American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Dec 2024
Meta AnalysisHypnotics on Obstructive Sleep Apnea Severity and Endotypes: A Systematic Review and Meta-Analysis.
Rationale: Low arousal threshold and poor muscle responsiveness are common determinants of obstructive sleep apnea (OSA). Hypnotics were hypothesized as an alternative OSA treatment via raising the arousal threshold and possibly genioglossus responsiveness. Objectives: To examine the effect of common hypnotics on arousal threshold, OSA severity, and genioglossus responsiveness. ⋯ However, people with very low arousal threshold or those who exhibited a 0-25% arousal threshold increase from placebo experienced the greatest, yet still modest, post-treatment AHI reductions (∼10%). Hypnotics did not affect genioglossus responsiveness (high QoE). Conclusions: Further research testing or clinical use of hypnotics as OSA alternative treatments should be discouraged, unless in the presence of comorbid insomnia or as part of combination therapy in individuals with very low arousal threshold.
-
Am. J. Respir. Crit. Care Med. · Dec 2024
Development, Progression, and Mortality of Suspected Interstitial Lung Disease in COPDGene.
Rationale: Some with interstitial lung abnormalities (ILA) are suspected to have interstitial lung disease (ILD), a subgroup with adverse outcomes. Rates of development and progression of suspected ILD and their effect on mortality are unknown. Objectives: To determine rates of development, progression, and mortality in those with suspected ILD and assess effects of individual ILD and progression criteria. ⋯ Mortality rates were 31%, 50%, 45%, and 45%, respectively; those with only CT progression had worse mortality than those with ILA (HR, 2.6; P = 0.005). At 5-year follow-up, incident ILD occurred in 148/4,842 participants without prevalent ILD (5.5/1,000 person-years) and had worse mortality than ILA (HR, 2.4; P < 0.001). Conclusion: Rates of mortality and progression are high among those with suspected ILD in COPDGene; fibrosis and radiologic progression are important predictors of mortality.
-
Am. J. Respir. Crit. Care Med. · Dec 2024
ReviewLentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-In-Human Trial.
Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Although CF is a multiorgan 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. ⋯ A third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV. F/HN) has been developed for the treatment of CF. 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.
-
Am. J. Respir. Crit. Care Med. · Dec 2024
Progressive Early Interstitial Lung Abnormalities in Persons At-Risk for Familial Pulmonary Fibrosis: A Prospective Cohort Study.
Rationale: Relatives of patients with familial pulmonary fibrosis (FPF) are at increased risk to develop FPF. Interstitial lung abnormalities (ILAs) are a radiologic biomarker of subclinical disease, but the implications of very mild abnormalities remain unclear. Objectives: To quantify the progression risk among FPF relatives with abnormalities below the threshold for ILAs as described by the Fleischner Society and to describe the characteristics of participants with new or progressive ILAs during observation. ⋯ During a mean follow-up period of 6.2 ± 3.0 years, progression occurred among 31 of 211 (15%) of those with absence of ILAs at enrollment, 32 of 49 (65%) of those with mild ILAs, and 10 of 13 (77%) of those with moderate ILAs. Subjects with mild ILAs had 9.15 (95% confidence interval, 4.40-19.00; P < 0.0001) times and those with moderate ILAs had 17.14 (95% confidence interval, 4.42-66.49; P < 0.0001) times the odds of progression as subjects without ILAs. Conclusions: In persons at risk for FPF, minor interstitial abnormalities, including reticulation that is unilateral or involves <5% of a lung zone, frequently represent subclinical disease.
-
Am. J. Respir. Crit. Care Med. · Dec 2024
Association of Ground Glass Opacities with Systemic Inflammation and Progression of Emphysema.
Rationale: Ground-glass opacities (GGOs) in the absence of interstitial lung disease are understudied. Objectives: To assess the association of GGOs with white blood cells (WBCs) and progression of quantified chest computed tomography emphysema. Methods: We analyzed data of participants in the SPIROMICS study (Subpopulations and Intermediate Outcome Measures in COPD Study). ⋯ We found no association between %GGOAMFM and 1-year FEV1 decline, but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up of 1,544 days (interquartile interval, 1,118-2,059). Among normal spirometry participants, we found similar results, except that %GGOAMFM was associated with progression to COPD at 1-year follow-up. Conclusions: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.