State of the art: Alternative overlap syndrome—asthma and obstructive sleep apnea

In the general population, Bronchial Asthma (BA) and Obstructive Sleep Apnea (OSA) are among the most prevalent chronic respiratory disorders. Significant epidemiologic connections and complex pathogenetic pathways link these disorders via complex interactions at genetic, epigenetic, and environmental levels. The coexistence of BA and OSA in an individual likely represents a distinct syndrome, that is, a collection of clinical manifestations attributable to several mechanisms and pathobiological signatures. To avoid terminological confusion, this association has been named alternative overlap syndrome (vs overlap syndrome represented by the chronic obstructive pulmonary disease-OSA association). This comprehensive review summarizes the complex, often bidirectional links between the constituents of the alternative overlap syndrome. Cross-sectional, population, or clinic-based studies are unlikely to elucidate causality or directionality in these relationships. Even longitudinal epidemiological evaluations in BA cohorts developing over time OSA, or OSA cohorts developing BA during follow-up cannot exclude time factors or causal influence of other known or unknown mediators. As such, a lot of pathophysiological interactions described here have suggestive evidence, biological plausibility, potential or actual directionality. By showcasing existing evidence and current knowledge gaps, the hope is that deliberate, focused, and collaborative efforts in the near-future will be geared toward opportunities to shine light on the unknowns and accelerate discovery in this field of health, clinical care, education, research, and scholarly endeavors.