe asthma that were labelled as: trajectory 1 "consistently severe asthma" (n=389 (8.6%)), trajectory 2 "gradual onset severe asthma" (n=942 (20.7%)), trajectory 3 "intermittent severe asthma" (n=1685 (37.1%)) and trajectory 4 "sudden onset severe asthma" (n=1527 (33.6%)). "Consistently severe asthma" had a higher daily inhaled corticosteroid dose and more prevalent osteoporosis compared with the other trajectories. Patients with "gradual onset severe asthma" and "sudden onset severe asthma" developed type 2-related comorbidities concomitantly with development of severe asthma. In the latter group, this primarily occurred within 1-3 years preceding onset of severe asthma. CONCLUSIONS: Four distinct trajectories of severe asthma were identified illustrating different patterns of progression of asthma severity. This may eventually enable the development of better preventive management strategies in severe asthma.

Real-Life Experience of Biologic Treatment for Asthma on Chronic Rhinosinusitis: A Finnish Cohort.

INTRODUCTION: Biologics are used in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of this retrospective study was to evaluate the effects of biologics initiated for asthma on coexistent CRS and the influence of comorbid factors, including aspirin-exacerbated respiratory disease (AERD) and secretory otitis media (SOM). METHODS: A review of electronic health records (2009-2020) at a Finnish tertiary center was conducted to identify CRS patients treated with biologics for their asthma. We identified the type of biologic and treatment response, by comparing nasal polyp score (NPS), sinonasal outcome test (SNOT)-22, need for oral corticosteroids (OCS) and antibiotics, frequency of visits, and endoscopic sinus surgeries (ESS) pretreatment and during treatment. RESULTS: 55 patients were treated with anti-immunoglobulin E (IgE) (n = 18) or anti-interleukin-5/5-receptor (IL-5/5R) (n = 37) biologics. Treatment lasted for an average of 4.1 years. Seventy-five percent (n = 41) had CRSwNP and 25% (n = 14) had CRSsNP. Of all patients, 24% (n = 13) had comorbid AERD and 22% (n = 12) had SOM. Biologic therapy reduced the need for OCS courses (anti-IgE, n = 17, p = 0.03; anti-IL-5/5R, n = 35, p = 0.01) and for daily OCS in anti-IL-5/5R (n = 35, p = 0.001) but not in anti-IgE patients (n = 16, p = 0.07). Biologics also improved NPS by 0.5 point (n = 32, p = 0.009) and SNOT-22 by 14 points (n = 7, p = 0.02) in CRSwNP patients. The overall discontinuation rate was 37.7% (n = 20) and was independent of type of biologic. CONCLUSION: Treatment with anti-IgE and/or anti-IL-5/5R biologics reduced the overall need for OCS medication in individuals with asthma and concomitant CRS, but despite this, the discontinuation rate was high.

The continuous laryngoscopy exercise test in severe or in difficult-to-treat asthma in adults: a systematic review.

OBJECTIVE: A systematic review was performed to determine if the continuous laryngoscopy exercise test (CLE) has been used in the diagnostics of exercise dyspnea in adults with asthma, and whether inducible laryngeal obstruction (ILO) is found in those with asthma or with severe or difficult-to-treat asthma. DATA SOURCES: We used Scopus and PubMed databases. The articles published up to 13 August 2019 were considered. STUDY SELECTIONS: We excluded manuscripts that did not contain information about adult patients with asthma. We included six studies from 59 search results in Scopus and none from the 17 search results in PubMed. RESULTS: The articles included 455 study individuals. Of these, 229 (50.3%) had diagnosed asthma or were treated with asthma medication. Altogether 31/229 (13.5%) subjects with diagnosis of asthma or previous asthma treatment had exercise-induced laryngeal obstruction (EILO) as comorbidity. The CLE test was performed on 229 patients with asthma. The method was used only for differential diagnosis of exercise-induced dyspnea to confirm EILO. At least 10/455 (2.2%) out of the 455 subjects experienced adverse events. CONCLUSIONS: This systematic review revealed that only a small proportion of patients with asthma had undergone the CLE test to assess exercise-induced dyspnea. None of the selected manuscripts reported severity of asthma. Whether CLE provides a valuable diagnostic tool for patients with severe or difficult-to-treat asthma cannot be determined according to this review.

Are there differences in the patient-reported medication-related problems among asthma and allergy patients? A community pharmacy survey in Finland.

