age-matched controls [34, 35]. Telomere length can also be measured at a single cell level in tissues.

When evaluated in blood cells (granulocytes monocytes or lymphocytes) from patients with FPF, mutations in TRG show shortened telomeres in 80–90% of the cases [19, 36]. Patients with TERT mutations have the shortest telomere among patients with FPF [36]. However, 15% of the TERT mutation carriers presented with normal telomere length in one study, and half of the patients with pulmonary brosis older than 60 years with TERT, TERC, or RTEL1 mutations had a telomere length > tenth percentile in another [19, 37].

Patients with TRG mutations transmit their short telomeres independently of transmission of the mutation and telomeres shorten at a younger age in subsequent generations [17, 19], consistent with the phenomenon of genetic anticipation (Fig. 24.3) [17, 38, 39].

Some experts suggest analyzing telomere length before genetic analysis of TRG [37, 40, 41]. A reduced telomere length in the recipient has been uniformly associated with reduced overall survival or post-lung transplantation survival in pulmonary brosis patients [28, 42].

a

c

Pulmonary Involvement

Interstitial Lung Disease

The prevalence of ILD in TRG mutation carriers increases in older patients [19]. In a North American cohort of TERT mutation carriers, none of the subjects younger than 40 years had ILD, although after the age of 60, the prevalence of ILD was more than 60% [19]. Among TRG mutation carriers, patients with TERC mutations may present with an ILD diagnosis at a younger age [17]. In a cohort of 114 patients with ILD carriers of a TRG mutation, ILD was diagnosed at a mean age of 51 years (n = 7) for TERC, 58 years (n = 75) for TERT, 60 years (n = 14) for RTEL1, and 65 years (n = 19) for PARN (p = 0.03) [17, 32]. The male/female ratio was reported to vary from 0.5 to 0.7. Tobacco smoking and other respiratory exposures are frequently reported in patients with ILD and TRG mutations in sporadic IPF cohorts (40–96%) [17, 19, 32].

The CT pattern is considered typical of UIP in 46–74% of cases (Fig. 24.4) [17, 19, 32]. It is considered indeterminate for UIP in 13–20% of cases because of atypical features:

b