In contrast to DC, which is a rare disorder largely limited to reported cases in the literature, and aplastic anemia, which has an incidence of 1 to 5 per million; IPF and related disorders are common and have a prevalence of at least 90,000 with an annual mortality of 15—20,000, similar to common cancers (53
). The prognosis for patients with IPF is poor, with a median survival of three years from the time of diagnosis (1
). Currently, there are no approved therapies, and progress in the area of treatment has been hampered by the poorly understood etiology of IPF, as the label idiopathic implies (1
). The presence of detectable telomerase mutations in this population (8–15% of families, 1–3% of sporadic cases) makes pulmonary fibrosis the most common manifestation of a syndrome of telomere shortening (2
). This prevalence rate also makes dominant inheritance the most common form of transmission of a syndrome of telomere shortening.
Although mutations in telomerase components have been identified only in a small subset of sporadic patients, the presence of short telomeres broadly may explain, at least in part, the predilection of this disorder to older individuals (2
). IPF is a disease of aging and its incidence increases 100-fold from 3 per 1,00,000 in adults less than 35 years to as much as 277 per 1,00,000 in men over 75 years (55
). In elderly populations, asymptomatic changes of IPF are also frequently observed on CAT scan, highlighting the fact that the IPF pattern may be a manifestation of aging in the lung (2
). That short telomeres mediate pulmonary fibrosis in the setting of IPF provides a rationale for pursuing translational strategies aimed at preventing telomere shortening or its cellular consequences as a therapeutic approach (6
IPF is the most common of idiopathic interstitial pneumonias, a group of interstitial lung disorders that commonly share a pattern of progressive scarring due to an unknown etiology (1
). IPF accounts for 70% cases of all idiopathic interstitial pneumonia. Different subtypes of idiopathic interstitial pneumonia histologies are often diagnosed in the same patient and within a single family, even though the pathophysiology is presumably identical (66, 66b
). Different subtypes have also been observed within families with known telomerase mutations (6
). Additionally, upper lobe predominant disease has been observed in some families with known telomerase mutations (15
). The new insights from genetics may, in the future, play a role in refining the diagnosis and molecular classification of interstitial lung disease.