Familial pulmonary fibrosis: a heterogeneous spectrum of presentations

Abstract

Objective: To describe the clinical, functional, and radiological features of index cases of familial pulmonary fibrosis (FPF) in Brazil. Methods: We evaluated 35 patients with FPF - of whom 18 (51.4%) were women - with a median age of 66.0 years (range, 35.5-89.3 years). All of the patients completed a standardized questionnaire, as well as undergoing pulmonary function tests and HRCT of the chest. In 6 cases, lung tissue samples were obtained: from surgical biopsies in 5 cases; and from an autopsy in 1 case. Results: A history of smoking and a history of exposure to birds or mold were reported in 45.7% and 80.0% of the cases, respectively. Cough and marked dyspnea were reported by 62.8% and 48.6% of the patients, respectively. Fine crackles were detected in 91.4% of the patients. In 4 patients, the findings were suspicious for telomere disease. The median FVC and DLCO, as percentages of the predicted values, were 64.9% (range, 48.8-105.7%) and 38.9% (range, 16.0-60.0%), respectively. Nine patients had reduced DLCO despite having normal spirometry results. Regarding HRCT, patterns typical of usual interstitial pneumonia were found in 6 patients (17.1%). In 25 cases (71.5%), the HRCT features were consistent with a diagnosis other than idiopathic pulmonary fibrosis. In 11 cases (31.4%), the radiological patterns were uncharacteristic of interstitial lung disease. Of the six lung tissue samples analyzed, four showed interstitial pneumonia with bronchiolocentric accentuation, and, on the basis of the clinical and radiological data, the corresponding patients were diagnosed with hypersensitivity pneumonitis. Conclusions: Patients with FPF can present with a wide variety of clinical features. Most HRCT scans of these patients exhibit patterns not typical of usual interstitial pneumonia. The family history of fibrotic lung diseases should be investigated in all patients under suspicion, regardless of their age.

Familial pulmonary fibrosis: a world without frontiers

“…Notably, only 4 patients (11%) had hematological and/or liver disease suggestive of a TRG mutation. (17) The study by Hortense et al (17) confirms that patients with FPF can present with a wide variety of clinical features. For instance, a study involving 111 families with FPF compared 309 individuals with ILD with 360 unaffected relatives, revealing that the risk factors for developing ILD were male gender (55.7% vs. 37.2%; p < 0.0001), older age (68.3 vs. 53.1 years; p < 0.0001), and a history of smoking (67.3% vs. 34.1%; p < 0.0001).…”

“…(20) Adults with FPF are essentially indistinguishable from patients with sporadic IPF in terms of clinical presentation, radiographic findings, and histopathology, except that those with FPF tend to present it at earlier ages. (21) In the current issue of the JBP, Hortense et al (17) report their findings in a sample of 35 patients with FPF. All of the patients were diagnosed with fibrosing ILD and had at least one member in the family with fibrosing ILD.…”

“…(14,15) In the present issue of the JBP, two groups of authors report their experience in the use of antifibrotic agents in IPF and in the characterization of FPF in Brazil. (16,17) Although there is no consensus definition, FPF is usually defined by a family history of two or more relatives with ILD. (18) The prevalence of IPF is estimated to be 20 per 100,000 population, (19) and approximately 10% of the cases are FPF.…”

“…(23) However, in most cases (60-70%), FPF remains genetically unexplained and might be related to unique, yet-to-be identified gene mutations or to non-Mendelian genetics associated with environmental risk factors. Hortense et al (17) suggested that it is necessary to make a precise specific diagnosis for each patient, including pulmonary phenotyping together with the genetic diagnosis, in order to propose and evaluate the treatment. However, access to genetic analysis and genetic expertise is limited, which could be a limiting factor for patients suspected of having a genetic form of pulmonary fibrosis.…”

Idiopathic pulmonary fibrosis: accurate diagnosis and early treatment

“…(5) The rigor of that evaluation protocol aligns the document (5) with international guidelines published in 2011, (1) which also recommend a more interventional strategy involving BAL and surgical lung biopsy in cases of probable UIP. Within the investigation of differential diagnosis of IPF, as is shown in this issue of the JBP, (6) researching the family context is highly relevant because that type of fibrosis tends to have a different evolution and therapeutic response profile, so any family relationship should always be documented in the diagnosis of interstitial lung disease.…”