Diagnosis Of Interstitial Lung Disease Research Articles

Role of impulse oscillometry together with diffusing capacity of the lungs for carbon monoxide and high-resolution computed tomography for the chest in early diagnosis of interstitial lung disease in patients with connective tissue diseases

Abstract Background Connective tissue diseases (CTDs) are systemic autoimmune disorders characterized by repeated lung involvement. Interstitial lung disease (ILD) can arise from nearly any CTD, imposing a significant burden on patients and strongly affecting their prognosis. Addressing the gaps in early diagnosis, monitoring, and treatment of these patients requires a comprehensive and multidisciplinary approach for optimal management. Aim To find the best modality for early diagnosis of ILD in patients with connective tissue disorders through the use of diffusing capacity of the lungs for carbon monoxide (DLCO), impulse oscillometry (IOS) and high-resolution computed tomography (HRCT) chest. Patients and methods This study was cross-sectional, analytical, and observational was conducted on 60 patients who were diagnosed with CTD, during the period from March 2022 to March 2023, who were admitted to Chest and Rheumatology Department or outpatient clinics visitors, to Ain Shams University Hospitals. Results The sensitivity of DLCO, HRCT, and IOS in detecting interstitial affection in CTD patients was 90, 81.5, and 72.2%, respectively. There is high statistical significance between DLCO and both CT chest and IOS in detecting ILD in CTD patients. There is a highly significant correlation between DLCO with Spirometric parameters (forced vital capacity, forced expiratory volume 1 s) and between DLCO with IOS parameters (actual ×5). Conclusion ILD should always be considered in patients with CTD. Diagnosis of CTD-ILD is challenging so early diagnosis of ILD using DLCO, HRCT chest or by using IOS is important as it could affect therapy plans.

The diagnostic pathway for patients with interstitial lung disease: a mixed-methods study of patients and physicians

ObjectivesThe diagnostic process for patients with interstitial lung diseases (ILD) remains complex. The aim of this study was to characterise the diagnostic care pathway and identify barriers and potential solutions...

Characteristics of chest high-resolution computed tomography in patients with anti-aminoacyl-tRNA synthetase antibody-positive interstitial lung disease.

Anti-aminoacyl-tRNA synthetase (ARS) antibodies form a condition called Antisynthetase syndrome (ASSD). While interstitial lung disease (ILD) is a particularly frequent manifestation of ASSD and is closely associated with morbidity and mortality, few studies have been conducted on its characteristics on high-resolution computed tomography (HRCT). In this study, we clarified the HRCT findings in patients with anti-ARS antibody-positive ILD (ARS-ILD). Methods: The HRCT findings at the time of the ILD diagnosis in 24 ARS-ILD patients were retrospectively evaluated by 2 pulmonologists and one radiologist. We also assessed the clinical symptoms, physical examination findings, and laboratory data including the type of anti-ARS antibodies. For a further analysis, the data of patients were divided into two groups: the polymyositis (PM)/dermatomyositis (DM) group and the non-PM/DM group. The ratio of men to women was almost 1:1. The median age at the time of the diagnosis was 53 years old. Anti-glycyl (anti-EJ) and anti-histidyl (anti-Jo-1) antibodies were more common than others. An analysis of the HRCT patterns of 23 ARS-ILD patients showed that the most common pattern was the nonspecific interstitial pneumonia (NSIP) pattern. The second most common pattern was the usual interstitial pneumonia (UIP) pattern. Between the PM/DM and non-PM/DM groups, no clear trends were noted in the age, sex ratio, proportion of HRCT patterns, or type of anti-ARS antibodies. This retrospective study demonstrated that ARS-ILD patients, regardless of myositis symptoms, most often showed the NSIP pattern on HRCT, as previously reported. However, unlike previous reports, the UIP pattern on HRCT was not rare.

The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope.

Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1.

Genetic Testing Goes Beyond Imaging and Histological Evaluation in Pleuroparenchymal Fibroelastosis

