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Abstract

Background:

The 2018 guidelines on the diagnosis of idiopathic pulmonary fibrosis (IPF) conditionally recommend multidisciplinary discussion (MDD) for diagnostic decision-making. However, limited data concerning the diagnostic impact of MDD on interstitial lung diseases (ILDs) are available.

Objectives:

The objective of this prospective study was to assess the impact of MDD at a tertiary referral ILD center on diagnostic trajectories, prognosis, and identification of potential treatable traits in ILD management.

Design:

This prospective study enrolled all consecutive adult ILD patients referred for MDD to a tertiary academic center in San Antonio, TX, USA from January 2017 to May 2020. The subjects were followed during a 3-year follow-up period after the MDD.

Methods:

Patients were stratified into three groups according to the pre-MDD diagnosis: unspecified ILD, IPF, and not IPF, and compared to the re-stratification post-MDD diagnosis into: unclassifiable ILD, IPF, and not IPF. The primary outcome was the percentage change in diagnostic trajectories after the MDD discussion.

Results:

A total of 201 ILD patients (61.7% male; mean (DS) age: 67.2 (10.4) years) were included in the study. The total diagnostic trajectory change occurred in 122 (60.7%) patients. The diagnostic trajectories changed in 40 (46.5%) patients in the IPF group and 8 (19.5%) in the non-IPF group (p-value = 0.0003). Patients with pre-MDD unspecified-ILD were classified as not-IPF in 32.4% (n = 24), IPF in 23% (n = 17), and unclassifiable-ILD in 44.6% (n = 33) post-MDD. Considering the post-MDD diagnosis, differences in mortality were detected among the three groups (p = 0.037).

Conclusion:

Our results suggest that MDD has a significant impact not only on the diagnostic trajectories (DT) but also on the prognosis of patients with ILDs.

Plain language summary

This study analyzes the impact of multidisciplinary discussion on diagnostic trajectories and the prognosis of interstitial lung disease patients

Study question: What is the impact of a multidisciplinary discussion on diagnostic trajectories and the prognosis of patients with an interstitial lung disease? Results: The total diagnostic trajectories change occurred in 122 (60.7%) patients after multidisciplinary discussion. Differences in mortality were detected among the study groups after multidisciplinary discussion although they were not detected before multidisciplinary discussion, underlying the importance of cooperation of several healthcare figures. Interpretation: Our study suggests that multidisciplinary discussion has a significant impact on the diagnostic trajectory, management and prognosis of patients with interstitial lung disease.

Keywords

diagnostic trajectories interstitial lung diseases multidisciplinary discussion

Introduction

Interstitial lung diseases (ILDs) comprise a diverse group of pulmonary disorders characterized by a wide array of management challenges and prognoses.¹ The most recent American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines conditionally recommend an integrated approach centered on multidisciplinary discussion (MDD) for diagnosis and management of idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), and progressive pulmonary fibrosis (PPF).^2
–4 Several studies reported that an integrated multidisciplinary team (MDT) improves diagnostic confidence and patient outcomes when compared to individual MDT components.^5
–8 The diagnosis of a specific ILD diagnosis requires not only the integration of imaging, laboratory, and histopathology data in the MDD but also the competencies and experiences of different healthcare figures to increase diagnostic confidence and improve patient outcomes. MDD may significantly change treatment and expedite referral to lung transplant and clinical trials.⁹ Despite these advances, challenges persist, particularly in the diagnosis of non-IPF ILD, where many patients remain as unclassifiable ILD despite extensive workup.

Standardization of the MDT is lacking, and MDT composition varies widely across countries based on available resources and center expertise.^10,11 An international Delphi survey identified essential components of an ILD MDD, which include the presence of at least one radiologist, a quiet setting with a visual projection system, high-quality chest high-resolution computed tomography (HR-CT), and a standardized template summarizing collated patient data.¹² Despite guideline recommendations, there are no widely standardized case report forms (CRFs) to be used during the MDD. The composition of members may depend on the purpose of an MDD with the inclusion of thoracic surgeons, palliative care physicians, and rheumatologists considered on a case-by-case basis in several centers running the MDD only for diagnosis purposes.^13,14 However, the MDD is vital for the identification and management of potential treatable traits tailored on an individual level with the aim of improving patients’ outcomes.^14,15

Thus, the objective of this prospective study was to assess the impact of MDD at a tertiary referral ILD center on diagnostic trajectories, prognosis, and identification of potential treatable traits in ILD management.

