Genetic testing in interstitial lung disease: An international survey.

BACKGROUND AND OBJECTIVE: Genetic analysis is emerging for interstitial lung diseases (ILDs); however, ILD practices are not yet standardized. We surveyed patients', relatives' and pulmonologists' experiences and needs on genetic testing in ILD to evaluate the current situation and identify future needs. METHODS: A clinical epidemiologist (MT) together with members of the ERS taskforce and representatives of the European Idiopathic Pulmonary Fibrosis and related disorders Federation (EU-IPFF) patient organisation developed a survey for patients, relatives and pulmonologists. Online surveys consisted of questions on five main topics: awareness of hereditary ILD, the provision of information, genetic testing, screening of asymptomatic relatives and clinical impact of genetic analysis in ILD. RESULTS: Survey respondents consisted of 458 patients with ILD, 181 patients' relatives and 352 pulmonologists. Most respondents think genetic testing can be useful, particularly for explaining the cause of disease, predicting its course, determining risk for developing disease and the need to test relatives. Informing patients and relatives on genetic analysis is primarily performed by the pulmonologist, but 88% (218) of pulmonologists identify a need for more information and 96% (240) ask for guidelines on genetic testing in ILD. A third of the pulmonologists who would offer genetic testing currently do not offer a genetic test, primarily because they have limited access to genetic tests. Following genetic testing, 72% (171) of pulmonologists may change the diagnostic work-up and 57% (137) may change the therapeutic approach. CONCLUSION: This survey shows that there is wide support for implementation of genetic testing in ILD and a high need for information, guidelines and access to testing among patients, their relatives and pulmonologists.

Clustering of lung diseases in the family of interstitial lung disease patients.

BACKGROUND: The presence of familial interstitial lung disease (ILD) has been found to predict development of progressive pulmonary fibrosis. However, the role of non-ILD lung diseases in ILD patients' families has not yet been investigated. We aimed to identify associations between ILDs and non-ILD lung diseases from ILD patients' self-reported family health history. METHODS: We analysed questionnaires on family health history of 1164 ILD patients for the occurrence of ILD and non-ILD lung disease in relatives. Logistic regression analysis was used to study associations with diagnosis groups. RESULTS: Familial pulmonary fibrosis was reported by 20% of patients with idiopathic pulmonary fibrosis (IPF; OR 9.2, 95% CI 4.7-17.9), and 15% of patients with unclassifiable pulmonary fibrosis (OR 4.1, 95% CI 2.0-8.2). Familial occurrence was reported by 14% of patients with sarcoidosis (OR 3.3, 95% CI 1.9-5.8). Regarding non-ILD lung disease, significantly more patients with IPF (36%) reported lung cancer in their family (OR 2.3, 95% CI 1.4-3.5), and patients with hypersensitivity pneumonitis (18%) mostly reported COPD (OR 2.3, 95% CI 1.3-4.2). Comparison of sporadic and familial ILD patients' reports showed that emphysema (OR 4.6, 95% CI 1.8-11.6), and lung cancer (OR 2.4, 95% CI 1.2-4.9) were predictive for familial pulmonary fibrosis, particularly when reported both in a family (OR 16.7, 95% CI 3.2-86.6; p < 0.001). CONCLUSIONS: Our findings provide evidence for clustering of ILD and non-ILD lung diseases in families and show that self-reported emphysema and lung cancer of relatives in this population predicts familial pulmonary fibrosis.

Clustering of immune-mediated diseases in sarcoidosis.

