Diagnosis Of Interstitial Lung Disease Research Articles

Comparison of Interstitial Lung Disease Between Antineutrophil Cytoplasmic Antibodies Positive and Negative Patients: A Retrospective Cohort Study.

Positive antineutrophil cytoplasmic antibodies (ANCAs) may occur in the setting of interstitial lung disease (ILD), with or without ANCA-associated vasculitis (AAV). We aim to compare the characteristics and clinical course of patients with ILD and positive ANCA (ANCA-ILD) to those with negative ANCA. We performed a single-center retrospective cohort study from 2018 to 2021. All patients with ILD and ANCA testing were included. Patient characteristics (symptoms, dyspnea scale, and systemic AAV), test results (pulmonary high-resolution computed tomography and pulmonary function tests), and adverse events were collected from electronic medical records. Descriptive statistics and the Fisher exact test were used to compare the outcomes of patients with ANCA-ILD to those with ILD and negative ANCA. A total of 265 patients with ILD were included. The mean follow-up duration was 69.3 months, 26 patients (9.8%) were ANCA positive, and 69.2% of those with ANCA-ILD had another autoantibody. AAV occurred in 17 patients (65.4%) with ANCA-ILD. In 29.4% of patients, AAV developed following ILD diagnosis. Usual interstitial pneumonia was the most common radiologic pattern in patients with ANCA-ILD. There was no association between ANCA status and the evolution of dyspnea,diffusing capacity of the lungs for carbon monoxide, and lung imaging. Forced vital capacity improved over time in 42% of patients with ANCA-ILD and in 17% of patients with negative ANCA (P = 0.006). Hospitalization occurred in 46.2% of patients with ANCA-ILD and in 21.8% of patients with negative ANCA (P = 0.006). Both groups had similar mortality rates. Routine ANCA testing should be considered in patients with ILD. Patients with ANCA-ILD are at risk for AAV. More research is required to better understand and manage patients with ANCA-ILD.

The impact of time from ILD diagnosis to referral to the transplant center on the probability of inclusion in the transplant waiting list

BackgroundLung transplant is a therapeutic option for patients with progressive interstitial lung disease (ILD). ObjectivesThe objective of this study was to determine whether time from ILD diagnosis to referral to a transplant center influences the probability of being included in the transplant waiting list. MethodsWe performed a retrospective cohort study including all ILD patients evaluated as lung transplantation (LT) candidates at a lung transplant center between 01/01/2017 and 31/12/2022. The primary endpoint was the probability of being included in the lung transplant waiting list according to the time elapsed from diagnosis to referral to the transplant center. ResultsA total of 843 lung transplant requests were received, of which 367 (43.5%) were associated with ILD. Thirteen patients were excluded because they did not attend the first visit, whereas another 11 were excluded because some information was missing. As a result, our final sample was composed of 343 patients. The median time from diagnosis to referral was 29.4 (10.9 – 61.1) months. The overall probability of inclusion in the waiting list was 29.7%. By time from diagnosis to referral, the probability of inclusion in the waiting list was 48.1% for the patients referred 〈 6 months from diagnosis; 27.5% for patients referred 6 to 24 months from diagnosis; and 25.8% for patients referred 〉 24 months from diagnosis (p = 0.007). ConclusionsEarly referral to a lung transplant center seemed to increase the probability of being included in the lung transplant waiting list. Further research is needed in this topic.

Serum CCL24 as a Biomarker of Fibrotic and Vascular Disease Severity in Systemic Sclerosis.