Materials and methods

Patient selection

We conducted a prospective observational study including all consecutive adults with ILD who presented at MDD meetings held every 2 weeks at a tertiary academic center in San Antonio, TX, USA, from January 2017 to May 2020. Patients were followed for 3 years after MDD or up to May 2023. Patients were excluded if they were discussed for reasons not related to ILD diagnosis or management (e.g., discussion of histopathology after lung explant). The study was approved by the institutional ethics committee. The present study protocol adheres to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) Statement.¹⁶

Multidisciplinary discussion

Cases were documented using a standard CRF that detailed complete medical history, physical examination, laboratory test results, pulmonary function test results, HR-CT findings, bronchoalveolar lavage (BAL) counts, and lung biopsy results (reported in the Supplemental Material). The MDD was led by an expert pulmonologist (A.N.), convened every other week for 80 min, and included pulmonologists (typically at least three, including two senior faculty pulmonologists each with 30 years of clinical experience, a lung transplant pulmonologist and pulmonary fellows-in-training), a thoracic radiologist, and a thoracic pathologist.

Patients were initially categorized as either unspecified ILD (patients without a diagnosis before MDD discussion), IPF, or non-IPF ILD (including patients with connective tissue disease-ILD (CTD-ILD), HP, non-specific interstitial pneumonia (NSIP), and other idiopathic interstitial pneumonias (IIP). Pre-MDD diagnoses were based on the referring pulmonologist’s diagnosis and current consensus classification for IIP.¹ Post-MDD diagnoses were unclassifiable ILD, IPF, or non-IPF ILD. Post-MDD diagnosis was classified according to Ryerson confidence terminology,¹⁷ with “confident diagnosis” reserved for >90% clinical likelihood or a provisional diagnosis, which was categorized as “high confidence” (70%–89% likelihood) or “low confidence” (51%–69% likelihood). Patients with <50% diagnostic confidence level post-MDD were categorized as “unclassifiable ILD”,¹⁸ which included patients categorized as interstitial pneumonia with autoimmune features (IPAF).¹⁹ The same CRF was used to document MDD-driven changes in management and diagnostic workup. Patients were presented again after additional diagnostic steps were completed prior to finalizing management changes.

Follow-up data

During the 3-year follow-up period, data on mortality, time to lung transplant or death, and causes of death (e.g., acute exacerbation, respiratory insufficiency, lung cancer, and heart failure) were collected. Forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide, and adverse events of therapy were also tracked.

Study outcomes

The primary outcome was the percentage change in diagnostic trajectory after MDD. Secondary outcomes included: (1) additional workup after MDD; (2) MDD-driven treatment changes; and (3) survival differences among the groups before and after MDD.

Statistical analysis

As the primary aim of the study was to explore if MDD will reduce the number of patients going from an IPF/non-IPF classification to unclassified, we hypothesized that before MDD we have a 28% misclassification, and we would like to demonstrate a reduction to 18% of misclassification post MDD. Considering a 0.7 correlation, a 5% alpha error, and an 80% power, the study needed to enroll 90 patients with a pre-MDD IPF/non-IPF classification. We would increase the number of patients going from a misclassification before MDD to an IPF/non-IPF diagnosis. Hypothesizing a 19% re-classification, we want to increase to 35%. Considering a correlation of 0.5, a 5% alpha error, and an 80% power, the study needed to enroll 66 patients with a pre-MDD unspecified ILD. We have considered that 20% of patients might be lost at follow-up; thus, we considered a sample size of 188 patients.

Qualitative data were described with absolute and relative (percentage) frequencies, and quantitative data used mean + standard deviation (SD) or medians (interquartile ranges) (IQR) depending on their normal or non-normal distribution, respectively. Comparative analyses employed chi-squared and Fisher exact tests, with Yates correction for small groups. Quantitative variables were compared using ANOVA or Kruskall–Wallis tests, based distribution, with Sidak correction for multiple comparisons. Chi-square testing assessed MDD impact on ILD categories. Kaplan–Meier estimates with log-rank testing compared survival across groups. Significance was set at a two-tailed p-value < 0.05. The analysis was performed using SPSS, version 21.0 (SPSS, Chicago, IL, USA).

Results

Baseline characteristics

A total of 201 ILD patients (61.7% male; mean (SD) age: 67.2 (10.4) years) were included in the study. Characteristics of the study cohort are reported in Supplemental Table 1.

Characteristics of the pre-MDD study groups are presented in Table 1. IPF patients were more frequently male compared to non-IPF ILD patients (n = 62, 72.1%, vs n = 18, 43.9%, p = 0.002) and compared to both unspecified ILD and non-IPF ILD patients (p = 0.003 and p < 0.001, respectively). Current or former smokers were more frequently identified in IPF group (n = 59, 68.6%) compared to non-IPF ILD group (n = 16, 39%), p = 0.006, and obesity was more common in the unspecified ILD group (n = 32, 43.2%) compared to the IPF group (n = 20, 23.3%), p = 0.007. IPF patients had a higher percent predicted FVC (67.1 (16.7)) compared to both non-IPF ILD (59.1 (17)) and unspecified-ILD (58.2 (17.3)) groups, (p = 0.044 and p = 0.003 respectively).

Table 1.

Characteristic of the pre-MDD study groups.

