Skip to main content
Download PDF

Diagnosis, screening, and follow-up of patients with familial interstitial lung disease: Results from an international survey

BMC Pulmonary Medicine volume 25, Article number: 59 (2025) Cite this article

Abstract

Background

Advances in the field of genetics of interstitial lung diseases (ILDs) have led to the recent consensus statements made by expert groups. International standards for genetic testing in ILD have not yet been established. We aimed to examine current real-world strategies employed by pulmonologists working with familial ILD.

Methods

A panel of pulmonologists with expertise in ILD developed an international survey aimed at clinicians working with ILD. The survey consisted of 74 questions divided into eight topics: characteristics of respondents, diagnosis, screening of first-degree relatives, screening tools, genetic testing methods, lung transplantation, ethical concerns, and future needs.

Results

Overall, 237 pulmonologists from 50 countries participated. A family history of ILD was asked for by 91% of respondents while fewer asked for symptoms related to telomere disorders. Respondents stated that 59% had access to genetic testing, and 30% to a genetic multidisciplinary team (MDT). Many respondents were unaware of specific genetic testing methods. Pathogenic genetic variants were seen as a potential contraindication for lung transplantation in 6–8% of respondents. Genetic screening of relatives was supported by 80% of respondents who indicated insufficient evidence and a lack of formal guidelines for genetics and ILD. Only 16% had a standardized program.

Conclusion

Most pulmonologists ask for a family history of ILD and recommend genetic testing for ILD and screening in relatives but have limited knowledge of specific tests and access to genetic MDT. Evidence-based guidelines to inform patients, relatives, and physicians are still warranted.

Peer Review reports

Introduction

Interstitial lung disease (ILD) is a large and heterogeneous group of rare diseases characterized by inflammation and/or fibrosis of the lung parenchyma [1, 2]. The most severe form is idiopathic pulmonary fibrosis (IPF) [3, 4]. A genetic predisposition is identifiable in 10–15% of IPF patients and their relatives have a 9- to tenfold increased risk of developing ILD [5,6,7]. Genetic studies of familial ILD or familial pulmonary fibrosis (FPF) have increased the knowledge on genetic factors and the risk of developing ILD [6, 8]. A recent European Respiratory Society (ERS) statement defined FPF as any fibrotic ILD in at least two blood relative first- or second-degree family members [8].

The most commonly identified genetic variants in ILD are involved in telomere homeostasis (telomere-related genes (TRGs)) and surfactant homeostasis (surfactant-related genes (SRGs)) and are associated with a risk of developing fibrotic and progressive ILD, especially in young adults [6, 9]. A genetic polymorphism in the MUC5B promoter is associated with the risk of developing fibrotic ILD, including IPF, hypersensitivity pneumonitis, and rheumatoid arthritis-associated ILD [8, 10,11,12]. Pathologic variants in TRGs and SRGs are associated with specific ILD features [6, 9], prognosis [13, 14], and tolerance and efficacy of treatment [15]. Furthermore, patients with pathogenic TRG variants may have worse outcomes following lung transplantation, including higher prevalence of infections and greater risk of drug toxicity [13, 16,17,18,19].

Due to emerging evidence and advances in genetics and ILD, genetic testing for familial ILD has been adopted into clinical practice in some centres [8]. Although expert task forces have evaluated the need for a standardized approach [8, 20], implementation of genetic analysis is not widely incorporated in ILD centres. International consensus regarding how, who, and when to test in a clinical program has not been established [8]. Furthermore, the tests included in routine practice vary between the centres that have incorporated genetic evaluation.

A recent survey of physicians, patients, and relatives identified widespread support for the implementation of genetic testing for ILD [21]. Of note, ethical concerns were raised by physicians, patients, and their relatives, highlighting a need for greater exploration of these issues and development of a framework.

We developed an international survey on diagnosis, screening, and follow-up of patients with familial ILD, aiming to better understand the ongoing real-world strategies employed by physicians managing patients with these diseases. In this survey, we sought to generate an overview of worldwide diagnostic approaches and screening programs for this important group of patients and their families.

Methods

Survey design

Prior to survey development, we conducted a literature search to identify areas relevant to the diagnosis, screening, and genetic testing of patients with familial ILD. Thereafter, an expert panel of pulmonologists with expertise in ILD was formed (Additional file 1). Questions for the survey were discussed until agreement was reached. The survey was provided by the online survey tool SurveyMonkey from May 2023 to October 2023. A network of ILD physicians identified by the expert panel were invited to participate in the study with study information, consent form, and confidentiality agreement. To ensure anonymity, participants were issued a code number and limited demographic data were collected. On the introductory page to the survey, participants gave consent to participate when choosing to participate in the survey.

The survey encompassed 74 questions grouped into 8 topics:

  1. 1.

    Respondent demographics

  2. 2.

    Diagnosis of familial ILD (patient history and availability of genetic testing)

  3. 3.

    Diagnosis and screening of first-degree relatives

  4. 4.

    Screening tools

  5. 5.

    Genetic testing

  6. 6.

    Lung transplantation

  7. 7.

    Treatment related to genetic testing (antifibrotic treatment and management following transplantation)

  8. 8.

