Caroline Stridsman

Aim: We estimated the coverage of children recorded in the Swedish National Airway Register (SNAR) and identified predictors of registration among those with asthma and moderate to severe asthma. Methods: This study comprised 85 656 children aged 5–17 years with asthma, born 2000–2019 and living in Stockholm. The children were identified through diagnoses and dispensed medication in national and regional health registers. Registration in the SNAR was assessed. Logistic regression compared characteristics of registered and unregistered children, with associations presented as odds ratios (OR) and 95% confidence intervals (CI). Results: Overall, 33 815 (39.5%) of children with asthma were registered in the SNAR. Registration was more common among children with allergic rhinitis (OR 1.83, 95% CI 1.77–1.88), parental asthma and allergic rhinitis (maternal OR 1.47, 95% CI 1.43–1.51), higher parental income and education (OR 1.09, 95% CI 1.05–1.12), and moderate to severe asthma (OR 1.37, 95% CI 1.32–1.42). Findings were similar in the moderate to severe asthma sub‐cohort. Conclusion: Nearly 40% of children with asthma in Stockholm were registered in the SNAR, and they were more likely to have familial atopy, higher socioeconomic status, and more severe disease. The SNAR is being developed to increase coverage, support standardized registration, and improve care.

Rationale: COPD exacerbations, often triggered by viral infections like COVID-19, are associated with increased cardiovascular risk. We hypothesized that COVID-19-related exacerbations carry higher short-term cardiovascular and mortality risks than non-COVID-19-related exacerbations. Objectives: To compare 28-day risk of stroke, pulmonary embolism (PE), acute myocardial infarction (AMI), major adverse cardiovascular events (MACE) and all-cause mortality following COVID-19-related vs. non-COVID-19-related COPD exacerbations and assess variation across the pandemic. Methods: Using Swedish national registers, we identified COPD with moderate (treated with oral corticosteroids with/without antibiotics) or severe (hospitalized) exacerbations from March 2020 to June 2023. Exacerbations with infection, hospitalization or intensive care admission for COVID-19 were defined as COVID-19-related. A target trial was emulated and adjusted hazard ratios (aHRs) with 95% confidence intervals (CI) estimated for each outcome, stratified by exacerbation severity and COVID-19 variants. Measurements and main results: Among 266,273 exacerbations (87.2% moderate, 12.8% severe), 5,425 (2%) were COVID-19-related. COVID-19-related vs. non-COVID-19-related moderate exacerbations were associated with risk of PE (aHR 2.26, 95%CI 1.49-3.42), overall cardiovascular (1.94, 1.47-2.56), MACE (1.88, 1.28-2.76), and mortality (4.58, 4.06-5.17), but not significantly with AMI and stroke. Severe COVID-19-related exacerbations were only associated with higher mortality (1.46, 1.28-1.66). Cardiovascular risks were highest during pre-Alpha and Delta for moderate exacerbations. Mortality remained elevated for both moderate and severe exacerbations, particularly during the same periods. Conclusions: COVID-19-related exacerbations increased MACE, short-term cardiovascular and mortality risks, mainly for moderate exacerbations, with attenuation during Alpha and Omicron, highlighting the need for proactive cardiovascular care during respiratory outbreaks.

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.

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. 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). 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. 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.

Purpose: There is an association between low socioeconomic status and chronic obstructive pulmonary disease (COPD), but it is not known whether this impacts on drug prescription for COPD treatment. The aim of the study was to explore whether drug prescription differs between COPD patients with low and high socioeconomic status. Patients and methods: Data from patients with incident and prevalent COPD (age> 40 years), without an asthma diagnosis, visiting primary care in 2021– 2022 were extracted from The Swedish National Airway Register (SNAR) and linked to Swedish National Health registries. Socioeconomic status was assessed by educational level and annual income. Statistical analyses were conducted by means of chi square tests, together with post-hoc test. Results: In total, 38692 patients (mean age 73.6 years, 55.5% women, FEV₁ 59.5% of predicted value) were included. Subdivision into GOLD group A, B and E was possible in 29128 patients. Triple therapy (long-acting antimuscarinic antagonists, LAMA + long-acting beta-2-agonist, LABA + inhaled steroids, ICS), was more often prescribed in the low education group (observed/expected ratio 1.09; p< 0.0001) and low income group (ratio 1.05; p< 0.05) and less often in the high education group (ratio 0.87; p< 0.0001) and high income group (ratio 0.88; p< 0.0001). Monotherapy (LAMA) was more often prescribed in patients with high income (ratio 1.09; p< 0.0001) and less often in patients with low income (ratio 0.93; p=0.0004). Differences between high and low education and income were driven by differences in group B. Conclusion: Prescription patterns were associated with small, statistically significant differences, between COPD patients with low and high socioeconomic status. Triple therapy was more often prescribed to patients with low socioeconomic status, and monotherapy with LAMA more often to patients with high. The reason for this is not clear but may be caused by differences in exacerbation rate between the socioeconomic groups.

Recently, we investigated separate and joint associations between perinatal factors and airflow obstruction into the fifth decade of life in patients with obstructive lung disease [1]. Results revealed that gestational age (GA) was an independent covariate of persistent airflow obstruction in patients of all ages and provided better predictions in risk sets. GA-adjusted birthweight further improved predictions. The contribution of GA and birthweight to adult lung function impairment provides an opportunity for prevention.

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 (FEV ₁ ) 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 FEV ₁ ≥ lower limit of normal (LLN) and FEV ₁ /forced vital capacity (FVC)≥LLN. PRISm was defined as forced FEV ₁ < LLN and FEV ₁ /FVC≥LLN, dysanapsis as FEV ₁ /FVC1 ≥LLN, and airflow obstruction with reduced FEV ₁ as FEV ₁ /FVC1 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 FEV ₁ 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 FEV ₁ 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 FEV ₁ . 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.