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Background: Chronic respiratory diseases (CRD) are a major public health problem worldwide. In the current epidemiological context, CRD have received much interest when considering their correlation with greater susceptibility to SARS-Cov-2 and severe disease (COVID-19). Increasingly more studies have investigated pathophysiological interactions between CRD and COVID-19. Area covered: Animal experimentation has decisively contributed to advancing our knowledge of CRD. Considering the increase in ethical restrictions in animal experimentation, researchers must focus on new experimental alternatives. Two-dimensional (2D) cell cultures have complemented animal models and significantly contributed to advancing research in the life sciences. However, 2D cell cultures have several limitations in studies of cellular interactions. Three-dimensional (3D) cell cultures represent a new and robust platform for studying complex biological processes and are a promising alternative in regenerative and translational medicine. Expert opinion: Three-dimensional cell cultures are obtained by combining several types of cells in integrated and self-organized systems in a 3D structure. These 3D cell culture systems represent an efficient methodological approach in studies of pathophysiology and lung therapy. More recently, complex 3D culture systems, such as lung-on-a-chip, seek to mimic the physiology of a lung in vivo through a microsystem that simulates alveolar-capillary interactions and exposure to air. The present review introduces and discusses 3D lung cultures as robust platforms for studies of the pathophysiology of CRD and COVID-19 and the mechanisms that underlie interactions between CRD and COVID-19.