Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutations in HPS-1

Objective: To describe and correlate pulmonary function and high-resolution CT (HRCT) scan scores in individuals with a high risk for development of p ulmonary fibrosis, ie, Hermansky-Pudlak syndrome (HPS) patients with mutati ons in the HPS-I gene. Design: Cross-sectional analysis of consecutive, eligible patients. Patients: Thirty-eight HPS inpatients at the National Institutes of Health Clinical Center with HPS-1 mutations. Results: Thirty-seven patients were Puerto Rican and exhibited the typical 16-base pair (bp) duplication in exon 15 of HPS-1. One non-Puerto Rican was homozygous for a different mutation (intervening sequence 17 -2 A --> C) p reviously reported in the HPS-1 gene; he died at age 35 of pulmonary insuff iciency. For the 23 patients who had pulmonary symptoms, the mean age of on set was 35 years. For all 38 patients (mean age, 37 +/- 2 years), the mean FVC was 71% of predicted; the mean FEV1, 76%; mean total lung capacity (TLC ), 72%; mean vital capacity (VC), 68%; and mean diffusing capacity of the l ung for carbon monoxide (DLCO), 72%. When patients were grouped according t o the extent of their reduction in FVC, the other four pulmonary function p arameters followed the FVC. Seventeen patients had abnormal chest radiograp hs, and 31 (82%) had abnormal HRCT scans of the chest, for which a scoring system of 0 (normal) to 3 (severe fibrosis) is presented. The mean +/- SEM HRCT score for 38 patients was 1.30 +/- 0.17. HRCT scores correlated invers ely with FVC and DLCO. Conclusions: Mutations in the HPS-1 gene, whether or not they involve the t ypical 16-bp duplication seen in Puerto Rican patients, are associated with fatal pulmonary fibrosis. In affected patients, the FVC, FEV1, TLC, VC, an d DLCO fall in concert, and this functional deficit correlates with HRCT sc an evidence of progression of interstitial lung disease.