Cystic Fibrosis Transmembrane Conductance Regulator ∆F508 Heterozygosity: A Spectrum of Disease Burden

J. Banipal1, B. L. Icard2, J. M. Sweet1, A. L. Loschner2;

Author address: 

1Department of Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, United States, 2Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, United States.


Introduction: The cystic fibrosis transmembrane conductance regulator (CFTR) ∆F508 mutation has been extensively studied in the pathogenesis of cystic fibrosis. However, less is certain regarding the clinical implications of being a heterozygous carrier. We present a young heterozygote diagnosed with hypercapnic respiratory failure due to allergic bronchopulmonary aspergillosis (ABPA) with diffuse cystic bronchiectasis and invasive fungal and pseudomonas pneumonia.
Case: A 34-year-old African-American man with a history of asthma, pneumonia and chronic obstructive lung disease (FEV1 36% predicted four years prior), presented with progressive dyspnea, subjective fevers, and productive cough over several weeks. He has not seen a physician in three years and his only current medication is albuterol, as needed. He works as a server in a hotel restaurant and continues to smoke 10 cigarettes daily. There is no recreational drug use. He is exclusively homosexual; he has never fathered any children. His mother has no pulmonary disease; his father is not known. The BMI was 23 kg/m2. There was diffuse wheezing. The vasa deferentia were not palpable. The white blood cell count was 13,700/uL with 8.7% eosinophils. Chest computed tomography (figure) demonstrated severe diffuse cystic bronchiectasis and mass-like left upper lobe consolidation. Tracheal intubation was required for hypercarbic respiratory failure. Serum IgE was 15,790 kU/L and Aspergillus IgE was present. Bronchoalveolar lavage grew Aspergillus and mucoid Pseudomonas aeruginosa and transbronchial biopsies showed eosinophilic infiltration with Aspergillus hyphae. Tests for HIV, AFB, actinomyces, nocardia, mycobacterial DNA, and (1,3)-beta-d-glucan were negative. A 45-gene cystic fibrosis panel revealed heterozygosity for the ∆F508 mutation. The patient improved with glucocorticoids, piperacillin-tazobactam and itraconazole; he was discharged on day 10.
Discussion: Cystic fibrosis (CF) is a single gene recessive disorder resulting from homozygous mutations of the CFTR gene, which codes for a protein that functions as a cyclic adenosine monophosphate-regulated chloride channel in the epithelial linings the respiratory, intestinal, exocrine gland and genitourinary systems. ∆F508 heterozygotes are generally considered free of disease, yet some studies have demonstrated increased associations with asthma, bronchiectasis, ABPA, chronic or hereditary pancreatitis, azoospermia, and congenital bilateral absence of the vas deferens in these patients. Given that there are >1000 identified CFTR mutations, it is possible this patient is a compound heterozygote or has some other unidentified modifier gene or acquired exposure that further attenuates CFTR function. The potential role or lack thereof of specialized CF-like care and/or CFTR modulators in such patients is not known.



abstract No: 

A6718 / P739

Full conference title: 

The American Thoracic Society Conference 2018
    • ATS 2018