Treatable traits and exacerbation risk in patients with uncontrolled asthma prescribed GINA step 1-3 treatment: A nationwide asthma cohort study.

BACKGROUND AND OBJECTIVE: Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non-pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1-3 treatment according to the Global Initiative for Asthma (GINA). METHODS: Twenty-eight thousand five hundred eighty-four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index-date). The database was linked to other national registers to obtain information on prescribed drugs 2-years pre-index and exacerbations 1-year post-index. Asthma treatment was classified into step 1-3 or 4-5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function. RESULTS: GINA step 1-3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1-3). In adjusted analyses, UCA 1-3 was associated with female sex (OR 1.34, 95% CI 1.27-1.41), older age (1.00, 1.00-1.00), primary education (1.30, 1.20-1.40) and secondary education (1.19, 1.12-1.26), and TTs such as smoking (1.25, 1.15-1.36), obesity (1.23, 1.15-1.32), cardiovascular disease (1.12, 1.06-1.20) and depression/anxiety (1.13, 1.06-1.21). Furthermore, UCA 1-3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74-2.09) and asthma hospitalization (2.55, 2.17-3.00), respectively, also when adjusted for treatment step 4-5. CONCLUSION: Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations.

Adherence to inhaled corticosteroid therapy and treatment escalation in the Swedish adult asthma population.

BACKGROUND: Patients with uncontrolled asthma should be evaluated for medication adherence. This study aimed to identify characteristics associated with poor adherence to inhaled corticosteroids (ICS) and to explore adherence prior to treatment escalation. METHODS: This nationwide longitudinal cohort study included adult asthma patients (n = 30880) with a healthcare visit including Asthma Control Test (ACT) and registered in the Swedish National Airway Register between 1 July 2017 and 28 February 2019 (index date). Patient data was crosslinked to other national registers. Treatment steps two years pre- and one year post-index, were identified by prescribed drugs. Poor adherence was defined as Medication Possession Ratio <80 %. RESULTS: Poor adherence was identified in 73 % of patients in treatment steps 2-5, where of 35 % had uncontrolled asthma (ACT≤19). In adjusted models, poor adherence was associated with better disease control; ACT≤19 (OR 0.78, 95 % CI 0.71-0.84), short-acting ß2-agonist (SABA) overuse (0.69, 0.61-0.79) and exacerbations (0.79, 0.70-0.89) in steps 2-3. Among patients with uncontrolled asthma, poor adherence was associated with SABA overuse (1.71, 1.50-1.95), exacerbations (1.29, 1.15-1.46), current smoking (1.38, 1.21-1.57) and inversely associated with asthma management education (0.85, 0.78-0.93. Similar results were observed in steps 4-5. When investigating post-index treatment, 53 % remained stationary, 30 % stepped down and 17 % escalated treatment. Prior to escalation, 49 % had poor adherence. CONCLUSIONS: Poor ICS adherence was associated with better asthma control. Among uncontrolled patients, poor adherence was associated with SABA overuse and exacerbations. Our result highlights the importance of asthma management education to improve adherence in uncontrolled patients.

Key Characteristics of Asthma Patients with COVID-19 Vary Substantially by Age.

Introduction: Assessing COVID-19 risk in asthma patients is challenging due to disease heterogeneity and complexity. We hypothesized that potential risk factors for COVID-19 may differ among asthma age groups, hindering important insights when studied together. Methods: We included a population-based cohort of asthma patients from the Swedish National Airway Register (SNAR) and linked to data from several national health registers. COVID-19 outcomes included infection, hospitalization, and death from Jan 2020 until Feb 2021. Asthma patients were grouped by ages 12-17, 18-39, 40-64, and ≥65 years. Characteristics of asthma patients with different COVID-19 outcomes were compared with those in their age-corresponding respective source population. Results: Among 201,140 asthma patients studied, 11.2% were aged 12-17 years, 26.4% 18-39, 37.6% 40-64, and 24.9% ≥65 years. We observed 18,048 (9.0%) COVID-19 infections, 2172 (1.1%) hospitalizations, and 336 (0.2%) COVID-19 deaths. Deaths occurred only among patients aged ≥40. When comparing COVID-19 cases to source asthma populations by age, large differences in potential risk factors emerged, mostly for COVID-19 hospitalizations and deaths. For ages 12-17, these included education, employment, autoimmune, psychiatric, and depressive conditions, and use of short-acting ß-agonists (SABA) and inhaled corticosteroids (ICS). In the 18-39 age group, largest differences were for age, marital status, respiratory failure, anxiety, and body mass index. Ages 40-64 displayed notable differences for sex, birth region, cancer, oral corticosteroids, antihistamines, and smoking. For those aged ≥65, largest differences were observed for cardiovascular comorbidities, type 1 diabetes, chronic obstructive pulmonary disease, allergic conditions, and specific asthma treatments (ICS-SABA, ICS-long-acting bronchodilators (LABA)). Asthma control and lung function were important across all age groups. Conclusion: We identify distinct differences in COVID-19-related risk factors among asthma patients of different ages. This information is essential for assessing COVID-19 risk in asthma patients and for tailoring patient care and public health strategies accordingly.

