American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2024
ReviewPremalignant Progression in the Lung: Knowledge Gaps and Novel Opportunities for Interception of Non-Small Cell Lung Cancer. An Official American Thoracic Society Research Statement.
Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. ⋯ Results: This research statement identifies significant gaps in knowledge and proposes potential research questions aimed at expanding our understanding of the mechanisms underlying the progression of premalignant lung lesions to lung cancer in an effort to explore potential innovative modalities to intercept lung cancer at its nascent stages. Conclusions: The identified gaps in knowledge about the biological mechanisms of premalignant progression in the lung, together with ongoing challenges in screening, detection, and early intervention, highlight the critical need to prioritize research in this domain. Such focused investigations are essential to devise effective preventive strategies that may ultimately decrease lung cancer incidence and improve patient outcomes.
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Am. J. Respir. Crit. Care Med. · Sep 2024
Susceptible Young Adults and Development of COPD Later in Life.
Rationale: Chronic obstructive pulmonary disease (COPD) has its origin in early life, and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposes a predisease state termed "pre-COPD." Objectives: We tested the hypothesis that susceptible young adults identified with chronic bronchitis and subtle lung function impairment will develop COPD later in life. Methods: We followed random individuals without COPD ages 20-50 years from two population-based cohorts from different smoking eras-the Copenhagen General Population Study from 2003 (N = 5,497) and the Copenhagen City Heart Study from 1976-1978 (N = 2,609)-for 10 and 25 years, for the development of COPD (FEV1/FVC <0.70) and COPD GOLD Stages 2-4 (additionally, FEV1 <80% predicted). Measurements and Main Results: After 10 years, 28% developed COPD and 13% developed COPD GOLD Stages 2-4 in individuals susceptible to COPD, compared with 8% and 1% in those without any susceptibility to COPD. ⋯ Compared with those without susceptibility to COPD, multivariable-adjusted odds ratios in those susceptible to COPD were 3.42 (95% confidence interval: 2.78-4.21) for COPD and 10.1 (6.77-15.2) for COPD GOLD Stages 2-4 after 10 years and were 1.54 (1.23-1.93) and 2.12 (1.64-2.73) after 25 years. The ability of a COPD risk score-consisting of the state of susceptibility to COPD with smoking and asthma as risk factors-to predict COPD later in life was high. Conclusions: Our study suggests the existence of a predisease state of COPD, which can be used for early identification of susceptible individuals at risk for COPD later in life.