Abstract Rationale Airway dysanapsis -an incongruency between the caliber of airways and the volume of the lung parenchyma- has been associated with asthma exacerbations. Here, we evaluate the association between dysanapsis and clinical characteristics in youth with and without asthma. We hypothesized that dysanapsis would be associated with lower lung function, higher inflammatory markers, and worse asthma outcomes. Methods The Genomics of Obesity-Related Asthma study (GenOAAT) is a cohort of youths ages 6-20 years with and without asthma. Participants completed spirometry, plethysmography, fractional exhaled nitric oxide (FeNO), and atopy/inflammatory biomarkers. Participants with asthma completed questionnaires assessing symptom frequency, asthma control (ACT/C-ACT and ATAQ), and asthma-related quality of life (PAQLQ). Dysanapsis was defined as a high FVC (100% of predicted), normal FEV1 (80%pred), and low FEV1/FVC (80%pred). The dysanapsis ratio (DR) was calculated as FEF2575/FVC (lower DR = dysanapsis). We used multivariable linear or logistic regression models adjusted for age, sex, race, and asthma status to estimate odds ratios (ORs) or beta coefficients (β) and 95% confidence intervals (CIs). Results Among 139 GenOAAT participants (mean age=14.1 years, 54% male, 82% White, 49% with asthma, mean BMI z-score=0.99), 32 met the definition of dysanapsis. Participants with dysanapsis had 9.7% higher total lung capacity (TLC) (β = 9.7, 95% CI = 2.8-16.6; p = 0.006) and 18% lower FEF2575 (β = 18.0, 95% CI= -27.9, -8.1; p 0.001) than those without dysanapsis (Figure 1a). Dysanapsis was associated with more frequent daytime asthma symptoms (β = 0.22, 95% CI = 0.03-0.42; p = 0.027) and higher bronchodilator responsiveness (β = 3.8%, 95% CI = 0.05-7.6%; p = 0.047) (Figure 1b). Dysanapsis was also associated with higher odds of asthma exacerbation (OR = 5.7, 95% CI = 1.8-20.4; p = 0.0042) and hospitalization (OR = 6.01, 95% CI = 1.61-24.5; p = 0.008). A lower DR was associated with higher CRP (β = 0.57, 95% CI = 0.14-1.01; p = 0.01). Conclusions In this cohort of youth with and without asthma, dysanapsis was associated with higher TLC, lower FEF2575, worse asthma symptoms, and more frequent exacerbations, and higher inflammatory markers. These findings suggest that dysanapsis is the result of larger lung volumes (rather than ‘airway obstruction’) and causes worse asthma morbidity through systemic (rather than atopic) inflammation. This abstract is funded by: NIH grant HL149693
Unruh et al. (Fri,) studied this question.