Variables	Unspecified ILD (n = 74)	IPF group (n = 86)	Non-IPF (n = 41)	p Value
Demographic
Sex male	44 (59.5%)	62 (72.1%)	18 (43.9%)	0.008^a
Age years average (SD)	66.5 (10.2)	71.5 (6.6)	59.6 (12.6)	<0.001^b–d
Current or former smoker	45 (60.8%)	59 (68.6%)	16 (39%)	0.023^e
Obesity (BMI > 30)	32 (43.2%)	20 (23.3%)	16 (39%)	0.021^f
Symptoms
Dyspnea	65 (87.8%)	73 (84.9%)	39 (95.1%)	0.250
Cough	58 (78.4%)	72 (83.7%)	30 (73.2%)	0.366
Sputum production	18 (24.3%)	23 (26.7%)	9 (22%)	0.835
Hemoptysis	1 (1.4%)	2 (2.3%)	4 (9.8%)	0.046
Chest pain	3 (4.1%)	2 (2.3%)	8 (4%)	0.404
Fatigue	14 (18.9%)	8 (9.3%)	7 (17.1%)	0.195
Weight loss	3 (4.1%)	6 (7%)	1 (2.4%)	0.492
Pulmonary function tests
FEV1 % (SD)	64.9 (18.5)	77.3 (19.2)	64 (18.3)	<0.001^g,h
FVC % (SD)	58.2 (17.3)	67.1 (16.7)	59.1 (17)	<0.001^i,j
TLC % (SD)	56.2 (13.1)	62.9 (12.8)	59.3 (15.8)	0.68
DLCO % (SD)	46.9 (16.5)	46.1 (16.6)	50.3 (17.2)	0.425
Comorbidities
Asthma	13 (17.6%)	10 (11.6%)	9 (22%)	0.294
COPD	1 (1.4%)	9 (10.5%)	3 (7.3%)	0.063
OSA	15 (20.3%)	14 (16.3%)	6 (14.6%)	0.699
TIA/Stroke	1 (1.4%)	7 (8.1%)	2 (4.9%)	0.144
Atrial fibrillation	1 (1.4%)	7 (8.1%)	3 (7.3%)	0.144
CAD	11 (14.9%)	22 (25.6%)	5 (12.2%)	0.106
CHF	5 (6.8%)	3 (3.5%)	1 (2.4%)	0.474
HTN	35 (47.3%)	49 (57%)	17 (41.5%)	0.214
DM	19 (25.7%)	13 (15.1%)	6 (14.6%)	0.173
GERD	29 (39.2%)	45 (52.3%)	17 (41.5%)	0.215
CKD	2 (2.7%)	5 (5.8%)	2 (4.9%)	0.631
HLP	29 (39.2%)	36 (41.9%)	13 (31.7%)	0.545
Malignancy	8 (10.8%)	15 (17.4%)	5 (12.2%)	0.452
Chemotherapy	2 (2.7%)	5 (5.8%)	0	0.223
Radiotherapy	0	3 (3.5%)	1 (2.4%)	0.282
History of exposure
Work	13 (17.6%)	20 (23.3%)	6 (14.6%)	0.456
Domestic	17 (23%)	22 (25.6%)	5 (12.2%)	0.224
Drug	4 (5.4%)	2 (2.3%)	1 (2.4%)	0.525
Test performed
HR-CT	74 (100%)	86 (100%)	41 (100%)	1
Bronchoscopy	15 (20.3%)	14 (16.3%)	10 (24.4%)	0.542
Biopsy	23 (31.3%)	27 (31.4%)	24 (58.5%)	0.005^k,l
Immunological screening	71 (95.9%)	86 (100%)	39 (95.1%)	0.142
Any positive findings at immunological screening	33 (44.6%)	34 (39.5%)	28 (68.3%)	0.005^m,n
Treatment
Oxygen	21 (28.4%)	24 (27.8%)	14 (34.1%)	0.750
Antifibrotic	6 (8.1%)	40 (46.5%)	1 (2.4%)	< 0.001^o,p
High dose steroid	9 (12.2%)	2 (2.3%)	16 (39%)	<0.001^q–s
Low dose steroid	16 (21.6%)	3 (3.5%)	16 (39%)	<0.001^t–v
Immunosuppressive agents	9 (12.2%)	0 (0%)	18 (43.9%)	<0.001^w–y

p < 0.05 for the following group comparison: ^aIPF versus non-IPF; ^bIPF versus unspecified ILD; ^cunspecified ILD versus non-IPF; ^dIPF versus non-IPF; ^eIPF versus unspecified ILD; ^fIPF versus unspecified ILD; ^gIPF versus unspecified ILD; ^hIPF versus non-IPF; ⁱIPF versus unspecified ILD; ^jIPF versus non-IPF; ^kunspecified ILD versus non-IPF; ^lIPF versus non-IPF; ^munspecified ILD versus non-IPF; ⁿIPF versus non-IPF; ^oIPF versus unspecified ILD; ^pIPF versus non-IPF; ^qIPF versus unspecified ILD; ^runspecified ILD versus non-IPF; ^sIPF versus non-IPF; ^tIPF versus unspecified ILD; ^uunspecified ILD versus non-IPF; ^vIPF versus non-IPF; ^wIPF versus unspecified ILD; ^xunspecified ILD versus non-IPF; ^yIPF versus non-IPF.

