Survey of physicians’ approaches to the clinical evaluation of interstitial lung disease in Singapore (SoPhoCLES)

Introduction

Significant progress has been made in the diagnosis of interstitial lung disease (ILD), primarily the change in diagnostic gold standard from histopathology to robust multidisciplinary discussion (MDD) consensus (1-3). Although the strength of MDDs are well-recognized (4,5), most studies involved expert centres where high quality clinical data was elicited by physicians with appropriate expertise and practice caseload (4-7).

Considerable variability exists in diagnostic practices and what physicians consider “key data” for MDD evaluation. Inadequate history-taking was cited in the 2002 American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus classification of idiopathic interstitial pneumonias as a common cause of misdiagnosis (8). A survey of physicians’ practices in idiopathic pulmonary fibrosis (IPF) diagnosis found differences between physician groups in utilization of supportive tests such as high resolution computed tomography (HRCT) and autoimmune serology (9). When bronchoalveolar lavage (BAL) was performed, the presence of lymphocytosis altered diagnostic perception in a proportion of patients from IPF to hypersensitivity pneumonitis (HP) (10). Cases presented with incomplete information may lead to inaccuracies in diagnosis and treatment, resulting in misleading conclusions if recruited into clinical trials without proper adjudication. In Singapore, less than five respiratory physicians offer a formal ILD service in their centres. Consequently, ILD patients may often be managed by non- fellowship-trained physicians who infrequently manage ILD, and whose diagnostic thought processes may not be similar to that of established ILD physicians.

We sought to determine if differences exist in ILD diagnostic approaches and between ILD and non-ILD physicians. We defined ILD physicians as respiratory specialists who received fellowship training and provided dedicated ILD services in their centre, and non-ILD physicians as respiratory specialists who neither received similar training nor provided dedicated ILD services in their centre. We present this article in accordance with the SURGE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1365/rc).

Methods

Questionnaire development

A focus group comprising five local respiratory physicians (three ILD and two non-ILD) discussed topics prior to the construction of the questionnaire until no further new ideas were generated. A pilot online questionnaire was developed by the principal investigator (PI) and completed independently by all focus group members. Based on feedback, the questionnaire was refined to minimize ambiguity in interpretation, and a final online version was created.

The survey was designed using the software, SoGoSurvey (Herndon, Virginia, USA), comprising the following sections (Appendix 1):

• Physicians characteristics and workload;
• ILD MDD structure and practice;
• Situational practices using case-based scenarios:
  • A case of newly diagnosed ILD;
  • Four case-based scenarios with HRCT (image acquisition; Appendix 2), pulmonary function test, BAL and other supporting data abstracted from de-identified electronic records of patients managed by the National University Health System. Patients involved had given consent for data to be used in the survey. None of the patients had undergone surgical lung biopsy. At the time of the study, these cases had been assessed independently by the PI and not discussed with any physician or MDD.

Online survey study

Certified respiratory specialists in all seven public hospitals in Singapore were invited to participate by email, followed by anonymized links to the online survey if they consented to proceed. The survey was conducted between 11 October 2017 to 2 January 2018. Five thoracic radiologists (3 local and 2 overseas) were also invited to independently rank their top three choices of HRCT diagnoses for the four case-based scenarios. As the number of ILD physicians in Singapore was small, four overseas ILD physicians from expert centres were invited to participate in the survey to benchmark local ILD physicians’ practices.

Due to the small numbers of academic thoracic radiologists in Singapore, overseas radiologists served to benchmark local radiologists’ responses.

Physicians were asked to rank their top three radiological diagnoses for cases 1–4, and clinical diagnoses for cases 1, 2 and 4. Radiological definitions of usual interstitial pneumonia (UIP) were referenced from the 2011 ATS/ERS/Japanese Respiratory Society (JRS)/Asociación Latinoamericana de Tórax (ALAT) IPF guidelines (2).

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Domain Specific Review Board of the National Healthcare Group (NHG), Singapore (No. 2017/00420). Informed consent was waived for study as it was an opt-in survey and anonymity was preserved.

Statistical analysis

STATA version 15.0 (version 15.0, StataCorp, College Station, TX, USA) was used to analyze the data. Associations between categorical variables were assessed with Fisher’s exact test, with P values <0.05 considered significant. Gwet’s AC (κ) was presented for the agreement of multiple raters defined in accordance with previous ILD literature on agreement (Appendix 3). For analysis of responses for the case scenarios, we focused only on first choice radiological and clinical diagnoses for analysis, due to the large number of variables in ranking of choices, and within constraints of the manuscript.