Why was the study done? Asthma patients may be more susceptible to COVID-19 outcomes. Asthma affects all ages, and COVID-19-related risk factors may vary with age. Investigating factors that contribute to COVID-19 infection, hospitalization, and mortality within distinct age groups of asthma patients can yield a more comprehensive understanding of the age-specific nuances of COVID-19 risk. What did the researchers do and find? We analyzed sociodemographic characteristics, comorbidities, prescribed medications, and clinical characteristics of asthma patients with COVID-19 in different age groups and compared them with their age-corresponding source asthma populations. Potential risk factors for COVID-19 and its outcomes differed by age group For ages 12-17, these included education, employment, autoimmune, psychiatric, and depressive conditions, and use of short-acting ß-agonists (SABA) and inhaled corticosteroids (ICS). In the 18-39 age group, largest differences were for age, marital status, respiratory failure, anxiety, and body mass index. Ages 40-64 displayed notable differences for sex, birth region, cancer, oral corticosteroids, antihistamines, and smoking. For those aged ≥65, largest differences were observed for cardiovascular comorbidities, type 1 diabetes, chronic obstructive pulmonary disease, allergic asthma, and specific asthma treatments (ICS-SABA, ICS-long-acting bronchodilators (LABA)). Asthma control and lung function were important across all age groups. What do these results mean? These results emphasize the importance of recognizing age-specific patterns contributing to COVID-19 risk for consideration in causal analyses. The findings also highlight the necessity for age-specific approaches in both clinical and public health interventions in managing COVID-19 in asthma patients.

Factors Associated with Patient Education in Patients with Chronic Obstructive Pulmonary Disease (COPD) - A Primary Health Care Register-Based Study.

Purpose: Patient education in chronic obstructive pulmonary disease (COPD) is recommended in treatment strategy documents, since it can improve the ability to cope with the disease. Our aim was to identify the extent of and factors associated with patient education in patients with COPD in a primary health care setting. Patients and Methods: In this nationwide study, we identified 29,692 COPD patients with a registration in the Swedish National Airway Register (SNAR) in 2019. Data on patient education and other clinical variables of interest were collected from SNAR. The database was linked to additional national registers to obtain data about pharmacological treatment, exacerbations and educational level. Results: Patient education had been received by 44% of COPD patients, 72% of whom had received education on pharmacological treatment including inhalation technique. A higher proportion of patients who had received education were offered smoking cessation support, had performed spirometry and answered the COPD Assessment Test (CAT), compared with patients without patient education. In the adjusted analysis, GOLD grade 2 (OR 1.29, 95% CI 1.18-1.42), grade 3 (OR 1.41, 95% CI 1.27-1.57) and grade 4 (OR 1.79, 95% CI 1.48-2.15), as well as GOLD group E (OR 1.17, 95% CI 1.06-1.29), ex-smoking (OR 1.70, 95% CI 1.56-1.84) and current smoking (OR 1.45, 95% CI 1.33-1.58) were positively associated with having received patient education, while cardiovascular disease (OR 0.92, 95% CI 0.87-0.98) and diabetes (OR 0.93, 95% CI 0.87-1.00) were negatively associated with receipt of patient education. Conclusion: Fewer than half of the patients had received patient education, and the education had mostly been given to those with more severe COPD, ex- and current smokers and patients with fewer comorbidities. Our study highlights the need to enhance patient education at an earlier stage of the disease.

Uncontrolled asthma in school-aged children-a nationwide specialist care study.

