Regular inhaled corticosteroids in adult-onset asthma and the risk for future cancer: a population-based cohort study with proper person-time analysis

Victor C Kok, Jorng-Tzong Horng, Hsu-Kai Huang, Tsung-Ming Chao, Ya-Fang Hong, Victor C Kok, Jorng-Tzong Horng, Hsu-Kai Huang, Tsung-Ming Chao, Ya-Fang Hong

Abstract

Background: Recent studies have shown that inhaled corticosteroids (ICS) can exert anti-inflammatory effects for chronic airway diseases, and several observational studies suggest that they play a role as cancer chemopreventive agents, particularly against lung cancer. We aimed to examine whether regular ICS use was associated with a reduced risk for future malignancy in patients with newly diagnosed adult-onset asthma.

Methods: We used a population-based cohort study between 2001 and 2008 with appropriate person-time analysis. Participants were followed up until the first incident of cancer, death, or to the end of 2008. The Cox model was used to derive an adjusted hazard ratio (aHR) for cancer development. Kaplan-Meier cancer-free survival curves of two groups were compared.

Results: The exposed group of 2,117 regular ICS users and the nonexposed group of 17,732 non-ICS users were assembled. After 7,365 (mean, 3.5 years; standard deviation 2.1) and 73,789 (mean, 4.1 years; standard deviation 2.4) person-years of follow-up for the ICS users and the comparator group of non-ICS users, respectively, the aHR for overall cancer was nonsignificantly elevated at 1.33 with 95% confidence interval (CI), 1.00-1.76, P=0.0501. The Kaplan-Meier curves for overall cancer-free proportions of both groups were not significant (log-rank, P=0.065). Synergistic interaction of concurrent presence of regular ICS use was conducted using "ICS-negative and chronic obstructive pulmonary disease (COPD)-negative" as the reference. The aHR for the group of "ICS-positive, COPD-negative" did not reach statistically significant levels with aHR at 1.38 (95% CI, 0.53-3.56). There was a statistically significant synergistic interaction of concurrent presence of regular ICS use and COPD with aHR at 3.78 (95% CI, 2.10-6.81).

Conclusion: The protective effect of regular ICS use in the studied East Asian patients with adult-onset asthma was not detectable, contrary to reports of previous studies that ICS might prevent the occurrence of future cancer.

Keywords: NHIRD; immortal time bias; population-based study; retrospective cohort study; risk of cancer.

Figures

Figure 1
Figure 1
The study flow diagram showing the study design using a population-based retrospective cohort study and the assembling of the ICS cohort and the comparator non-ICS use cohort. Abbreviations: ICS, inhaled corticosteroids; LHID, Longitudinal Health Insurance Database.
Figure 2
Figure 2
Comparison of either overall cancer or lung cancer-specific Kaplan–Meier survival curves between ICS users and non-users or using different cut-offs of the ICS dosage. Notes: (A) Kaplan–Meier model for estimating the overall cancer-free proportions of ICS regular users and non-ICS users with the proper person-time approach. (B) Kaplan–Meier model for estimating the lung cancer-specific cancer-free proportions in ICS regular users versus non-ICS users with the proper person-time approach. (C) Kaplan–Meier model for estimating the lung cancer-free proportions by ICS dosage at 1,500 μg per day among ICS regular users with the proper person-time approach. (D) Kaplan–Meier model for estimating the lung cancer-free proportions by ICS dosage at 2,000 μg per day among ICS regular users with the proper person-time approach. Abbreviation: ICS, inhaled corticosteroids.

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