ASSOCIATION OF ADIPOKINES AND OBESITY-RELATED PATHWAYS WITH LUNG FUNCTION AND PULMONARY VASCULAR DISTENSIBILITY

Abstract

SESSION TITLE: Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Obesity has multifactorial effects on lung function and pulmonary hypertension. The contributions of adipose related cytokine (adipokine) pathways to alterations in lung function remain unclear. In this context, we examined the role of adipokines and obesity-related biomarkers in relationship to pulmonary function and dynamic pulmonary vascular response to exercise. METHODS: We examined patients who underwent clinically indicated cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring at Massachusetts General Hospital between December 2006 and June 2017. We excluded patients with low LVEF or who failed to reach adequate exercise threshold (defined at RER>1.0). We examined the association of adiponectin, leptin, resistin, IL6, CRP, and insulin resistance (HOMA-IR) with pulmonary function (% predicted FEV1, FVC, FEV1/FVC, TLC and DLCO) using multivariable linear regression. Analyses were adjusted for age, sex, BMI, smoking status, diabetes, prior MI, and heart failure. Adipokines were log-transformed and standardized. RESULTS: Among 695 individuals (mean age 57 years, 60% women), we found that leptin, CRP and HOMA-IR were all associated with lower FEV1, FVC, TLC and DLCO (multivariable p<0.05 for all), with minimal effect on FEV1/FVC ratio indicating restrictive physiology. For example, a 1-SD higher leptin level was associated with a 3% lower FEV1, 2.7% lower FVC, 4.5% lower TLC and 3.5% lower DLCO (p<0.05 for all). By contrast, adiponectin was associated with lower FEV1 and FEV1/FVC ratio (p<0.05 for both), indicating obstructive physiology. In addition, leptin, resistin, IL6, CRP, and HOMA-IR were associated with lower peak VO2 (p<=0.001 for all). When examining measures of pulmonary vascular function, we observed that higher adiponectin, IL6, and CRP were associated with worse pulmonary distensibility, and higher leptin, IL6, and CRP were associated with worse pulmonary artery compliance (p<0.05 for all). CONCLUSIONS: Adipokines and obesity-related pathways including leptin, IL6, CRP, and HOMA-IR were associated with worse pulmonary function in a pattern suggestive of restrictive physiology, in addition to worse functional capacity. IL6 and CRP were associated with both a lower pulmonary artery distensibility and compliance. CLINICAL IMPLICATIONS: Adipokine and obesity-related biomarkers were associated with restrictive lung physiology demonstrated by a reduction in % predicted FEV1, FVC, TLC and DLCO. In addition, higher levels of adipokines, in particular IL6 and CRP, demonstrated worsening pulmonary distensibility as well as pulmonary compliance indicating a negative effect on the pulmonary vascular system. These results may shed light onto potential mechanisms by which obesity can lead to lung disease and pulmonary hypertension. DISCLOSURES: No relevant relationships by Robyn Farrell, source=Web Response No relevant relationships by Jennifer Ho, source=Web Response No relevant relationships by Emily Lau, source=Web Response no disclosure on file for Gregory Lewis; No relevant relationships by Elizabeth Liu, source=Web Response Owner/Founder relationship with Patch Please note: >$100000 Added 04/06/2020 by Rajeev Malhotra, source=Web Response, value=Ownership interest Consultant relationship with Third Pole Please note: $1001 - $5000 Added 04/06/2020 by Rajeev Malhotra, source=Web Response, value=Consulting fee Consultant relationship with MyoKardia Please note: $20001 - $100000 Added 04/06/2020 by Rajeev Malhotra, source=Web Response, value=Consulting fee No relevant relationships by Jenna McNeill, source=Web Response No relevant relationships by Matthew Nayor, source=Web Response No relevant relationships by John Sbarbaro, source=Web Response No relevant relationships by Mark Schoenike, source=Web Response No relevant relationships by Emily Zern, source=Web Response