Systemic sclerosis (SSc) is a heterogeneous disease, characterized by variable tissue and vascular fibrosis in the context of autoimmune activation. CCL24 (or Eotaxin2) has been shown to promote microangiopathic, proinflammatory, and profibrotic processes in preclinical models of SSc. Here, we study serum CCL24 levels in a real-life cohort of patients with SSc, to determine its distribution across disease features and its value in predicting disease progression and related mortality. Serum CCL24 was assessed in an observational cohort of consecutively enrolled patients with SSc. A high CCL24 cutoff was defined based on its distribution in a matched cohort of healthy controls. Disease progression and mortality were analyzed from the date of serum assessment. Two-hundred thirteen consecutively enrolled patients with SSc were included in this analysis. Median disease duration was six years (interquartile range 3-14), 28.6% of patients presented with interstitial lung disease (ILD), 46.9% had digital ulcers, and 25.3% showed high CCL24 serum concentration. High-CCL24 patients were more frequently male and positive for anti-scl-70, with a diagnosis of ILD and synovitis (P < 0.05 for all). Notably, high-CCL24 patients had lower diffusion of carbon monoxide and higher prevalence of digital ulcers, telangiectasias, and calcinosis (P < 0.05 for all). In a longitudinal setting, high CCL24 was associated with greater lung function decline and with higher disease-related mortality. Serum CCL24 is a biomarker of disease severity across fibrotic and vascular disease manifestations. These data support the development of therapies targeting CCL24 as a novel comprehensive therapeutic target in SSc.

Interstitial Lung Disease and Progressive Pulmonary Fibrosis: a World Trade Center Cohort 20-Year Longitudinal Study.

World Trade Center (WTC) exposure is associated with obstructive airway diseases and sarcoidosis. There is limited research regarding the incidence and progression of non-sarcoidosis interstitial lung diseases (ILD) after WTC-exposure. ILD encompasses parenchymal diseases which may lead to progressive pulmonary fibrosis (PPF). We used the Fire Department of the City of New York's (FDNY's) WTC Health Program cohort to estimate ILD incidence and progression. This longitudinal study included 14,525 responders without ILD prior to 9/11/2001. ILD incidence and prevalence were estimated and standardized to the US 2014 population. Poisson regression modeled risk factors, including WTC-exposure and forced vital capacity (FVC), associated with ILD. Follow-up time ended at the earliest of incident diagnosis, end of study period/case ascertainment, transplant or death. ILD developed in 80/14,525 FDNY WTC responders. Age, smoking, and gastroesophageal reflux disease (GERD) prior to diagnosis were associated with incident ILD, though FVC was not. PPF developed in 40/80 ILD cases. Among the 80 cases, the average follow-up time after ILD diagnosis was 8.5 years with the majority of deaths occurring among those with PPF (PPF: n = 13; ILD without PPF: n = 6). The prevalence of post-9/11 ILD was more than two-fold greater than the general population. An exposure-response gradient could not be demonstrated. Half the ILD cases developed PPF, higher than previously reported. Age, smoking, and GERD were risk factors for ILD and PPF, while lung function was not. This may indicate that lung function measured after respirable exposures would not identify those at risk for ILD or PPF.

Abstract PO4-12-06: Interstitial Lung Disease (ILD) in Sequential Antibody Drug Conjugate (ADC) use in patients with Metastatic Breast Cancer (MBC): A Multi-Institutional experience

