Sputum and nasal lavage lung-specific biomarkers in occupational exposure to nanomaterials; a mixed methods systematic review with meta-synthesis and meta-analysis.

The main route of occupational exposure to nanomaterials is inhalation. Sputum and nasal lavage are the most important biological samples to analyze lung-specific biomarkers in occupational exposure. So, the aim of this study is to conduct a mixed-method systematic review with meta-synthesis and meta-analysis for assessment of sputum and nasal lavage lung-specific biomarkers in occupational exposure to nanomaterials. This systematic review was conducted through the end of June 2025. Search was done using 'Biomarkers', 'Occupational exposure', 'Sputum', 'Nanomaterials' and 'Nasal Lavage' keywords on PubMed, Scopus and WOS. After the data extraction, qualitative data was used to draw a qualitative model. Comprehensive Meta-Analysis Software (CMA) was used for meta-analysis and the pooled mean concentration of the biomarkers were calculated by the random effect model (REM). Thirty-three studies were primarily achieved, and six studies were finally analyzed. Pro-inflammatory, inflammatory, oxidative stress, cancer/fibrosis and cardiovascular biomarkers were the most important biomarkers investigated. Inflammatory biomarkers including IL-6, IL-8, IL-1β and TNF-α were involved better than other inflammatory biomarkers in nasal, in occupational exposure to nanomaterials. The pooled mean concentration of sputum inflammatory biomarkers interleukin including IL-1β, IL-2, IL-4, IL5, IL-6, IL-8 was estimated 404.76, 196.9, 156.47, 219.26, 33.98 and 2344.42 pg/mL, respectively. Moreover, concentration of Nasal lavage inflammatory biomarkers interleukin including IL-1β, IL-6, and IL-8 were 1.438, 0.911 and 17.847 pg/mL, respectively. Due to a lack of information about OEL for nanomaterials, evaluating the occupational exposure to them through measuring the level of specific biomarkers, especially in the upper respiratory system, requires more studies.