The abnormal inflammatory responses due to the lung tissue damage and ineffective repair/resolution in response to the inhaled toxicants result in the pathological changes associated with chronic respiratory diseases. Investigation of such pathophysiological mechanisms provides the opportunity to develop the molecular phenotype-specific diagnostic assays and could help in designing the personalized medicine-based therapeutic approaches against these prevalent diseases. As the central hubs of cell metabolism and energetics, mitochondria integrate cellular responses and interorganellar signaling pathways to maintain cellular and extracellular redox status and the cellular senescence that dictate the lung tissue responses. Specifically, as observed in chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, the mitochondria-endoplasmic reticulum (ER) crosstalk is disrupted by the inhaled toxicants such as the combustible and emerging electronic nicotine-delivery system (ENDS) tobacco products. Thus, the recent research efforts have focused on understanding how the mitochondria-ER dysfunctions and oxidative stress responses can be targeted to improve inflammatory and cellular dysfunctions associated with these pathologic illnesses that are exacerbated by viral infections. The present review assesses the importance of these redox signaling and cellular senescence pathways that describe the role of mitochondria and ER on the development and function of lung epithelial responses, highlighting the cause and effect associations that reflect the disease pathogenesis and possible intervention strategies.

由于肺组织损伤和对吸入毒物的无效修复/消退而导致的异常炎症反应导致与慢性呼吸道疾病相关的病理变化。对此类病理生理机制的研究提供了开发分子表型特异性诊断测定的机会，并有助于设计针对这些流行疾病的基于个性化医学的治疗方法。作为细胞代谢和能量学的中心枢纽，线粒体整合细胞反应和细胞间信号传导途径，以维持细胞和细胞外氧化还原状态以及决定肺组织反应的细胞衰老。具体来说，正如在慢性阻塞性肺病（COPD）和肺纤维化中观察到的那样，线粒体-内质网（ER）串扰被吸入毒物（例如可燃和新兴电子尼古丁输送系统（ENDS）烟草产品）扰乱。因此，最近的研究工作集中在了解如何针对线粒体-ER功能障碍和氧化应激反应来改善与这些因病毒感染而加剧的病理性疾病相关的炎症和细胞功能障碍。本综述评估了这些氧化还原信号传导和细胞衰老途径的重要性，这些途径描述了线粒体和 ER 对肺上皮反应的发育和功能的作用，强调了反映疾病发病机制和可能的干预策略的因果关系。