Background: Uncontrolled asthma (UCA) is different from severe asthma and can be identified in children across all ranges of prescribed treatment. Objective: Our aim was to characterize uncontrolled childhood asthma in pediatric specialist care. Methods: We performed a nationwide cross-sectional study of 5497 children (aged 6-17 years) with asthma who were treated by pediatricians at outpatient clinics during 2019 and registered in the Swedish National Airway Register. UCA was defined as an Asthma Control Test score of 19 or lower and/or 2 or more exacerbations in the past year and/or an FEV1 value less than 80% predicted. Treatment was categorized from step 1 to step 5 according to the Global Initiative for Asthma. Results: UCA was identified in 1690 children (31%), of whom 64% had an Asthma Control Test score of 19 or lower, 20% had recurrent exacerbations, and 31% had an FEV1 value less than 80% predicted. UCA was associated with female sex (odds ratio [OR] = 1.29 [95% CI = 1.15-1.45]), older age (OR = 1.02 [95% CI = 1.00-1.04]), obesity (OR = 1.43 [95% CI = 1.12-1.83]), and more treatment using steps 1 and 2 as a reference (step 3, OR = 1.28 [95% CI = 1.12-1.46]); steps 4-5, OR = 1.32 [95% CI = 1.10-1.57]). UCA in children prescribed treatment steps 1 and 2 (group UCA1-2) occurred in 28% of all children at this treatment step (n = 887). Children in group UCA1-2 had exacerbations more frequently than did those children with UCA who were prescribed steps 4 and 5 treatment (24% vs 15% [P = .001]). Conclusion: UCA was common and associated with female sex, increasing age, obesity, and higher Global Initiative for Asthma treatment step. Surprisingly, UCA was also common in children prescribed less than the maximum treatment, and those children could be considered undertreated patients.

All-cause and cause-specific mortality by spirometric pattern and sex - a population-based cohort study.

BACKGROUND: Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated. OBJECTIVES: To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF). DESIGN: Population-based prospective cohort study. METHODS: Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC ⩾ 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC ⩾ 0.70 and FVC ⩾ 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years. RESULTS: The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes. CONCLUSION: The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.

All-cause and cause specific mortality in relation to different lung function patterns and sex; normal, obstructive and restricted lung functionChronic airway obstruction and restrictive spirometry pattern are associated with mortality, but sex specific patterns have hardly been evaluated.Aim: To study possible sex-dependent differences of all-cause and cause-specific mortality among men and women with chronic airway obstruction and restrictive spirometry pattern, respectively, compared to that of normal lung function.Methods: Individuals with chronic airway obstruction, restrictive spirometry pattern and normal lung function were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-04. Mortality data were collected through April 2016, totally covering 19,000 patient-years of observation time. We analyzed the Hazard Ratios for all-cause and cause-specific death comparing chronic airway obstruction and restrictive spirometry pattern to that of normal lung function, adjusting for age, body mass index, sex, smoking habits and pack-years. Similar analyses were conducted separately for men and women.Results: The hazard for all-cause mortality was higher in both chronic airway obstruction and restrictive spirometry pattern than in normal lung function and, the higher hazards were male-driven. In chronic airway obstruction the hazard of respiratory and cardiovascular deaths higher than in those with normal lung function. The increased hazard of respiratory death was significant in women while the increased hazard of cardiovascular death was significant in men. In restrictive spirometry pattern, the higher hazard for respiratory but not cardiovascular death persisted after adjustment, similarly in both sexes.Conclusions: The higher hazard for all-cause mortality in chronic airway obstruction and restrictive spirometry pattern than in normal lung function was male-driven. Chronic airway obstruction associated with respiratory death in women and cardiovascular death in men, while restrictive pattern associated with respiratory death, similarly in both sexes.

Electronic cigarette use in relation to changes in smoking status and respiratory symptoms.