BackgroundLung biopsy remains the gold standard in the diagnosis of fibrotic interstitial lung disease (F-ILD), but there is a growing appreciation of the role of pathogenic gene variants in telomere and surfactant protein genes, especially in familial pulmonary fibrosis (FPF). Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that can coexist with different patterns of F-ILD, including FPF. It can be progressive and often leads to respiratory failure and death. This study tested the hypothesis that genetic testing goes beyond radiological and histological findings in PPFE and other F-ILD further informing clinical decision-making for patients and affected family members by identifying pathological gene variants in telomere and surfactant protein genes.MethodsThis is a retrospective review of 70 patients with F-ILD in the setting of FPF or premature lung fibrosis. Six out of 70 patients were diagnosed with PPFE based on radiological or histological characteristics. All patients underwent telomere length evaluation in peripheral blood by Flow-FISH or genetic testing using a customized exome-based panel that included telomere and surfactant protein genes associated with lung fibrosis.ResultsHerein, we identified six individuals where radiographic or histopathological analyses of PPFE were linked with telomere biology disorders (TBD) or variants in surfactant protein genes. Each case involved individuals with either personal early-onset lung fibrosis or a family history of the disease. Assessments of telomere length and genetic testing offered insights beyond traditional radiological and histopathological evaluations.ConclusionDetecting anomalies in TBD-related or surfactant protein genes can significantly refine the diagnosis and treatment strategies for individuals with PPFE and other F-ILD.

The Relationship Between Anti-SSA-52 and Interstitial Lung Disease.

The aims of this study were to assess whether a relationship between anti-SSA-52 and interstitial lung disease (ILD) can be further defined, and to enhance screening, detection, and potentially guide treatment. A historical cohort study of 201 patients was conducted at a single tertiary care center between January 1, 2016 and December 31, 2020. All included patients were anti-SSA-52 antibody positive. Chart review was performed for laboratory values, symptoms, pulmonary function tests, treatment, and imaging. Chest computed tomographies were reviewed by chest radiologists. Among anti-SSA-52 antibody-positive patients, ILD was found in 125 (62.2%) compared with 76 (37.8%) with no ILD (p = 0.001). For those with ILD, 78 (62.4%) were diagnosed with connective tissue disease (CTD)-associated ILD, 28 (22.4%) were diagnosed ILD only, and 19 (15.2%) met the criteria for interstitial pneumonia with autoimmune features. In patients with CTD-ILD, 18 (23.0%) had their ILD diagnosis made over 6 months before a CTD diagnosis, and an additional 43 (55.1%) had their ILD and CTD diagnosed within 6 months of each other (p < 0.001). Common computed tomography patterns were nonspecific interstitial pneumonia/organizing pneumonia overlap in 44 (35.2%), 25 (20.0%) nonspecific interstitial pneumonia, and 15 (12%) usual interstitial pneumonia. Twenty-eight (35.9%) had antisynthetase syndrome, followed by 16 (20.5%) with dermatomyositis, 10 (12.8%) with CTD overlap, and 6 (7.7%) with systemic scleroderma. There was a significant association between anti-SSA-52 antibodies and ILD across a wide spectrum of rheumatological diagnoses. A significant portion of patients were diagnosed with ILD either at the same time or before their CTD diagnosis. Further study will be needed to assess effective treatment and response.

Imaging in the diagnosis and management of fibrosing interstitial lung diseases.

High-resolution computed tomography (HRCT) plays a pivotal role in the diagnosis and management of interstitial lung diseases (ILDs), particularly given the approval of antifibrotic agents for conditions like idiopathic pulmonary fibrosis and progressive pulmonary fibrosis. Diagnosing fibrotic pulmonary disorders through HRCT involves a detailed and methodical examination. The identification of specific lung tissue changes, including ground-glass opacities and reticulation, along with signs of fibrosis like honeycombing, traction bronchiectasis and lung volume loss, establishes clear HRCT patterns indicative of various ILDs. The reliability of these patterns in predicting pathological conditions depends largely on the clinical context. For instance, when a usual interstitial pneumonia pattern is present, the predictive value of this diagnosis is so high that a lung biopsy is considered to be redundant. This review intends to delineate the HRCT signs of fibrosis, elucidate the specific radiological patterns of fibrotic lung diseases, and identify the clinical circumstances under which these patterns emerge. Additionally, we introduce and discuss novel imaging techniques that hold promise for the diagnosis, screening and early detection of ILDs.

Relative incidence of interstitial lung diseases in Brazil.

To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

The Clinical Frailty Scale for Risk Stratification in Patients With Fibrotic Interstitial Lung Disease

Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD). Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in patients with fibrotic ILD? Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits. Patients were stratified into fit (CFS score 1-3), vulnerable (CFS score 4), and frail (CFS score 5-9) subgroups. Cox proportional hazards and logistic regression models with mixed effects were used to estimate time to death or lung transplantation. A derivation and validation cohort was used to establish prognostic performance. Trajectories of functional tests were compared using joint models. Of the 1,587 patients with fibrotic ILD, 858 (54%) were fit, 400 (25%) were vulnerable, and 329 (21%) were frail. Frailty was a risk factor for early mortality (hazard ratio, 5.58; 95%CI, 3.64-5.76, P< .001) in the entire cohort, in individual ILD diagnoses, and after adjustment for potential confounders. Adding frailty to established risk prediction parameters improved the prognostic performance in derivation and validation cohorts. Patients in the frail subgroup had larger annual declines in FVC %predicted than patients in the fit subgroup (-2.32; 95%CI,-3.39 to-1.17 vs-1.55; 95%CI,-2.04 to-1.15, respectively; P= .02). The simple and practical CFS is associated with pulmonary and physical function decline in patients with fibrotic ILD and provides additional prognostic accuracy in clinical practice.

