Abstract
The effect of air pollutants on mortality risk in patients with IPF is independent of their smoking status https://bit.ly/3rLUAva
Reply to T. Yasuma and co-workers:
We thank T. Yasuma and co-workers for their valuable comments on our paper describing the association between individual-level long-term concentrations of air pollutants at the residential addresses of patients with idiopathic pulmonary fibrosis (IPF) and mortality among them [1]. We agree that the release of nitrogen dioxide (NO2) or particulate matter in cigarette smoke is one of the considerations in interpreting our results. Thus, we stratified all patients into ever- and non-smokers according to their smoking status and analysed the effect of air pollutants on mortality risk in these patients using our health analysis models that included different sets of confounders (figure 1).
Among the 1114 patients with IPF, 846 (75.9%) were ever-smokers and 268 (24.1%) were non-smokers. Ever-smokers had a higher proportion of males (97.2% versus 25.0%; p<0.001) and higher baseline forced vital capacity (71.6% versus 67.0% predicted; p<0.001) than non-smokers. Furthermore, the former were less frequently treated with anti-inflammatory agents compared to the latter (38.4% versus 48.1%; p=0.004); however, there were no significant between-group differences in age (65.6 versus 65.9 years; p=0.659), body mass index (24.1 versus 24.2 kg·m−2; p=0.460), and diffusing capacity for carbon monoxide (57.1% versus 58.2% predicted; p=0.427). Furthermore, no significant between-group differences were found in the annual average concentrations of NO2 (22.4 versus 22.9 parts per billion; p=0.439) and particulate matter with a 50% cut-off aerodynamic diameter of 10 μm (PM10) (55.9 versus 58.2 μg·m−3; p=0.901). Moreover, there was no significant between-group difference in the median survival period (4.3 years versus 3.9 years; p=0.815).
Hazard ratios of mortality for NO2 were relatively similar between the ever- and non-smokers; furthermore, the confidence intervals of the two groups overlapped, indicating no significant difference between these two smoking statuses in models 1–4, adjusted for different sets of individual- or area-level variables (figure 1a). Hazard ratios of mortality for PM10 did not show significant between-group differences in all models (figure 1b).
Our subgroup analysis based on the smoking status of the patients with IPF did not show any differences between ever-smokers and non-smokers in the association between air pollutants and mortality risk. IPF mostly occurs in old males and ever-smokers [2]; furthermore, cigarette smoking is associated with IPF development [3, 4]. Meanwhile, the effect of smoking on the prognosis of IPF remains controversial [5, 6]. Smokers exhibit higher survival rates [5–7] and lower frequency of experiencing acute exacerbations [7, 8] than non-smokers. Kishaba et al. [7], in their study including 98 patients with IPF, reported that ever-smokers (n=66) exhibited a lower frequency of experiencing acute exacerbations (18.2% versus 50.0%; p<0.001) and a longer median survival period (26.3 versus 18.5 months; p<0.001) than never-smokers (n=32). Furthermore, Song et al. [8], in their study on 461 patients with IPF, found that smoking was a protective factor for acute exacerbations (HR 0.585, 95% CI 0.342–1.001; p=0.050). These findings may be attributable to the “healthy smoker” effect [9]: i.e. diseases are diagnosed early in smokers owing to their frequent hospital visits due to smoking-related respiratory symptoms, or people whose lungs are relatively resistant to the effects of smoking become smokers. Cigarette smoking releases particulate matter and free radicals, particularly reactive oxygen and nitrogen species [10]; therefore, exposure to cigarette smoke-derived pollutants may exacerbate air pollutant-related mortality in patients with IPF having a smoking history. However, our analysis did not show any differences in the association between air pollutants and IPF mortality after stratification by smoking status. Nevertheless, some points related to these findings require consideration. We could not explore the effects of current or passive smoking because limited data are available on the smoking history of the patients’ family members or neighbours. Moreover, the risk might be similar in former smokers and non-smokers owing to the ceased influx of air pollutants from cigarette smoke.
In conclusion, our results suggest that the effect of air pollutants on mortality risk in patients with IPF is independent of their smoking status. Well-designed prospective studies evaluating the interaction between smoking and air pollution are warranted to explore the effect of cigarette smoke-derived pollutants on mortality risk in patients with IPF.
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Footnotes
Conflict of interest: H-Y. Yoon has nothing to disclose.
Conflict of interest: S-Y. Kim has nothing to disclose.
Conflict of interest: O-J. Kim has nothing to disclose.
Conflict of interest: J.W. Song has nothing to disclose.
Support statement: This study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea, which is funded by the Ministry of Science and Technology (NRF-2019R1A2C2008541). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 19, 2021.
- Accepted July 20, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org