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A6717 - Comorbid Pulmonary Disease May Mask Adult Cystic Fibrosis with Clinical Benefit from Initiation of CF-Specific Therapies - An Illustrative Case
Author Block: Y. Matusov1, N. Achamallah1, R. A. Belkin2; 1Department of Medicine, Santa Barbara Cottage Hospital, Santa Barbara, CA, United States, 2Pulmonary Diseases and Critical Care Medicine, Santa Barbara Pulmonary Consultants / Cottage Cystic Fibrosis Program, Santa Barbara, CA, United States.
Introduction
Adult-diagnosed cystic fibrosis (CF) is often delayed or missed and characterized by an atypical presentation with milder symptoms than CF diagnosed in childhood. Correct diagnosis facilitates initiation of targeted CF therapies, allows for genetic counseling for family members and can relieve patient anxiety for unexplained symptoms.
Case Presentation
A 52-year-old woman with extensive tobacco use, diabetes mellitus, and a long standing history of oxygen-dependent severe COPD/emphysema, treated with triple inhaler therapy, presented with persistent productive cough, intermittent sweats, generalized fatigue, severe dyspnea and wheezing and recurrent MRSA lung infections.
Physical examination revealed bilateral wheezing. Chest CT showed predominantly upper lobe emphysema, multifocal areas of bronchiectasis with associated tree-in-bud opacities, areas of nodular consolidation, peribronchial thickening and mucous plugging. Pulmonary function testing (PFT) revealed severe obstructive ventilatory defect.
Sweat chloride testing was intermediate at 52 mmol/L. CF genetic testing revealed D1152H(p.Asp1152His) and R1162X(p.Arg1162X) mutations. Vitamin A and D levels were low and fecal elastase was normal. Sinus CT scan showed submucosal periosteal thickening suggestive of chronic sinusitis. The patient was started on CF therapies, including rhDNase, hypertonic saline, chronic macrolide therapy and aggressive airway clearance therapies. Despite these measures, including two courses of IV antibiotics for MRSA and inhaled vancomycin, she had marginal improvement. Within 4 weeks of initiation of ivacaftor, however, the patient reported marked improvement in clinical symptoms, reduced supplemental oxygen needs and significant physiologic improvement above that seen in clinical studies with ivacaftor. Repeat PFT showed improvement in FEV1 from 0.74 L(38% predicted) to 1.14 L(54% predicted). The patient is now followed closely by our comprehensive CF care team.
Discussion
Adult-diagnosed CF patients tend to have mutations leading to residual CFTR function, leading to reduced severity of symptoms with delayed diagnosis. Sweat chloride testing is often variable and genetic studies may be inconclusive due to the presence of rare mutations. Older age and coexistent pulmonary diseases should not dissuade from testing for cystic fibrosis.
Ivacaftor, a CFTR potentiator recently FDA approved for patients with the D1152H mutation, had a significant impact on the patient’s course.
Testing for cystic fibrosis in patients with unexplained chronic sinopulmonary disease is of paramount importance. Treatment with CF-specific therapies at an accredited CF care center can lead to significant clinical and physiologic improvement with long-term improvement in quality of life and mortality.