Abstract

ObjectiveWe investigated the effects of medication on heart disease and ischemic stroke (HDS) risk in patients with predominant bronchiectasis-asthma combination (BCAS).MethodsBCAS and non-BCAS cohorts (N = 588 and 1,118, respectively) were retrospectively enrolled. The cumulative incidence of HDS was analyzed using Cox proportional regression; propensity scores were estimated using non-parsimonious multivariable logistic regression. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for HDS were calculated, adjusting for sex, age, comorbidities, and medication {long- and short-acting β2 agonists and muscarinic antagonists (LABAs/SABAs and LAMAs/SAMAs), steroids [inhaled corticosteroid steroids (ICSs), oral steroids (OSs)], antiarrhythmics, antidepressants (fluoxetine), benzodiazepines (alprazolam, fludiazepam), statins and antihypertensive drugs (diuretics, cardioselective beta blockers, calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEi), angiotensin II blockers)}.ResultsCompared with the non-BCAS cohort, the BCAS cohort taking LABAs, SABAs, SAMAs, ICSs, OSs, antiarrhythmics, and alprazolam had an elevated HDS risk [aHRs (95% CIs): 2.36 (1.25–4.33), 2.65 (1.87–3.75), 2.66 (1.74–4.05), 2.53 (1.61–3.99), 1.76 (1.43–2.18), 9.88 (3.27–30.5), and 1.73 (1.15–2.58), respectively except fludiazepam 1.33 (0.73–2.40)]. The aHRs (95% CIs) for LABAs ≤ 30 days, DDDs <415, ICSs ≤ 30 days were 1.10 (0.38–3.15), 2.95 (0.22–38.8), 1.45 (0.76–2.77). The aHRs (95% CIs) for current and recent alprazolam were 1.78 (1.09–2.93) and 777.8 (1.34–451590.0); for current and past fludiazepam were 1.39 (0.75–2.59) and 1.29 (0.42–4.01) and for past alprazolam was 1.57 (0.55–4.46); respectively. The aHRs (95% CIs) for alprazolam >30 DDDs, fludiazepam >20 DDDs, ICSs ≦415 DDDs, and OSs DDDs ≦15 were 1.60 (0.78–3.29), 2.43 (0.90–6.55), 5.02 (1.76–14.3), and 2.28 (1.43–3.62), respectively.ConclusionThe bronchodilators, steroids, and antiarrhythmics were associated with higher risk of HDS, even low dose use of steroids. However, the current use of LABAs/ICSs were not associated with HDS. Benzodiazepines were relatively safe, except for current or recent alprazolam use. Notably, taking confounders into account is crucial in observational studies.

Highlights

  • Asthma and bronchiectasis are chronic inflammatory diseases [1–4]

  • The current use of long-acting beta2 agonist (LABA)/inhaled corticosteroids (ICSs) were not associated with heart disease and ischemic stroke (HDS)

  • Patorno et al revealed little to no increase in all-cause mortality associated with BZDs initiation in the general population [48]. These findings indicate that BZDs are not associated with significant risk of HDS support our results

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Summary

Introduction

Asthma and bronchiectasis are chronic inflammatory diseases [1–4]. Bronchiectasis may be linked to asthma (BCAS) and is a frequent comorbidity [3, 5–7]. BCAS is associated with frequent hospitalization, and a high blood eosinophil count is an additional phenotypic feature of severe eosinophilic asthma. To ensure precise and personalized treatment, BCAS should be considered as a separate entity [3, 5–7]. In the era of COVID-19, heart disease and ischemic stroke (HDS) has been reported as the most severe complication in patients with BCAS [8]. BCAS is associated with diseases related to arterial thrombosis, such as myocardial infarction and ischemic stroke [9]. Psychiatric problems have been observed in patients with COVID-19 and BCAS [10]. The effect of medications such as antianxiety drugs [benzodiazepines (BZDs)] in patients with BCAS is an urgent Research Topic

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