Diagnostic approaches and treatments of systemic sclerosis patient with interstitial lung disease

Background: Systemic sclerosis or scleroderma is a rare disease with multiple complications which may include interstitial lung disease. The findings of diffuse type of systemic sclerosis, moderate restriction in pulmonary function test, interstitial pneumonia in chest x-ray, and ground glass opacity in thoracic CT-scan establish the diagnosis of interstitial lung disease associated with systemic sclerosis. We present a case of interstitial lung disease in a systemic sclerosis case, which was approached and treated comprehensively to slow the progression. Case Presentation: A 40-year-old female was admitted to the rheumatology polyclinic of Dr. Soetomo Hospital Surabaya with persistent dry cough for two years in June 2021. The patient also complained of breathlessness, painful joints, swollen knees, and morning stiffness three months prior to admission. The positive results of antinuclear antibody and rheumatoid factor were identified in 2016, which suggested autoimmune disease of scleroderma and being treated with azathioprine 50 mg twice a day, methylprednisolone 4 mg once a day, chloroquine 200 mg once a day, and calcium lactate once a day. The examinations in 2020 showed moderate restriction from the pulmonary function test, bilateral lung parenchymal infiltrates from the chest x-ray, and ground-glass opacity from the chest computed tomography scan (CT-scan). The patient was monthly prescribed cyclophosphamide 500 mg intravenously for six months as the substitution of azathioprine, methylprednisolone 4 mg once a day, and aspirin 100 mg once a day. The latest worsening condition led the patient to receive the substitution of cyclophosphamide which was mycophenolate mofetil 360 mg twice a day, along with aspirin 100mg and methylprednisolone 4 mg once a day, respectively. Conclusion: As a rare disease, the complications of systemic sclerosis should be anticipated. In this case, interstitial lung disease occurred following nearly five years of systemic sclerosis course which required immunosuppressive agents to enhance the efficacy of treatment. Comprehensive treatment with tight monitoring is necessary to slow the disease progression.

Presentation and progression of MPO-ANCA interstitial lung disease

The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate. Here we aim to describe presentation and progression of MPO-ANCA ILD. We conducted a retrospective evaluation of a cohort of individuals diagnosed with MPO-ANCA ILD, with or without accompanying renal impairment, at the Immunology and Cell Therapy Unit, Careggi University Hospital, Florence, Italy, between June 2016 and June 2022. Clinical records, imaging studies, pathologic examinations, and laboratory test results were collected. Among the 14 patients identified with MPO-ANCA ILD, we observed a significant association between MPO-ANCA titers assessed at the time of ILD diagnosis and renal involvement. Renal impairment in these cases often manifested as subclinical or slowly progressive kidney damage. Interestingly, complement C3 deposits were consistently found in all renal biopsy specimens, thereby suggesting the potential for novel therapeutic targets in managing renal complications associated with MPO-ANCA ILD. The presentation of MPO-ANCA vasculitis as ILD can be the first and only clinical manifestation. MPO-ANCA levels at ILD diagnosis could warn on the progression to renal involvement in patients with MPO-ANCA ILD, hence caution is needed because renal disease can be subclinical or smoldering.

Lung ultrasound is a promising screening tool to rule out interstitial lung disease in patients with rheumatoid arthritis.

It is still controversial how to screen for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). We aimed to evaluate the performance of lung ultrasound (LUS) as a screening tool for RA-ILD and to compare it with the performance of chest auscultation, chest x-ray and pulmonary function tests (PFTs). Cross-sectional study of consecutive RA patients evaluated at a Rheumatology Clinic in Buenos Aires between January and December 2022. High-resolution computed tomography (HRCT) was the gold standard for diagnosing ILD and was performed within 30 days of the LUS, chest x-ray and PFTs. Investigators were blinded to HRCT results and patients' clinical data. LUS was performed by exploring 14 areas and was considered positive when the sum of B lines was ≥5. Performance for the diagnosis of ILD was reported for each diagnostic test. One hundred and six patients were included; 87 (82%) were women. Median age was 60.9 (±9.5) years-old. A total of 32 (30.2%, 95% CI: 21.6%-39.9%) had ILD. The sensitivity and negative predictive value of LUS were 90.6% (95% CI 75.0%-98.0%) and 94.7% (95% CI 85.4%-98.9%), respectively. LUS performance was superior to that of the other evaluated diagnostic tests for screening ILD. Given that the US is a low-cost point-of-care tool with a high negative predictive value, it is emerging as a valuable tool for ruling out ILD in patients with RA.