BMI, body mass index; CAD, chronic artery disease; CHF, chronic heart failure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DLCO, diffusion lung capacity for carbon monoxide; DM, diabetes mellitus; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; GERD, gastro-esophageal reflux disease; HLP, hyperlipemia; HR-CT, high-resolution computed tomography; HTN, systemic hypertension; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; MDD, multidisciplinary discussion; OSA, obstructive sleep apnea; SD, standard deviation; TIA, transient ischemic attack; TLC, total lung capacity.

No differences in exposure history were identified among the three groups, although domestic exposure was more frequently reported in HP patients within the non-IPF group. Lung biopsy was more frequently available in patients with non-IPF (n = 24, 58.5%) compared to both IPF (n = 27, 31.4%) and unspecified ILD (n = 23, 31.3%) groups, p = 0.004 and p.0004 respectively. The immunological screening was more frequently positive in non-IPF patients (n = 28, 68.3%) compared to both IPF (n = 34, 39.5%) and unspecified ILD (n = 33, 44.6%) groups, p < 0.001 and p = 0.027, respectively.

Change in diagnostic trajectories

Before MDD, IPF was the most common diagnosis (42.8% (n = 86)) followed by unspecified ILD (36.8% (n = 74)). After MDD, 31.3% (n = 63) patients were diagnosed with IPF, 31.3% (n = 63) with unclassifiable ILD, and 37.3% (n = 75) with non-IPF ILD (Figure 1). Notably, diagnostic trajectory changed in 60.7% of cases, specifically 46.5% (n = 40) in the IPF and 19.5% (n = 8) in the non-IPF ILD groups (Figure 1). The IPF group had the most significant change in diagnosis (p-value = 0.0003). Patients with pre-MDD unspecified ILD were classified as non-IPF ILD (33.8% (n = 25)), IPF (23% (n = 17)) and unclassifiable ILD in 43.2% (n = 32) post-MDD.

Figure 1.

Sankey diagram showing change in diagnostic trajectories among ILD patients.

Additional tests and workup required after MDD

After MDD, additional evaluations were recommended in 63.2% (n = 127) of patients (Table 2 and Figure 2), of which, 68.2% (n = 60) were IPF patients, 56.1% (n = 23) were non-IPF patients and 59.5% (n = 44) were unspecified ILD patients. Additional diagnostic testing and evaluation included either those to confirm or exclude a diagnosis (e.g., BAL, lung biopsies, rheumatological evaluation, etc.) or those to assess disease severity and progression (e.g., lung transplant team evaluation, echocardiogram, and cardiac catheterization). BAL was more frequently required in IPF patients (n = 17, 19.8%), compared to non-IPF patients (n = 1, 2.4%), p = 0.009. After MDD, an indication for any type of biopsy was identified more frequently in IPF patients (n = 15, 17.4%) compared to non-IPF patients (n = 1, 2.4%), p = 0.017. The MDT identified an indication for surgical lung biopsy more frequently in IPF patients (n = 10, 11.6%) compared to unspecified ILD patients (n = 1, 1.4%), p = 0.002.

Table 2.

Work-up required and treatment change after MDD.

Additional work-up required and treatment change	Entire cohort (n = 201)	Unspecified ILD(n = 74)	IPF group(n = 86)	Non-IPF(n = 41)	p Value
No further work-up	74 (36.8%)	30 (40.5%)	26 (30.2%)	18 (43.9%)	0.131
BAL	27 (13.4%)	9 (12.2%)	17 (19.8%)	1 (2.4%)	0.026^a
Biopsy	23 (11.4%)	7 (9.5%)	15 (17.4%)	1 (2.4%)	0.036^b
Surgical lung biopsy	11 (5.5%)	0 (0%)	10 (11.6%)	1 (2.4%)	0.003^c
TBB biopsy	10 (5%)	5 (6.8%)	5 (5.8%)	0 (0%)	0.250
Cryobiopsy	2 (1%)	2 (2.7%)	0 (0%)	0 (0%)	0.177
Rheumatological evaluation	27 (13.4%)	10 (13.5%)	16 (18.6%)	5 (12.2%)	0.548
Lung transplant evaluation	52 (25.9%)	20 (27.7%)	19 (22.1%)	13 (31.7%)	0.492
Echo	23 (11.4%)	6 (8.1%)	13 (15.1%)	4 (9.8%)	0.355
Cardiac catheterization	7 (3.5%)	4 (5.4%)	2 (2.3%)	1 (2.4%)	0.525
Treatment change
No treatment change	95 (47.3%)	36 (48.5%)	41 (47.7%)	18 (43.9%)	0.883
Add new treatment/s	91 (45.3%)	32 (43.2%)	40 (46.5%)	19 (46.3%)	0.907
Stop previous treatment/s	2 (1%)	0 (0%)	2 (2.3%)	0 (0%)	0.259
Add new treatment/s AND stop previous treatment/s	12 (6%)	5 (6.8%)	3 (3.5%)	4 (9.8%)	0.355
Treatment added after MDD
Antifibrotic	26 (12.9%)	10 (13.5%)	16 (18.6%)	0 (0%)	0.014^d,e
High dose steroid	11 (5.5%)	6 (8.1%)	1 (1.2%)	4 (9.8%)	0.063
Low dose steroid	23 (11.4%)	9 (12.2%)	9 (10.5%)	5 (12.2%)	0.932
Immunosuppressive agents	42 (20.9%)	18 (24.3%)	10 (11.6%)	14 (34.1%)	0.09^f,g
Clinical trial	24 (11.9%)	5 (6.8%)	16 (18.6%)	3 (7.3%)	0.042^h
Oxygen therapy	13 (6.5%)	3 (4.1%)	7 (8.1%)	3 (7.3%)	0.560
Rehabilitation	18 (9%)	6 (8.1%)	7 (8.1%)	5 (12.2%)	0.718