BACKGROUND: A medication-related problem is an event involving medication that interferes with desired health outcomes. Those are largely studied among asthma patients, but little is known about medication-related problems among allergy patients. The objective of this study was to determine the most common patient-reported medication-related problems among asthma patients compared to allergy patients during the self-management of diseases. The other objective was to identify how demographic variables and the received treatment information influence reported problems. METHODS: A nationwide survey was conducted in Finnish community pharmacies (n = 785) in September 2016. The survey targeted patients buying prescription medicines for asthma or allergy. RESULTS: Responses were received from 46% of targeted pharmacies from 956 respondents. At least one medication problem was reported by 24% of asthma patients and 12% of allergy patients. The most common problems among asthma patients were having problems taking medicines on time (16%), problems in the administration technique (7%) and in the use of the inhaler (4%). Among allergy patients, 10% reported problems remembering to take medicines on time. Severe asthma and allergy increased the risk for medication-related problems (OR 1.20, 95% CI 1.04-1.40 and OR 1.17, 95% CI 1.0-1.37). A higher age and less education were associated with fewer reported medication-related problems among both patient groups. CONCLUSIONS: Asthma patients reported more medication-related problems than allergy patients. Among both investigated patient groups, remembering to take medicines on time was the most common. Health care professionals should educate younger patients but also older and less educated asthma and allergy patients to recognize and, to solve medication-related problems. In addition, severe asthma patients still need medication counseling.

Impact of a digital web-based asthma platform, a real-life study.

BACKGROUND: Digital health technology (DHT) is a growing area in the treatment of chronic diseases. Study results on DHT's effect on asthma control have been mixed, but benefits have been seen for adherence, self-management, symptoms, and quality of life. The aim was to evaluate the impact of an interactive web-based asthma treatment platform on asthma exacerbations and health care visits. METHODS: In this real-life study, we retrospectively collected data on adult patients registered on a web-based interactive asthma treatment platform between December 2018 and May 2021. Patients who activated their accounts were active users, and patients who did not were inactive users and considered as controls. We compared the number of exacerbations, total number of exacerbation events defined as the sum of oral corticosteroid (OCS) and antimicrobial courses, emergency room visits, hospitalizations, and asthma-related health care visits before and one year after the registration on the platform. Statistical tests used included the t-test, Pearson's chi-square test and Poisson regression models. RESULTS: Of 147 patients registered on the platform, 106 activated their accounts and 41 did not. The active users had significantly fewer total number of exacerbation events (2.56 per person years, relative decline 0.78, 95% CI 0.6 to 1.0) and asthma-related health care visits (2.38 per person years, relative decline 0.84, 95% CI 0.74 to 0.96) than before registration to the platform, whereas the reductions in health care visits and the total number of exacerbation events were not significant in the inactive users. CONCLUSIONS: An interactive web-based asthma platform can reduce asthma-related health care visits and exacerbations when used actively.

Introduction and Rapid Spread of SARS-CoV-2 Omicron Variant and Dynamics of BA.1 and BA.1.1 Sublineages, Finland, December 2021.

Multiple introductions of SARS-COV-2 Omicron variant BA.1 and BA.1.1. lineages to Finland were detected in early December 2021. Within 3 weeks, Omicron overtook Delta as the most common variant in the capital region. Sequence analysis demonstrated the emergence and spread through community transmission of a large cluster of BA.1.1 virus.

Effectiveness of mepolizumab in patients with severe eosinophilic asthma: results from real-world clinical practice in Finland.

OBJECTIVES: Mepolizumab treatment provides clinical benefits for patients with severe eosinophilic asthma in randomized controlled trials. However, real-world data for patients in Finland are lacking. METHODS: This retrospective, non-interventional, chart review study included patients with severe eosinophilic asthma ≥18 years of age initiating mepolizumab between January 1, 2016 and January 31, 2019 at three investigational sites in Finland. Patient characteristics during the 12 months prior to mepolizumab initiation (baseline) were recorded and primary and secondary endpoints included changes from baseline in disease outcomes during follow-up (up to 24 months following mepolizumab initiation). Exploratory endpoints included association between patient characteristics and exacerbation frequency/annual cumulative oral corticosteroid (OCS) dose. RESULTS: Overall, 51 patients were included (mean 17.8 months follow-up). At baseline, patients had a mean (standard deviation) blood eosinophil count of 550 (410) cells/µL; impaired lung function and health-related quality of life; poor symptom control; frequent exacerbations (2.78/year); and 90% were using OCS (mean: 9.80 mg/day). At the last follow-up visit, reductions from baseline in blood eosinophil count (84%) and fractional exhaled nitric oxide (26%) were observed, as were improvements in Asthma Quality of Life Questionnaire score (36%) and Asthma Control Test score (34%). Reductions in the mean number of annual exacerbations (82%) and mean daily OCS dose (39%) were also seen; reductions were observed even after adjustment for several patient baseline characteristics. CONCLUSIONS: Results are consistent with previous randomized clinical trials, indicating that Finnish patients experience clinically relevant improvements when treated with mepolizumab in real-world clinical practice.

