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A 2025 nationwide cohort study of more than 91,000 matched COPD patients found that long-term NAC use was associated with a lower overall cancer risk compared with non-NAC mucolytic use

4.4 Challenges and future directions Although significant progress has been made, key challenges remain, including genetic heterogeneity such as MTHFR variants complicating folate dosing, limited clinical validation of oxidative stress biomarkers for infertility, and reliance on animal models, highlighting the need for human RCTs with stratified cohorts (Vitagliano et al., 2021