Late-Diagnosed Cystic Fibrosis in an Octogenarian With an Atypical Phenotype of Pancreatic Sufficiency and Preserved Pulmonary Function

Abstract

Cystic fibrosis (CF) was historically described as a severe childhood disease associated with pancreatic destruction, malnutrition, recurrent respiratory infection, and early mortality. Advances in sweat chloride testing, cystic fibrosis transmembrane conductance regulator (CFTR) gene discovery, newborn screening, multidisciplinary care, and CFTR modulator therapy have transformed the natural history of the disease. However, CF remains clinically heterogeneous, and patients with residual CFTR function may present later in life with chronic bronchiectasis, sinus disease, atypical respiratory infections, or nonspecific gastrointestinal symptoms. Diagnosis in advanced age is uncommon and may be delayed when pancreatic function is preserved and sweat chloride values are intermediate. An 87-year-old woman with late-diagnosed cystic fibrosis was followed longitudinally for chronic sinopulmonary disease. She had a history of recurrent sinus infections and was evaluated at a tertiary institution, where CF was diagnosed at approximately age 62. Her family history was notable for a maternal aunt who died from an unspecified respiratory illness. Diagnostic evaluation demonstrated an intermediate sweat chloride value of 41 mmol/L and CFTR testing showing one copy of F508del, M470V polymorphism, and a rare C76W variant. Her phenotype included chronic bronchiectasis, chronic sinusitis with nasal polyps, two prior sinus surgeries, and prior Mycobacterium avium complex infection treated in 1995. She had pancreatic sufficiency, with normal fecal elastase and no clinical response to pancreatic enzyme replacement therapy. Pulmonary function testing showed preserved lung function with stage I obstruction, including FEV1 1.33 L, 89% predicted; FVC 1.95 L, 85% predicted; and FEV1/FVC ratio of 68%, stable compared with the prior year. Her course was also notable for osteoporosis with prior vertebral compression fractures, which limited tolerance of vest-based airway clearance. Management included airway clearance with an oscillatory positive expiratory pressure device, individualized bronchodilator therapy due to tachycardia with albuterol, surveillance respiratory cultures, nutritional and weight monitoring, otolaryngology follow-up for chronic sinusitis and nasal polyps, osteoporosis management, and treatment with vanzacaftor/tezacaftor/deutivacaftor, to which she reported symptomatic improvement. This case highlights an uncommon late-diagnosed CF phenotype in an octogenarian with pancreatic sufficiency, intermediate sweat chloride, chronic sinopulmonary disease, preserved lung function, and new isolation of Pseudomonas aeruginosa. The case emphasizes that preserved pancreatic function and advanced age do not exclude CF and that adult patients with chronic bronchiectasis, sinus disease, and atypical respiratory infections should be evaluated for CFTR dysfunction when clinically appropriate.