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Background: Severe asthma outcomes in primary care are poorly documented. This study characterizes adults with severe uncontrolled asthma and evaluates modifications of prescribed inhalation therapy and exacerbations over 12 months.

Methods: Adult primary care asthma patients, with visits recorded in the Swedish National Airway Register from July 2017 to February 2019 (index date), were included. Data were linked to National Prescribed Drug Register. Severe asthma was defined by adherence to high dose inhaled corticosteroids (ICS) ± long-acting beta-agonists (LABA) or ICS+LABA+long-acting muscarinic antagonists. Inhalation therapy was assessed 12 months pre- and post-index. All other variables were collected up to 24 months pre-index and 12 months post-index. Uncontrolled asthma was defined as Asthma Control Test ≤19.

Results: Severe asthma was identified in 2789 patients, of which, 1261 had uncontrolled disease. Severe uncontrolled asthma associated with regular OCS use 24 months pre-index (OR 1.77, 95% CI 1.42–2.20), obesity (1.63, 1.32–2.02), primary school education (1.55, 1.22–1.96) and inversely associated with asthma management education (0.77, 0.66–0.90). Post-index, 5%, 55% and 45% increased, maintained or reduced their inhalation therapy, respectively. Patients increasing inhalation therapy had lower mean FEV1% predicted (67.8 vs. 80.9 and 79.4), more regular OCS uses pre-index (34.8% vs. 17% and 21.9%), and high SABA use (33.3% vs. 27.3% and 21.3%). Post-index asthma exacerbations in severe uncontrolled asthma associated with rhinitis (1.46, 95% CI 1.14–1.88), cardiovascular disease (1.38, 1.06–1.80), high SABA use (1.79, 1.38–2.34), and treatment increase (1.83, 1.08–3.10).

Conclusion: In primary care, severe uncontrolled asthma was among other factors associated with regular OCS use, obesity, lower educational level and absence of asthma management education. Uncontrolled patients already adhering to high dose ICS medication and further increased inhalation therapy were at greater risk of exacerbations, indicating the need for referral to secondary care.

Background: Daily sublingual immunotherapy (SLIT) for 3 years reduces symptoms of allergic disease and induces tolerance. Real-life data from children with asthma receiving SLIT are scarce.

Objective: We used population-based data to describe characteristics, SLIT duration, and changes in morbidity in children with asthma prescribed SLIT.

Methods: The study included children (5-17 years) with asthma who were prescribed SLIT, and who were registered in the Swedish National Airway Register (SNAR) before SLIT initiation (N = 1,514), of whom 782 had post-SLIT recordings in the SNAR. Age, sex, Asthma Control Test score (≤19 denotes uncontrolled asthma), spirometry data, number of SLIT tablets dispensed, and socioeconomic background were extracted from the SNAR and other national registers. SLIT duration was classified as <4, ≥4, >12, or >24 months.

Results: SLIT was more common in boys (69%) and adolescents (71%). Most children had parents with higher education (70%), and 25% had uncontrolled asthma. SLIT duration of ≥4, >12, and >24 months was identified in 86%, 50%, and 30%, respectively. Parents with higher education were associated with SLIT duration of ≥4 months (odds ratio = 3.69; 95% confidence interval 2.75-4.96). SLIT duration of >12 months was associated with lower risk of post-SLIT uncontrolled asthma (adjusted odds ratio = 0.49; 95% confidence interval, 0.25-0.99). No associations were found between SLIT duration of ≥4, >12, or >24 months and changes in spirometry.

Conclusion: Longer SLIT duration was associated with higher education in parents and lower risk of uncontrolled asthma. Measures to improve persistence in SLIT in children with asthma may have important clinical implications.

Purpose: Asthma control is multifaceted, involving symptoms and risk of adverse outcomes. Emerging evidence suggests a bidirectional link between poor asthma control and severe COVID-19, but large studies addressing all components of asthma control in this context are lacking. Our aims were to evaluate if 1) uncontrolled asthma was a risk factor for COVID-19 hospitalization and death, 2) asthma control changed during the pandemic and 3) COVID-19 hospitalization was a risk factor for future uncontrolled asthma.