Low bleeding rates following transbronchial lung cryobiopsy in unclassifiable interstitial lung disease.

Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield. A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%. TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC.

Radiological assessment of interstitial lung disease: what can lung ultrasound do?

The use of lung ultrasound in the screening, diagnosis, and evaluation of interstitial lung disease has been relatively well studied, but has not been widely accepted and applied in clinical practice. There are also some differences in the examination methods applied in these studies. This paper summarized the application, advantages, and disadvantages of lung ultrasound in the diagnosis and follow-up of interstitial lung disease by comprehensively reviewing the examination methods, research results and progress of new technologies of lung ultrasound in interstitial lung disease.

Disease Behaviour Classification: A pragmatic model for predicting outcomes in Interstitial Lung Disease

Background and objectiveThe interstitial lung diseases (ILD) are a heterogenous group of disorders with similar clinical presentation, but widely varying prognoses. The use of a pragmatic disease behaviour classification (DBC), first proposed in international guidelines in 2013, categorises diseases into five behavioural classes based on their predicted clinical course. This study aimed to determine the prognostic utility of the DBC in an ILD cohort. MethodsConsecutive patients presented at the weekly multidisciplinary meeting (MDM) of a specialist ILD centre were included. MDM consensus was obtained for diagnosis and DBC category (1–5). Baseline and serial clinical and physiological data were collected over the study period (median 3.9 years, range 0–5.4 years). The relationship between DBC and prognostic outcomes was explored. Results137 ILD patients, [64 (47%) female] were included with mean age 67.0 ± 1.1 years, baseline FVC% 72.7 ± 1.7, and baseline DLco% 57.8 ± 1.6%. Patients were stratified into DBC by consensus at MDM: DBC1 n = 0 (0%), DBC2 n = 16 (12%), DBC3 n = 10 (7.3%), DBC4 n = 55 (40%), and DBC5 n = 56 (41%). On univariable Cox regression, increasing DBC class was associated with poorer progression-free survival (HR 1.6, 95% CI 1.2–2.0, p < 0.001). On multivariable Cox regression, DBC remained predictive of PFS when combined with age and gender (HR 1.4, 95% CI 1.1–1.9, p = 0.011), baseline FVC% (HR 1.5, 95% CI 1.1–1.8, p = 0.003) and ILD diagnosis (HR 1.6, 95% CI 1.2–2.2, p < 0.0001). ConclusionDBC as determined at ILD multidisciplinary meeting may be a useful prognostic tool for the management of ILD patients.

Selection of the appropriate treatment for the combination of interstitial lung disease and lung cancer: A retrospective observational study.

Interstitial lung disease (ILD) independently heightens the risk of lung cancer (LC), often necessitating chemoradiotherapy (CRT) due to advanced disease stages. However, CRT may compromise survival through complications such as ILD exacerbation or radiation pneumonitis. The aim of this study was to determine the optimal surgical or nonsurgical treatment approaches for patients with concurrent ILD and LC. Over a 10-year period, a retrospective evaluation was conducted on 647 patients with confirmed diagnoses of LC and ILD from a total of 4541 patients examined in the polyclinic. This assessment included a comprehensive review of demographic, treatment, and survival records. Study groups included those treated for both ILD and LC with surgical treatment (ST), chemotherapy (CT), radiotherapy (RT), or CRT. A control group comprised ILD-only cases. In the whole sample of 647 patients with complete data, the length of stay in hospital and respiratory intensive care unit was significantly shorter in the ST group and longer in the CT group. Significant differences in discharge status (P < .001) were observed, with higher recovery rates in the ST and RT groups. The CT group showed an increased rate of transfer to other centers, in-hospital mortality was determined to be higher in the CRT group, and the control group exhibited no change in discharge. No statistically significant difference was determined between the groups with respect to the 24- and 48-month survival rates (P = .100). Although no disparity was found in 2- and 4-year survival rates, there were seen to be advantages in survival and quality of life with the addition of radiotherapy to regions aligning with surgical margins for LC patients with ILD, evaluated as radiological N0, undergoing wedge resection. This underscores the need for personalized treatment strategies to balance effective cancer control and to minimize ILD-related complications.