Abstract Introduction: Interstitial Lung Disease (ILD) is a known adverse event associated with Antibody Drug Conjugates (ADCs), causing fibrosis of the lung. In the DESTINY-Breast 04, TROPICS-02, and ASCENT trials the rate of ILD/Pneumonitis was 12.1%, 0.4%, and 0% respectively. In these studies, the time to first cross-sectional imaging after initiation of ADC was 6 weeks. However, prior treatment with a topoisomerase-1 inhibitor ADC was not permitted in these studies, so the influence of sequential ADC treatments remains unknown. Here, we aimed to characterize the frequency and management of ILD in sequential use of ADCs in a multi-institution retrospective analysis. Methods: We identified patients (pts) with HR+/HER2-low and HR-/HER2-low MBC who had received both Trastuzumab-deruxtecan (T-DXd) and Sacituzumab govitecan (SG) monotherapy (in either order, with or without intervening therapies) who were treated at five academic centers between 2020-2023. Patients had received treatment with the ADC in either routine clinical treatment or as a prior participant on a clinical trial with ADC monotherapy. Information regarding ILD diagnosis, imaging, timing of onset, peak and resolution along with management information was collected and analyzed. Retrospective assessment of ILD toxicity was graded using CTCAE v5.0, based on available clinical and radiographic reports. Results: 10/60 pts who received ADC therapy in this multi-institutional cohort were diagnosed with ILD (all grades). No differences in age or BMI were observed in those who developed ILD versus those who did not, and 9/10 pts were White, 1 was Asian, with a median age of 59 years (47-79 years). Pertinent history in these pts included 3/10 had a prior smoking history, 8/10 had a prior cardiac or pulmonary comorbidity (including sleep apnea, lung cancer, hypertension, hyperlipidemia, thrombosis, or stroke). Prior to receiving their first ADC, 7/10 patients had metastatic disease to the lung. All 10 patients were diagnosed with ILD during treatment with T-DXd. 4 pts initially received T-DXd, then developed ILD and then upon recovery, subsequently received SG. The remaining 6 pts initially received SG (with no reports of ILD), and then received T-DXd and subsequently developed ILD. In the entire cohort, the median time from ADC initiation to first CT scan was 8 weeks (range 1-22 weeks). Within the cohort that developed ILD, the median time from initiation of T-DXd to first CT scan was also 8 weeks (range 6-13 weeks). The median time to diagnoses of ILD was 3 months after initiation of T-DXd (range 0.4-14.5 months). Dyspnea was the most common presenting symptom in 9/10 pts and at diagnosis of ILD, dyspnea was graded as III in 6/10 pts, II in 3/10 pts, and I in 1/10 pts. Diagnostic evaluation included CT chest (9/10), pulmonary consultation (8/10), pulmonary function testing (2/10), and bronchoscopy (1/10). 4/10 patients presented at their highest-grade toxicity at diagnosis. All patients stopped T-DXd treatment, 7 were hospitalized, 7 required supplemental oxygen, and 8 were prescribed steroids for treatment. Of those receiving steroids, the most common starting dose was prednisone 1 mg/kg and doses ranged from 0.5 mg/kg to 9mg/kg prednisone equivalents. No patient received a secondary immunosuppressive agent. The steroid treatment duration ranged from 1-4 months. None of the 10 pts underwent re-challenge with T-DXd and 3/10 developed grade V ILD (death). Conclusion: We observed a 16.6% incidence of all grade ILD (5% grade V ILD) with T-DXd and 0% with SG. In this small cohort study, we did not observe a clear increased risk for ILD with sequential treatment of ADCs. Practice patterns were consistent with recommended diagnostic evaluation and steroid management. Additional strategies are needed to characterize pts most at risk for developing ILD and to identify situations where re-challenge may be safe. Citation Format: Sarah Premji, Laura Huppert, Reshma Mahtani, Samantha Fisch, Naomi Dempsey, Angelina Raimonde-Taylor, Saya Jacob, Laura Quintal, Jo Chien, Michelle Melisko, Ana Sandoval-Leon, Lauren Carcas, Manmeet Ahluwalia, Natasha Harpalani, Jenna Hoppenworth, Dame Idossa, Ruta Rao, Hope Rugo, Karthik Giridhar. Interstitial Lung Disease (ILD) in Sequential Antibody Drug Conjugate (ADC) use in patients with Metastatic Breast Cancer (MBC): A Multi-Institutional experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-06.

Abstract PO5-12-12: Implementation of a comprehensive monitoring protocol for the prevention and treatment of interstitial lung disease in patients undergoing treatment with trastuzumab deruxtecan