    Ethical concerns

Survey questions were structured in different formats including closed (multiple-choice) and open-ended questions. All questions provided the possibility to elaborate an answer in free writing. The respondents were also permitted to skip any question.

Data analysis

Results are presented as the number and percentage of respondents to each question. Continuous variables are reported as means and standard deviation (SD) or median and interquartile range (IQR) as appropriate.

Results

Respondents

A total of 870 were invited and 244 (28%) physicians from 50 different countries responded to the survey. Seven respondents were excluded (six respondents did not work with ILD, one respondent did not answer this question), resulting in 237 pulmonologists included in the analysis.

From Europe, there were 119 respondents (50.2%), 44 (18.6%) from South America, 33 (13.9%) from Asia, 30 (12.7%) from North America, 10 (4.2%) from Oceania including Australia, and 1 (0.4%) from Africa.

Respondents could provide multiple answers and many respondents had more than one workplace. Of the respondents, 32% worked in a specialized ILD center/university hospital, 15% in general pulmonology departments/non-university centers, and 3% in an intensive care unit. Sixty-five percent worked in a public academic center, 8% in a public non-academic center, 15% in a private academic center, and 15% in a private non-academic center. Respondents had a median experience as an ILD physician of 13 years (IQR 9–20 years). The median number of ILD patients per center was 400 (IQR 160–1000) and the median number of new referrals per year was 100 (IQR 40–200). The respondents estimated that a median of 10% (IQR 5–15%) of their patients had a history of familial ILD.

Diagnosis and awareness of familial ILD

Components of the diagnostic process pertaining to a potential genetic predisposition are summarized in Fig. 1. A family history of ILD was requested by 91% of respondents when interviewing newly referred ILD patients. Specific questions relating to extrapulmonary diseases or telomeric traits associated with TRG variants (such as a family history of early grey hair), were routinely posed by 48% of the respondents. Fewer respondents asked for a family history of liver cirrhosis or bone marrow disease. Even fewer drew a pedigree when interviewing newly referred patients. If a family history was present or the patient was diagnosed with idiopathic ILD before the age of 50 years, the respondent more often asked for symptoms or diseases associated with TRG variants.

Fig. 1
figure 1

Awareness of the possibility of hereditary ILD or extrapulmonary symptoms associated with telomerase complex mutations. *(n) = Number of respondents for the individual question ** Early grey hair: Before the age of 30

Full size image

Genetic testing for familial ILD was available to 59% of the respondents. Half of those who performed genetic testing had access to a genetic multidisciplinary team (MDT) meeting (Table 1). Participating specialties in the MDT were pulmonologist 96%, clinical geneticist 46%, genetic counselor 28%, hepatologist 11%, and hematologist 18%. Furthermore, 54% mentioned participation of other medical specialties such as rheumatologists, radiologists, pathologists, thoracic surgeons, pediatricians, and immunologists.

Table 1 Questions addressing genetic testing and genetic multidisciplinary team meetings (MDT)
Full size table

A variety of responses were seen with respect to age of patients with recognized familial ILD and referral for genetic testing (Fig. 2). Only 34% of respondents would refer patients with a family history of ILD for genetic testing at any age, 9% in patients < 60 years, and 24% answered that age of patient prompting such a referral depended on an individual or family history of liver cirrhosis or bone marrow disease. For fibrotic ILD patients without a family history, 33% would refer for genetic testing in patients < 50 years, and 23% in patients < 60 years.

Fig. 2
figure 2

Questions addressing timing for referral for genetic testing *(n) = Number of respondents for the individual question ** Age depends on personal or family history of liver cirrhosis or bone marrow disease

Full size image

On the methods used for genetic testing, 32% used next-generation sequencing (NGS), 24% whole exome sequencing (WES), and 22% measurement of peripheral blood leukocyte telomere length. Many of the respondents did not have specific knowledge of the form of genetic tests used (Table 1). Regarding specific genetic variants, 40% of respondents tested for surfactant protein gene mutations and 44% for mutations in telomere-related genes. A minority also tested for MUC5B promotor polymorphisms (Table 1). Respondents answered that only a minority of patients with ILD asked for genetic testing.

Genetic testing and lung transplantation considerations

Only 12% of respondents routinely measured peripheral blood leukocyte telomere length during lung transplantation work-up in patients with familial ILD. The majority had no knowledge of whether it was measured at the transplant centre (Table 2). In patients with familial ILD, 29% referred patients for genetic testing as a part of their lung transplantation work-up program (Table 2). Interestingly, some physicians considered telomere- or surfactant-related gene variants and short telomeres as contraindications for lung transplantation. However, most of the respondents answered that identification of these gene variants would not prevent transplantation (Table 2). In patients with telomere length below the 10th percentile or TRG variants, 33% of respondents would modify their treatment protocol for lung transplant recipients (Table 2).

Table 2 Clinical genetic and questions addressing lung transplantation
Full size table

Regarding disease-modifying treatment before transplant evaluation, many answered that they would not use immunomodulatory therapy in non-IPF fibrotic ILD patients with pathogenic TRG variants (Table 2).