INTRODUCTION: How e-cigarette use relates to changes in smoking status and respiratory symptoms in the population remains controversial. The aim was to study the association between e-cigarette use and, changes in smoking status and changes in respiratory symptoms. METHODS: A prospective, population-based study of random samples of the population (age 16-69 years) was performed within The Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). A validated postal questionnaire containing identical questions was used in OLIN and WSAS at baseline in 2006-2008 and at follow-up in 2016. In total, 17325 participated on both occasions. Questions about respiratory symptoms and tobacco smoking were included in both surveys, while e-cigarette use was added in 2016. RESULTS: In 2016, 1.6% used e-cigarettes, and it was significantly more common in persistent tobacco smokers (10.6%), than in those who quit smoking (2.1%), started smoking (7.8%), or had relapsed into tobacco smoking at follow-up (6.4%) (p<0.001). Among current smokers at baseline, tobacco smoking cessation was less common in e-cigarette users than e-cigarette non-users (14.2% vs 47.6%, p<0.001) and there was no association with a reduction in the number of tobacco cigarettes smoked per day. Those who were persistent smokers reported increasing respiratory symptoms. In contrast, the symptoms decreased among those who quit tobacco smoking, but there was no significant difference in respiratory symptoms between quitters with and without e-cigarette use. CONCLUSIONS: E-cigarette use was associated with persistent tobacco smoking and reporting respiratory symptoms. We found no association between e-cigarette use and tobacco smoking cessation, reduction of number of tobacco cigarettes smoked per day or reduction of respiratory symptoms.

Severity of adult-onset asthma - a matter of blood neutrophils and severe obesity.

BACKGROUND: Adult-onset asthma is associated with a poor treatment response. The aim was to study associations between clinical characteristics, asthma control and treatment in adult-onset asthma. METHODS: Previous participants within the population-based Obstructive Lung Disease in Northern Sweden studies (OLIN) were in 2019-2020 invited to clinical examinations including structured interviews, spirometry, fractional exhaled nitric oxide (FeNO), skin prick test and blood sampling. In total, n = 251 individuals with adult-onset asthma (debut >15 years of age) were identified. Uncontrolled asthma was defined according to ERS/ATS and treatment step according to GINA (2019). RESULTS: Among individuals with uncontrolled asthma (34%), severe obesity (16.3% vs 7.9%, p = 0.041) and elevated levels of blood neutrophils, both regarding mean level of blood neutrophils (4.25*109/L vs 3.67*109/L, p = 0.003), and proportions with ≥4*109/L (49.4% vs 33.3%, p = 0.017) and ≥5*109/L (32.1% vs 13.7%, p < 0.001) were more common than among those with controlled asthma. Adding the dimension of GINA treatment step 1-5, individuals with uncontrolled asthma on step 4-5 treatment had the highest proportions of blood neutrophils ≥5*109/L (45.5%), severe obesity (BMI≥35, 26.1%), dyspnea (mMRC≥2) (34.8%), and most impaired lung function in terms of FEV1%<80% of predicted (42.9%), FEV1

Underdiagnosis and misclassification of COPD in Sweden - A Nordic Epilung study.

INTRODUCTION: The prevalence of COPD tends to level off in populations with decreasing prevalence of smoking but the extent of underdiagnosis in such populations needs further investigation. AIM: To investigate underdiagnosis and misclassification of COPD with a focus on socio-economy, lifestyle determinants and healthcare utilization. METHOD: The 1839 participants were selected from two ongoing large-scale epidemiological research programs: The Obstructive Lung Disease in Northern Sweden Studies and the West Sweden Asthma Study. COPDGOLD was defined according to the fixed post-bronchodilator spirometric criteria FEV1/FVC<0.70 in combination with respiratory symptoms. RESULTS: Among the 128 participants who fulfilled the criteria for COPDGOLD, the underdiagnosis was 83.6% (n = 107) of which 57.9% were men. The undiagnosed participants were younger, had higher FEV1% of predicted and less frequently a family history of bronchitis. One in four of the undiagnosed had utilized healthcare and had more frequently utilized healthcare due to a burden of respiratory symptoms than the general population without COPD. Underdiagnosis was not related to educational level. Misclassification of COPD was characterized by being a woman with low education, ever smoker, having respiratory symptoms and having a previous asthma diagnosis. CONCLUSION: In the high income country Sweden, the underdiagnosis of COPD was highly prevalent. Reduced underdiagnosis can contribute to risk factor modification, medical treatment and self-management strategies in early stages of the disease, which may prevent disease progression and improve the quality of life among those affected. Therefore, there is a need to increase the use of spirometry in primary care to improve the diagnostic accuracy.

Age-related differences in associations between uncontrolled asthma, comorbidities and biomarkers in adult-onset asthma.