Abstract Background: In the DESTINY-BREAST studies, Trastuzumab deruxtecan (T-DXd) demonstrated significant antitumor activity in heavily pretreated patients (pts) with HER2-positive and HER2-low advanced breast cancer (ABC). T-DXd is associated with an increased risk of interstitial lung disease (ILD), which occurs in 10-15% of patients with a 2.2% rate of fatal events. Increased monitoring for ILD within DESTINY-BREAST03 showed a reduction in grade 3-5 events. Patients with a history of clinically significant lung disease were excluded from this study, however this may not be reflective of the standard community patient population treated with T-DXd. There are currently no standardized monitoring protocols for ILD/pneumonitis for pts treated with T-DXd. We conducted a retrospective chart review to assess the benefit of implementing an ILD monitoring protocol in a cohort of patients receiving treatment with T-DXd at the Duke Cancer Institute. Methods: Patients with HER2-positive or HER2-low ABC who received ≥ five cycles of T-DXd between Jan 1, 2020- April 30, 2022 were included. Imaging with CT chest ILD protocol and pulmonary function testing with diffusing capacity for carbon monoxide (DLCO) were performed at baseline prior to initiation of T-DXd, prior to cycle 3 and cycle 5 in conjunction with ILD chest CT and then every 6 weeks to monitor for ILD. DLCO was corrected for hemoglobin. Clinical symptoms including cough, shortness of breath, dyspnea, and new or worsening respiratory symptoms were recorded. For pts that experienced more than a 10% decrease in corrected DLCO (DLCOc), a pulmonology consult was recommended. DLCOc was reviewed in combination with chest imaging and clinical history to evaluate for ILD and guidance was provided for continuation or cessation of T-DXd. Results: A total of 33 patients with HER2-positive (N=27) and HER2-low (N=6) ABC were monitored as per the predefined ILD monitoring protocol. There were 5 confirmed cases of ILD/pneumonitis within the pt cohort. 16 patients (48%) experienced DLCOc decreases &amp;gt;10% warranting a pulmonology consult or further review. Upon further assessment, ILD/pneumonitis was ruled out based on chest imaging and/or asymptomatic presentation in 11 patients and therapy continued without treatment delay or discontinuation. There were 5 confirmed cases of ILD/pneumonitis within the patient cohort. 3 of the 5 patients diagnosed with ILD experienced DLCOc decreases ≥10%, while 2 of the 5 diagnosed patients had DLCOc changes of &amp;lt; 10% but had concern for ILD on ILD/chest CT and were diagnosed after pulmonology consult. Additional results to be presented at meeting. Conclusion: For patients receiving T-DXd, implementation of a comprehensive protocol to monitor and assess for ILD secondary to treatment may allow patients with suspected ILD to begin treatment sooner or prevent permanent discontinuation by excluding ILD diagnosis. While PFT monitoring can be helpful for some patients to monitor for ILD, continuous PFT monitoring is not recommended for all patients given inconsistency. However, baseline PFTs prior to initiation and with suspected ILD in combination with imaging warrants further investigation. The use of a multidisciplinary team including pulmonologists experienced with T-DXd-induced ILD may assist in diagnosing or excluding ILD and allow for continuation of T-DXd therapy. Citation Format: Heather Moore, Kelly Westbrook, Thomas Bagwell, Scott Shofer, Carey Anders, Amy Guisinger, Olivia White, Susan Dent. Implementation of a comprehensive monitoring protocol for the prevention and treatment of interstitial lung disease in patients undergoing treatment with trastuzumab deruxtecan [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-12.

Slowly Progressive ANCA-associated Glomerulonephritis with Strong Mesangial MPO Deposits Following a Diagnosis of Interstitial Lung Disease.

An elderly woman showed positive conversion of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCAs) following the diagnosis of interstitial lung disease (ILD) and glomerular hematuria and subsequently experienced slowly progressive glomerulonephritis. A kidney biopsy revealed chronic damage and necrotizing crescentic glomerulonephritis with mesangial MPO deposits. After corticosteroid treatment, the patient's urinalysis results and MPO-ANCA titers almost normalized and her renal function stabilized. This case is similar to recently reported cases of slowly progressive ANCA-associated glomerulonephritis. ILD likely triggered the production of MPO-ANCAs, and the accumulation of MPO deposits in the glomeruli may have contributed to the progression of her renal disease.

Anti‐nuclear matrix protein 2 antibody‐positive amyopathic dermatomyositis presenting in a patient with prostate cancer: A case report

Key Clinical MessageNuclear matrix protein (NXP‐2) positive amyopathic dermatomyositis (DM) may present without classic symptoms like muscle weakness, dysphagia, and edema, and mimic conditions like cutaneous lupus. Given DM's association with malignancy and interstitial lung disease, prompt and accurate diagnosis is important. Testing for myositis‐specific antibodies aids diagnosis in ambiguous cases.

Diagnosis of interstitial lung disease after surgery in an adolescent.

Diagnosis of interstitial lung disease after surgery in an adolescent.