Due to the diverse clinical diagnoses offered by the non-ILD physicians, we regrouped clinical diagnoses for analysis in accordance with management strategies as follows:

Hence:

• IPF (managed with antifibrotics);
• Autoimmune (managed with immunosuppressants +/− antifibrotics);
• Environmental: drug-induced and HP (managed with removal of offending agent +/− immunosuppression;
• Other (included rare entities like occupational lung disease which did not fall into the common categories, but constituted a minority).

In case 4, we grouped physicians who did not order basic autoimmune serology or chose no further testing after diagnosing a radiological pattern of UIP with those who diagnosed IPF.

Results

Fifty-nine (61%) out of 96 local respiratory physicians, and three overseas ILD physicians completed the questionnaire (recruitment pathway in Figure S1). One overseas ILD physician only completed responses to the diagnoses for case-based scenarios. Local and overseas ILD physicians’ responses were grouped and analysed together as “ILD physicians” as no significant differences were found between physician characteristics and responses in both groups apart from sources of ILD referral (Tables S1,S2; Figure S2).

Physician characteristics and workload

There were no significant differences between physician groups in years’ post-specialist experience or university affiliation, although non-ILD physicians tended to be younger (Table 1). ILD physicians diagnosed more ILD cases (at least 45 cases a year) than non-ILD physicians (P<0.001). Although not reaching statistical significance, the proportion of cases diagnosed as IPF tended to be greater in the non-ILD group: 17% of ILD (n=1) vs. 57% (n=32) of non-ILD physicians reported IPF as comprising more than 30% of ILD cases (P=0.09) (Figure S3). Most referrals to ILD physicians were from respiratory physicians (50%) and rheumatologists (18%), while most referrals to non-ILD physicians were from inpatient (50%) and primary care (30%).

MDD structure and practice

Eighty-nine percent (n=55) of physicians had MDD support, of whom 53% had ILD-specific MDD while 35% discussed ILD cases at a general respiratory MDD. ILD physicians presented cases more frequently (more than 50% of the time, P=0.03) during meetings. When asked which specialty input (physician versus radiologist versus pathologist) would most likely influence their diagnostic confidence during MDD, 100% of ILD physicians rated physician input as being most important, while 46%, 38% and 16% of non-ILD physicians rated physician, radiologist and pathologist input as being most important, respectively. All ILD physicians rated a moderate-to-high (defined as >70%) level of confidence in formulating an independent radiological diagnosis from specific HRCT patterns, compared with 25% of non-ILD physicians (P<0.001).

Apart from BAL (100% ILD vs. 36% non-ILD physicians, P<0.02), supporting data was presented with equal frequency during meetings (Figure S4).

Situational practices

A hypothetical 65-year-old patient with newly diagnosed ILD without any symptoms and signs of connective tissue disease was presented. Physicians were asked what tests they would order if the HRCT pattern reported (I) definite UIP; (II) possible UIP and (III) inconsistent with UIP. In both groups, as the uncertainty of a UIP pattern increased on HRCT, there was increased likelihood in performing BAL, autoimmune serology and lung biopsy (Table 2).

Case-based scenarios (Appendix 1; Figure S5)

Cases 2 and 3: physicians were asked to select their radiological diagnosis, followed by what they would do if their top three radiological choices were discordant with their radiologist. Of 52 discordant diagnoses, 12 non-ILD vs. 1 ILD physician would not seek a second radiologists’ opinion. Case 4: a 63-year-old male ex-smoker with progressive respiratory and intermittent joint symptoms (without any signs of joint disease) was presented. Physicians were evaluated on the decision to order first tier autoimmune serology [defined as antinuclear antibody (ANA) and rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies] if the HRCT suggested a UIP pattern. Physicians who did not select basic serology would be directed to the next question, while the remaining physicians would be shown serology results, then asked for a final clinical diagnosis. Seventy percent of non-ILD physicians diagnosed the HRCT as UIP, of which 21% would not order serology or further tests. All ILD physicians diagnosed UIP and would order serology.

Diagnoses of four cases

Radiological diagnoses

First choice radiological diagnoses by each specialist group are shown (Figure 1).

Figure 1 First choice radiological diagnoses for cases 1 to 4. The above diagnoses were reflected in each case as ratings by the majority of thoracic radiologists and ILD physicians. Definite and possible UIP were grouped together. HP, hypersensitivity pneumonitis; ILD, interstitial lung disease; NSIP, non-specific interstitial pneumonia; OP, organising pneumonia; Others, other diagnoses; UIP, usual interstitial pneumonia.

Diagnoses for radiologists more closely matched that of ILD than non-ILD physicians. There was a wider range of diagnoses offered by non-ILD physicians in each case.