Methods: Patients with asthma (n = 125,362) were identified in the Swedish National Airway Register from January 2014 to 2020, whereof n = 2377 were hospitalized and n = 305 died due to COVID-19 during follow-up until December 2022. Asthma control was evaluated by symptoms (Asthma Control Test (ACT) ≥ 20: well controlled, ACT 16–19 not well-controlled and ACT < 16 very poorly controlled asthma), lung function (FEV1% predicted (pp)) and frequent and/or severe exacerbations (dispensed oral corticosteroids and asthma inpatient care).

Results: ACT 16–19 (RR 1.57, 95% CI 1.34–1.84), ACT < 16 (1.72, 1.46–2.02), FEV1 < 80pp (1.29, 1.13–1.48), frequent (1.99, 1.79–2.21) and severe exacerbations (2.54, 2.09–3.08) were associated with a higher risk for COVID-19 hospitalization. COVID-19 death was associated with ACT < 16, frequent and severe exacerbations. Overall, at follow-up, proportions of ACT < 20 (36.1%) and FEV1 < 80pp (48.3%) were stable, while exacerbations decreased (frequent; 7.9% to 6.8%, severe; 1.3% to 0.4%). COVID-19 hospitalization was a risk factor for frequent (1.35, 1.22–1.51) and severe (3.42, 1.22–1.51) future asthma exacerbations.

Conclusion: All dimensions of poor asthma control were associated with an increased risk of severe COVID-19. In contrast, only exacerbation risk was elevated following COVID-19.

Background: Severity of airflow obstruction in patients with asthma can be influenced by features beyond lung function impairment. The aim of this study was to assess the severity of obstruction according to the 2022 European Respiratory Society/American Thoracic Society standards, and its associations with perinatal factors, as well as potential interactions with background and clinical factors.

Methods: The study population consisted of 44,394 patients with asthma, aged 7–49 years, with at least one measurement of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) recorded in the Swedish National Airway Register in 2014–2022, who were included in the Medical Birth Register between 1973 and 2015 with data on gestational age (GA) and birthweight. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC < lower limit of normal and categorized as mild, moderate, or severe based on FEV1z-score. Normal FEV1served as the reference category.

Results: Among 7873 (17.7 %) patients with airflow obstruction, the prevalence of severe obstruction pre-bronchodilator was 6.1 %. Patients born extremely-to-very preterm or small for GA (SGA) had increased relative risk ratios for severe obstruction pre-bronchodilator (RRRadj2.34, 95 % CI 1.24–4.41, and 2.03, 1.38–2.98) compared with those born at term and appropriate for GA, respectively, with obstruction and normal FEV1. For GA and birthweight, there were non-significant interactions with background or clinical factors.

Conclusions: Severe obstruction was prevalent in children and adults with asthma. Patients born extremely-to-very preterm or SGA exhibited a significant association with severe obstruction pre-bronchodilator, regardless of background and clinical factors.

Rationale: Few studies have identified risk sets for perinatal factors and airflow obstruction into middle adulthood.

Objectives: To investigate associations between gestational age (GA), GA-adjusted birthweight, and mode of delivery and persistent airflow obstruction among patients 7-49 years old with obstructive lung diseases.

Methods: The study population encompassed 44,778 individuals with asthma or chronic obstructive pulmonary disease (COPD) and one or more registration of post-bronchodilator values of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) recorded in the Swedish National Airway Register in 2014-2022 and with both GA and birthweight data in the Medical Birth Register between 1973-2015. Persistent airflow obstruction was defined as a FEV1/FVC z-score below the lower limit of normal. Analyses were done separately for children, young adults, and middle-aged adults.

Results: Subjects who were extremely, very, moderate, and late preterm-born all had increased odds ratios (ORs) of persistent airflow obstruction up to age 49 years compared with those term-born. Middle-aged adults born small for GA had increased OR of persistent airflow obstruction compared with those appropriate for GA (OR, 1.49; 95% confidence interval, 1.23-1.81). In the risk sets, GA was the most significant covariate for persistent airflow obstruction. GA-adjusted birthweight was an additional covariate for those born late preterm, term, or postterm. Mode of delivery did not contribute.

