Molecular patho-mechanism of biomass smoke induced chronic obstructive pulmonary disease among women: Population based- and in vitro exposure studies

Background: Biomass smoke (BMS) exposure is a risk factor for chronic obstructive pulmonary disease (COPD) in the same order of magnitude as tobacco smoking. The use of biomass fuel is closely linked to poverty and gender inequality. Predominance of BMS induced COPD (BMS-COPD) among non-smoking women in Asia and Africa is due to 4-6h/day exposure while cooking using biomass fuel. Since, 2019 we have initiated this project at Mysuru, India and till date screened 308 women exposed to BMS.

Objectives: Investigation of BMS exposure specific outcomes and clinical phenotypes amongst women to identify putative early biomarkers together with an understanding of the molecular patho-mechanisms.

Methods: The cross-sectional field study includes survey using a validated and structured questionnaire (general characteristics, premorbid conditions, BMS exposure etc.), spirometry, exhaled CO, FeNO, and blood O2 saturation levels among BMS- exposed and unexposed non-smoking women (n=1500-1600). We will perform cluster analysis to identify BMS exposure specific outcomes and clinical phenotypes.

In outcome specific sub-groups (eg. BMS-restriction, BMS-COPD, BMS-high-FeNO) we would examine sputum eosinophil and neutrophil counts, tuberculosis and gram staining compared to appropriate controls (n=25-30/subgroup; total=125-150) and high resolution computed tomography of lung. Differential cell counts, carboxyhemoglobin, C-reactive protein, and oxidative stress markers in blood would be assessed.

Concentrations of inflammatory and homeostatic cytokines/chemokines will be measured in sputum and serum.

In vitro BMS exposure studies using physiologically relevant alveolar mucosa model cultured at air liquid interface will be performed similar to the already assessed bronchial (normal and chronic bronchitis-like) models. Markers for molecular toxicity (eg oxidative stress, inflammation) at gene/protein level would be measured. Our research team include students, pulmonary physicians, field workers, toxicologists, and lung biologists along with scientific exchange visits.

Outcomes: The study will lead to the identification of BMS exposure specific respiratory outcomes and putative biomarkers associated with those outcomes. Our initial findings indicate restrictive lung function impairment, COPD, and elevated FeNO as plausible outcomes/biomarker. In vitro BMS exposure studies will provide insight of BMS induced molecular patho-mechanisms at different levels of respiratory tree.