For agreement analysis, “definite and possible UIP” were grouped as “UIP”. Inter-rater agreement among different groups of specialists are reflected in Table 3. On first choice radiological diagnosis, agreement was moderate [κ=0.55 (−0.07 to 1.00)] among ILD physicians, moderate among thoracic radiologists [κ=0.53 (−0.06 to 1.00)] and moderate among radiologists and ILD physicians [κ=0.56 (0.10 to 1.00)]. Agreement was fair among non-ILD physicians [κ=0.29 (0.08 to 0.46)], fair among ILD and non-ILD physicians [κ=0.25 (−0.02 to 0.51)] and fair among radiologists and non-ILD physicians [κ=0.25 (0.02 to 0.47)].

Clinical diagnoses

First choice clinical diagnoses by physician groups (Figure 2) are shown. Non-ILD physicians offered a wider range of clinical diagnoses. These were regrouped into discrete categories of IPF, autoimmune, environmental and other, in accordance with different management strategies.

Figure 2 First choice clinical diagnoses for cases 1, 2 and 4. Autoimmune (NSIP/CTD-ILD/CEP), IPF, environmental (DILD/HP), Other-other diagnoses. CEP, chronic eosinophilic pneumonia; CTD-ILD, connective-tissue disease associated ILD; DILD, drug-induced ILD; HP, hypersensitivity pneumonitis; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; NSIP, non-specific interstitial pneumonia; Other, other diagnosis.

Agreement in the different physician groups are as shown in Table 4. This was moderate [κ=0.52 (−0.74 to 1.00)] among ILD physicians, fair [κ=0.35 (−0.31 to 1.00)] among non-ILD physicians, and fair [κ=0.36 (−0.35 to 1.00)] between the ILD and non-ILD physician groups. Using a dichotomised “IPF” vs. “Non-IPF” approach, agreement was perfect [κ=0.90 (0.40 to 1.00)] among ILD physicians, substantial [κ=0.63 (−0.52 to 1.00)] among non-ILD physicians, and substantial as a group [κ=0.65 (−0.34 to 1.00)].

Discussion

In our first nationwide ILD survey, we found distinct differences in diagnostic approaches and practices between ILD and non-ILD physicians. In particular, case volume (9,11-13), frequent MDD presentations (12), confidence in HRCT interpretation, physician-based decision-making at MDD (4) and case diagnosis differed between both groups, with local ILD physicians’ responses comparable to that of physicians from overseas expert centres. Consistent with prior studies (11,13), these attributes reflect prior training and sufficient caseload through dedicated ILD services to acquire expertise. Despite a lower ILD caseload, IPF diagnosis constituted a significant proportion of total ILD caseload in non-ILD physicians, exceeding most epidemiological data citing approximately 17–37% (14,15). There are a few possible reasons for this: firstly, non-ILD physicians may truly have a different case-mix of patients referred to them (e.g., primary care and inpatients), as subspecialty colleagues (e.g., rheumatologists and other respiratory physicians) may tend to refer patients with connective tissue disease or more complex patients to ILD physicians. Another reason could be narrower differential diagnoses amongst non-ILD physicians in evaluating complex ILD patients, resulting in a tendency to diagnose IPF as the most common form of fibrosing ILD by default. Previous studies on ILD subspecialty vs. non-subspecialty-based physicians had found the latter group more likely to ascribe a diagnosis to IPF (9,11), with potential management (16,17) and prognostic implications (18).

Flaherty’s study on the effect of a multidisciplinary approach to ILD diagnosis (4) demonstrated that as information was incrementally provided to experts, radiologists were more likely to change their diagnoses than physicians. Furthermore, physicians identified pathologically-confirmed IPF cases more frequently (75%) than radiologists (48%) prior to presentation of histopathological information. It is likely, therefore, that skilled physicians must possess a certain level of radiological proficiency to integrate both imaging and clinical data before making a provisional diagnosis. Our study findings demonstrate this in the ILD group by a high level of confidence in independent HRCT interpretation and subsequent high concordance in radiological diagnosis with radiologists and overseas ILD physicians.

The relatively lower confidence level in HRCT interpretation among non-ILD physicians may be associated with the significant proportion who placed radiology input as most likely to influence their diagnostic confidence during an MDD, where nearly a quarter would not challenge a diagnosis discordant with their radiologist. Yet the ability to challenge, and the need for radiology expertise, is shown in a review of 200 second opinion ILD computed tomography reports by fellowship-trained thoracic radiologists: a specific diagnosis was more likely to be provided in 97% vs. 59% of initial reports, and be concordant with multidisciplinary consensus (19).

