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Emphysema is a chronic respiratory disorder characterized by destruction of alveoli, usually due to cigarette smoking or exposure to noxious particles or gases. Dysfunction of proteins that are involved in lung development and maintenance, such as alpha-1 antitrypsin, also contributes to emphysema. Filamin A (FLNA) is an actin-binding protein involved in cytoskeleton reorganization. Mutations in the FLNA gene classically lead to abnormal neuronal migration and connective and vascular tissue anomalies. Pulmonary manifestations consist of a wide range of pulmonary disorders that occur during infancy. We report the first familial case of emphysema in non- and very low-smoking adults who carry a loss-of-function mutation of the FLNA gene. The identification of this new risk factor for emphysema encourages (1) screening, prevention and monitoring of pulmonary disorders in patients with FLNA mutation and (2) screening for FLNA mutation in patients with early-onset emphysema that is associated with low-smoking or vascular or connective tissue anomalies.

Emphysema is a chronic respiratory disorder characterized by destruction of alveoli, usually due to cigarette smoking or exposure to noxious particles or gases. Dysfunction of proteins that are involved in lung development and maintenance, such as alpha-1 antitrypsin, also contributes to emphysema. Filamin A (FLNA) is an actin-binding protein involved in cytoskeleton reorganization. Mutations in the FLNA gene classically lead to abnormal neuronal migration and connective and vascular tissue anomalies. Pulmonary manifestations consist of a wide range of pulmonary disorders that occur during infancy. We report the first familial case of emphysema in non- and very low-smoking adults who carry a loss-of-function mutation of the FLNA gene. The identification of this new risk factor for emphysema encourages (1) screening, prevention and monitoring of pulmonary disorders in patients with FLNA mutation and (2) screening for FLNA mutation in patients with early-onset emphysema that is associated with low-smoking or vascular or connective tissue anomalies.

The 6-min walk test (6MWT) is commonly used to assess exercise capacity in patients with fibrotic idiopathic interstitial pneumonia (f-IIP). However, it is not known whether patients with f-IIP have reduced levels of physical activity in daily life (DLPA) or whether pulmonary function tests and the 6MWT correlate with their DLPA.The aim of this study was to measure DLPA in patients with f-IIP and to determine the relationships between DLPA and the 6MWT, pulmonary functional parameters, and anxiety and depression scores. Fifty patients with f-IIP and 25 sex- and age-matched healthy control subjects were enrolled. Markers of DLPA were assessed with a physical activity monitor for 4 consecutive days. Hospital Anxiety and Depression Scale (HADS) scores were evaluated.DLPA parameters were significantly reduced in patients with f-IIP compared with control subjects (all P.001). The mean number of steps per day correlated strongly with diffusing capacity of the lung for carbon monoxide (Dlco), FVC, the 6MWT distance, and the 6MWT lowest oxygen saturation as measured by pulse oximetry (Spo₂). DLPA was unrelated to HADS scores. Multivariate analysis showed that Dlco and 6MWT distance explained only 31% of the variance in the number of steps per day. Dlco, 6MWT distance, 6MWT lowest Spo₂, and DLPA were significant predictors of mortality, but only Dlco and 6MWT distance were independent predictors.Quantitation of DLPA is a novel patient-centered approach to assess function in f-IIP and may be a useful tool for clinical care and assessing response to therapy.