As far as we know, this is the first cohort study to evaluate the association between long-term ozone exposure and lung function in young adults in China. Our results identified consistent associations between long-term ozone exposure and decreased lung functions such as FEF25, FEF50 and FEF25-75. In the subgroup analysis, we found that these associations were more prominent in female and BMI ≥ 24 kg/m2 population.
Few previous studies have estimated the impact of the exposure to ozone on small airways. Small airways are airways with a lumen diameter less than 2 mm during inspiration [30]. The small airways can become compromised before the proximal airways become obstructed and/or before any symptoms appear. It is considered to be a precursor to common respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma [31, 32]. Studies have shown that FEF25, FEF50, FEF75 and FEF25-75 are feasible indicators for early identification of small airway function[33]. Studies have found that ozone has adverse effects on lung function, and it is particularly important to investigate the effects of ozone on small airways of young people and to understand how ozone exposure affects the respiratory system at an early stage [34, 35]. In our study, we found that exposure to ambient ozone had statistically negative significant associations with three indicators of small airways function (FEF25, FEF50, FEF25-75). The results of previous studies were consistent with our study. A cross-sectional study of German adolescents found negative effects of ozone exposure on FEF25, FEF50 and FEF25-75 [36]. A recent cross-sectional study by Niu et al. using 50,991 participants from the China Pulmonary Health (CPH) study to explore whether ozone exposure impairs lung function found an independent association between long-term ozone exposure and impaired small airway function, each 1 SD (10.5 µg/m3) increase in ozone was associated with a 37.4 (95% CI: 24.8, 50.0) ml/s and 29.5 (95% CI: 19.6, 39.5) ml/s decrease in FEF50 and FEF25-75, respectively [9]. Our estimated effects of ozone exposure on FEF50 and FEF25-75 [ -146.3 (95% CI: -264.1,-28.4) ml/s and − 132.8 (95% CI: -239.2,-26.4) ml/s per IQR (8.9 µg/m3) increase in ozone] were stronger than the results of Niu et al. This discrepancy may be attributable to the higher ozone concentrations reported in our study (mean: 110.7 µg/m3 vs 90.1 µg/m3). Studies have shown that the lung function parameters of participants exposed to high concentrations decreased more rapidly than those exposed to low concentrations of ozone [37]. In addition, the ozone exposure time window of Niu et al. was average concentration of ozone from May to October, while our ozone concentration was the annual average concentration. Different exposure time may lead to different results. Difference in study populations may also partly explain the differences in results, which may vary by individual's physical condition, lifestyle, education, and activity pattern. It is difficult to directly compare our effect size with other studies, given the differences in study design, target participants and statistical methods. Nevertheless, our study provides new evidence that long-term exposure to ozone can impair small airways.
The mechanism by which ozone damages the small airways remains unclear. But animal studies revealed that ozone was more likely to damage central and terminal bronchi, and its effects on small airways last longer [38]. Additionally, ozone was inadequately cleared by the upper respiratory tract due to its low water solubility, it may remain in the respiratory system [39]. As a result, the lower respiratory tract accumulates the most of the inhaled ozone [39]. These may lead to long-term ozone hazards to the lower respiratory tract.
In the sex stratified analysis, we found female’s lung function appeared to be more susceptible to ozone than male. Females are reported to be more susceptible to inflammatory lung diseases caused by air pollution than males. A repeated measure study of children in Tianjin, China, showed an obvious sex difference, suggesting that ozone has a more prominent effect on the female group [40]. This is consistent with our results. Toxicological evidence suggested there are gender differences in lung impairment caused by ozone [41]. Fuentes et al. measured the mice for changes in lung function and inflammatory gene expression after gonadectomy in female and male mice exposed to ozone. They found that in female mice, gonadectomy reduced ozone-induced airway hyperresponsiveness (AHR) and lung interleukin 6 (IL-6) expression. Suggesting that female gonadal hormone levels could possibly mediate an inflammatory response in the lungs. However, the gonadectomy male mice showed higher expression of AHR and inflammatory genes compared to controls [42]. This may be one of the reasons for the sex differences in ozone induced lung inflammation and injury. This finding suggests that we should pay attention to the health effects of ozone, especially in females.
In the BMI stratified analysis, we found the association between ozone and lung function impairment was stronger for participants with BMI ≥ 24 kg/m2. Inconsistent with our results, a cross-sectional study by Doiron et al,. in the United found that being overweight or obese deteriorated the effects of air pollution on adult lung function [43]. The Seven Northeastern Chinese Cities (SNEC) study also found that obese individuals were more susceptible to the adverse effects of air pollutants on lung function [44]. Obesity may lead to significant changes in lung and chest wall mechanics with age due to excessive fat deposits in the diaphragm, chest wall and abdominal cavity [45, 46]. These mechanical changes can lead to restrictive ventilatory dysfunction by reducing lung and chest wall compliance [45]. Toxicological evidence found that ozone causes an increase in pulmonary resistance (RL) in obese mice, but not in lean mice [47]. In addition, ozone caused a greater increase in bronchoalveolar lavage neutrophils and AHR in obese mice compared with lean mice [47]. Our study further confirmed that the lung function of overweight and obese people was more vulnerable to ozone exposure. Overweight people, especially obese people, should pay more attention to self-protection.
This study had many strengths. The nature of the cohort allowed us to longitudinally investigate the relationship of ozone exposure on lung function. Furthermore, the 10 km×10 km grid data was used to estimate ozone exposure, which allowed us to overcome the spatial coverage limitations that typically arose with monitoring stations. Thirdly, the stratification analysis allowed us to understand sensitive populations more accurately.
However, this study also has some limitations. Firstly, our study population consisted of young adults from Shandong, China. The generalizability of our findings may be limited. Secondly, the exposure level of ozone was assigned to the participant’s fixed address. There was no information about the patterns of daily activities. Thirdly, self-reported questionnaires may have recall bias. Finally, even though we designed the questionnaire as detailed as possible, we still missed some information, such as data on parental factors that may confound the association, we cannot rule out residual confounding by these and other factors.