[HTML][HTML] Is telomeropathy the explanation for combined pulmonary fibrosis and emphysema syndrome?: report of a family with TERT mutation

H Nunes, I Monnet, C Kannengiesser… - American journal of …, 2014 - atsjournals.org
H Nunes, I Monnet, C Kannengiesser, Y Uzunhan, D Valeyre, M Kambouchner…
American journal of respiratory and critical care medicine, 2014atsjournals.org
We read with interest the article by Alder and colleagues (1), demonstrating that short
telomeres lowered the threshold of cigarette smoke–induced damage in a model of
telomerase null mice, and may contribute to the age-related onset of emphysema in
humans. Telomere length, with or without germline mutation in telomerase genes (TERC or
TERT), is known to be associated with familial and sporadic idiopathic interstitial
pneumonias (IIPs)(2). Heterogeneous pulmonary disease phenotypes have been observed …
We read with interest the article by Alder and colleagues (1), demonstrating that short telomeres lowered the threshold of cigarette smoke–induced damage in a model of telomerase null mice, and may contribute to the age-related onset of emphysema in humans. Telomere length, with or without germline mutation in telomerase genes (TERC or TERT), is known to be associated with familial and sporadic idiopathic interstitial pneumonias (IIPs)(2). Heterogeneous pulmonary disease phenotypes have been observed in telomerase mutation carriers within the same family. Interestingly, the authors identified a family with a deletion in the box H domain of TERC, including the proband affected with emphysema, her father with idiopathic pulmonary fibrosis, and her sister with combined pulmonary fibrosis and emphysema syndrome (CPFE)(1). We report a family with TERT mutation and a similar combined emphysema–fibrosis spectrum of lung disease.
A 53-year-old male, a current smoker (56 pack-years), was referred to our department for the detection of IIP in September 2009 in a context of recurrent respiratory infections. He worked as a general practitioner and declared no other environmental exposure. Highresolution computed tomography (HRCT) showed characteristic CPFE. Surgical lung biopsy revealed a pattern of nonspecific interstitial pneumonia, which was particular for the presence of scarce, ill-defined granulomas. The patient was given low-dose steroids. At last visit in July 2013 he was doing well. FVC was 97% of the predicted value, FEV1 was 97%, and diffusing capacity of the lungs for carbon monoxide (DLCO) was 47%. His mother was a secretary. She had quit smoking 6 years before being diagnosed with IIP in 1998 at the age of 63. Apart from premature hair graying (3), her previous history was irrelevant. HRCT showed a pattern suggestive of nonspecific interstitial pneumonia without associated emphysema. On surgical lung biopsy, pulmonary fibrosis was unclassifiable, but scattered granulomas were also
ATS Journals