Significance of Inducible Laryngeal Obstruction Phenotypes Identified by Latent Class Analysis

BACKGROUND: Inducible laryngeal obstruction (ILO) is characterized by symptomatic inappropriate adduction of the vocal cords during respiration. There is a spectrum of clinical ILO presentations, and it is unknown whether this heterogeneity reflects pathogenesis or natural history. OBJECTIVES: We aimed to objectively identify clinically relevant ILO phenotypes. METHODS: We included consecutive patients assessed between March 2016 and September 2023 with laryngoscopy evidence of ILO. Patients were analyzed using latent class analysis (LCA) by age, self-reported symptom triggers, and comorbidities. LCA models were assessed by statistical criteria and for clinical plausibility. ILO phenotypes from the selected model were compared by clinical course, laryngoscopy findings, and patient-reported outcomes. RESULTS: LCA of 192 patients with ILO identified 4 phenotypes labeled by predominant clinical characteristics: isolated ILO (32.8%, n = 63) characterized by inhaled and airborne triggers without comorbidities; hyperventilation-associated ILO (41.7%, n = 80) characterized by hyperventilation, anxiety, and sinonasal disease and triggered by inhaled and airborne exposures; polymorbid ILO (18.2%, n = 35) characterized by anxiety, sinonasal disease, lower airway obstruction, obesity, and gastroesophageal reflux symptoms; and pseudoallergic ILO (7.3%, n = 14) characterized by patient-presumed exposure to an allergen in the absence of specific IgE sensitization. Polymorbid ILO was associated with higher Vocal Cord Dysfunction Questionnaire, higher Chemical Sensory Hyper-reactivity and lower Laryngeal Hypersensitivity Questionnaire scores, and expiratory phase-limited ILO (all P < .01). Pseudoallergic ILO had the shortest duration of illness (P = .03) and was least likely to respond to laryngeal retraining (P = .02). CONCLUSIONS: Four identified ILO phenotypes with heterogeneous and distinct clinical characteristics are further differentiated by clinical course and laryngoscopy providing support for distinct pathogenic pathways in ILO.