Conclusions: GA was an independent covariate of persistent airflow obstruction and, in the risk sets, proved to be the most important covariate in patients of all ages with either asthma or COPD. GA-adjusted birthweight further improved the prediction.

Background: Airway obstruction is a characteristic spirometric finding in asthma but the clinical significance of other abnormal spirometric patterns is less well described. We aimed to explore pre-and post-bronchodilator (BD) prevalences and clinical characteristics of preserved ratio impaired spirometry (PRISm), dysanapsis and airflow obstruction with low forced expiratory volume in 1 s (FEV₁) in children diagnosed with asthma.

Methods: We extracted specialist care data (clinical and spirometry) from the Swedish National Airway Register (n=3301, age 5–17 years). Normal spirometry was defined as FEV₁⩾ lower limit of normal (LLN) and FEV₁/forced vital capacity (FVC)⩾LLN. PRISm was defined as forced FEV₁< LLN and FEV₁/FVC⩾LLN, dysanapsis as FEV₁/FVC<LLN and FEV₁⩾LLN, and airflow obstruction with reduced FEV₁ as FEV₁/FVC<LLN and FEV₁<LLN. The BD response (BDR) was calculated as ((post-BD(L)−pre-BD(L))/predicted (L))×100. Values >10% were considered positive (BDRpos). Groups were compared using parametric tests and associations were explored using logistic regression analysis.

Results: Pre-/post-BD PRISm, dysanapsis and obstruction with low FEV₁ were identified in 9%/7%, 10%/4% and 8%/2%, respectively. Compared with normal spirometry, all three groups were associated with older age and BDRpos in pre-BD analyses. Furthermore, dysanapsis was associated with overweight/ obesity and obstruction with low FEV1 with uncontrolled asthma and more treatment.

Interpretation: In this paediatric asthma cohort, PRISm and dysanapsis were associated with BDRpos and they were at least as common as airflow obstruction with reduced FEV₁. These spirometric phenotypes should be addressed in the management of childhood asthma and testing of BDR should be considered also in children with PRISm and dysanapsis.

Background: COPD is largely underdiagnosed. Active identification of cases is crucial to establish preventive measures before manifestation of clinical disease. The significance of different spirometric patterns preceding COPD, especially preserved ratio impaired spirometry (PRISm), has been highlighted but remains unclear.

Research Question: Which clinical characteristics, smoking habits, and spirometric patterns, with primary focus on PRISm findings, precede the development of airway obstruction (AO)?

Study Design and Methods: The OLIN COPD Study was established from 2002 through 2004. After re-examination of population-based cohorts, individuals with AO (n = 993; FEV1 to VC ratio < 0.70) were identified together with control participants without AO (n = 993; FEV1 to VC ratio ≥ 0.70). Most of these people had participated in examinations during the 1980s or 1990s, and in total, 902 cases and 819 control participants had previous clinical data. Logistic regression was performed with case status as outcome and spirometric patterns, age, sex, smoking habits, and BMI at first examination as covariates.

Results: The mean (SD) person-years between first examination and inclusion in the OLIN COPD Study was 10.5 (4.0) years. At first examination, the prevalence of PRISm was higher in cases (18.6%) vs control participants (13.4%). Current smoking was more common in cases (45.1% vs 18.2%), whereas former smoking was similar (31.8% vs 34.9%). Cases reported more respiratory symptoms (78.0% vs 44.3%) than control participants. At first examination, PRISm, current smoking, and former smoking were strongly associated with becoming a case when adjusted for confounders, with adjusted OR (aOR) of 3.5, 4.1, and 1.5, respectively. When stratifying for smoking habits, aORs for PRISm in those with current smoking, former smoking, and nonsmoking status were 2.9, 3.8 and 3.7, respectively.

Interpretation: In this study, PRISm was associated with transition into AO corresponding to COPD within 1 decade, independent of smoking habits and with similar strength of association among those who have never smoked, who formerly smoked, and who currently smoke.