Screening and genetic testing of first-degree relatives and potential ethical concerns

If a pathogenic gene variant was proven in a first-degree relative, 80% recommended screening of relatives (Table 3). On the timing of screening initiation, 28% of respondents answered at 40 years of age and 15% answered 10 years before the index patient, to take genetic anticipation into account. If a pathogenic TRG gene variant was found, most recommended screening for liver (66%) and bone marrow disease (61%). Only 25% recommended screening for other organ involvement (Table 3). A standardized screening program was present at 16% of the respondents’ hospitals for first-degree relatives with a pathogenic gene variant. Evaluation of first-degree relatives was recommended by 57% of respondents and 84% recommended a high-resolution-computed-tomography (HRCT) scan as part of the program. Most respondents (85%) recommended pulmonary function testing of first-degree relatives (Table 3), including spirometry and diffusing capacity as part of the screening program. Pulmonologist indicated that they experienced that 25% of first-degree relatives asked for HRCT and pulmonary function testing.

Table 3 Questions addressing screening and screening programs for relatives
Full size table

Ethical concerns regarding testing of first-degree relatives of affected patients was expressed by 33%. In free writing respondents mentioned potential impact on mental wellbeing, insurance coverage, the lack of genetic counsellors, and specific treatment options as reasons for not testing. Respondents estimated 15% of first-degree relatives asked for genetic testing and a further 19% declined genetic testing when suggested by their physician/genetic counselor. Reasons for first-degree relatives to decline genetic testing included cost of the test and fear of results could negatively affect either their mental wellbeing or insurance coverage.

Usefulness of genetic testing and future needs

When determining if familial screening was necessary, most respondents found genetic testing of ILD patients useful and many respondents found it useful to better evaluate the risk of extrapulmonary disease. Genetic testing was not considered useful by 9% of respondents (Fig. 3). As part of lung transplantation work-up, 45% of respondents found genetic testing useful and relevant for determining treatment options for ILD patients, and 54% found genetic testing to be diagnostically helpful.

Fig. 3
figure 3

Usefulness of genetic testing and current challenges. *Multiple answers were possible.**Number of respondents for the individual question. ***Respondents were able to elaborate in free writing

Full size image

Most respondents stated that the lack of evidence-based specific treatment options for familial ILD and the lack of guidelines for screening for familial ILD were the current major challenges regarding genetics and ILD. Many respondents stated lack of guidelines for diagnosis of patients with familial fibrosis and the lack of trials focusing on patients with familial fibrosis as the most important current challenges. Other challenges included low availability of genetic testing and lack of evidence to support genetic testing.

Discussion

Our survey results reveal the current differences in diagnostic, treatment, and screening strategies, highlighting the need for an evidence-based and pragmatic approach to standardization. The impact of pathogenic variants on transplant candidates and potential ethical concerns following genetic testing in patients and relatives were also areas requiring further evaluation and guidance. Although most respondents considered genetic testing in ILD useful, only 59% had access to these tests in clinical practice and solely one-third had access to a genetic MDT.

Several studies have proven that family aggregation and genetic predisposition are risk factors for familial ILD and worse prognosis [5, 6, 13, 14, 22]. Furthermore, the disease trajectory of an individual with familial ILD seems to be predictive of a worse prognosis for other affected family members [23]. Like Terwiel, most respondents in our study asked for a family history of ILD in newly referred patients [21]. This reassuringly indicates that ILD physicians are aware of familial ILD. Previous studies found familial ILD patients to be indistinguishable from sporadic IPF patients on several clinical parameters, however familial ILD patients tended to be younger with worse survival [8, 24,25,26]. Regarding extrapulmonary diseases associated with TRG gene variants, the answers were more variable; respondents more often looked for extrapulmonary features of telomere dysfunction if the patient had a known familial history or in sporadic fibrotic ILD younger than 50 years. Previous studies indicate that fibrotic ILD in young adults are more likely to represent monogenic TRG or SRG variant cases than in older ILD patients [8, 13, 14, 27,28,29]. Features such as early grey hair, hematological abnormalities, liver disease, or abnormal liver parameters may indicate a TRG variant [13, 14, 30,31,32,33,34]. Respondents most often asked about early grey hair in patients and relatives followed by questions of a family history of liver disease and bone marrow disease. Overall, there seems to be high awareness of the importance of a familial background in newly referred ILD patients, but less focus on extrapulmonary symptoms or findings.

In recent years, genetic testing for familial ILD has been implemented in some, but not all specialized ILD centres [8, 35]. In our study, the majority considered genetic testing in ILD useful. Despite this, just over half of our respondents had access to genetic testing and one third did not offer genetic testing due to limited resources. This proportion is unchanged from the findings by Terwiel [21]. Our results regarding access to genetic testing may even be overestimated as we do not know if non-responders to this question choose not to answer due to limited access to genetic testing or because they had no knowledge of this topic. A recent ERS statement recommends genetic testing for any patient with an idiopathic fibrosing ILD before the age of 50 years, irrespective of family history [8]. In our survey, only 33% of respondents would refer an ILD patient without a family history under 50 years of age for genetic testing. Lack of availability might explain the limited incorporation of genetic evaluation, but other factors like lack of international consensus or awareness of the recommendation for genetic testing have been suggested [8]. Another explanation could be that some of the younger patients might have a connective tissue disease related ILD and thus not qualify for genetic testing. A recent study recommended genetic MDTs as standard care for patients with suspected or confirmed genetic ILD and found that the diagnosis was modified for 10% of the patients after an MDT evaluation [36]. The study recommended that the genetic MDT should include ILD specialists, a geneticist, pediatrician, chest radiologist, and other medical specialists such as hepatologist and hematologist, especially if the patients were carriers of TRG mutations [36]. Contrary to this, our study found that only a third of the respondents had access to genetic MDTs. Most respondents had pulmonologists in the genetic MDT, whereas a clinical geneticist was participating in less than half of the MDTs. Many mentioned radiologists and only few mentioned pediatricians as participants. These findings highlight the need for more research in genetic MDTs and consensus on the medical specialties involved when evaluating patients suspected and diagnosed with familial ILD.