The case-based scenarios were designed to evaluate physicians’ practices in “real-world” situations, e.g. joint symptoms with occupational exposure (case 4), radiologic-pathologic (trans-bronchial biopsy) mismatch (case 2), discordant radiology opinions (cases 2 and 3) and classic UIP radiology pending decisions for serologic testing (case 4). Prior to the 2018 ATS/ERS/JRS/ALAT guidelines which placed a motherhood statement on serological testing to exclude connective tissue disease (20), only a weak recommendation was placed on its role, with specific mention of ANA, RF and anti-CCP antibodies as first tier tests (3). Although this may explain the decision not to order autoimmune serologies in a minority of non-ILD physicians, all ILD physicians judged the need for serological testing to be mandatory and would do so without exception. However, there is debate among experts on which specific tests to perform (20). Hence, we allowed physicians who had chosen, at minimum, “ANA, RF and/or anti-CCP antibodies” in case 4 to view further data, taking into consideration that CTD (in particular, RA) can present with a UIP pattern and ILD may precede overt clinical manifestations of specific connective tissue diseases (21). This strategy revealed a small number of non-ILD physicians who diagnosed IPF solely based on a HRCT pattern of UIP.

In our study, ILD and non-ILD physicians were generally able to distinguish an IPF vs. non-IPF diagnosis as evidenced by the high levels of agreement between both groups for final clinical diagnosis when dichotomized into “IPF vs. non-IPF”. This mirrors previous studies reporting greater consensus among multidisciplinary teams in expert centres for IPF versus non-IPF (e.g., chronic HP) diagnoses (12,22,23). It may be argued that this broad distinction is sufficient where anti-fibrotic therapy is considered. However, we believed that subtle distinctions may be important in certain situations, such as when the identification and removal of an offending environmental or drug agent may impact upon survival (“DILD/HP”) (24), as opposed to treatment solely focused on immunosuppression (“NSIP/CTD-ILD/CEP”). Hence, we regrouped clinical diagnoses to reflect these differences.

Although agreement does not equate to diagnostic accuracy, we have shown that for both radiological and clinical diagnosis, the level of agreement among ILD physicians, both in expert centres and in our local setting, was higher than among non-ILD physicians. This suggests that pattern recognition skills, fine judgement with respect to exposures or the presence of an underlying CTD and a common language are pivotal in the diagnostic evaluation of ILD and better understood among physicians who manage similar rare diseases.

Our study was limited by the small number of ILD physicians in Singapore, accounting for the wide confidence intervals in agreement scores, although we had tried to demonstrate general trends between the ILD and non-ILD groups in the graphical comparisons. We believe that these trends are important and may be hypothesis-generating for future surveys when our numbers of local ILD physicians grow. With a lack of true gold standard in ILD diagnosis, we attempted to benchmark our approach with physicians from expert centres, which reflected similarities. However, it was not appropriate to recruit a disproportionate number of overseas physicians as the study largely aimed to compare local practices. Inaccurate recall and interpretation biases of questions are also possible. To avoid respondent fatigue, we restricted case scenarios to only four, which may not have been wholly reflective of physician’s diagnostic choices. Nonetheless, our survey response of 61% reflected a majority compared to previous similar surveys (9), and agreement levels among physicians in our survey, using different parameters, appeared consistent. Although our study demonstrated significant differences in the diagnostic processes, and in some instances, treatment strategies between ILD and non-ILD physicians, it was not designed to assess how these differences affect clinical outcomes. However, prior work on the diagnostic separation between IPF and non-IPF had demonstrated prognostic differences (12,13).

Conclusions

This survey underscores the importance of individual domain expertise in ILD beyond the mere consortium of an MDD, stressing the importance of early referral to expert centres when managing rare diseases. In situations where there may truly be a lack of access to ILD subspecialty expertise, the discussion may default to being image- or pathology-driven (25). A compromise may be to collaborate with an expert centre to conduct online MDD meetings. Additionally, deep learning models using artificial intelligence may have an evolving role in radiological MDD input for the diagnosis of ILD (26). Notwithstanding, expert input with a central co-ordinating physician remains paramount. The ideal MDD setup, as recommended by the Australian position paper, should consist of a group of specialists with sufficient expertise in different domains to assess and make recommendations (23,27). Such skills must first be developed through subspecialty training (28), then further honed by managing a sufficient volume of cases.