Background: Physician diagnosed COPD with normal spirometry (dnsCOPD) (sometimes labeled pre-COPD) and Preserved Ratio Impaired Spirometry (PRISm) has been studied in population-based cohorts, but not in physician diagnosed COPD (dCOPD) patients from routine clinical practice. The Swedish National Airway Register (SNAR) is a large nationwide register including data from dCOPD patients from over 1000 clinics across all regions of Sweden and is representative of the COPD care in Sweden. We aimed to identify and characterize patients with dnsCOPD, PRISm and spirometrically confirmed COPD (sCOPD) from dCOPD patients in SNAR, stratify them further according to symptoms and exacerbations risk using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) A/B/E classification, and assess differences in risk for exacerbations, cause-specific hospitalisations and mortality.

Methods: We enrolled patients aged ≥30 years with dCOPD in the SNAR from 1 January 2014 to 30 June 2022 with complete spirometry i.e., postbronchodilator values for both forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (index date). Patients with concomitant asthma were excluded. Patients were stratified into dnsCOPD (FEV1/FVC ≥0.7 and FEV1 ≥80% predicted), PRISm (FEV1/FVC ≥0.7 and FEV1 <80% predicted) and sCOPD (FEV1/FVC <0.7). Further substratification was based on GOLD A/B/E (A: COPD assessment test (CAT) score <10 points and <2 moderate, 0 severe exacerbations within 1 year before the index date, B: CAT-score ≥10 points and <2 moderate, 0 severe exacerbations, E: ≥2 moderate or ≥1 severe exacerbation(s)). Patients were followed until 31 November 2022. Competing risk regression was used to calculate subdistribution hazard ratios (SHR)s with 95% confidence intervals (CIs) for exacerbation, hospitalisation and mortality.

Findings: Of 45,653 patients with dCOPD, 5.4% had dnsCOPD, 11.4% had PRISm and 83.3% had sCOPD. Smoking history was similar between groups (ever smoker: dnsCOPD: 79% PRISm: 82% sCOPD: 86%) and inhalation therapy was common in all groups (any inhaler: 75%, 80% and 80%, triple combination: 22%, 28% and 35%). Patients with PRISm had a high prevalence of obesity (dnsCOPD: 30%, PRISm: 43%, COPD: 22%), cardiovascular disease (dnsCOPD: 39%, PRISm: 48%, COPD: 41%) and diabetes (dnsCOPD: 10%, PRISm: 17%, COPD: 9%). Baseline GOLD group B or E were highly prevalent in dnsCOPD (B: 54%, E: 11%), PRISm (B: 59%, E: 14%), as well as in COPD (B: 54%, E: 17%). DnsCOPD and PRISm patients had lower risk of exacerbations (SHR 0.69, 95%CI 0.64–0.74 and 0.85, 95%CI 0.81–0.89), respiratory hospitalisation (0.40, 95%CI 0.34–0.46 and 0.68, 95%CI 0.62–0.73), and respiratory mortality (0.22, 95%CI 0.13–0.37 and 0.60, 95%CI 0.48–0.75) compared to sCOPD. Cardiovascular mortality was lower in dnsCOPD (0.41, 95%CI 0.19–0.86), but similar in PRISm (0.73, 95%CI 0.49–1.08) compared to sCOPD. The A/B/E classification was predictive for all outcomes in dnsCOPD and PRISm. DnsCOPD and PRISm group E patients had higher risks for all outcomes than sCOPD group A or B.

Interpretation: DnsCOPD and PRISm are prevalent in a real-life cohort of patients with a physician diagnosis of COPD. These patients are symptomatic, might suffer from exacerbations and are commonly treated with inhaled therapy, equally to sCOPD. Patients with PRISm had a high prevalence of obesity, diabetes and cardiovascular disease. DnsCOPD and PRISm had generally lower overall risks of exacerbation or respiratory events, although PRISm patients showed similar cardiovascular risk to sCOPD. The A/B/E classification predicted future events, even in dnsCOPD and PRISm patients.

Funding: This study is performed with support from The Swedish Heart-Lung Foundation ( 20200150) and the Swedish government and country council ALF grant ( ALFGBG-824371).