Around 30% of patients with familial ILD are carriers of TRGs, SRGs, or other rare genes [6]. Terwiel found that nearly half of their respondents would analyze for TRG variants and that less than half would test for SRG mutations or measure peripheral blood leukocyte telomere length [21]. Thirty-seven percent would leave the decision to the clinical geneticist. In our study, fewer would test for mutations in TRGs and SRGs. Like Terwiel, we found that a significant proportion of the respondents suggested testing for MUC5B even though the MUC5B promoter variant is not especially associated with familial fibrotic ILD. This mutation may be seen in a minority of familial cases and some experts suggest testing for MUC5B especially if TRG or SRG mutations are not found [6, 8]. Many of the respondents did not know if their geneticist tested for these mutations and the majority were unaware of which methods were used for genetic testing [21]. These findings indicate an unmet need for further education as many pulmonologists are not fully aware of which genes and methods to use for genetic evaluation, perhaps partly due to their limited access to MDT expert geneticists and/or genetic counsellors.

In contrast to Terwiel, we found respondents more prone to refer for genetic testing when considering lung transplantation [21]. Studies have shown transplantation outcomes in patients with TRG mutations to be similar to patients without mutations [16, 18, 37, 38], whereas other studies indicate that short telomere length may affect transplant prognosis negatively [37, 39]. In our study, few respondents answered that TRG and SRG mutation or a telomere length below the 10th percentile would directly prevent transplantation. In the recent ERS statement, it was recommended that familial ILD patients be considered potential lung transplantation recipients, adjusting the immunosuppressive treatment regimen where short telomere syndrome was present, to minimize potential hematological and renal complications [8, 16,17,18]. Accordingly, many of our respondents would modify treatment following transplantation if short telomere or telomere-related gene mutations were identified. Although practice appeared to generally align with expert recommendations for transplant work-up and referral, some misconceptions and limited awareness of specific genetic screening highlight the need for more education in this area.

In the absence of formal guidelines on evidence-based practice for screening programs for first-degree relatives of familial ILD patients, recent expert statements endorsed by ERS [8] and the Pulmonary Fibrosis Foundation [20] seek to provide frameworks for clinical practice. The ERS statement suggests screening with chest CT and pulmonary function tests in symptomatic first-degree relatives, with less certainty and greater variation in practice for asymptomatic first-degree relatives [8]. As it is not uncommon for patients to have early CT findings and reduced lung function even without respiratory symptoms, a standardized practice of screening all first-degree relatives irrespective of symptoms may be prudent, and likely to be of high yield [20]. Antifibrotic treatment in early ILD is warranted and may result in better survival, thus emphasizing the importance of early diagnosis and potential need for screening in asymptomatic first-degree relatives. However, it is important to note that research on specific treatment strategies for familial ILDs and the benefit/burden balance of very early treatment is limited.

Given the high frequency of hematological and hepatic abnormalities in TRG disorders, screening with a complete blood count and liver function tests for relatives of patients with short telomere syndrome is recommended by the ERS panel [8]. Due to the risk of liver cirrhosis in patients with TRG, it could be speculated if they had a higher risk of drug-induced hepatitis due to antifibrotic therapy. However, retrospective studies have shown a similar safety profile in these patients compared to patients with sporadic IPF and progressive pulmonary fibrosis [8]. Few of our respondents had standardized screening programs even though the majority supported screening for ILD among relatives. The majority recommended HRCT and pulmonary function test as screening methods with many respondents screening for liver- or bone marrow disease if a TRG mutation was found, similar to the findings by Terwiel [21]. Genetic testing or screening for ILD may have ethical considerations for physicians, patients, and their relatives. A recent study by Carmichael asking relatives of pulmonary fibrosis patients found that these were generally in support of screening for early disease, but as would be anticipated, receipt of abnormal test results were associated with more negative feelings [40]. Many of our respondents indicated ethical concerns for testing of first-degree relatives, often due to potential impact on insurance coverage, incomplete penetrance, and potential psychological consequences for patients and relatives. As indicated by Carmichael amongst relatives [40], the experience of our respondents was that only 19% of first-degree relatives declined genetic testing. These results indicate different views between physicians, patients, and relatives, underscoring the need for guidance concerning shared decision making.