p < 0.05 for the following group comparison: ^aIPF versus non-IPF; ^bIPF versus non-IPF; ^cIPF versus unspecified ILD; ^dunspecified ILD versus non-IPF; ^eIPF versus non-IPF; ^fIPF versus unspecified ILD; ^gIPF versus non-IPF; ^hIPF versus unspecified ILD.

BAL, bronchoalveolar lavage; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; MDD, multidisciplinary discussion; TBB, transbronchial biopsy.

Figure 2.

Additional tests/evaluation required after MDD. Single or multiple tests could be required for each ILD patient.

Treatment change

The MDD led to a treatment change in 52.7% (n = 106) of ILD patients (Table 2), specifically in 52.3% (n = 45) of IPF patients, 56.1% (n = 23) of non-IPF ILD, and 51.5% (n = 38) of unspecified ILD. New treatment was started in 44.4% (n = 91) of patients; pre-MDD treatment was stopped in 1% (n = 2) of patients, and previous treatments were discontinued with the introduction of a new treatment in 6% (n = 12) of patients.

Before MDD, antifibrotics (nintedanib or pirfenidone) were most frequently used in IPF patients (n = 40, 46.5%), compared to both non-IPF (n = 1, 2.4%) and unspecified ILD (n = 6, 8.1%) patients, p < 0.001 and p < 0.001, respectively. Antifibrotics were more frequently added in pre-MDD both unspecified (n = 10, 13.5%) and IPF (n = 16, 18.6%) groups compared to pre-MDD non-IPF (n = 0, 0%) group, p = 0.014 and p = 0.003, respectively.

High-dose corticosteroids were more frequently administered in non-IPF ILD patients both before MDD (n = 16, 39%), compared to IPF and unspecified ILD (p < 0.001 and p = 0.001). After MDD, high-dose systemic corticosteroids were most commonly added in unspecified ILD patients compared to IPF patients (p = 0.014). Low-dose corticosteroids were also more frequently administered in non-IPF ILD patients (n = 16, 39%) compared to IPF and unspecified ILD (n = 16, 21.6%) (p < 0.001 and p < 0.001). Immunosuppressive agents (including azathioprine, mycophenolate, and rituximab) were more frequently administered in the non-IPF ILD group (n = 18, 43.9%) compared to both IPF (n = 0, 0%) and unspecified ILD (n = 9, 12.2%) groups, p < 0.001 and p < 0.001, respectively. Immunosuppressive agents were most frequently added in unspecified ILD (n = 18, 24.3%) and non-IPF ILD (n = 14, 34.1%) groups compared to pre-MDD IPF group (p = 0.035 and p = 0.002). Finally, clinical trials were more frequently proposed to patients in IPF group (n = 16, 18.6%) compared to pre-MDD unspecified ILD group (n = 5, 6.8%), p = 0.035.

Survival

Among the 201 included patients, 168 patients have completed data at the 3-year follow-up. 33 patients were excluded from the survival analysis due to insufficient follow-up (n = 10) or transfer to another ILD center/referral pulmonologist without access to medical records (n = 23). Considering the post-MDD diagnosis, 56 of 63 IPF patients, 51 of 63 unclassifiable ILD patients, and 61 of 75 non-IPF ILD patients were included in the analysis. No differences in the composite survival outcome were identified according to the pre-MDD groups. However, there were significant 3-year survival differences among the post-MDD groups (p = 0.037) (Figure 3). In the post-MDD IPF group, 28.6% (n = 16) patients died at 3-year follow-up whereas 12.5% (n = 7) patients underwent lung transplants. The cause of death was related to respiratory events in 62.5% (n = 10) of the patients. In the non-IPF group, 19.7% (n = 12) patients died at 3-year follow-up whereas 6.6% (n = 4) patients underwent lung transplant. The cause of death was related to respiratory events in 41.7% (n = 5) of the patients. Unclassifiable ILD carried significant mortality (33.3% (n = 17)) with death most commonly related to respiratory events in 47.1% (n = 8). 17.6% (n = 9) of unclassifiable ILD patients underwent lung transplant.