Acknowledgments

We would like to thank the following individuals who may not have been directly involved in the study design, but who have helped us facilitate participation in the survey in their respective centres: Drs JHY Tan (SKH), SK Tan (KTPH), CG Choo (NTFGH). We would also like to thank all the respiratory physicians from the following hospitals who had kindly taken the time to participate in this anonymous study: National University Hospital (NUH), Tan Tock Seng Hospital (TTSH), Singapore General Hospital (SGH), Changi General Hospital (CGH), Seng Kang General Hospital (SKH), Ng Teng Fong General Hospital (NTFGH), Khoo Teck Puat Hospital (KTPH).

Footnote

Reporting Checklist: The authors have completed the SURGE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1365/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1365/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1365/prf

Funding: This work was partially supported by a grant from Boehringer-Ingelheim, who sponsored the one-time purchase of the online survey.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1365/coif). All authors declare that this work was partially supported by a grant from Boehringer-Ingelheim, who sponsored the one-time purchase of the online survey. F.S.W.T. has received honorarium from Yungjin Pharmaceutical for speaker fees in 2025, Glaxo Smithkline for conference sponsorship to ERS in 2025, and Boehringer Ingelheim for advisory board fees in 2025. G.T.C. has received consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim paid to his institution. Boehringer Ingelheim also paid honoraria for lectures and support for attending meetings to S.Y.L. via her institution. S.L.F.W. is a paid employee of Qureight, an Imaging-analysis machine learning startup from Cambridge University, UK. S.L.F.W. has received research grant from Boehringer-Ingelheim, Galapagos and NIHR research fellowship, and consulting fees from Boehringer Ingelheim, Roche, Galapagos, Open Source Imaging consortium, Puretech, Pliant, Oncorendi Therapeutics, FLUIDDA, and advisory board fees from Boehringer-Ingelheim and Roche. S.L.F.W. has stock options in Qureight, an Imaging-analysis machine learning start up from Cambridge University, UK. M.K. has received educational fees from SAVARA pharma and consultancy fees from Boehringer Ingelheim. W.A.W. receives grants from the following companies, paid to his institution: Boehringer Ingelheim, Alentis, Endevor, NIH and fund for scientific research Flanders. L.L.S.T. has received grants from National Medical Research Council, Singapore for the projects, IMPACT-2 - FC 1c lead Theme PI and MOlecular Markers, MEchaNisms and their TherapeUtic Manipulation in Cardiovascular Disease, MOMMENTUM-CVD - Theme 4 member Co-I, SingHealth and A*STAR’s Healthcare Translation Partnership (HTP) grant 2023 for the project, SENSE: Singapore hEart lesioN analySEr Co-I. L.L.S.T. has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from: Siemens Healthineers, GE Healthcare, Philips Healthcare, Asian society of Cardiovascular Imaging, support for meetings by Siemens Healthineers, GE Healthcare. L.L.S.T. has sponsorship from Singapore Patent Application: “Systems And Methods For Vasculature Centreline Extraction” (“the Invention”), which has been filed as Patent Cooperation Treaty (PCT) Application No. PCT/SG2024/050796 on 13 December 2024 claiming priority from Singapore Patent Application No. 10202303513W filed 14 December 2023 and “Systems and Methods For Analysing Arterial Calcium” (“the Invention”), which has been filed as Patent Cooperation Treaty (PCT) Application No. PCT/SG2024/050795 on 13 December 2024 claiming priority from Singapore Patent Application No. 10202303520R filed on 14 December 2023 (“Patent Applications”). L.L.S.T. has participated in an advisory board by Roche Singapore Immunotherapy in Early stage NSCLC Patient Journey Advisory Board. L.L.S.T. is co-chair in the organizing Committee for the 19th Asian Congress of Cardiovascular Imaging 2026 Singapore, NHG Domain Specific Review Board (Domain C) (Ethics Board) deputy chair, and has stock options with MedClarity AI as co-founder, and has receipt of equipment, materials, drugs, medical writing, gifts or other services by MIMS Pte. Ltd. (Singapore), funded by Roche Singapore Pte. Ltd and AstraZeneca Singapore. J.W.S. was supported by grants from the Basic Science Research Program (NRF-2022R1A2B5B02001602) and the Bio & Medical Technology Development Program (NRF-2022M3A9E4082647) of the National Research Foundation of Korea (NRF) funded by the Ministry of Science & ICT, Republic of Korea, and also supported by the National Institute of Health research project (2024ER090500) and by Korea Environment Industry & Technology Institute through Core Technology Development Project for Environmental Diseases Prevention and Management Program funded by Korea Ministry of Environment (RS-2022-KE002197), Republic of Korea. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Domain Specific Review Board of the National Healthcare Group (NHG), Singapore (No. 2017/00420). Informed consent was waived for study as it was an opt-in survey and anonymity was preserved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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