Clinical characteristics of patients with familial idiopathic pulmonary fibrosis (f-IPF)

Abstract

Background: The aim of this study was to analyze the relative frequency, clinical characteristics, disease onset and progression in f-IPF vs. sporadic IPF (s-IPF).

Methods: Familial IPF index patients and their family members were recruited into the European IPF registry/biobank (eurIPFreg) at the Universities of Giessen and Marburg (UGMLC). Initially, we employed wide range criteria of f-IPF (e.g. relatives who presumably died of some kind of parenchymal lung disease). After narrowing down the search to occurrence of idiopathic interstitial pneumonia (IIP) in at least one first grade relative, 28 index patients were finally identified, prospectively interviewed and examined. Their family members were phenotyped with establishment of pedigree charts.

Results: Within the 28 IPF families, overall 79 patients with f-IPF were identified. In the same observation period, 286 f-IIP and s-IIP patients were recruited into the eurIPFreg at our UGMLC sites, corresponding to a familial versus s-IPF of 9.8%. The both groups showed no difference in demographics (61 vs. 79% males), smoking history, and exposure to any environmental triggers known to cause lung fibrosis. The f-IPF group differed by an earlier age at the onset of the disease (55.4 vs. 63.2 years; p < 0.001). On average, the f-IPF patients presented a significantly milder extent of functional impairment at the time point of inclusion vs. the s-IPF group (FVC 75% pred. vs. FVC 62% pred., p = 0.011). In contrast, the decline in FVC was found to be faster in the f-IPF vs. the s-IPF group (4.94% decline in 6 months in f-IPF vs. 2.48% in s-IPF, p = 0.12). The average age of death in f-IPF group was 67 years vs. 71.8 years in s-IPF group (p = 0.059). The f-IIP group displayed diverse inheritance patterns, mostly autosomal-dominant with variable penetrance. In the f-IPF, the younger generations showed a tendency for earlier manifestation of IPF vs. the older generation (58 vs. 66 years, p = 0.013).

Conclusions: The 28 f-IPF index patients presented an earlier onset and more aggressive natural course of the disease. The disease seems to affect consecutive generations at a younger age.

Trial registration: Nr. NCT02951416 http://www.www.clinicaltrials.gov.

Keywords: Diffuse parenchymal lung diseases (DPLD); European IPF biobank (eurIPFbank); European IPF registry (eurIPFreg); Familial idiopathic pulmonary fibrosis (f-IPF); Idiopathic pulmonary fibrosis (IPF); Interstitial idiopathic pneumonia (IIP).

Fig. 1

Decline of forced vital capacity (FVC) over time in both groups. Abbreviations: Patients with f-IPF, n = 21; s-IPF patients, n = 54. Day 0 corresponds to the first lung function test and approximately to the day of the first diagnosis. Each line represents the FVC course of a one patient; the points on the lines mark the individual values of FVC. Red trend line: Interpolated mean percent FVC decline of all patients; red area shows 95% confidence band for model prediction

Fig. 2

Pedigree chart one. Generations (I-IV) with 13 members, index patient III: 3. Abbreviations: DPLD = diffuse parenchymal lung disease, IPF = idiopathic pulmonary fibrosis, def. = definite, NSIP = nonspecific interstitial pneumonia, CD = cause of death, FD = first diagnosis year / age at first diagnosis in years; LTX = lung transplantation

Fig. 3

Pedigree chart two. Generations (I-VI) with 39 members, index patient III: 4; IPF = idiopathic pulmonary fibrosis, NSIP = non-specific interstitial pneumonia, CD = cause of death, colon Ca = colon carcinoma, RA = rheumatoid Arthritis, COPD = chronic obstructive pulmonary disease, FD = initial diagnosis year / age at first diagnosis in years, MOF = multi organ failure, radiol. = radiological, recrt = recurrent, DD = differential diagnosis, MTX = methotrexate

Fig. 4

Pedigree chart three. Generations (I-VI) with 42 members, index patient IV: 6. Abbreviations: def. IPF = definitive idiopathic pulmonary fibrosis, Heart-Dis = heart disease; OP = operation; DPLD = diffuse parenchymal lung disease; CD = cause of death; Laryngeal Ca = laryngeal carcinoma; FD = initial diagnosis year / age at first diagnosis in years; rapidly prog. IPF = rapidly progressive idiopathic pulmonary fibrosis; resp. insuff. = respiratory insufficiency

Fig. 5

Pedigree chart four. Generations I-V with 53 members, index patient III: 5. Abbreviations: def IPF = definitive idiopathic pulmonary fibrosis; DPLD = diffuse parenchymal lung disease; CD = cause of death; FD = initial diagnosis year / age at first diagnosis in years; colon Ca = colon carcinoma; LTX = lung transplantation; Mamma Ca = breast cancer; Heart Dis = heart disease; Joint Dis = joint disease