Lung function and exercise capacity 6 months after hospital discharge for critical COVID-19.

BACKGROUND: The significant morbidity caused by COVID-19 necessitates further understanding of long-term recovery. Our aim was to evaluate long-term lung function, exercise capacity, and radiological findings in patients after critical COVID-19. METHODS: Patients who received treatment in ICU for COVID-19 between March 2020 and January 2021 underwent pulmonary function tests, a 6MWD and CXR 6 months after hospital discharge. RESULTS: A restrictive ventilatory defect was found in 35% (23/65) and an impaired diffusing capacity in 52% (32/62) at 6 months. The 6-minute walk distance was reduced in 33% (18/55), and 7% (4/55) of the patients had reduced exercise capacity. Chest X-ray was abnormal in 78% (52/67) at 6 months after hospital discharge. CONCLUSION: A significant number of patients had persisting lung function impairment and radiological abnormalities at 6 months after critical COVID-19. Reduced exercise capacity was rare.

Self-Reported Physician Diagnosed Asthma with COPD is Associated with Higher Mortality than Self-Reported Asthma or COPD Alone - A Prospective 24-Year Study in the Population of Helsinki, Finland.

Asthma and COPD are common chronic obstructive respiratory diseases. COPD is associated with increased mortality, but for asthma the results are varying. Their combination has been less investigated, and the results are contradictory. The aim of this prospective study was to observe the overall mortality in obstructive pulmonary diseases and how mortality was related to specific causes using postal questionnaire data. This study included data from 6,062 participants in the FinEsS Helsinki Study (1996) linked to mortality data during a 24-year follow-up. According to self-reported physician diagnosed asthma, COPD, or smoking status, the population was divided into five categories: combined asthma and COPD, COPD alone and asthma alone, ever-smokers without asthma or COPD and never-smokers without asthma or COPD (reference group). For the specific causes of death both the underlying and contributing causes of death were used. Participants with asthma and COPD had the highest hazard of mortality 2.4 (95% CI 1.7-3.5). Ever-smokers without asthma or COPD had a 9.5 (3.7-24.2) subhazard ratio (sHR) related to lower respiratory tract disease specific causes. For asthma, COPD and combined, the corresponding figures were 10.8 (3.4-34.1), 25.0 (8.1-77.4), and 56.1 (19.6-160), respectively. Ever-smokers without asthma or COPD sHR 1.7 (95% CI 1.3-2.5), and participants with combined asthma and COPD 3.5 (1.9-6.3) also featured mortality in association with coronary artery disease. Subjects with combined diseases had the highest hazard of overall mortality and combined diseases also showed the highest hazard of mortality associated with lower respiratory tract causes or coronary artery causes.Abbreviations: CigCigaretteCOPDChronic obstructive pulmonary diseaseCVDCardiovascular diseaseFEV1Forced Expiratory Volume in one secondFVCForced Vital CapacityFinEsSFinland, Estonia, and Sweden study on chronic obstructive pulmonary diseasesHRHazard RatiosHRSubhazard RatioICD-10International Statistical Classifications of Diseases and Related Health Problems (Version 10).

The Finnish Allergy Program 2008-2018: Society-wide proactive program for change of management to mitigate allergy burden.

A 10-year national program to improve prevention and management of allergic diseases and asthma was implemented in Finland (population 5.5. million) in 2008-2018. The main aim was to reduce the long-term burden of these conditions. The strategy was changed from traditional avoidance to tolerance and resilience of the population. Health was endorsed instead of medicalization of mild symptoms. Disease severity was reevaluated, and disabling clinical manifestations were given high priority. For health care, 5 quantitative goals and 1 qualitative goal were set. For each of the goals, specific tasks, tools, and outcome evaluation were stipulated. During the program, 376 educational sessions gathered 24,000 health care participants. An information campaign targeted the lay public, and social media was used to contact people. In the 10 years of the program, the prevalence of allergic diseases and asthma leveled off. Asthma caused fewer symptoms and less disability, and 50% fewer hospital days. Food allergy diets in day care and schools decreased by half. Occupational allergies were reduced by 45%. In 2018, the direct and indirect costs of allergic diseases and asthma ranged from €1.5 billion to €1.8 billion, with the 2018 figures being 30% less than in the respective figures in 2007. The Finnish proactive and real-world intervention markedly reduced the public health burden of allergic disorders. The allergy paradigm was revisited to improve management with systematic education.