A validation of register-derived diagnoses of interstitial lung disease in patients with inflammatory arthritis: data from the NOR-DMARD study

Objective There is a lack of knowledge concerning the validity of the interstitial lung disease (ILD) diagnoses used in epidemiological studies on rheumatic diseases. This paper seeks to verify register-derived ILD diagnoses using chest computed tomography (CT) and medical records as a gold standard. Method The Norwegian Anti-Rheumatic Drug Register (NOR-DMARD) is a multicentre prospective observational study of patients with inflammatory arthritis who start treatment with disease-modifying anti-rheumatic drugs. NOR-DMARD is linked to the Norwegian Patient Registry (NPR) and Cause of Death Registry. We searched registers for ILD coded by ICD-10 J84 or J99 among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. We extracted chest CT reports and medical records from participating hospitals. Two expert thoracic radiologists scored examinations to confirm the ILD diagnosis. We also searched medical records to find justifications for the diagnosis following multidisciplinary evaluations. We calculated the positive predictive values (PPVs) for ILD across subsets. Results We identified 71 cases with an ILD diagnosis. CT examinations were available in 65/71 patients (91.5%), of whom ILD was confirmed on CT in 29/65 (44.6%). In a further 10 patients, medical records confirmed the diagnosis, giving a total of 39/71 verified cases. The PPV of a register-derived ILD diagnosis was thus 54.9%. In a subset of patients who had received an ILD code at two or more time-points and had a CT scan taken within a relevant period, the PPV was 72.2%. Conclusion The validity of register-based diagnoses of ILD must be carefully considered in epidemiological studies.

Health care costs and utilization of progressive fibrosing lung disease by underlying interstitial lung disease type.

Fibrosing interstitial lung disease (ILD) encompasses more than 200 diverse pulmonary disorders, of which up to 40% become progressive. The 4 underlying ILD types most likely to result in progression are unclassified ILD/idiopathic interstitial pneumonia (IIP), autoimmune ILDs, exposure-related ILD/hypersensitivity pneumonitis, and sarcoidosis. To compare health care resource utilization (HCRU) and costs among patients with fibrosing ILD that has progressed ("progressive" fibrosing cohort) vs patients whose fibrosis did not meet criteria set for progression ("not yet progressed" cohort). This was a noninterventional study of commercial enrollees and Medicare Advantage with Part D beneficiaries, which used administrative claims data for the period from October 1, 2015, through May 31, 2021. Adult patients (aged ≥18 years) with fibrosing ILD and 12 months of continuous health plan enrollment were included. Patients with idiopathic pulmonary fibrosis, baseline ILD diagnoses, or missing demographic data were excluded. Patients were first classified according to the underlying type of fibrosing ILD. For statistical analyses of outcomes, 2 cohorts were compared within each subtype: progressive fibrosing ILD vs not yet progressed ILD. The final study population included propensity score-matched (PSM) patients (1:1) based on pre-ILD baseline demographic and clinical characteristics. HCRU categories included inpatient hospitalization counts and the number of inpatient days and total costs (in 2021 US dollars), analyzed descriptively and weighted by the per-patient-per-month cost. Lin's regression was used to predict 12-month total cost estimates for comparison by cohort. The distribution by underlying conditions was as follows: autoimmune ILD (n = 4,156), HP (n = 8,181), sarcoidosis (n = 775), and unclassified ILD/IIP (n = 18,635). After PSM, pre-ILD baseline variables were generally well balanced between the progressive and not yet progressed fibrosing ILD cohorts. For all underlying subtypes of ILD, patients in the progressive cohort had significantly more utilization and higher costs compared with patients in the not yet progressed cohort. Progressive cohorts had significantly higher adjusted rates of inpatient days among patients with at least 1 inpatient stay compared with the not yet progressed cohorts (all P < 0.01). In addition, the progressive cohorts had significantly higher adjusted 12-month total costs, with the differences ranging from $24,493 to $55,072 (all comparisons P < 0.001). Irrespective of underlying ILD type, patients with progressive fibrosing ILD had significantly increased HCRU and cost relative to those whose fibrosing ILD had not yet progressed.

Key learnings from the INBUILD trial in patients with progressive pulmonary fibrosis.

In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.

Mycophenolate and azathioprine efficacy in interstitial lung disease: a systematic review and meta-analysis

ObjectivesMycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in...