INDOOR ENVIRONMENTAL QUALITY IN HEALTHCARE FACILITIES: BIOLOGICAL PATHWAYS AND MOLECULAR BIOMARKERS ASSOCIATED WITH PATIENT RECOVERY—A SYSTEMATIC REVIEW

Abstract

Indoor Environmental Quality (IEQ), including indoor air quality, thermal conditions, lighting, acoustics, and the visual environment, may influence physiological processes relevant to recovery. However, evidence linking architectural exposures to molecular and epigenetic outcomes in healthcare settings is dispersed across clinical, environmental-health, and controlled indoor studies, and the directness of this evidence varies considerably. This systematic review synthesizes and critically evaluates evidence on associations between IEQ exposures and molecular, neuroendocrine, inflammatory, oxidative-stress, circadian, and autonomic biomarkers relevant to patient recovery. A secondary objective is to distinguish direct healthcare evidence from mechanistic or indirect evidence derived from controlled indoor and non-hospital settings. The review was structured in accordance with PRISMA 2020 guidelines. A comprehensive search was conducted across PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library for studies published from January 2000 to February 2026. Eligibility was defined using a PICO/PECO framework. Due to substantial heterogeneity in populations and biomarker outcomes, findings were synthesized narratively. Risk of bias was evaluated using design-appropriate JBI critical appraisal instruments. Forty-eight studies were included. The most consistent biomarker evidence concerned indoor air quality, where particulate exposure and filtration studies reported changes in inflammatory and oxidative-stress markers (e.g., IL-6, CRP, 8-OHdG). Lighting interventions, particularly circadian-relevant exposures, were associated with altered expression of clock genes (BMAL1, PER1) and melatonin timing. Noise studies supported associations with cortisol and autonomic dysregulation (heart rate variability). Evidence linking thermal conditions to heat-shock pathways (HSP70/90) was predominantly mechanistic. Biophilic studies supported neuroendocrine stress reduction, while evidence for DNA methylation effects (e.g., BDNF, SLC25A10) was largely indirect and derived from green-space or prenatal exposure studies. The findings indicate that IEQ represents a potentially modifiable aspect of healthcare environments that may influence biological pathways associated with patient recovery. The available evidence is most consistent for inflammatory responses associated with air-quality exposures and circadian and neuroendocrine responses to lighting and noise. However, direct evidence that architectural or environmental interventions in healthcare settings induce changes in gene expression or epigenetic profiles remains limited. This evidence gap underscores the need for longitudinal, hospital-based studies integrating standardized IEQ measurements with transcriptomic and epigenomic analyses and clinically relevant recovery outcomes.