Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts.

BACKGROUND: Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults. OBJECTIVE: We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis. METHODS: Participants with rhinitis from 2 multicenter European cohorts (Epidemiological Study on the Genetics and Environment on Asthma and the European Community Respiratory Health Survey) were included. Annual exposure to NO2, PM10, PM2.5, and PMcoarse (calculated by subtracting PM2.5 from PM10) was estimated using land-use regression models derived from the European Study of Cohorts for Air Pollution Effects project, at the participants' residential address. The score of rhinitis severity (range, 0-12), based on intensity of disturbance due to symptoms reported by questionnaire, was categorized into low (reference), mild, moderate, and high severity. Polytomous logistic regression models with a random intercept for city were used. RESULTS: A total of 1408 adults with rhinitis (mean age, 52 years; 46% men, 81% from the European Community Respiratory Health Survey) were included. The median (1st quartile-3rd quartile) score of rhinitis severity was 4 (2-6). Higher exposure to PM10 was associated with higher rhinitis severity (adjusted odds ratio [95% CI] for a 10 µg/m3 increase in PM10: for mild: 1.20 [0.88-1.64], moderate: 1.53 [1.07-2.19], and high severity: 1.72 [1.23-2.41]). Similar results were found for PM2.5. Higher exposure to NO2 was associated with an increased severity of rhinitis, with similar adjusted odds ratios whatever the level of severity. Adjusted odds ratios were higher among participants without allergic sensitization than among those with, but interaction was found only for NO2. CONCLUSIONS: People with rhinitis who live in areas with higher levels of pollution are more likely to report more severe nasal symptoms. Further work is required to elucidate the mechanisms of this association.

Influence of exposure assessment methods on associations between long-term exposure to outdoor fine particulate matter and risk of cancer in the French cohort Gazel.

BACKGROUND: Many studies investigated the relationship between outdoor fine particulate matter (PM2.5) and cancer. While they generally indicated positive associations, results have not been fully consistent, possibly because of the diversity of methods used to assess exposure. OBJECTIVES: To investigate how using different PM2.5 exposure assessment methods influences risk estimates in the large French general population-based Gazel cohort (20,625 participants at enrollment) with a 26-year follow-up with complete residential histories. METHODS: We focused on two cancer incidence outcomes: all-sites combined and lung. We used two distinct exposure assessment methods: a western European land use regression (LUR), and a chemistry-dispersion model (Gazel-Air) for France, each with a time series ≥20-years annual concentrations. Spearman correlation coefficient between the two estimates of PM2.5 was 0.71 across all person-years; the LUR tended to provide higher exposures. We used extended Cox models with attained age as time-scale and time-dependent cumulative exposures, adjusting for a set of confounders including sex and smoking, to derive hazard ratios (HRs) and their 95% confidence interval, implementing a 10-year lag between exposure and incidence/censoring. RESULTS: We obtained similar two-piece linear associations for all-sites cancer (3711 cases), with a first slope of HRs of 1.53 (1.24-1.88) and 1.43 (1.19-1.73) for one IQR increase of cumulative PM2.5 exposure for the LUR and the Gazel-Air models respectively, followed by a plateau at around 1.5 for both exposure assessments. For lung cancer (349 cases), the HRs from the two exposure models were less similar, with largely overlapping confidence limits. CONCLUSION: Our findings using long-term exposure estimates from two distinct exposure assessment methods corroborate the association between air pollution and cancer risk.

Duration of nivolumab for pretreated, advanced non-small-cell lung cancer.

