Association between Outdoor Air Pollution Exposure and Handgrip Strength: Findings from the French CONSTANCES Study

Mohammad Javad Zare Sakhvidi,1 Antoine Lafontaine,1 Jun Yang,1 Emeline Lequy,2 Fanny Artaud,3 Marianne Canonico,3 Anna Ozguler,2 Danielle Vienneau,4,5 Marie Zins,2 and Bénédicte Jacquemin1 Université de Rennes, Institut national de la santé et de la recherche médicale (Inserm, National Institute of Health & Medical Research), Ecole des hautes études en santé publique (EHESP), Irset (Institut de recherche en santé, environnement et travail)—UMR_S 1085, Rennes, France Université de Paris, Unité UMS 011 “Cohortes en Population,” Inserm, Université Paris Saclay, Université de Versailles-Saint-Quentin-en-Yvelines (UVSQ), Paris, France Paris-Saclay University, UVSQ, Université Paris-Sud, Inserm, Gustave Roussy, “Exposome and Heredity Team,” Centre de recherche en Epidémiologie et Santé des Populations, Villejuif, France Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland


Introduction
Hand grip strength (HGS) is a powerful predictor of disability, morbidity, and mortality in middle-age and elderly subjects. Available evidence on the link between poor HGS and cigarette smoking 1 suggests the potential for a similar association for air pollution due to shared mechanisms. 2 Furthermore, evidence of a reduction in dopamine production in the brain following exposure to diesel exhaust particles 3 supports the hypothesized association between air pollution and HGS. We aimed to evaluate whether exposure to outdoor air pollution is associated with poor HGS in a large study on adults from all over mainland France.

Materials and Methods
We used data on 51,845 out of 85,612 participants over 45 y old from the enrollment phase of the French CONSTANCES study until December 2017 (approved by the institutional review board of the Inserm: institutional review board de l'Inserm IRB00003888, IORG0003254, FWA00005831). 4 These participants were asked to attend physical and cognitive assessments, including three repeated HGS measurements in standing position for the dominant hand with a JAMAR portable Hand Dynamometer. Because a sex difference has been reported for HGS values, the sex-specific z-score of the maximum measurement (HGS max ) was used as the outcome. Annual mean exposure for the year 2010 was assigned from a hybrid land-use regression model (LUR) at a fine spatial resolution (100 × 100 m) for western Europe for particulate matter (PM) with an aerodynamic diameter <2:5 lm (PM 2:5 ), black carbon (BC), and nitrogen dioxide (NO 2 ) (see supporting information: https://github. com/mjzare/AP_HGS_CONSTANCES/blob/main/Air_pollution_ HGS_CONSTANCES_Supporting_Information_20220326.docx? raw=true). 5 The estimated concentrations for 2010 were assigned to each participant's residential address at enrollment; participants' residential history before enrollment could not be accounted for in the exposure assessment.
We used linear mixed models with a random intercept per recruitment center separately for each sex (and both sexes together for the interaction test) and reported adjusted regression coefficients (b) and 95% confidence intervals (CIs) for each pollutant separately. We used multiple imputed data sets for missing covariates; exposures and outcome were neither imputed nor included in the imputation process. We defined two models: a) model 1 adjusted for covariates selected based on univariate analysis and b) model 2 additionally adjusted for possible mediators. For sensitivity analysis, we included women and men together in the same single-pollutant model (for models 1 and 2). We also tested the interaction by sex with inclusion of an interaction term between each pollutant and sex and checked the interaction term's p-value. We conducted stratified analyses based on selected personal and contextual variables and conducted additional analyses using the zscores of average HGS (HGS average ). For these variables, we tested the interaction by including an interaction term between each pollutant and variable of interest and checked the significance of interaction by the likelihood-ratio test p-value.
Significant negative associations were found between exposure to all three pollutants (PM 2:5 , BC, and NO 2 ) and HGS max in both men and women ( Table 1). The associations with BC and NO 2 were weaker for women in comparison with those for men. Further adjustment for potential mediators in model 2 did not substantially change the size and direction of the estimates from model 1. Exposureresponse analyses showed a linear and monotonic decrease in HGS max with increasing exposure to all pollutants in men (likelihoodratio test p-values were as follows: 0.12 for PM 2:5 ; 0.76 for BC; 0.74 for NO 2 ). The findings for women suggested nonlinear trends for NO 2 , using models with spline term (likelihood-ratio test p-values: 0.67 for PM 2:5 ; 0.24 for BC; 0.03 for NO 2 ).
A significant interaction between pollutant and sex was found for all pollutants (Table 1). For men living in urban or suburban areas, all three air pollutants were significantly associated with poorer HGS max . We found stronger associations in men age 65 y and older, with low and middle education, and nonsmokers in comparison with the rest of the study participants. For women, we found no significant interaction with age. The findings were similar using average HGS (Table 2).

Discussion
Our study adds to the scarce literature on the association between air pollution and HGS. 2 We found that an increase in PM 2:5 , BC, Address correspondence to Bénédicte Jacquemin. Email: benedicte.jacquemin@ inserm.fr The authors declare they have nothing to disclose. Note to readers with disabilities: EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact ehpsubmissions@niehs.nih.gov. Our staff will work with you to assess and meet your accessibility needs within 3 working days. and NO 2 was associated with weaker HGS; estimates were higher in men for NO 2 and BC, but not for PM 2:5 . Because PM 2:5 contains many different hazardous components that cannot be distinguished by using the total mass of PM 2:5 , the effect of all these components may affect HGS differently than specific components such as BC. Considering the previously reported hazard ratio of 1.2 (95% CI: 1.17, 1.23) for all-cause mortality per 5 kg lower HGS, 6 estimated effect sizes for an interquartile range increase in the air pollutants included in our study would be roughly equivalent to 2.2%-2.8% and 1.1%-1.6% increase in all-cause mortality in men and women, respectively (from Celis-Morales et al. 6 study estimates). Direct evidence to compare our findings for BC and NO 2 is not available; however, considering a degree of analogy between air pollution and exposure to cigarette smoke, pesticides, solvents, and heavy metals (shares some chemical components) and reported associations for exposure to these compounds and impaired HGS, 1,7 the observed associations in our study seem physiologically plausible. Sex differences have been reported in the risk factors of the HGS decline, and air pollution epidemiology studies also justify our findings on men and women. 8,9 A higher level of deprivation in rural areas could be an explanation for our findings on women residing in rural areas. 10 The study benefits from a large sample size, good spatial variation in exposure from a validated LUR model, the inclusion of a wide range of personal and area-level covariates, and from being the first to provide results on BC and NO 2 . However, the cross-sectional study design limited us to drawing a cause-effect association. Exposure allocation with the LUR models from a single year assigned to the residential address at the time of enrollment may have introduced some nondifferential exposure misclassification. We excluded participants Table 1. Association between exposure to outdoor air pollution and maximum HGS in the French CONSTANCES study participants (n = 51,845).
without suitable HGS data, which could potentially result in healthier and more resilient retained participants. Even with these limitations, we found a significant association between air pollution exposure and lower HGS, which highlights the importance of evaluating frailty in relation to air pollution.