The air pollution exposome in a Mumbai vulnerable population: impact on communicable and non-communicable diseases

Principal Investigator Professor Paolo Vineis, Imperial College London

Collaborators Dr.Nerges Mistry, The Foundation for Medical Research

Dr Harish Phuleria, IIT Bombay

Dr Augustin Scalbert, InternationalAgency for Research on Cancer

Dr Ka Lai, Hong Kong Baptist University

Professor DavidPhillips King's College London
Dr Valentina Gallo, Queen Mary, University of London

Professor Nicole Probst-Hensch, Swiss Tropical & Public Health Institute"

Project team Dr. PurvaBhatter, Dr. Anirvan Chatterjee, Dr. Kayzad Nilgiriwala, Mr. Rahul Upadhyay

Funder Submitted to Medical Research Council, UK (Under Review)

Duration September 2014 - September 2016 (Expected)

Budget Rs.65.94 Lakhs

Executive summary

Indian slums have heavily contaminated air (because of multiple sources including small factories, dumping sites, indoor use of cooking fuels such as dung and coal, tobacco smoking, incense burning and vehicle exhaust, among others). To investigate the overall health implications of these exposures, i.e. the impact on both communicable and non-communicable diseases, an exposome approach based on omic technologies is proposed. The study will provide key information to set up a larger investigation to improve understanding of how indoor and outdoor air pollution impact on the risk of disease in India, in particular tuberculosis and its co-morbidity with type 2 diabetes mellitus (T2DM). Both TB and T2DM are highly prevalent conditions in low- and middle-income countries and particularly in Asia.

We hypothesize that the internal biochemistry of human body can be changed by heavy exposure to biological and chemical air pollutants, and those changes can directly lead to a disease phenotype or may facilitate the impact of other agents such as M. tuberculosis. T2DM is a metabolic disease in which a systemic failure in metabolic regulation occurs;however the causal agents for the initiation of T2DM remain elusive. A large proportion of the population in slums in Indiahas latent TB and changes in the internal biochemistry can trigger the conversion of latent TB into an active disease. Thus,there is a need tosystematically study exposures, changes in internal biochemistry and onset of T2DM and TB insusceptible populations. Comprehensive profiling of small molecules in blood (metabolomics) would provide a global viewof internal biochemistry as well as the compounds that originate from the exposures. Exposure-associated changes thatare also associated with disease can be identified and proposed as mechanisms facilitating the onset of T2DM and TB insusceptible populations.

Over 55% of the Mumbai's population resides in slums both notified and non-notified. Pulmonary TB is highly endemic witha prevalence of 300/100,000 and high levels of all forms of drug resistance have been recorded. Simultaneously the city'sdiabetes burden is reported to be greater than for the country as a whole. Thus the slum population faces the dual burdenof both communicable and non-communicable diseases. The main aim of the present study is to identify specificbiomarkers for different air pollutants, and the biochemical pathways that are affected by the exposure to air pollution, invulnerable populations residing in two urban Mumbai slums. In a larger study, the association of both exposures andpathways with the onset of T2DM and TB will be subsequently investigated. To investigate the complex interactionsbetween air pollution, TB and diabetes, biospecimens from subjects who are exposed to high levels of pollution fromdifferent sources in typical Indian slums will be analyzed using metabolomic and adductomic methodologies, within anagnostic "exposome" project. Two-hundred subjects from a highly exposed area and 200 from a lower exposed area will beinvestigated. Based on the study, a ranking of the air pollutants will be proposed according to their impact on the pathwaysfor the two diseases. Plasma/serum and urine samples will be analysed by high resolution mass spectrometry coupled toUltra Performance Liquid Chromatography. Metabolic features characterizing the different groups of subjects according totheir levels of exposure to air pollutants will be identified by multivariate statistics. Adductomics involves both an untargetedinvestigation of the internal exposome based on the measurement of protein adducts, and a targeted approach based onthe investigation of defined external sources of exposure.

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