BACKGROUND: A standard of care for pretreated, advanced non-small-cell lung cancers (NSCLCs), nivolumab has demonstrated long-term benefit when administered for 2 years. We aimed to better discern an optimized administration duration by retrospectively analyzing real-life long-term efficacy in a prospective cohort. METHODS: All nivolumab-treated adults with advanced NSCLCs (01/09/2015 to 30/09/2016) from nine French centers were eligible. On 31/12/2018, patients who are alive ≥ 2 years after starting nivolumab were defined as long-term survivors (LTSs) and were divided into three nivolumab treatment groups: <2, 2, or > 2 years. Co-primary endpoints were LTSs' progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up was 32 months (95% CI, 31.0 to 34.0). The 3-year OS rate for the 259 cohort patients was 16.6%. Among them, 65 were LTSs: 47 treated < 2 years, 7 for 2 years, and 11 > 2 years. Their respective characteristics were: median age: 59, 52, and 58 years; smoking history: 92.9, 100, and 100%; adenocarcinomas: 66, 57.1, and 54.5%. LTSs' median (m)PFS was 28.4 months; mOS was not reached. LTSs' objective response rate was 61.6%. mOS was 32.7 months for those treated < 2 years and not reached for the others. The > 2-year group's 3-year OS was longer. Twenty-eight LTSs experienced no disease progression; 7 had durable complete responses. However, LTSs had more frequent and more severe adverse events. CONCLUSION: In real-life, prolonged nivolumab use provided long-term benefit with 16.6% 3-year OS and 25% LTSs. Survival tended to be prolonged with nivolumab continued beyond 2 years. Prospective randomized trials with adequate design are needed.

The Role of Socioeconomic Status in the Association of Lung Function and Air Pollution-A Pooled Analysis of Three Adult ESCAPE Cohorts.

Ambient air pollution is a leading environmental risk factor and its broad spectrum of adverse health effects includes a decrease in lung function. Socioeconomic status (SES) is known to be associated with both air pollution exposure and respiratory function. This study assesses the role of SES either as confounder or effect modifier of the association between ambient air pollution and lung function. Cross-sectional data from three European multicenter adult cohorts were pooled to assess factors associated with lung function, including annual means of home outdoor NO2. Pre-bronchodilator lung function was measured according to the ATS-criteria. Multiple mixed linear models with random intercepts for study areas were used. Three different factors (education, occupation and neighborhood unemployment rate) were considered to represent SES. NO2 exposure was negatively associated with lung function. Occupation and neighborhood unemployment rates were not associated with lung function. However, the inclusion of the SES-variable education improved the models and the air pollution-lung function associations got slightly stronger. NO2 associations with lung function were not substantially modified by SES-variables. In this multicenter European study we could show that SES plays a role as a confounder in the association of ambient NO2 exposure with lung function.

Association between air pollution and rhinitis incidence in two European cohorts.

BACKGROUND: The association between air pollution and rhinitis is not well established. AIM: The aim of this longitudinal analysis was to study the association between modeled air pollution at the subjects' home addresses and self-reported incidence of rhinitis. METHODS: We used data from 1533 adults from two multicentre cohorts' studies (EGEA and ECRHS). Rhinitis incidence was defined as reporting rhinitis at the second follow-up (2011 to 2013) but not at the first follow-up (2000 to 2007). Annual exposure to NO2, PM10 and PM2.5 at the participants' home addresses was estimated using land-use regression models developed by the ESCAPE project for the 2009-2010 period. Incidence rate ratios (IRR) were computed using Poisson regression. Pooled analysis, analyses by city and meta-regression testing for heterogeneity were carried out. RESULTS: No association between long-term air pollution exposure and incidence of rhinitis was found (adjusted IRR (aIRR) for an increase of 10 µg·m-3 of NO2: 1.00 [0.91-1.09], for an increase of 5 µg·m-3 of PM2.5: 0.88 [0.73-1.04]). Similar results were found in the two-pollutant model (aIRR for an increase of 10 µg·m-3 of NO2: 1.01 [0.87-1.17], for an increase of 5 µg·m-3 of PM2.5: 0.87 [0.68-1.08]). Results differed depending on the city, but no regional pattern emerged for any of the pollutants. CONCLUSIONS: This study did not find any consistent evidence of an association between long-term air pollution and incident rhinitis.

Socioeconomic position and outdoor nitrogen dioxide (NO2) exposure in Western Europe: A multi-city analysis.

