Julia Carlens, K. Taneille Johnson, Andrew Bush, Diane Renz, Ute Hehr, Florian Laenger, Claire Hogg, Martin Wetzke, Nicolaus Schwerk, Jonathan H. Rayment
Imperial College London and Royal Brompton Hospital. University of Regensburg. Hannover Medical School. University of British Columbia and British Columbia Children’s Hospital Research Institute.
United Kingdom, Germany and Canada
Annals of the American Thoracic Society
Ann Am Thorac Soc 2022; 19: 2021-2030
DOI: 10.1513/AnnalsATS.202202-142OC
Abstract
Rationale: Variable disease course and outcomes have been reported in children’s interstitial lung disease associated with FLNA (Filamin A gene) variants.
Objectives: To further delineate long-term respiratory outcomes and identify potential contributing factors to severe disease course.
Methods: We retrospectively collected longitudinal data from three centers on nine cases (one male) with FLNA variants and early respiratory disease onset (within the first 24 mo of life). Clinical, radiographic, and histopathologic data were analyzed, focusing on cardiorespiratory disease course.
Results: All required early respiratory support (three invasive ventilation, three noninvasive ventilation, three supplemental oxygen), and all experienced frequent severe infective respiratory exacerbations. Three died in infancy from refractory respiratory failure and pulmonary hypertension (PH). The six surviving individuals were 3, 10, 11, 15, 18, and 33 years old at time of reporting. The extent of functional respiratory impairment decreased with age; at last follow-up, there were no individuals on home invasive ventilation, one on nocturnal noninvasive ventilation, four on oxygen, and one on no respiratory support. Spirometry consistently demonstrated moderate to severe obstructive defects (forced expiratory volume in 1 s/forced vital capacity [FVC] z-score, -3.76 to -1.77; percent predicted FVC, 31.5% to 92.1%). Seven required PH treatment in early childhood (7/9), and three of the survivors (3/6) still receive treatment. Radiologic and histopathologic findings were consistent among cases.
Conclusions: Early mortality was common, but many survivors stabilized even after severe symptoms in infancy. All survivors had persistent obstructive defects on spirometry, and half have persistent or recurrent PH. These typical findings are suggestive of this rare diagnosis and should prompt consideration of genetic testing.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
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