D1.79 - Heterogeneity of Non-Allergic Non-Eosinophilic Asthma: Clinical Subphenotypes and Allergy Belief Patterns

Non-allergic, non-eosinophilic (NANE) asthma represents aheterogeneous T2-low endotype frequently associated with obesity, late onset, systemiccomorbidities, and persistent airflow limitation. Despite negative objective allergy testing,some patients perceive their disease as allergy-related. We aimed to characterize the demographic and clinical features of NANE asthma, identify distinguishable subphenotypes, and evaluate the presence and clinical correlates of self-reported allergy belief.

In this cross-sectional study with retrospective data collection and prospective assessment of symptom triggers and allergy perception, 66 patients with NANE asthma followed at a tertiary clinic were included. NANE asthma was defined by persistently low blood eosinophil counts and absence of sensitization on skin prick testing and/or specific IgE measurement. Demographic, clinical, and spirometric data were analyzed. Patients were categorized into predefined subphenotypes, and comparisons were performed using appropriate statistical tests.

Patients were predominantly female (90.9%) with a median age of 58.5 years; 54.5% were obese and 87.9% had systemic comorbidities. Patients were categorized into following NANE asthma subphenotypes: NANE asthma witha smoking history, obese NANE asthma, late-onset NANE asthma, elderly patients with NANE asthma, NANE asthma with persistent airway obstruction, NANE asthma with systemic comorbidity and NANE asthma with allergic comorbidity, accounting for 34.8%, 54.5%, 36.4%, 31.8%,27.3%, 87.9%, and 22.7% of the patients, respectively. Persistent airflow limitation and severe asthma were present in 27.3% and 16.7%, respectively. Subphenotype comparisons revealed substantial heterogeneity, particularly in pulmonary function test (PFT) parameters. Patients with a smoking history had significantly lower FEV1/FVC ratios than never-smokers. Obese NANE asthma patients showed reduced FEV1 compared with non-obese patients. Late-onset NANE asthma was characterized by significantly lower FEV1 and FVC, with preserved FEV1/FVC ratios. Elderly patients similarly exhibited reduced FEV1 and FVC. Persistent airway obstruction was associated with a higher prevalence of severe asthma, significantly decreased FEV1, and lower FEV1/FVC ratios, whereas FVC remained comparable.  A total of 26 patients (39.4%) reported believing that their asthma was allergy-related. Compared to those without this belief, these patients tended to be younger (median age: 56.5 [21–74] years vs. 59.5 [21–76] years, p = 0.146) and had a significantly later asthma onset (39.4 ± 11.1 vs. 32.1 ± 11.5 years, p = 0.012). Upper airway symptoms—such as nasal obstruction, nasal itching, rhinorrhea, sneezing, pharyngeal itching, and postnasal drip—were significantly more frequent in this group. Among environmental triggers, pollen (p = 0.020) and chemical exposure (p = 0.048) were significantly associated with allergy belief. Additionally, a family history of allergic rhinitis was more common in patients with this belief (p < 0.001).

NANE asthma is a heterogeneous condition in which allergy-like symptom perception may occur independently of objective sensitization. Clinical assessment should integrate phenotypic characteristics, symptom perception, and environmental exposures to improve characterization and management of this population.