ABCA3-related interstitial lung disease beyond infancy.

Area of Science:

• Pediatric Pulmonology
• Genetic Respiratory Diseases
• Interstitial Lung Disease

Background:

• Childhood interstitial lung disease (chILD) from ATP binding cassette subfamily A member 3 (ABCA3) variants typically leads to severe respiratory insufficiency and high mortality in the first year of life.
• Lung transplantation is often the only option for survival in severe ABCA3-related chILD.
• This study focuses on the long-term outcomes of patients with ABCA3 lung disease who survive beyond infancy.

Purpose of the Study:

• To review the long-term clinical course, oxygen requirements, and pulmonary function in children with ABCA3 deficiency who survived past one year of age.
• To understand the natural history and progression of ABCA3-related interstitial lung disease in a pediatric cohort.
• To identify factors influencing survival and disease progression in this patient group.

Main Methods:

• A register-based cohort study utilizing the Kids Lung Register database over a 21-year period.
• Identification and review of 44 patients diagnosed with chILD due to ABCA3 deficiency who survived beyond their first year.
• Assessment of long-term clinical course, oxygen supplementation, pulmonary function, chest CT scans, and histopathology, with blind scoring.

Main Results:

• Of 44 patients, 82% (36/44) were alive without transplantation at a median age of 6.3 years.
• Survival was significantly longer for patients never requiring oxygen supplementation compared to those requiring persistent oxygen (9.7 years vs. 3.0 years).
• Evidence of progressive interstitial lung disease was observed through declining lung function (-1.1% FVC/year) and increasing cystic lesions on CT scans.

Conclusions:

• ABCA3-related interstitial lung disease follows a progressive natural history throughout childhood and adolescence.
• The findings underscore the urgent need for disease-modifying therapies to slow the progression of ABCA3-related lung disease.
• Residual ABCA3 transporter function may be present in some patients with missense variants or small indels.