Objective: To describe and correlate pulmonary function
and high-resolution CT (HRCT) scan scores in individuals with a high
risk for development of pulmonary fibrosis, ie,
Hermansky-Pudlak syndrome (HPS) patients with mutations in the
analysis of consecutive, eligible 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) previously reported in the
HPS-1 gene; he died at age 35 of pulmonary insufficiency.
For the 23 patients who had pulmonary symptoms, the mean age of onset
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 lung for carbon monoxide (Dlco),
72%. When patients were grouped according to the extent of their
reduction in FVC, the other four pulmonary function parameters followed
the FVC. Seventeen patients had abnormal chest radiographs, 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
inversely with FVC and Dlco.
Mutations in the HPS-1 gene, whether or not they involve
the typical 16-bp duplication seen in Puerto Rican patients, are
associated with fatal pulmonary fibrosis. In affected patients, the
FVC, FEV1, TLC, VC, and Dlco fall in concert,
and this functional deficit correlates with HRCT scan evidence of
progression of interstitial lung disease.