OBJECTIVE: Adult-onset asthma is a recognized but heterogeneous phenotype and has been described to associate with poor asthma control. Knowledge about associations between clinical characteristics including comorbidities and control of adult-onset asthma is limited, especially in older populations. We aimed to study how clinical biomarkers and comorbidities are associated with uncontrolled asthma among middle-aged and older individuals with adult-onset asthma. METHODS: Clinical examinations including structured interview, asthma control test (ACT), spirometry, skin prick test (SPT), blood sampling, and measurement of exhaled fractional nitric oxide (FeNO) was performed in a population-based adult-onset asthma cohort in 2019-2020 (n = 227, 66.5% female). Analyses were performed among all included, and separately in middle-aged (37-64 years, n = 120) and older (≥65 years, n = 107) participants. RESULTS: In bivariate analysis, uncontrolled asthma (ACT ≤ 19) was significantly associated with a blood neutrophil count ≥5/µl, BMI ≥30, and several comorbidities. In multivariable regression analysis, uncontrolled asthma was associated with neutrophils ≥5/µl (OR 2.35; 95% CI 1.11-4.99). In age-stratified analysis, BMI ≥30 (OR 3.04; 1.24-7.50), eosinophils ≥0.3/µl (OR 3.17; 1.20-8.37), neutrophils ≥5/µl (OR 4.39; 1.53-12.62) and allergic rhinitis (OR 5.10; 1.59-16.30) were associated with uncontrolled asthma among the middle-aged. Among the older adults, uncontrolled asthma was only associated with comorbidities: chronic rhinitis (OR 4.08; 1.62-10.31), ischemic heart disease (OR 3.59; 1.17-10.98), malignancy (OR 3.10; 1.10-8.73), and depression/anxiety (OR 16.31; 1.82-146.05). CONCLUSIONS: In adult-onset asthma, comorbidities were strongly associated with uncontrolled asthma among older adults, while clinical biomarkers including eosinophils and neutrophils in blood were associated with uncontrolled asthma among middle-aged.

Lung Function Trajectories and Associated Mortality among Adults with and without Airway Obstruction.

Rationale: Spirometry is essential for diagnosis and assessment of prognosis in patients with chronic obstructive pulmonary disease (COPD). Objectives: To identify FEV1 trajectories and their determinants on the basis of annual spirometry measurements among individuals with and without airway obstruction (AO) and to assess mortality in relation to trajectories. Methods: From 2002 through 2004, individuals with AO (FEV1/VC < 0.70, n = 993) and age- and sex-matched nonobstructive (NO) referents were recruited from population-based cohorts. Annual spirometry until 2014 was used in joint-survival latent-class mixed models to identify lung function trajectories. Mortality data were collected during 15 years of follow-up. Measurements and Main Results: Three trajectories were identified among the subjects with AO and two among the NO referents. Trajectory membership was driven by baseline FEV1% predicted (FEV1%pred) in both groups and also by pack-years in subjects with AO and current smoking in NO referents. Longitudinal FEV1%pred depended on baseline FEV1%pred, pack-years, and obesity. The trajectories were distributed as follows: among individuals with AO, 79.6% in AO trajectory 1 (FEV1 high with normal decline), 12.8% in AO trajectory 2 (FEV1 high with rapid decline), and 7.7% in AO trajectory 3 (FEV1 low with normal decline) (mean, 27, 72, and 26 ml/yr, respectively) and, among NO referents, 96.7% in NO trajectory 1 (FEV1 high with normal decline) and 3.3% in NO trajectory 2 (FEV1 high with rapid decline) (mean, 34 and 173 ml/yr, respectively). Hazard for death was increased for AO trajectories 2 (hazard ratio [HR], 1.56) and 3 (HR, 3.45) versus AO trajectory 1 and for NO trajectory 2 (HR, 2.99) versus NO trajectory 1. Conclusions: Three different FEV1 trajectories were identified among subjects with AO and two among NO referents, with different outcomes in terms of FEV1 decline and mortality. The FEV1 trajectories among subjects with AO and the relationship between low FVC and trajectory outcome are of particular clinical interest.

Pre- and post-vaccination characteristics and risk factors for COVID-19 outcomes in a Swedish population-based cohort of COPD patients.

