Risk Factors of Nonsteroidal Anti-inflammatory Drug-exacerbated Respiratory Disease: A Systematic Review and Meta-analysis of Observational Studies

Objectives: This meta-analysis aimed to identify the risk factors associated with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD), a chronic eosinophilic, inflammatory respiratory disorder characterized by hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs in patients with asthma and chronic rhinosinusitis with nasal polyps. Methods: We systematically reviewed 19 eligible studies and assessed their quality using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. Descriptive statistics and meta-analyses were conducted to estimate the pooled odds ratio and identify the risk factors associated with NERD. The analysis considered factors such as age, gender, body mass index, family history, smoking, and atopy. Results: Being female, having atopy, a history of smoking, and a family history of asthma were significant risk factors for NERD. Female gender was associated with hormonal differences and the effects of progesterone and estrogen on inflammation and bronchial hyperresponsiveness. Atopy increased the risk through heightened airway sensitivity, persistent inflammation, and increased mast cell activation. Smoking contributes to NERD by causing chronic airway inflammation, excess mucus production, airway remodeling, and decreased lung function. A family history of asthma indicated a genetic predisposition to bronchial hyperresponsiveness. Conclusions: The meta-analysis identified several risk factors associated with NERD, including being female, having atopy, a history of smoking, and a family history of asthma. These factors contribute to increased susceptibility and inflammation in patients with NERD.