Only few studies have assessed pulmonologists and patients attitudes towards the use of genetic testing among familial ILD patients and their relatives [21, 40]. We found that pulmonologists were in favor of genetic testing of ILD patients and especially found testing useful for several indications, including to determine if familial screening was necessary, to evaluate extra-pulmonary health issues, as part of lung-transplant work-up, to inform treatment options, and to predict the course of the disease with higher precision. Respondents stated a need for evidence-based treatment options and formal guidelines for diagnosis and screening of familial ILD. Importantly, several of the respondents stated in free writing, that one of the biggest challenges was the lack of access to genetic testing and genetic counselling of ILD patients and relatives.

Our survey has several potential limitations. To secure the privacy and anonymization of the respondents, responses were de-identified; hence we could not verify the respondents. There were only few respondents from Oceania and Africa. Respondents were invited from a network of the authors and participation was voluntary which potentially may have caused selection bias with an over-representation of participants with a specific interest in familial ILD. Respondent answers may thus not reflect broader current practice. As a challenge for surveys in general, the response rate of our survey may have an impact when drawing definitive conclusions. Our study has several strengths. Since the survey was anonymous, the answers are anticipated to be less biased. Also, the survey was sent out world-wide and we received answers from most parts of the world with a significant number of responding pulmonologists.

Conclusions

In conclusion, we found a high awareness of the possibility of familial ILD in this international survey. Pulmonologists were open towards genetic testing and screening of ILD patients and relatives. Our findings strongly support further international collaborations between ILD specialists to develop this important area of research.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

ILD:

Interstitial lung disease

MDT:

Multidisciplinary team

IPF:

Idiopathic pulmonary fibrosis

FPF:

Familial pulmonary fibrosis

TRG:

Telomere-related gene

SRG:

Surfactant-related gene

NGS:

Next generation sequencing

WES:

Whole genome sequencing

HRCT:

High resolution-computed-tomography

References

  1. Cottin V, Wollin L, Fischer A, et al. Fibrosing interstitial lung diseases: knowns and unknowns. Eur Respir Rev. 2019;28(151):180100.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Borie R, Guen PL, Ghanem M, et al. The genetics of interstitial lung diseases. Eur Respir Rev. 2019;28(153):190053.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018;378(19):1811–23.

    Article  CAS  PubMed  Google Scholar 

  4. Kapnadak SG, Raghu G. Lung transplantation for interstitial lung disease. Eur Respir Rev. 2021;30(161): 210017.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Steele MP, Speer MC, Loyd JE, et al. Clinical and pathologic features of familial interstitial pneumonia. Am J Respir Crit Care Med. 2005;172(9):1146–52.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Borie R, Kannengiesser C, Sicre de Fontbrune F, et al. Management of suspected monogenic lung fibrosis in a specialised centre. Eur Respir Rev. 2017;26(144):16012.

    Article  Google Scholar 

  7. Hunninghake GM, Quesada-Arias LD, Carmichael NE, et al. Interstitial Lung Disease in Relatives of Patients with Pulmonary Fibrosis. Am J Respir Crit Care Med. 2020;201(10):1240–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Borie R, Kannengiesser C, Antoniou K, et al. European Respiratory Society Statement on Familial Pulmonary Fibrosis. European Respiratory Journal. 2022;61:2201383.

    Article  Google Scholar 

  9. van Moorsel CHM, van der Vis JJ, Grutters JC. Genetic disorders of the surfactant system: focus on adult disease. Eur Respir Rev. 2021;30(159):200085.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Seibold MA, Wise AL, Speer MC, et al. A Common MUC5B Promoter Polymorphism and Pulmonary Fibrosis. N Engl J Med. 2011;364(16):1503–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Horimasu Y, Ohshimo S, Bonella F, et al. MUC5B promoter polymorphism in Japanese patients with idiopathic pulmonary fibrosis. Respirology. 2015;20(3):439–44.

    Article  PubMed  Google Scholar 

  12. Borie R, Crestani B, Dieude P, et al. The MUC5B variant is associated with idiopathic pulmonary fibrosis but not with systemic sclerosis interstitial lung disease in the European Caucasian population. PLoS ONE. 2013;8(8):e70621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Borie R, Tabèze L, Thabut G, et al. Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis. Eur Respir J. 2016;48(6):1721–31.

    Article  CAS  PubMed  Google Scholar 

  14. Newton CA, Batra K, Torrealba J, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J. 2016;48(6):1710–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Justet A, Klay D, Cottin V, et al. Tolerance and efficacy of antifibrotic treatments in IPF patients carriying telomere related gene mutations. European Respiratory Journal. 2019;54(suppl 63):OA2140.

  16. Borie R, Kannengiesser C, Hirschi S, et al. Severe hematologic complications after lung transplantation in patients with telomerase complex mutations. J Heart Lung Transplant. 2015;34(4):538–46.

    Article  PubMed  Google Scholar 

  17. Silhan LL, Shah PD, Chambers DC, et al. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis. Eur Respir J. 2014;44(1):178–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tokman S, Singer JP, Devine MS, et al. Clinical outcomes of lung transplant recipients with telomerase mutations. J Heart Lung Transplant. 2015;34(10):1318–24.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Planas-Cerezales L, Arias-Salgado EG, Berastegui C, et al. Lung Transplant Improves Survival and Quality of Life Regardless of Telomere Dysfunction. Front Med (Lausanne). 2021;8:695919.