BACKGROUND: Inconsistent associations between socioeconomic position (SEP) and outdoor air pollution have been reported in Europe, but methodological differences prevent any direct between-study comparison. OBJECTIVES: Assess and compare the association between SEP and outdoor nitrogen dioxide (NO2) exposure as a marker of traffic exhaust, in 16 cities from eight Western European countries. METHODS: Three SEP indicators, two defined at individual-level (education and occupation) and one at neighborhood-level (unemployment rate) were assessed in three European multicenter cohorts. NO2 annual concentration exposure was estimated at participants' addresses with land use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE; http://www.escapeproject.eu/). Pooled and city-specific linear regressions were used to analyze associations between each SEP indicator and NO2. Heterogeneity across cities was assessed using the Higgins' I-squared test (I2). RESULTS: The study population included 5692 participants. Pooled analysis showed that participants with lower individual-SEP were less exposed to NO2. Conversely, participants living in neighborhoods with higher unemployment rate were more exposed. City-specific results exhibited strong heterogeneity (I2>76% for the three SEP indicators) resulting in variation of the individual- and neighborhood-SEP patterns of NO2 exposure across cities. The coefficients from a model that included both individual- and neighborhood-SEP indicators were similar to the unadjusted coefficients, suggesting independent associations. CONCLUSIONS: Our study showed for the first time using homogenized measures of outcome and exposure across 16 cities the important heterogeneity regarding the association between SEP and NO2 in Western Europe. Importantly, our results showed that individual- and neighborhood-SEP indicators capture different aspects of the association between SEP and exposure to air pollution, stressing the importance of considering both in air pollution health effects studies.

Susceptibility Factors Relevant for the Association Between Long-Term Air Pollution Exposure and Incident Asthma.

In this review, we identified 15 studies in children and 10 studies in adults that assessed the association between long-term exposure to air pollution and incident asthma and that conducted stratified analyses to explore potential susceptibility factors. Overall, adult never-/former smokers seem to be at higher risk of incident asthma due to air pollution. Children without atopy and children from low socioeconomic status families also seem to be at higher risk of incident asthma due to air pollution. While interaction between air pollution and genes involved in the response to oxidative stress pathways have been explored, results are somewhat inconsistent and in need of replication. To evaluate interactions, large sample sizes are necessary, and much more research, including data pooling from existing studies, is needed to further explore susceptibility factors for asthma incidence due to long-term air pollution exposure.

Characterization of Rhinitis According to the Asthma Status in Adults Using an Unsupervised Approach in the EGEA Study.

BACKGROUND: The classification of rhinitis in adults is missing in epidemiological studies. OBJECTIVE: To identify phenotypes of adult rhinitis using an unsupervised approach (data-driven) compared with a classical hypothesis-driven approach. METHODS: 983 adults of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) were studied. Self-reported symptoms related to rhinitis such as nasal symptoms, hay fever, sinusitis, conjunctivitis, and sensitivities to different triggers (dust, animals, hay/flowers, cold air…) were used. Allergic sensitization was defined by at least one positive skin prick test to 12 aeroallergens. Mixture model was used to cluster participants, independently in those without (Asthma-, n = 582) and with asthma (Asthma+, n = 401). RESULTS: Three clusters were identified in both groups: 1) Cluster A (55% in Asthma-, and 22% in Asthma+) mainly characterized by the absence of nasal symptoms, 2) Cluster B (23% in Asthma-, 36% in Asthma+) mainly characterized by nasal symptoms all over the year, sinusitis and a low prevalence of positive skin prick tests, and 3) Cluster C (22% in Asthma-, 42% in Asthma+) mainly characterized by a peak of nasal symptoms during spring, a high prevalence of positive skin prick tests and a high report of hay fever, allergic rhinitis and conjunctivitis. The highest rate of polysensitization (80%) was found in participants with comorbid asthma and allergic rhinitis. CONCLUSION: This cluster analysis highlighted three clusters of rhinitis with similar characteristics than those known by clinicians but differing according to allergic sensitization, and this whatever the asthma status. These clusters could be easily rebuilt using a small number of variables.