Abstract Rationale Severe uncontrolled asthma (SUA) is a heterogeneous syndrome often perpetuated by systemic and airway comorbidities that worsen symptoms, limit lung function recovery, and blunt biologic response. We wanted to characterize the burden and spectrum of comorbidities among adults with SUA in a large integrated health system and discuss potential therapeutic implications, including metabolic modulation with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). A comprehensive understanding of comorbidity patterns in SUA may inform integrative, phenotype-directed management strategies. Methods We performed a retrospective cohort analysis of 740 adults with SUA treated across the Allegheny Health Network (09/2023-09/2024). Demographics, comorbidities, inhaler use, and biologic therapy were extracted from electronic health records. Descriptive statistics quantified prevalence, and chi-square or Fisher’s exact tests evaluated categorical associations (α = 0.05). A subgroup analysis examined patients on biologic therapy (n = 81). Results Mean age was 55.6 ± 17.6 years; 72.3 % female and 76.6 % White. The cohort demonstrated a striking multimorbidity profile: obesity (52.8 %), hypertension (62.8 %), COPD (34.5 %), obstructive sleep apnea (35.3 %), anemia (41.2 %), dyslipidemia (59 %), and chronic rhinosinusitis (27.3 %). Among biologic users, comorbidity burden was even greater—obesity 66.7 %, OSA 53.1 %, and COPD 50.6 %—illustrating the clustering of systemic metabolic and inflammatory conditions within the most treatment-resistant subgroup. Gender and race were analyzed for testing and specialty-follow-up patterns but not specifically for comorbidity prevalence in this dataset. Median cumulative prednisone exposure was 300 mg (IQR 49-668 mg), reflecting substantial corticosteroid dependence despite advanced therapy. Discussion Multimorbidity in SUA represents an under-recognized driver of persistent disease activity.i Obesity emerged as a dominant, biologically relevant comorbidity linking metabolic dysregulation to airway inflammation, reduced lung compliance, and steroid resistance. Converging evidence from observational studies and early clinical trials suggests that GLP-1 RAs—now approved for obesity and obstructive sleep apnea—improve weight, systemic inflammation, and may attenuate asthma and COPD exacerbations.ii Given that over half of this cohort is obese with frequent overlap of OSA and COPD, randomized controlled trials assessing GLP-1 RAs as adjunctive therapy for obese SUA patients are urgently warranted. These should evaluate exacerbation frequency, lung mechanics, oral corticosteroid reduction, and inflammatory biomarkers. i Listyoko et al., “Exploring the Association between Asthma and Chronic Comorbidities.” ii Tooba and Wu, “Obesity and Asthma.” This abstract is funded by: None
Gul et al. (Fri,) studied this question.