Biologicals in atopic disease in pregnancy: An EAACI position paper.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

Effectiveness of inhalation technique assessment service for patients with Respimat® inhaler.

OBJECTIVES: The objective of this study was to examine how Inhalation Technique Assessment Service (ITAS) by community pharmacies affect patients' inhalation techniques when using the Respimat® soft mist inhaler. The inhaler was simultaneously updated into a reusable inhaler. The study focused on the Respimat® inhaler because its use is known to be challenging for patients. METHODS: The study was performed as a pre-post design in 33 community pharmacies (CPs) in Finland. Patients' inhalation technique was assessed before ITAS (baseline) and immediately after ITAS (follow-up 1). Follow-up 2 was performed when the patient came to the pharmacy for a refill (1-3 months after the baseline and the follow-up 1). A Respimat specific twenty item checklist was used to assess inhalation technique. The checklist included 1) preparation steps before the first use of the Respimat® inhaler (8 items) and 2) daily use steps of the Respimat® inhaler (12 items). After ITAS, the patients received a brief questionnaire to assess their asthma/COPD history. RESULTS: A total of 228 patients were enrolled at the first visit (mean age 67.8 years, 61.0% female, 85.5% had previous Respimat® use experience) and 42 of them attended the follow-up 2, 1-3 months later (mean age 70.1 years, 69.0% female, 92.9% had previous Respimat® use experience. The median number of the steps performed correctly increased from 17/20 at the baseline to all the 20 steps at the follow-up 1 (p < 0.001). At the baseline, 27.6% of the patients (n = 228) performed all preparation steps correctly, while 87.3% at the follow-up 1 and 71.4% at the follow-up 2. The percentage of the patients with acceptable inhalation technique (all critical daily use steps correct) increased from 69.7% at the baseline to 93.0% at the follow-up 1 (p < 0.001). The corresponding figure at the follow-up 2 was 69.0%. At the baseline, 30.3% of patients had optimal inhalation technique (all daily use steps correct). At the follow-up 1 corresponding figure was 85.1%, and 54.8% at the follow-up 2. CONCLUSIONS: A pharmacist-led intervention significantly improved asthma and COPD patients' inhalation technique with the Respimat® inhaler. Significant improvements were found in the daily use steps and the preparation steps before the first use.

Transcriptomic Profiling of Adult-Onset Asthma Related to Damp and Moldy Buildings and Idiopathic Environmental Intolerance.

A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.

Eosinophilia, asthma, NERD and the use of oral corticosteroids predict uncontrolled chronic rhinosinusitis with nasal polyps after surgery.

BACKGROUND: Severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenging condition to treat. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) has the following criteria when considering biological therapy for severe uncontrolled CRSwNP: eosinophilia, need for oral corticosteroids (OCS), symptom score, loss of sense of smell and co-morbid asthma. OBJECTIVE: This study aimed at finding associations of baseline factors with uncontrolled CRSwNP after endoscopic sinus surgery (ESS). METHODS: Electronic health record data of CRSwNP patients (N = 137) undergoing ESS in 2002-17 were used. Endpoints of uncontrolled CRSwNP were revision ESS, purchased OCS and antibiotic courses during follow up. Baseline factors were chosen based on EPOS2020 and the data available: nasal polyp (NP) eosinophilia, peripheral blood eosinophilia, co-existing asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD), need for OCS during the previous year, previous ESS, endoscopic NP score, and Lund-Mackay score of sinus computed tomography scans. RESULTS: During the follow-up of 10.1 ± 3.1 (mean ± standard deviation) years, 35 (25.5%) individuals underwent revision ESS. The best predictive model was obtained by a sum of baseline (1) blood eosinophilia ≥ 250 cells/≥l and/or NP eosinophilia ≥ 30% (Eos), (2) asthma/NERD, and (3) ≥ 1 OCS/year. It was significantly associated with revision ESS, purchased doctor-prescribed OCS and antibiotic courses during follow-up. CONCLUSIONS: We identified similar predictive variables for uncontrolled CRSwNP that are used in the EPOS2020 indications of biological therapy, thus suggesting that these estimates are usable in clinical practice.

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement.

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.