Higher BMI is associated with greater fatigue and dyspnea in interstitial lung disease: a Pulmonary Fibrosis Foundation Registry study

Background Obesity affects one third of patients with interstitial lung disease (ILD) and increases both fatigue and dyspnea in the general population. Fatigue and dyspnea are commonly reported by patients with ILD and are difficult to treat. We hypothesized that higher body mass index (BMI) would associate with greater fatigue and dyspnea, worse health-related quality of life (HRQoL), and greater changes in symptoms over time in a real-world ILD cohort. Methods We performed a retrospective analysis of a cohort study of participants in the Pulmonary Fibrosis Foundation Registry with BMI and at least one questionnaire available at enrollment. Symptoms were assessed at enrollment, 6, and 12 months using the Fatigue Severity Scale, UCSD Shortness of Breath, and Short-Form Six-Dimension questionnaires. Linear mixed models with random intercept for participant and interaction between time and BMI evaluated whether BMI correlated with symptoms and changes in symptoms over time. We used random-intercept cross-lagged panel models to evaluate the reciprocal relationship between BMI and symptoms. All models were adjusted for baseline age; sex; ILD diagnosis, diabetes, hypertension, coronary artery disease, and depression diagnoses; use of antifibrotics and corticosteroids; use of supplemental oxygen, and pulmonary function, with forced vital capacity and diffusing capacity of the lung for carbon monoxide as time-varying covariates. Results 1544 participants were included, 1029 (67%) had 12-month data, with mean (standard deviation) age of 68 (10.3) years, 35% were female, 63% had IPF, percent predicted forced vital capacity of 68% (18.1%), and BMI of 29 (5.8) kg/m2; 87% were using anti-fibrotic therapy at enrollment. Higher BMI was associated with greater fatigue and dyspnea but not with HRQoL. BMI did not moderate changes in fatigue (p-value = 0.29), dyspnea (p-value = 0.98), or HRQoL (p-value = 0.91) over time. BMI and fatigue had bidirectional associations over time wherein lower BMI was associated with greater subsequent symptoms, and greater symptoms were associated with lower subsequent BMI. Conclusion Higher BMI is associated with greater fatigue and dyspnea on average in patients with ILD, independent of comorbidities and medications. Longitudinally, BMI did not moderate change in these symptoms over time. Further work should investigate whether intentional weight loss can improve fatigue and dyspnea in patients with obesity and ILD.