Figure 3.

Kaplan–Maier showing 3-year survival among the post-MDD groups.

Discussion

This study shows that MDD significantly modifies the ILD trajectory and emphasizes the importance of an integrated multidisciplinary approach to ILD. A confident ILD diagnosis was changed in 60% and specific treatment changed in 52.7% of ILD patients. These data are consistent with previous studies showing change in diagnosis following MDD in 40%–62% of cases.^7,8,20
–22 Of note, 46.5% (n = 40) in the pre-MDD IPF group were identified not to have IPF after MDD. In these patients, the MDD hypothesized an alternative diagnosis for which a biopsy (indicated in 17.4% of the pre-MDD IPF group) or additional tests were required. This highlights the importance of referral centers for ILD patients. However, MDD might not be readily available in many small or rural centers. Implementation of some procedures, such as a minimum bundle of rheumatological tests or a standardized questionnaire to assess for exposures, is of paramount importance in improving diagnostic confidence.²³

Importantly, patients with a pre-MDD diagnosis of unspecified ILD achieved a specific diagnosis in 56.8% of cases (23% as IPF and 33.8% as non-IPF ILD). Unclassifiable ILD was associated with the highest mortality in our cohort and remains a challenge to study as the incidence of unclassifiable ILD varies widely.^{7,8,18,20
–24} In our cohort, ILD was deemed unclassifiable in 31.3% of unspecified ILD cases, which may be due to several factors. Firstly, our hospital is a tertiary referral hospital, which biases toward challenging patients who were referred as unspecified ILD after inconclusive MDDs at primary and secondary centers. Secondly, our cohort of patients had advanced disease (~30% requiring home oxygen), which likely affected the feasibility and risk profile of invasive lung biopsy. This emphasizes the importance of an early evaluation in ILD referral centers, particularly for patients who may require additional diagnostic tests and lung biopsy to reach a diagnosis. Thirdly, we included IPAF patients in the unclassifiable ILD group given the evidence that IPAF is currently a “research label” rather than a diagnostic label.²⁵

In this study, MDD had a significant impact on the management of patients with ILD. Further investigations were pursued in 63.2% of ILD patients—at least one additional test was required in 68.2% of pre-MDD IPF patients, 56.1% of pre-MDD non-IPF patients and 59.5% of pre-MDD unspecified ILD patients. These tests were required not only to confirm or exclude a diagnosis but also to assess disease severity and progression. The active involvement of a lung transplant pulmonologist on the MDT resulted in a high rate of lung transplant referral in 25.9% (n = 52) of patients, which is often the only available curative treatment for many ILDs. This again underlines the importance of an early evaluation in ILD referral centers.

This study also emphasizes the central role of expert opinion for both accurate diagnosis and initiation of treatment, as evidenced by MDD leading to a treatment change in 52.7% of ILD patients. Despite a change in the diagnostic category in 19.5% of the pre-MDD non-IPF ILD group, 43.9% in this group of patients changed treatment. MDD improved concordance with ATS/ERS guidelines for the management of IPF and PPF, as antifibrotics were frequently added in the pre-MDD IPF and unspecified ILD group, while immunosuppressive agents were more frequently added in the pre-MDD non-IPF. Of note, nintedanib was not approved for PPF phenotype at the time when MDD discussions were conducted.

A strength of this study is the inclusion of long-term follow-up on mortality post-MDD. While there are no established independent reference standards to validate an MDT diagnosis, it has been proposed that the MDD can be indirectly assessed by comparing outcomes, especially mortality, between IPF and non-IPF ILD diagnoses after MDD.^5,26 In our study, the diagnostic reclassification by the MDD led to a distinct prognostic separation among the three groups. Notably, 41.3% of IPF patients died or were transplanted within 3 years versus 26.3% of patients in the non-IPF ILD group. However, this did not reach statistical significance, possibly due to the small sample size and confounding by comorbidities, as evidenced by significant non-respiratory related death (59.3% in non-IPF ILD vs 38.5% in IPF). Moreover, baseline FVC was highest in the IPF group, suggesting an early referral for these patients. Additionally, this underscores the tendency for patients with advanced non-IPF ILD or unspecified ILD to be referred to tertiary centers for expertise beyond primary or secondary centers.

We used a standardized CRF to organize important patient data and facilitate discussing patients, providing a diagnostic label, and suggesting further investigations and interventions. Thus, our MDD is a step toward more personalized medicine. While diagnostic ILD labels have standardized criteria based on consensus documents of standardized diagnostic ontology ILDs,¹⁷ we validated the impact of the diagnostic and treatment change with 3-year mortality.

