Health effects of exposure to residential air pollution in patients with pulmonary arterial hypertension: a cohort study in Belgium

Abstract

We read with interest the paper by SOFIANOPOULOU et al. [1]. The authors have significantly contributed to highlighting the potential link between air pollution and health outcomes among pulmonary arterial hypertension (PAH) patients, by showing that exposure to particulate matter with an aerodynamic diameter smaller than 2.5 µm (PM 2.5) was significantly associated with transplant-free survival, and that traffic-related air pollution was correlated with the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk categories and haemodynamics at baseline. In this letter we would like to report our results exploring a potential association between exposure to residential PM 2.5 , PM 10 , nitrogen dioxide (NO 2), black carbon (BC) and traffic-related air pollution, and parameters related to prognosis, pathophysiology, progression and survival, in a cohort of PAH patients. Consecutive patients with a haemodynamically proven diagnosis of idiopathic/heritable/anorexigen-associated PAH between January 1995 and September 2018 and long-term follow-up (at least two follow-up visits) at University Hospitals of Leuven (median follow-up of 4.8 years) were included (figure 1a). To assess exposure to air pollution, each residential address at baseline visit was geocoded and linked with annual average levels of PM 2.5, PM 10 , NO 2 and BC (year 2015), estimated with land use regression models, as previously described [2]. In addition, traffic-related exposure was determined based on the distance between the residence and the nearest major roads. Multivariate Cox regression was applied to model the association with survival and adverse outcome including pulmonary hypertension-related hospitalisation or treatment with i.v./s.c. prostanoids or lung transplantation. We used multivariate linear regression modelling for 6-min walking distance (6MWD), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), cardiac index (CI), pulmonary vascular resistance (PVR) and circulating levels of C-reactive protein (CRP) at diagnosis. Multivariate ordinal logistic regression was used for New York Heart Association functional class (NYHA FC) and an abbreviated version of the ESC/ERS risk stratification [3]. We adjusted for age, gender, body mass index, smoking habits and level of obtained education. Additional adjustment for treatment with i.v./s.c. prostanoids and presence of bone morphogenetic protein receptor 2 mutations did not modify our results. The patient population was further stratified by 1) age (younger than and older or equal to 65 years at diagnosis), considering that elderly individuals have been exposed for a longer time and may experience greater risk of adverse outcome when exposed to air pollution, and 2) aetiology (only patients with idiopathic PAH and heritable PAH (IPAH and HPAH)). The associations are shown per increase of 10 µg·m −3 for PM 2.5 , PM 10 and NO 2 , per increase of 1 µg·m −3 for BC and per interquartile range increase (IQR, 1338 m) for the distance to major roads. To control for type I errors and to adjust for the overall false-positive rate, the p-values were Bonferroni-corrected, accounting for at least five multi-comparisons. A total of 211 patients (37% male) were studied with median age of 57 years. Patients displayed a severe haemodynamic profile and reduced exercise capacity (figure 1a). During the observation period, 29% of the patients were treated with i.v./s.c. prostanoids, 12% underwent a lung transplantation and 53% of the patients died (not mutually exclusive; figure 1a).