American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2024
Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-In-Human Trial.
Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. While cystic fibrosis is a multi-organ disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of CFTR mutations on CFTR function has allowed for the development of CFTR modulator therapies. ⋯ F/HN) has been developed for the treatment of cystic fibrosis. Promising preclinical results support the progression of this vector carrying a full-length CFTR transgene (BI 3720931) into a first-in-human clinical trial expected to begin in 2024. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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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.