Rationale: Evidence on risk factors for Coronavirus disease 2019 (COVID-19) outcomes among patients with COPD in relation to COVID-19 vaccination remains limited. The objectives of the present study were to characterise determinants of COVID-19 infection, hospitalisation, intensive care unit (ICU) admission and death in COPD patients in their unvaccinated state compared to when vaccinated. Methods: We included all COPD patients in the Swedish National Airway Register (SNAR). Events of COVID-19 infection (test and/or healthcare encounter), hospitalisation, ICU admission and death were identified from 1 January 2020 to 30 November 2021. Using adjusted Cox regression, associations between baseline sociodemographics, comorbidities, treatments, clinical measurements and COVID-19 outcomes, during unvaccinated and vaccinated follow-up time, were analysed. Results: The population-based COPD cohort included 87 472 patients, among whom 6771 (7.7%) COVID-19 infections, 2897 (3.3%) hospitalisations, 233 (0.3%) ICU admissions and 882 (1.0%) COVID-19 deaths occurred. During unvaccinated follow-up, risk of COVID-19 hospitalisation and death increased with age, male sex, lower education, non-married status and being foreign-born. Comorbidities increased risk of several outcomes, e.g. respiratory failure for infection and hospitalisation (adjusted hazard ratios (HR) 1.78, 95% CI 1.58-2.02 and 2.51, 2.16-2.91, respectively), obesity for ICU admission (3.52, 2.29-5.40) and cardiovascular disease for mortality (2.80, 2.16-3.64). Inhaled COPD therapy was associated with infection, hospitalisation and death. COPD severity was also associated with COVID-19, especially hospitalisation and death. Although the risk factor panorama was similar, COVID-19 vaccination attenuated HRs for some risk factors. Conclusion: This study provides population-based evidence on predictive risk factors for COVID-19 outcomes and highlights the positive implications of COVID-19 vaccination for COPD patients.

Obesity associates with increased all-cause and cardiovascular mortality in adults with asthma.

BACKGROUND: Asthma and obesity are prevalent conditions that are increasing worldwide. Asthma is characterized by airway inflammation and bronchial variability, while obesity is a complex metabolic disorder that poses significant morbidity and mortality risks. Obesity is a risk factor for asthma and a plethora of other non-communicable diseases. OBJECTIVE: To compare all-cause and cause-specific mortality between obese, overweight and normal weight adults with asthma in a cohort with long-term follow-up. METHODS: Individuals from a population-based adult asthma cohort recruited in Norrbotten county, Sweden, were clinically examined between 1986 and 2001 and grouped into body mass index (BMI) categories. Underlying causes of death until December 31st, 2020 were categorized as cardiovascular, respiratory, cancer and other mortality by linking cohort data to the Swedish National Board of Health and Welfare's National Cause of Death register. Hazard ratios (HR) with 95% confidence intervals (CI) for all-cause and cause-specific mortality associated with overweight and obesity were calculated via Cox proportional hazard models. RESULTS: In total, 940 individuals were normal weight, 689 overweight and 328 obese while only 13 were underweight. Obesity increased the hazard for all-cause (HR 1.26, 95% CI 1.03-1.54) and cardiovascular mortality (HR 1.43, 95% CI 1.03-1.97). Obesity was not significantly associated with respiratory or cancer mortality. Overweight did not increase the hazard of all-cause or any cause-specific mortality category. CONCLUSION: Obesity, but not overweight, was significantly associated with increased hazard of all-cause and cardiovascular mortality in adults with asthma. Neither obesity nor overweight were associated with increased hazard of respiratory mortality.

Multiple manifestations of uncontrolled asthma increase the risk of severe COVID-19.

OBJECTIVE: Asthma control is of importance when assessing the risk of severe outcomes of COVID-19. The aim of this study was to explore associations of clinical characteristics and the effect of multiple manifestations of uncontrolled asthma with severe COVID-19. METHODS: In 2014-2020, adult patients with uncontrolled asthma, defined as Asthma Control Test (ACT) ≤19 were identified in the Swedish National Airway Register (SNAR) (n = 24533). The SNAR database, including clinical data, was linked with national registers to identify patients with severe COVID-19 (n = 221). The effect of multiple manifestations of uncontrolled asthma was based on: 1) ACT ≤15, 2) frequent exacerbations and 3) previous asthma inpatient/secondary care and evaluated stepwise. Poisson regression analyses were conducted with severe COVID-19 as the dependent variable. RESULTS: In this cohort with uncontrolled asthma, obesity was the strongest independent risk factor for severe COVID-19 in both sexes, but even greater in men. Multiple manifestations of uncontrolled asthma were more common among those with severe COVID-19 vs. without: one, 45.7 vs. 42.3%, two, 18.1 vs. 9.1% and three, 5.0 vs. 2.1%. The risk ratio (RR) of severe COVID-19 increased with an increasing number of manifestations of uncontrolled asthma: one, RR 1.49 (95% CI 1.09-2.02), two, RR 2.42 (95% CI 1.64-3.57) and three, RR 2.96 (95% CI 1.57-5.60), when adjusted for sex, age, and BMI. CONCLUSIONS: It is important to consider the effect of multiple manifestations of uncontrolled asthma and obesity when assessing patients with COVID-19, as this increases the risk of severe outcomes substantially.