The limitations to our study are inherent in the study design as it was conducted at a single-center tertiary referral center: patients were often more severe compared to other centers or referred for persistent diagnostic uncertainty in a primary or a secondary center. Moreover, while the MDD diagnoses were consistent within our center, they lacked external validation for inter-MDD agreement. Although it would be of interest to know which investigation(s) changed the most in the final diagnosis, we were not able to assess the weight of each investigation discussed within the MDD. The experience of the MDD increased over the study period, which may have affected the diagnostic accuracy, but it is noteworthy that our team was highly experienced in ILD before the study. The absence of rheumatologists, occupational medicine specialists, and respiratory physiotherapists may have also affected rates of CTD-ILD and HP diagnoses as well as referrals for pulmonary rehabilitation. Emerging novel diagnostic tools for ILD such as a genomic UIP classifier,²⁷ artificial intelligence for image assessment, and computer-based deep learning algorithms for digital histology slides^28
–30 were not a part of this study and will undoubtedly further improve ILD diagnostic trajectories. Finally, our study did not incorporate phenotyping and endotyping of ILD patients, which may be crucial for identifying treatable traits, such as PPF^31
–34 because the results of the INBUILD trial were unavailable during our MDD study period. The timing of this study also likely affected the rates of antifibrotic use in non-IPF ILD, as nintedanib was approved by the United States Food and Drug Administration after our study period for PPF.

Conclusion

Our study suggest that MDD has a significant impact on the diagnostic and prognostic trajectory of ILD patients. Moreover, our study highlights a pragmatic approach as in the real world not every patient with ILD can get a lung biopsy due to several reasons such as disease severity or respiratory failure severity. Our study also suggests that MDD has a significant impact on the management of ILD patients, as demonstrated by the high rate of lung transplant referrals, which is often the only available curative treatment for many ILDs.

Supplemental Material

sj-docx-1-tar-10.1177_17534666251323487 – Supplemental material for Diagnostic and prognostic trajectories of interstitial lung diseases after the multidisciplinary discussion

Supplemental material, sj-docx-1-tar-10.1177_17534666251323487 for Diagnostic and prognostic trajectories of interstitial lung diseases after the multidisciplinary discussion by Francesco Amati, Dean L. Kellogg, Marcos I. Restrepo, Francesco Blasi, Stefano Aliberti and Anoop M. Nambiar in Therapeutic Advances in Respiratory Disease

Supplemental Material

sj-docx-2-tar-10.1177_17534666251323487 – Supplemental material for Diagnostic and prognostic trajectories of interstitial lung diseases after the multidisciplinary discussion

Supplemental material, sj-docx-2-tar-10.1177_17534666251323487 for Diagnostic and prognostic trajectories of interstitial lung diseases after the multidisciplinary discussion by Francesco Amati, Dean L. Kellogg, Marcos I. Restrepo, Francesco Blasi, Stefano Aliberti and Anoop M. Nambiar in Therapeutic Advances in Respiratory Disease

Supplemental Material

sj-docx-3-tar-10.1177_17534666251323487 – Supplemental material for Diagnostic and prognostic trajectories of interstitial lung diseases after the multidisciplinary discussion

Supplemental material, sj-docx-3-tar-10.1177_17534666251323487 for Diagnostic and prognostic trajectories of interstitial lung diseases after the multidisciplinary discussion by Francesco Amati, Dean L. Kellogg, Marcos I. Restrepo, Francesco Blasi, Stefano Aliberti and Anoop M. Nambiar in Therapeutic Advances in Respiratory Disease

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

Francesco Amati

Dean L. Kellogg III

Anoop M. Nambiar

Supplemental material

Supplemental material for this article is available online.

References

Travis

Costabel

Hansell

, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013; 188: 733–748.

Raghu

Remy-Jardin

Myers

, et al. Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018; 198(5): e44–e68.

Raghu

Remy-Jardin

Richeldi

, et al. Idiopathic pulmonary fibrosis (an Update) and progressive pulmonary fibrosis in adults: an Official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2022; 205(9): e18–e47.

Fernández Pérez

Travis

Lynch

, et al. Diagnosis and evaluation of hypersensitivity pneumonitis: CHEST guideline and expert panel report. Chest 2021; 160(2): e97–e156.

Walsh

Wells

Desai

, et al. Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case–cohort study. Lancet Respir Med 2016; 4: 557–565.

Thomeer

Demedts

Behr

, et al. Multidisciplinary interobserver agreement in the diagnosis of idiopathic pulmonary fibrosis. Eur Respir J 2008; 31: 585–591.

De Sadeleer

Meert

Yserbyt

, et al. Diagnostic ability of a dynamic multidisciplinary discussion in interstitial lung diseases: a retrospective observational study of 938 Cases. Chest. 2018; 153(6): 1416–1423.

