Umeå University's logo

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: Longitudinal data addressing the impact of asthma severity on mortality are lacking. We aimed to explore all-cause and cause-specific mortality according to asthma severity.

Methods: The present registry-based cohort study is based on Danish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. Adult patients with severe asthma were matched on age and sex to 10 patients with mild-to-moderate asthma and followed from 2000 to 2020. Patients with COPD diagnosed prior to inclusion were excluded. Absolute and relative measures of all-cause and cause-specific mortality were compared between severe and mild-to-moderate asthma.

Results: We included 11 881 and 118 810 patients with severe and mild-to-moderate asthma, respectively. All-cause mortality was significantly higher in patients with severe asthma compared to patients with mild-to-moderate asthma, both in absolute measures of the cumulative mortality (34% (95% CI 32–35%) versus 20% (95% CI 19–20%); p<0.001) after 20 years of follow-up and in relative measures (hazard ratio (HR) 1.99, 95% CI 1.90–2.09; p<0.001). The HR of all-cause mortality was attenuated after adjustment for oral corticosteroid (OCS) use (HR 1.30, 95% CI 1.23–1.37; p<0.001) and type 2 (T2) inflammatory markers (HR 1.34, 95% CI 1.09–1.64; p<0.001). The increased cumulative mortality risk was mainly due to respiratory diseases (12.6% (95% CI 11.7–13.6%) versus 3.3% (95% CI 3.2–3.5%); p<0.001), with cancer (7.5% (95% CI 6.8–8.3%) versus 5.9% (95% CI 5.7–6.2%); p<0.001) and cardiovascular diseases (4.7% (95% CI 4.1–5.3%) versus 3.8% (95% CI 3.6–4.0%); p<0.001) also contributing. Although rare, the relative risk of asthma-related deaths was three-fold in severe asthma patients (HR 2.95, 95% CI 2.08–4.18; p<0.001).

Conclusions: In this nationwide cohort, severe asthma was associated with a significantly higher mortality risk compared to mild-to-moderate asthma. The increased risk was primarily driven by respiratory-related deaths, with OCS use and T2 inflammation as contributing mortality risk factors.

Background: The link between the use of oral corticosteroids (OCS) and adverse events (AEs) in asthma is well described. In contrast, whether the use of high-dose inhaled corticosteroids (ICS) poses a risk to these is unknown.

Objective: To examine the association between ICS exposure and corticosteroid (CS)-related AEs.

Methods: We conducted an observational cohort study using nationwide Swedish registry data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration. We included patients with asthma aged ≥18 years between 2009 and 2019 and calculated their current ICS exposure and average daily ICS dose (budesonide equivalent) in follow-up. The association between ICS exposure and CS-related AEs was analyzed using Cox proportional hazards models adjusting for age, sex, and OCS dose.

Results: We included 529,203 patients with asthma. Overall, we observed increased hazard ratios (HRs) in those exposed to high-dose (≥800-1599 μg) and very high dose (≥1600 μg) ICS for several AEs, including cardiovascular disease, type 2 diabetes mellitus (T2DM), osteoporosis, and pneumonia compared with those not exposed to ICS. HRs for the current use of high-dose ICS ranged from 1.11 (95% confidence interval [CI]: 1.06-1.16) for T2DM to 1.65 (95% CI: 1.58-1.72) for pneumonia. Likewise, HRs linked to average daily high-dose ICS ranged from 1.16 (95% CI: 1.02-1.33) for pneumonia to 1.70 (95% CI: 1.38-2.08) for osteoporosis. Sensitivity analysis excluding patients using OCS showed that high-dose ICS was still associated with an increased risk of CS-related AEs. Overall, ICS <800 μg per day had no increased risk, except for cataract.

Conclusion: High-dose ICS is associated with an increased risk of several CS-related AEs. This highlights the importance of clinicians considering this risk in patients treated with high-dose and very high dose ICS.

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 β2-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.