    Article  PubMed  Google Scholar 

  20. Newton CA, Oldham JM, Applegate C, et al. The Role of Genetic Testing in Pulmonary Fibrosis: A Perspective From the Pulmonary Fibrosis Foundation Genetic Testing Work Group. Chest. 2022;162(2):394–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Terwiel M, Borie R, Crestani B, et al. Genetic testing in interstitial lung disease: An international survey. Respirology. 2022;27(9):747–57.

    Article  PubMed  Google Scholar 

  22. Cutting CC, Bowman WS, Dao N, et al. Family History of Pulmonary Fibrosis Predicts Worse Survival in Patients With Interstitial Lung Disease. Chest. 2021;159(5):1913–21.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Goos T, Dubbeldam A, Vermant M, et al. Intrafamilial Correlation and Variability in the Clinical Evolution of Pulmonary Fibrosis. Chest. 2023;164(6):1476–80.

    Article  PubMed  Google Scholar 

  24. Krauss E, Gehrken G, Drakopanagiotakis F, et al. Clinical characteristics of patients with familial idiopathic pulmonary fibrosis (f-IPF). BMC Pulm Med. 2019;19(1):130.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lee HL, Ryu JH, Wittmer MH, et al. Familial idiopathic pulmonary fibrosis: clinical features and outcome. Chest. 2005;127(6):2034–41.

    Article  PubMed  Google Scholar 

  26. Bennett D, Mazzei MA, Squitieri NC, et al. Familial pulmonary fibrosis: Clinical and radiological characteristics and progression analysis in different high resolution-CT patterns. Respir Med. 2017;126:75–83.

    Article  PubMed  Google Scholar 

  27. Borie R, Bouvry D, Cottin V, et al. Regulator of telomere length 1 (<em>RTEL1</em>) mutations are associated with heterogeneous pulmonary and extra-pulmonary phenotypes. Eur Respir J. 2019;53(2):1800508.

    Article  CAS  PubMed  Google Scholar 

  28. Juge P-A, Borie R, Kannengiesser C, et al. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis. Eur Respir J. 2017;49(5):1602314.

    Article  PubMed  Google Scholar 

  29. Legendre M, Butt A, Borie R, et al. Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer. Eur Respir J. 2020;56(6):2002806.

    Article  CAS  PubMed  Google Scholar 

  30. Gorgy AI, Jonassaint NL, Stanley SE, et al. Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders. Chest. 2015;148(4):1019–26.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Papiris SA, Tsirigotis P, Kannengiesser C, et al. Myelodysplastic syndromes and idiopathic pulmonary fibrosis: a dangerous liaison. Respir Res. 2019;20(1):182.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Alder JK, Chen JJ, Lancaster L, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc Natl Acad Sci U S A. 2008;105(35):13051–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Diaz de Leon A, Cronkhite JT, Yilmaz C, et al. Subclinical lung disease, macrocytosis, and premature graying in kindreds with telomerase (TERT) mutations. Chest. 2011;140(3):753–63.

  34. Diaz de Leon A, Cronkhite JT, Katzenstein AL, et al. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PLoS One. 2010;5(5):e10680.

  35. Cottin V, Crestani B, Valeyre D, et al. [French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis. From the National Reference and the Competence centers for rare diseases and the Société de Pneumologie de Langue Française]. Rev Mal Respir. 2013;30(10):879–902.

  36. Borie R, Kannengiesser C, Gouya L, et al. Pilot experience of multidisciplinary team discussion dedicated to inherited pulmonary fibrosis. Orphanet J Rare Dis. 2019;14(1):280.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Swaminathan AC, Neely ML, Frankel CW, et al. Lung Transplant Outcomes in Patients With Pulmonary Fibrosis With Telomere-Related Gene Variants. Chest. 2019;156(3):477–85.

    Article  PubMed  Google Scholar 

  38. Alder JK, Sutton RM, Iasella CJ, et al. Lung transplantation for idiopathic pulmonary fibrosis enriches for individuals with telomere-mediated disease. J Heart Lung Transplant. 2022;41(5):654–63.

    Article  PubMed  Google Scholar 

  39. Newton CA, Kozlitina J, Lines JR, et al. Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival. J Heart Lung Transplant. 2017;36(8):845–53.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Carmichael N, Martinez Manzano JM, Quesada-Arias LD, et al. Psychological impact of genetic and clinical screening for pulmonary fibrosis on asymptomatic first-degree relatives of affected individuals. Thorax. 2021;76(6):621–3.

    Article  PubMed  Google Scholar 

  41. Overview of Mandatory Reporting. https://researchethics.dk/information-for-researchers/overview-of-mandatory-reporting. Accessed 22 November 2024

Download references

Acknowledgements

Not applicable

Funding

None do declare.

