Ultrasound reference equations for diaphragm thickness and thickening fraction in healthy adults: protocol for an individual participant data meta-analysis.

INTRODUCTION: Sonographic assessment of diaphragm thickness at end-expiration (DTe) and diaphragm thickening fraction (DTF) is increasingly recognised as a readily available bedside method for evaluating diaphragm structure and function. However, currently available reference values for DTe and DTF vary substantially across populations and between sexes, limiting their clinical interpretability. We hypothesise that an individual participant data meta-analysis (IPD-MA) incorporating readily available anthropometric variables can be used to derive robust population-adjusted ultrasound reference values for DTe and DTF.

METHODS AND ANALYSIS: We will conduct a systematic review and IPD-MA of studies that measured right-sided diaphragm thickness in adult subjects using ultrasound. PubMed/MEDLINE, Embase, CENTRAL, Scopus, Web of Science Core Collection and LILACS/BVS will be searched from inception without language or publication-status restrictions. Anonymised individual participant data will be requested from study authors and harmonised according to a prespecified statistical analysis plan. The primary study aim is to develop prediction equations for DTF and DTe in quietly breathing healthy subjects using linear mixed-effects regression models and derive corresponding 95% reference limits. Model performance and generalisability will be evaluated using internal-external cross-validation. The study is currently at the planning stage-no definitive searches or other formal steps have been performed.

ETHICS AND DISSEMINATION: Ethical approval is not required for this study as it is based on secondary analysis of anonymised data from previously conducted studies. The findings will be submitted for publication in peer-reviewed journals and disseminated to relevant clinical and research stakeholders.

PROSPERO REGISTRATION NUMBER: CRD420261321987.