PURPOSE OF REVIEW: Sarcoidosis is an immune-mediated disease of unknown cause. Immune-mediated diseases appear to cluster in patients and in families. We review what is known on this topic for sarcoidosis, and what factors may underlie disease clustering. RECENT FINDINGS: In populations of patients with sarcoidosis, relative risk estimates of Sjögren's syndrome, systemic lupus erythematosus, autoimmune hepatitis, ankylosing spondylitis, multiple sclerosis (MS), celiac disease, autoimmune thyroid disease, and ulcerative colitis, varied between 2.1 and 11.6. In relatives of patients with sarcoidosis, relative risk estimates varied between 1.3 and 5.8 for sarcoidosis, MS, celiac disease, type 1 diabetes, Graves' disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. Shared risk loci in key immunological pathways provide evidence for a contribution to development of multiple diseases. Identical changes in the immune status, epigenetic alterations, and environmental triggers have been detected in several diseases, and drug-induced disease is likely responsible for a small portion of co-occurring disease. SUMMARY: Clustering of sarcoidosis and other immune-mediated diseases in patients and in their relatives occurs for sarcoidosis, MS, celiac disease, Graves' disease, and ulcerative colitis. Further research is needed to substantiate causal links and risk estimates in patients and their relatives.

Risk and outcome of COVID-19 infection in sarcoidosis patients: results of a self-reporting questionnaire.

BACKGROUND: It has been suggested that sarcoidosis patients, especially those on immunosuppressive medications, are at increased risk for COVID-19 infection and more severe disease. METHODS: A questionnaire was developed in four languages (English, Dutch, Italian, and Spanish). The questionnaire queried whether patients had been infected with COVID-19 and outcome of the infection. Risk factors for COVID-19 infection were collected. RESULTS: A total of 5200 sarcoidosis patients completed the questionnaire with 116 (2.23%) reporting infection and 18 (15.8%) required hospitalization. Increased hazard ratio (HR) for COVID-19 infection were seen for those with a COVID-19 infected roommate (HR=27.44, p<0.0001), health care provider (HR=2.4, p=0.0001), pulmonary sarcoidosis (HR=2.48, p=0.001), neurosarcoidosis (HR=2.02, p<0.01), or rituximab treatment (HR=5.40, p<0.0001). A higher rate of hospitalization was found for those with underlying heart disease (HR=3.19 (1.297-7.855), p<0.02). No other feature including race, other immunosuppressive agent, age, or underlying condition was associated with a significant increased risk for infection or more severe disease. CONCLUSION: The overall rate of COVID-19 was 2.23%, suggesting an increased rate of COVID-19 infection. However, when an analysis of the questionnaires of sarcoidosis and non-sarcoidosis patients was performed in one localized area over this time period, the rate of COVID-19 infection was similar in both groups. Sarcoidosis patients who cohabitated with COVID-19 infected individuals, worked in health care, had pulmonary or neurologic sarcoidosis, or were treated with rituximab had an increased risk for COVID-19 infection. No significant increased risk for hospitalization could be identified based on age, race, gender or any specific immunosuppressive treatment. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (4): e2020009).

Clinical epidemiology of familial sarcoidosis: A systematic literature review.

INTRODUCTION: Although the presence of familial sarcoidosis has been confirmed, clinical and epidemiological data on its characteristics are scattered and sometimes paradoxical. The objective of this review is to assess what is known on the clinical epidemiology of familial sarcoidosis, by combining data from early case reports with recent population based data; aiming to support in clinical decision making and providing information to patients. METHOD: A systematic review of the literature in PubMed was done and 27 studies with clinical or epidemiological data on familial sarcoidosis, published between 1947 and 2017, were included. RESULTS: The pooled prevalence proportion of familial sarcoidosis, based on twelve study populations, was 9.5% (CI 4.6-16.1), highest in French, African American, Dutch and Irish patients. A heritability of 60-70% was estimated in diverse studies. Relative types and relationships most often reported in familial sarcoidosis were siblings and mother-child relationships. Familial risk is heterogeneous. In African Americans specific environmental factors have been associated with familial sarcoidosis (OR between 1.5 and 3.2). European American and African American subjects had different relative risks for first degree familial relationships (OR of 16.6 vs 3.1) and relative risk differed between relative types. Clinical findings in familial sarcoidosis are still obscure. CONCLUSIONS: Prevalence of familial sarcoidosis is high in specific study populations from countries worldwide. The estimated heritability of 60-70%, suggests a shared determinant, and the heterogeneous familial risk, associated with both genetic and environmental factors. Familial relative risks and clinical phenotypes may differ between ethnic groups and relative types, but require further study.