Obesity and respiratory diseases: mechanisms, phenotypes, and clinical implications.

Abstract

<h4>Background</h4>Obesity has emerged as a global pandemic with profound implications for respiratory health. The complex interplay between excessive adiposity and pulmonary function encompasses mechanical, metabolic, and inflammatory pathways that significantly impact morbidity and mortality.<h4>Objectives</h4>This comprehensive review synthesizes current evidence on obesity-related respiratory disorders, examining pathophysiological mechanisms, clinical phenotypes, epidemiological trends, and therapeutic considerations across the spectrum of respiratory diseases. This review provides a novel integrative framework unifying mechanical, inflammatory, and metabolic mechanisms across all major obesity-related respiratory conditions, with emphasis on clinically actionable phenotyping and emerging pharmacological therapies.<h4>Methods</h4>We conducted a narrative review of peer-reviewed literature (PubMed/MEDLINE, Embase, and Cochrane Database, January 2000 - December 2024, using pre-specified MeSH terms; study selection and quality assessment followed SANRA guidelines focusing on the relationship between obesity and respiratory disorders including asthma, obstructive sleep apnea (OSA), obesity hypoventilation syndrome (OHS), chronic obstructive pulmonary disease (COPD), respiratory infections, and lung cancer.<h4>Results</h4>Obesity profoundly affects respiratory mechanics through a right-shift of the static volume-pressure relationship of the chest wall, reducing FRC and ERV without a true restrictive pattern, altered respiratory muscle function, and systemic inflammation. Asthma prevalence increases with body mass index, demonstrating distinct phenotypes including atopic, insulin-resistant, dyslipidemic, and non-Th2 neutrophilic subtypes. OSA affects 22% of men and 17% of women, with obesity being the principal modifiable risk factor. OHS occurs in 8-20% of obese patients with sleep-disordered breathing, characterized by daytime hypercapnia (arising from impaired neuromuscular ventilatory drive and progressive nocturnal hypoventilation) and increased cardiovascular mortality. Paradoxically, obesity appears protective in advanced COPD by reducing FRC, thereby increasing inspiratory capacity and limiting dynamic pulmonary hyperinflation, and ARDS-the so-called obesity paradox-while conferring increased risk in COVID-19 pneumonitis. In lung cancer, obesity demonstrates complex relationships with risk and prognosis that vary by sex, smoking status, and disease stage.<h4>Conclusions</h4>Obesity-related respiratory disorders represent a multifaceted clinical challenge requiring integrated multidisciplinary approaches. Understanding distinct phenotypes and pathophysiological mechanisms is essential for personalized therapeutic strategies addressing both weight management and respiratory-specific interventions. Emerging pharmacological therapies including GLP-1 receptor agonists and dual GIP/GLP-1 agonists show particular promise in improving OSA severity and airway inflammation.