Author information

Authors and Affiliations

  1. Department of Respiratory Diseases and Allergy, Centre for Rare Lung Diseases, Aarhus University Hospital, Aarhus, Denmark

    Emil Vilstrup Moen, Thomas Skovhus Prior & Elisabeth Bendstrup

  2. Lung Center Mainz, Department of Pneumology, Mainz University Medical Center and Department of Pulmonary, Critical Care & Sleep Medicine, Marienhaus Clinic Mainz, Mainz, Germany

    Michael Kreuter

  3. Unit for Interstitial Lung Diseases, Dept Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium

    Wim A. Wuyts

  4. ILD Unit, Respiratory Department, University Hospital of Bellvitge. IDIBELL. CIBERES, Barcelona, Spain

    Maria Molina-Molina

  5. Centre for Interstitial Lung Diseases and Sarcoidosis, Department of Respiratory Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Marlies Wijsenbeek

  6. Pulmonology Department, Centro Hospitalar São João, Porto, Portugal Faculty of Medicine, University of Porto, Porto, Portugal i3S Instituto de Biologia Molecular E Celular/Instituto de Investigação E Inovação Em Saúde, University of Porto, Porto, Portugal

    Antonió Morais

  7. Department of Respiratory Medicine, University of Patras, Patras, Greece

    Argyrios Tzouvelekis

  8. Department of Medicine and Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada

    Christopher J. Ryerson

  9. ILD Unit, “Maria Ferrer” Hospital. Buenos Aires City, Buenos Aires, Argentina

    Fabian Caro

  10. Laboratory of Traslational Research in Aging and Fibrosis Lung Disease. Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico

    Ivette Buendia-Roldan

  11. Departement of Respiratory Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

    Jesper M. Magnusson

  12. Department of Medicine, University of CO Denver – Anschutz Medical Campus, Aurora, CO, USA

    Joyce S. Lee

  13. Département de Médecine, Centre Hospitalier de L’Université de Montréal, Montréal, Québec, Canada

    Julie Morisett

  14. Division of Pulmonary and Critical Care Medicine, University of Michigan, Michigan, USA

    Justin M. Oldham

  15. Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia

    Lauren K. Troy

  16. Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Manuela Funke-Chambour

  17. ILD Unit, “Maria Ferrer” Hospital. Buenos Aires, Buenos Aires, Argentina

    Maria Laura Alberti

  18. Service de Pneumologie A Hôpital Bichat, APHP, Paris, France, Université Paris Cité, Inserm, PHERE, Université Paris Cité, 75018, Paris, France

    Raphael Borie

  19. National Heart and Lung Institute Imperial College, London, England

    Simon L. F. Walsh

  20. Department of Chest Medicine, Interstitial Lung Disease, Bombay Hospital Institute of Medical Sciences, and Bhatia Hospital, Mumbai, India

    Sujeet Rajan

  21. Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan

    Yasuhiro Kondoh

  22. Respiratory Research@Alfred, School of Translational Medicine, Monash University, Melbourne, VIC, Australia

    Yet H Khor

  23. Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, VIC, Australia

    Yet H Khor

  24. Institute for Breathing and Sleep, Heidelberg, VIC, Australia

    Yet H Khor

  25. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Elisabeth Bendstrup

Authors
  1. Emil Vilstrup Moen
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Thomas Skovhus Prior
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Michael Kreuter
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Wim A. Wuyts
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Maria Molina-Molina
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Marlies Wijsenbeek
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Antonió Morais
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Argyrios Tzouvelekis
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Christopher J. Ryerson
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Fabian Caro
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Ivette Buendia-Roldan
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Jesper M. Magnusson
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Joyce S. Lee
    View author publications

    You can also search for this author inPubMed Google Scholar

  14. Julie Morisett
    View author publications

    You can also search for this author inPubMed Google Scholar

  15. Justin M. Oldham
    View author publications

    You can also search for this author inPubMed Google Scholar

  16. Lauren K. Troy
    View author publications

    You can also search for this author inPubMed Google Scholar

  17. Manuela Funke-Chambour
    View author publications

    You can also search for this author inPubMed Google Scholar

  18. Maria Laura Alberti
    View author publications

    You can also search for this author inPubMed Google Scholar

  19. Raphael Borie
    View author publications

    You can also search for this author inPubMed Google Scholar

  20. Simon L. F. Walsh
    View author publications

    You can also search for this author inPubMed Google Scholar

  21. Sujeet Rajan
    View author publications

    You can also search for this author inPubMed Google Scholar

  22. Yasuhiro Kondoh
    View author publications

    You can also search for this author inPubMed Google Scholar

  23. Yet H Khor
    View author publications

    You can also search for this author inPubMed Google Scholar

  24. Elisabeth Bendstrup
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

EVM: Conceptualization (lead); data curation (lead); project administration (lead); formal analysis (lead); investigation (lead); methodology (lead); visualization (lead); writing – original draft (lead); writing – review and editing (lead). TSP: Conceptualization (equal); data curation (lead); formal analysis (lead); methodology (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). MK: Conceptualization (equal); formal analysis (equal); investigation (equal), methodology (equal); writing – review and editing (equal). WAW: Conceptualization (equal); formal analysis (equal); investigation (equal), methodology (equal); writing – review and editing (equal). MMM Conceptualization (equal); formal analysis (equal); investigation (equal), methodology (equal); writing – review and editing (equal). MW: Conceptualization (equal); formal analysis (equal); investigation (equal), methodology (equal); writing – review and editing (equal). AM: Investigation (equal), writing – review and editing (equal). AT: Investigation (equal), writing – review and editing (equal). CJR: Investigation (equal), writing – review and editing (equal). FC: Investigation (equal), writing – review and editing (equal). IB: Investigation (equal), writing – review and editing (equal). JM Investigation (equal), writing – review and editing (equal). JL: Investigation (equal), writing – review and editing (equal). JMO: Investigation (equal), writing – review and editing (equal). LKT: Investigation (equal), writing – review and editing (equal). MFC: Investigation (equal), writing – review and editing (equal). MLA: Conceptualization (equal); formal analysis (equal); investigation (equal), methodology (equal); writing – review and editing (equal). RB: Investigation (equal), writing – review and editing (equal). SLW: Investigation (equal), writing – review and editing (equal). SR: Investigation (equal), writing – review and editing (equal). YK: Investigation (equal), writing – review and editing (equal). YHK: Investigation (equal), writing – review and editing (equal). EB: Conceptualization (lead); data curation (lead); supervision (lead); formal analysis (lead); investigation (lead); methodology (lead); visualization (lead); writing – original draft (lead); writing – review and editing (lead). All authors approved the final manuscript to be published and were involved in critically drafting or assessing the content of this paper.

