Chronic exposure to water-pipe smoke induces alveolar enlargement, DNA damage and impairment of lung function in mice

Water-pipe smoking (WPS) is a method of tobacco smoking commonly practiced in the Middle East, and is now popular among the youth in the West. However, the mechanisms underlying the chronic pulmonary effects of WPS exposure remain unknown.Here, we evaluated the respiratory effects and their possible mechanism of nose-only exposure to mainstream WPS in mice. The duration of the session was 30 min/day and 5 days/week for 6 consecutive months. Control mice were exposed using the same protocol to air only. WPS induced an increase of airway resistance in vivo. The analysis of bronchoalveolar lavage fluid (BALF) showed an increase in neutrophil and lymphocyte numbers, as well as in lactate dehydrogenase, myeloperoxidase and matrix metallopeptidase 9 activities, and proinflammatory cytokines including tumour necrosis factor α, interleukin-6 and interleukin 1β. Histological analysis of lungs revealed the presence of foci of mixed inflammatory cells infiltration in the interalveolar interstitium which consisted of neutrophils, lymphocytes and macrophages. Notably, the mean diameter of alveolar spaces and ducts were increased in WPS-exposed mice compared to air only. In lung tissue, lipid peroxidation, reactive oxygen species, superoxide dismutase activity and reduced glutathione were all increased by WPS exposure. Moreover, WPS exposure caused an increase in lung DNA damage index. We conclude that chronic nose-only WPS exposure impaired pulmonary function and induced enlargement of alveolar spaces and ducts, inflammation, oxidative stress and DNA damage. Our findings provide novel mechanistic elucidation for the long-term effects of WPS on the respiratory system.