Exacerbation Risk and Mortality in Global Initiative for Chronic Obstructive Lung Disease Group A and B Patients with and without Exacerbation History.

Rationale: Risk stratification of patients according to chronic obstructive pulmonary disease severity is clinically important and forms the basis of therapeutic recommendations. No studies have examined the association for Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and group B patients with (A1 and B1, respectively) and without (A0 and B0, respectively) an exacerbation in the past year with future exacerbations, hospitalizations, and mortality in perspective with the new GOLD ABE classification. Objectives: The aim was to examine the association between GOLD A0, A1, B0, B1, and E patients and future exacerbations, respiratory and cardiovascular hospitalizations, and mortality. Methods: In this nationwide cohort study, we identified patients with a diagnosis of chronic obstructive pulmonary disease, aged ⩾30 years, and registered in the Swedish National Airway Register between January 2017 and August 2020. Patients were stratified in GOLD groups A0, A1, B0, B1, and E and were followed until January 2021 for exacerbations, hospitalizations, and mortality in national registries. Measurements and Main Results: The 45,350 eligible patients included 25% A0, 4% A1, 44% B0, 10% B1, and 17% E. Moderate exacerbations, all-cause and respiratory hospitalizations, and all-cause and respiratory mortality increased by GOLD group A0-A1-B0-B1-E, except for moderate exacerbations, which were higher in A1 than in B0. Group B1 had a substantially higher hazard ratio for future exacerbation (2.56; 95% confidence interval [95% CI] 2.40-2.74), all-cause hospitalization (1.28; 1.21-1.35), and respiratory hospitalization (1.44; 1.27-1.62), but not all-cause (1.04; 0.91-1.18) or respiratory (1.13; 0.79-1.64) mortality than group B0. The exacerbation rate for group B1 was 0.6 events per patient-year versus 0.2 for group B0 (rate ratio, 2.55; 95% CI, 2.36-2.76). Results were similar for group A1 versus group A0. Conclusions: Stratification of GOLD A and B patients with one or no exacerbation in the past year provides valuable information on future risk, which should influence treatment recommendations for preventive strategies.

Postural control among individuals with and without chronic obstructive pulmonary disease: A cross-sectional study of motor and sensory systems.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is considered a heterogenic syndrome with systemic effects, including muscle dysfunction. There is evidence of postural control impairments among individuals with COPD, partly related to muscle weakness. However, research is scarce regarding the other underlying systems of postural control, such as the visual, somatosensory and vestibular system. The aim was to compare postural control, as well as the motor and sensory systems, between individuals with and without COPD. METHODS: Twenty-two participants with COPD (mean age 74.0 ±6.2 years) and 34 non-obstructive references (mean age 74.9 ±4.9 years) participated in this cross-sectional study. Postural control was assessed with center of pressure trajectory of postural sway in quiet as well as a limits of stability test, calculating mediolateral and anteroposterior amplitudes for each test. Assessment of function in the motor system included maximum hand grip strength, as well as maximum strength in muscles around the hip, knee and ankle joints. Visual acuity, pressure sensibility, proprioception, vestibular screening, and reaction time were also included. Data was compared between groups, and significant differences in postural control were further analyzed with an orthogonal projection of latent structures regression model. RESULTS: There was a significantly increased sway amplitude in the mediolateral direction in quiet stance on soft surface with eyes open (p = 0.014) as well as a smaller anteroposterior amplitude in the limits of stability test (p = 0.019) in the COPD group. Regression models revealed that the mediolateral amplitude was related to visual acuity and the burden of tobacco smoking assessed as pack-years. Further, muscle strength associated with anteroposterior amplitude in limits of stability test in the COPD group, and with age and ankle dorsal flexion strength among the referents. Besides for lower ankle plantar flexion strength in the COPD group, there were however no significant differences in muscle strength. CONCLUSIONS: Individuals with COPD had a decreased postural control and several factors were associated with the impairments. The findings imply that the burden of tobacco smoking and reduced visual acuity relate to increased postural sway in quiet stance, and that muscle weakness is related to decreased limits of stability, among individuals with COPD.

