American journal of respiratory and critical care medicine
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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.
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Am. J. Respir. Crit. Care Med. · Dec 2024
Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.
Rationale: Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objectives: By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. ⋯ A higher dysanapsis genetic risk score was associated with obstructive spirometry among 5-year-old children and among adults in the fifth, sixth, and seventh decades of life. Conclusions: CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development, and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endophenotype link between the genetic variations associated with lung function and COPD.