Exposure to pollutants of ambient origin contributes significantly to the global disease burden (Cohen et al., 2017). Mounting evidence has demonstrated disproportionately high ambient PM2.5 and NO2 concentrations in the U.S. among nonwhite and low-income populations, potentially contributing to environmental health disparities (Bell and Ebisu, 2012; Clark et al., 2014; Morello-Frosch and Lopez, 2006). There is limited understanding of temporal trends and underlying causes of exposure inequalities (EIs), and whether residential building characteristics modify observed EIs. Further, while ambient pollutants have been linked to cardiometabolic disease in adulthood, few studies have documented the link between early-life ambient air pollution exposure and weight growth trajectories in early childhood- an informative step on the causal pathway between early life exposures and chronic outcomes. Using 1 km2 PM2.5 and NO2 predictions in Massachusetts and Census data, we quantify longitudinal EI between sociodemographic groups over a decade. We estimate AER for all Massachusetts residential parcels using publicly available data and assess whether accounting for AER exacerbates or ameliorates PM2.5 inequalities. We examine associations of weight growth trajectories in early childhood with residential prenatal and postnatal PM2.5 and distance to road (traffic) exposure in the Boston-based Children’s HealthWatch cohort. PM2.5 and NO2 inequalities increased across the study period in urban areas, and EIs were more pronounced for NO2 than PM2.5 and among racial/ethnic groups compared to other population subgroups. Analyzing EI longitudinally revealed that spatio-temporal shifts in air pollution, and not demographic distributions, contributed to exposure disparities. We found substantial variability in estimated AER across the state, and that PM2.5 EIs were magnified when AER was considered. Prenatal PM2.5 >9.5 µg/m3 predicted higher weight growth rates among females, but with an opposite direction of effect in males. This association was modified by birth weight and AER, with a stronger magnitude of effect in low-birthweight and higher-AER females. These findings underscore the importance of considering vulnerable communities and residential characteristics in ambient air pollution reduction strategies. This dissertation provides an opportunity to understand susceptible phenotypes and periods of potential intervention to reduce ambient air pollution impacts on cardiometabolic outcomes. / 2020-03-17T00:00:00Z

Contexte : La survie à long terme après la transplantation pulmonaire est compromise par le rejet chronique (chronic lung allograft dysfunction (CLAD)), une complication qui touche 50% des patients à 5 ans post-greffe. Le CLAD regroupe quatre phénotypes distincts caractérisés par une atteinte pulmonaire obstructive (Bronchiolitis obliterans syndrome (BOS)) ou restrictive (Restrictive allograft syndrome (RAS)), ou une combinaison des deux (phénotypes mixte et non défini). L’obésité est associée à une diminution de la fonction pulmonaire en raison de facteurs mécaniques, métaboliques et inflammatoires qui lui sont associés. Le gain de poids suite à la greffe pulmonaire est fréquent et parfois considérable, ce qui peut compromettre la fonction pulmonaire. Or, le lien entre le gain de poids post-greffe et la survenue des phénotypes du CLAD demeure inconnu. Objectifs : 1) Décrire les trajectoires pondérales post-greffe pulmonaire des patients ayant développé ou non l’un des quatre phénotypes du CLAD; 2) Déterminer si le statut pondéral à la greffe et la variation de poids et d’IMC après la greffe sont associés à la survenue des phénotypes du CLAD; 3) Examiner si les phénotypes du CLAD influencent la survie post-greffe. Méthodologie : Étude rétrospective des dossiers médicaux de patients ayant reçu une transplantation pulmonaire bilatérale au CHUM entre 2000 et 2020. En utilisant la classification de l’International Society for Heart and Lung Transplantation, les patients ont été classés parmi les cinq catégories suivantes : Absence ou présence de l’un des quatre phénotypes du CLAD. Résultats : Parmi les 579 patients inclus; 412 (71.1%) n’ont pas développé de CLAD, et 81 (14.0%), 20 (3.5%), 59 (10.2%) and 7 (1.2%) ont respectivement développé les phénotypes BOS, RAS, mixte et non-défini. Les trajectoires post-greffe de poids des patients qui développent une restriction pulmonaire (RAS, mixte et non-défini) se distinguent par des gains de poids plus importants. Une augmentation du poids (kg) (Hazard ratio [HR] : 1,04, IC 95% [1,01-1,08]; P = 0,008) et de l’IMC (kg/m2) (HR : 1,13, IC 95% [1,03-1,23]; P = 0,008) en post-greffe sont associés à une augmentation du risque de RAS. La survie post-greffe (années) est plus faible chez les patients ayant développé les phénotypes RAS (9,07 [IC 95% 7,43-10,70]), mixte (8,41 [IC 95% 6,56-10,25]) et non défini (9,99 [IC 95% 4,67-15,31]; p<0,001). Conclusion : Les liens entre le gain de poids post-greffe et la survenue des phénotypes restrictifs du CLAD doivent être clarifiées pour déterminer si une gestion optimale du poids préviendrait leur développement. / Background: Chronic lung allograft dysfunction (CLAD) is a common complication after lung transplant (LTx), affecting 50% of patients by five years post-LTx. It is associated with poor survival, limited to 1 to 5 years after CLAD diagnosis. Four CLAD clinical phenotypes have been defined: Bronchiolitis Obliterans Syndrome (BOS), Restrictive allograft syndrome (RAS), mixed and undefined phenotypes. Weight gain is commonly observed after LTx and may negatively impact lung function and post-LTx survival. Yet, the association between post-LTx weight gain and the development of CLAD and its phenotypes remains to be explored. Objectives: 1) To describe post-LTx weight trajectories of CLAD-free patients and patients who developed the various CLAD phenotypes; 2) To determine the associations between BMI at transplant, post-LTx variation of weight and BMI, and the risk of developing the various CLAD phenotypes and; 3) To examine whether the development of the CLAD phenotypes impacted post-LTx survival. Methods: This is a retrospective cohort study of patients who received a first bilateral LTx at the CHUM between 2000 and 2020. We extracted demographic, anthropometric, and clinical data from medical charts. Using the 2019 International Society for Heart and Lung Transplantation classification, patients were categorized among these five categories: CLAD-free or presence of one of the four CLAD phenotypes. Results: Our sample consisted of 579 patients; 412 (71.1%) remained CLAD-free, and 81 (14.0%), 20 (3.5%), 59 (10.2%), and 7 (1.2%) developed BOS, RAS, the mixed and the undefined phenotype, respectively. Weight trajectories showed that patients who developed restrictive CLAD (RAS, mixed and undefined) experienced weight gains of greater amplitude within the first five years post-LTx than CLAD-free patients and patients with BOS. An increase in weight (kg) (Hazard ratio [HR]: 1.04, 95% CI [1.01- 1.08]; P = 0.008) and BMI (kg/m2 ) (HR: 1.13, 95% CI [1.03-1.23]; P = 0.008) during post-LTx follow-up was associated with a greater risk of RAS. Worse survival (years) was seen in patients who developed the RAS (9.07 [95% CI 7.43-10.70]), mixed (8.41 [95% CI 6.56-10.25]), and undefined (9.99 [95% CI 4.67-15.31]; p<0.001) phenotypes. Conclusion: Future studies must clarify the associations between post-LTx weight gain and the onset of restrictive CLAD and whether it could be prevented with appropriate weight management strategies.