Lingappan Krithika, Sundar Isaac Kirubakaran, Prakash Y S, Redente Elizabeth F, Sin Don D, Han MeiLan K, Lahm Tim, Krymskaya Vera P, Kotton Darrell N, Kulkarni Hrishikesh S, Jain Raksha, Königshoff Melanie, Eghbali Mansoureh, Anguera Montserrat, Arnold Arthur, Silveyra Patricia, DeMeo Dawn L
Am J Respir Crit Care Med. 2025 Aug;211(8):1346-1368. doi: 10.1164/rccm.202506-1361ST.
Pulmonary diseases have sex-specific predilections across the lifespan. The rigor of preclinical research is paramount to ensure the reproducibility and applicability of findings to clinical studies. The overarching goal was to identify current research gaps and the need for consideration of sex as a biological variable (SABV) in preclinical pulmonary research. The objective was to provide a roadmap and the best standards to incorporate and investigate the role of biological sex in preclinical models of lung diseases. A multidisciplinary working group of 17 international investigators from the American Thoracic Society Assembly on Allergy, Immunology, and Inflammation, external content experts, and researchers engaged in lung basic and translational research. They reviewed the literature, identified critical knowledge gaps, and provided recommendations. The research statement provides an updated summary of the currently available evidence on the standards of SABV research in preclinical models and then offers specific research recommendations focused on the needs of researchers in the pulmonary field. The statement identifies knowledge gaps and develops guidance for experimental design and key considerations for incorporating SABV in two major topic areas: ) ; and ) models. Furthermore, the group developed a checklist to guide researchers in including SABV in preclinical studies. This statement provides a roadmap for the investigation of SABV in preclinical models. This will increase the applicability of findings to both sexes, uncover sex-biased mechanisms in lung diseases, and identify novel therapeutic targets.
肺部疾病在整个生命周期中存在性别特异性倾向。临床前研究的严谨性对于确保研究结果在临床研究中的可重复性和适用性至关重要。总体目标是确定当前的研究差距，以及在临床前肺部研究中考虑将性别作为生物学变量（SABV）的必要性。目的是提供一个路线图和最佳标准，以纳入并研究生物学性别在肺部疾病临床前模型中的作用。一个由来自美国胸科学会过敏、免疫学和炎症大会的17名国际研究人员、外部内容专家以及从事肺部基础和转化研究的人员组成的多学科工作组。他们查阅了文献，确定了关键的知识差距，并提出了建议。该研究声明提供了关于临床前模型中SABV研究标准的现有证据的最新总结，然后针对肺部领域研究人员的需求提出了具体的研究建议。该声明确定了知识差距，并为实验设计以及在两个主要主题领域纳入SABV的关键考虑因素制定了指导方针：（1）；以及（2）模型。此外，该小组制定了一份清单，以指导研究人员在临床前研究中纳入SABV。本声明为在临床前模型中研究SABV提供了路线图。这将提高研究结果对两性的适用性，揭示肺部疾病中的性别偏见机制，并确定新的治疗靶点。