Corresponding author

Correspondence to Emil Vilstrup Moen.

Ethics declarations

Ethics approval and consent to participate

This study, a health science survey questionnaire, was conducted in Denmark and was not subject to medical research involving human biological material. According to Danish Legislation no registration details were therefore required [41]. In this study, participants were not subject to procedures and participated voluntarily. To ensure the anonymity of the participants no email addresses were collected, participants were issued a code number and limited data were collected. It was therefore exempted from research ethics approval according to Danish legislation [41]. Prior to participating in the survey, the respondents were informed on the study, handling of the data and gave consent to participate when accepting to participate in the survey. All respondents were free to participate in the survey and skip any questions.

Consent for publication

Not applicable.

Competing interests

Thomas Skovhuus Prior has received honoraria for steering committee of scientific meetings from Boehringer Ingelheim, support for attending international meetings from Boehringer Ingelheim. Michael Kreuter has received grants and fees for consulting and lectures from BI, Roche, GSK and AstraZeneca. Wim A Wuyts has received grants or consultancy or speaker fees from Boehriner Ingelheim, Roche, Galapagos, Sanofi, Alentis, Pliant, Insilico, all payed to the institution. Maria Molina-Molina has received grants and fees for scientific advises from Boehringer, Roche, Ferrer and Chiesi. Marlies Wijsenbeek has received grants and fees for consulting and lectures from Astra Zeneca, Bristol Myers Squibb, Boehringer Ingelheim, Galapagos, Galecto, GSK, Hoffman la Roche, Horizon therapeutics, Kinevant Sciences, Molecure, Nerre Therapeutics, Novartis, PureTech Health, Thyron, Trevi, Vicore. Antonió Morias has received grants and fees for scientific advise or speaker fees from Roche, Boehringer Ingelheim, Bial, GSK and Sanofi-Aventis. Christopher J. Ryerson has received consulting fees from Boehringer-Ingelheim, Pliant Therapeutics, Astra Zeneca, Trevi Therapeutics, Veracyte and honoraria for lectures from Hofmann-La Roche and Boehringer-Ingelheim. Jesper Magnusson has received research grants from Boehringer-Ingelheim and consulting fees from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Takada Pharma, Vicore Pharma and Mallinckrodt. Joyce Lee has received grants from the NIH and Boehringer-Ingelheim, unrestricted research gift from Pliant and consulting fees from Blade, Boehringer Ingelheim, United Therapeutics, Astra Zeneca, Elima and Eleven P15. Justin Oldham have received consulting fees from Boehringer-Ingelheim and Roche. Lauren K. Troy have received speaker fees from Boehringer-Ingelheim and grant support from the NHMRC Centre of Research Excellence in Pulmonary Fibrosis. Manuela Funke-Chambour has received research support from BI, advisory board, consultancy fees from BI, MSD, GSK, Pfizer, Sanofi. Presentations: BI, Astra, GSK. Raphael Borie has received consulting fees from Boehringer-Ingelheim, Ferrer and Sanofi. Honoria for lectures from Boehringer-Ingelheim. Yasuhiro Kondoh serves as a consultant to Asahi Kasei Pharma Corp., Shionogi & Co.Ltd., Boehringer Ingelheim Co., Ltd., Janssen Pharmaceutical K.K., Healios K.K., Chugai Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd., received lecture fees from Asahi Kasei Pharma Corp., Shionogi & Co.Ltd., and Boehringer Ingelheim Co., Ltd., AstraZaneca K.K, Eisai inc., KYORIN Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma, and Novartis Pharma K.k., outside the presentation work. Yet. H Khor has received grants from NHMRC Investigator Grant during the conduct of the study and non-financial support from the Air Liquide Healthcare outside the submitted work. Elisabeth Bendstrup has received fees for presentations for Boehringer-Ingelheim, Daichii-Sankyo, AstraZeneca, Novartis. Advisory board meeting Boehringer-Ingelheim, travel support from Boehringer-Ingelheim. The other authors have nothing to disclose.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moen, E.V., Prior, T.S., Kreuter, M. et al. Diagnosis, screening, and follow-up of patients with familial interstitial lung disease: Results from an international survey. BMC Pulm Med 25, 59 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03532-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03532-0

Keywords

BMC Pulmonary Medicine

ISSN: 1471-2466

Contact us