Socioeconomic inequalities in asthma and respiratory symptoms in a high-income country: changes from 1996 to 2016.

Objective: Low socioeconomic status based both on educational level and income has been associated with asthma and respiratory symptoms, but changes over time in these associations have rarely been studied. The aim was to study the associations between educational or income inequality and asthma and respiratory symptoms among women and men over a 20-year period in northern Sweden. Methods: The study was performed within the Obstructive Lung disease in Northern Sweden (OLIN) research program. Mailed questionnaire surveys were administered to a random sample of adults (20-69 years of age) living in Sweden, in 1996, 2006 and 2016. Data on educational level and income were collected from the national integrated database for labor market research. Results: The educational inequality associated with asthma and asthmatic wheeze tended to decrease from 1996 to 2016, while it increased for productive cough, the latter among men not among women. The income inequality decreased for productive cough, especially for women, while no clear overall trends were found for asthmatic wheeze and asthma, apart from a decrease in income inequality regarding asthma among men. Conclusion: The patterns for socioeconomic inequality differed for asthma and wheeze compared to productive cough, and the results emphasize that education and income do not mirror the same aspects of socioeconomic inequality in a high-income country. Our findings are important for decision makers, not the least on a political level, as reduced inequality, e.g. through education, could lead to reduced morbidity.

Determinants of Severe Asthma - A Long-Term Cohort Study in Northern Sweden.

Background: Risk factors for severe asthma are not well described. The aim was to identify clinical characteristics and risk factors at study entry that are associated with severe asthma at follow-up in a long-term prospective population-based cohort study of adults with asthma. Methods: Between 1986 and 2001, 2055 adults with asthma were identified by clinical examinations of population-based samples in northern Sweden. During 2012-2014, n = 1006 (71% of invited) were still alive, residing in the study area and participated in a follow-up, of which 40 were identified as having severe asthma according to ERS/ATS, 131 according to GINA, while 875 had other asthma. The mean follow-up time was 18.7 years. Results: Obesity at study entry and adult-onset asthma were associated with severe asthma at follow-up. While severe asthma was more common in those with adult-onset asthma in both men and women, the association with obesity was observed in women only. Sensitization to mites and moulds, but not to other allergens, as well as NSAID-related respiratory symptoms was more common in severe asthma than in other asthma. Participants with severe asthma at follow-up had lower FEV1, more pronounced FEV1 reversibility, and more wheeze, dyspnea and nighttime awakenings already at study entry than those with other asthma. Conclusion: Adult-onset asthma is an important risk factor for development of severe asthma in adults, and obesity increased the risk among women. The high burden of respiratory symptoms already at study entry also indicate long-term associations with development of severe asthma.

Body mass index increase: a risk factor for forced expiratory volume in 1†s decline for overweight and obese adults with asthma.

Background: With increasing prevalence of overweight and obesity, it is important to study how body mass index (BMI) change may affect lung function among subjects with asthma. There are few prospective studies on this topic, especially with separate analyses of those with normal and high BMI. The aim of the present study was to prospectively study the association between annual BMI change and annual lung function decline, separately among those with normal initial BMI and overweight/obesity, in an adult asthma cohort. Methods: A population-based adult asthma cohort was examined at study entry between 1986 and 2001 and at follow-up between 2012 and 2014 (n=945). Annual BMI change was analysed in association with annual decline in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC separately in those with normal weight (BMI 18.5-24.9) and overweight/obese subjects (BMI ≥25) at study entry. Regression models were used to adjust for sex, age, smoking, inhaled corticosteroids use and occupational exposure to gas, dust or fumes. Results: Overweight/obese subjects had lower FEV1 and FVC but slower annual FEV1 and FVC decline compared to those with normal weight. After adjustment through regression modelling, the association between BMI change with FEV1 and FVC decline remained significant for both BMI groups, but with stronger associations among the overweight/obese (FEV1 B[Overweight/obese]=-25 mL versus B[normal weight]=-15 mL). However, when including only those with BMI increase during follow-up, the associations remained significant among those with overweight/obesity, but not in the normal-weight group. No associations were seen for FEV1/FVC. Conclusions: BMI increase is associated with faster FEV1 and FVC decline among overweight and obese adults with asthma in comparison with their normal-weight counterparts.