Grewal

Morisset

Fisher

, et al. Role of a Regional multidisciplinary conference in the diagnosis of interstitial lung disease. Ann Am Thorac Soc 2019; 16(4): 455–462.

Biglia

Ghaye

Reychler

, et al. Multidisciplinary management of interstitial lung diseases: a real-life study. Sarcoidosis Vasc Diffuse Lung Dis 2019; 36(2): 108–115.

10.

Richeldi

Launders

Martinez

, et al. The characterisation of interstitial lung disease multidisciplinary team meetings: a global study. ERJ Open Res 2019; 5(2): 00209-2018.

11.

Walsh

SLF

. Multidisciplinary evaluation of interstitial lung diseases: current insights. Eur Respir Rev 2017; 26: 170002.

12.

Teoh

AKY

Holland

Morisset

, et al. Essential features of an interstitial lung disease multidisciplinary meeting: an international Delphi survey. Ann Am Thorac Soc 2022; 19(1): 66–73.

13.

Lee

CT.

Multidisciplinary meetings in interstitial lung disease: polishing the gold standard. Ann Am Thorac Soc 2022; 19: 7–9.

14.

Cottin

Martinez

Smith

, et al. Multidisciplinary teams in the clinical care of fibrotic interstitial lung disease: current perspectives. Eur Respir Rev 2022; 31(165): 220003.

15.

Amati

Spagnolo

Oldham

, et al. Treatable traits in interstitial lung diseases: a call to action. Lancet Respir Med 2023; 11(2): 125–128.

16.

von Elm

Altman

Egger

, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370(9596): 1453–1457.

17.

Ryerson

Corte

Lee

, et al. A Standardized diagnostic ontology for fibrotic interstitial lung disease. An international working group perspective. Am J Respir Crit Care Med 2017; 196(10): 1249–1254.

18.

Ryerson

Urbania

Richeldi

, et al. Prevalence and prognosis of unclassifiable interstitial lung disease. Eur Respir J 2013; 42(3): 750–757.

19.

Fischer

Antoniou

Brown

, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015; 46: 976–987.

20.

Glaspole

Levin

, et al. Clinical impact of the interstitial lung disease multidisciplinary service. Respirology 2016; 21(8): 1438–1444.

21.

Ageely

Souza

De Boer

, et al. The impact of multidisciplinary discussion (MDD) in the diagnosis and management of fibrotic interstitial lung diseases. Can Respir J 2020; 2020: 9026171.

22.

Fujisawa

Mori

Mikamo

, et al. Nationwide cloud-based integrated database of idiopathic interstitial pneumonias for multi-disciplinary discussion. Eur Respir J 2019; 53(5): 1802243.

23.

Perluk

Friedman Regev

Freund

, et al. Importance of physician history taking in complementing patient-reported interstitial lung disease questionnaire. BMC Pulm Med 2022; 22(1): 489.

24.

Hyldgaard

Bendstrup

Wells

, et al. Unclassifiable interstitial lung diseases: clinical characteristics and survival. Respirology 2017; 22(3): 494–500.

25.

Mackintosh

Wells

Cottin

, et al. Interstitial pneumonia with autoimmune features: challenges and controversies. Eur Respir Rev 2021; 30(162): 210177.

26.

Castillo

Walsh

Hansell

, et al. Validation of multidisciplinary diagnosis in IPF. Lancet Respir Med 2018; 6: 88–89.

27.

Kheir

Becerra

JPU

Bissell

, et al. Use of a genomic classifier in patients with interstitial lung disease: a systematic review and meta-analysis. Ann Am Thorac Soc 2022; 19: 827–832.

28.

Walsh

SLF

Humphries

Wells

, et al. Imaging research in fibrotic lung disease; applying deep learning to unsolved problems. Lancet Respir Med 2020; 8(11): 1144–1153.

29.

Jacob

Bartholmai

Rajagopalan

, et al. Mortality prediction in idiopathic pulmonary fibrosis: evaluation of computer-based CT analysis with conventional severity measures. Eur Respir J 2017; 49(1): 1601011.

30.

Walsh

SLF

Calandriello

Silva

, et al. Deep learning for classifying fibrotic lung disease on high-resolution computed tomography: a case-cohort study. Lancet Respir Med 2018; 6(11): 837–845.

31.

Flaherty

Wells

Cottin

, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 2019; 381(18): 1718–1727.

32.

Hoffmann-Vold

Weigt

Saggar

, et al. Endotype-phenotyping may predict a treatment response in progressive fibrosing interstitial lung disease. Ebiomedicine 2019; 50: 379–386.

33.

Waxman

Restrepo-Jaramillo

Thenappan

, et al. Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease. N Engl J Med 2021; 384(4): 325–334.

34.

Amati

Spagnolo

Ryerson

, et al. Walking the path of treatable traits in interstitial lung diseases. Respir Res 2023; 24(1): 251.

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