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

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

Feasibility and acceptability of remotely monitoring spirometry and pulse oximetry as part of interstitial lung disease clinical care: a single arm observational study

BackgroundRemote monitoring of patient-recorded spirometry and pulse oximetry offers an alternative approach to traditional hospital-based monitoring of interstitial lung disease (ILD). Remote spirometry has been observed to reasonably reflect clinic spirometry in participants with ILD but remote monitoring has not been widely incorporated into clinical practice. We assessed the feasibility of remotely monitoring patients within a clinical ILD service.MethodsProspective, single-arm, open-label observational multi-centre study (NCT04850521). Inclusion criteria included ILD diagnosis, age ≥ 18 years, FVC ≥ 50% predicted. 60 participants were asked to record a single spirometry and oximetry measurement at least once daily, monitored weekly by their local clinical team. Feasibility was defined as ≥ 68% of participants with ≥ 70% adherence to study measurements and recording measurements ≥ 3 times/week throughout.ResultsA total of 60 participants were included in the analysis. 42/60 (70%) were male; mean age 67.8 years (± 11.2); 34/60 (56.7%) had idiopathic pulmonary fibrosis (IPF), Median ILD-GAP score was 3 (IQR 1–4.75). Spirometry adherence was achieved for ≥ 70% of study days in 46/60 participants (77%) and pulse oximetry adherence in 50/60 participants (83%). Recording ≥ 3 times/week every week was provided for spirometry in 41/60 participants (68%) and pulse oximetry in 43/60 participants (72%). Mean difference between recent clinic and baseline home spirometry was 0.31 L (± 0.72). 85.7% (IQR 63.9–92.6%) home spirometry attempts/patient were acceptable or usable according to ERS/ATS spirometry criteria. Positive correlation was observed between ILD-GAP score and adherence to spirometry and oximetry (rho 0.24 and 0.38 respectively). Adherence of weekly monitoring by clinical teams was 80.95% (IQR 64.19–95.79). All participants who responded to an experience questionnaire (n = 33) found remote measurements easy to perform and 75% wished to continue monitoring their spirometry at the conclusion of the study.ConclusionFeasibility of remote monitoring within an ILD clinical service was demonstrated over 3 months for both daily home spirometry and pulse oximetry of patients. Remote monitoring may be more acceptable to participants who are older or have more advanced disease.Trial Registrationclinicaltrials.gov NCT04850521 registered 20th April 2021

Imaging Innovations in the Screening, Diagnosis, and Monitoring of Systemic Autoimmune Disease-Related Interstitial Lung Disease

Interstitial lung disease (ILD) is a common and serious complication of systemic autoimmune rheumatic diseases (SARD). The prevalence and prognosis of ILD vary depending on the type and severity of the underlying SARD. Recently, two drugs have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ILD in SARD, and the American College of Rheumatology (ACR) has issued guidelines for the screening and monitoring of these patients. Therefore, it is essential to detect and manage ILD in SARDs as early as possible. High-resolution CT of the chest is the current gold standard test for diagnosis of ILD, yet, it is not uniformly performed as an initial diagnostic test. This review discusses the latest advances in imaging techniques for the diagnosis, assessment, and follow-up of SARD-ILDs.

Integration of Artificial Intelligence into Chest Computed Tomography

The integration of Artificial Intelligence (AI) in radiology, especially for chest computed tomography (CT) scan analysis, marked a significant advancement in medical diagnostics, aiming to improve patient care and streamline the workflow for radiologists. This review article examined the role of current AI technologies, including machine learning (ML), deep learning (DL), convolutional neural networks (CNN), and radiomics, in enhancing the detection and characterisation of lung diseases. These technologies are instrumental in identifying complex patterns within imaging data and constructing more informed decisions regarding disease severity, progression, and potential treatment options. Deep learning and CNN have demonstrated effectiveness in analysing the intricate details present in chest CT scans, offering a high degree of accuracy. Radiomics complements these methods by extracting quantitative features from medical images, providing deeper insights into disease characteristics that are not visible through standard imaging techniques. The application of AI has shown promise in improving the diagnosis and management of interstitial lung diseases and lung cancers, contributing to the development of personalised treatment plans. However, this review also highlights limitations, such as small sample sizes in studies, which may impact the generalisability of AI applications in this field. Despite these challenges, the ongoing incorporation of AI into radiological practices is anticipated to significantly enhance the accuracy and efficiency of lung disease diagnostics, setting a foundation for future research and improvements in clinical practice.

Rare interstitial lung diseases in infants

The diagnosis of interstitial lung disease in infants (chILD) is challenging due to the fact that the differential range encompasses more than 200 variants of nosologies with an overall estimated prevalence of 1.6–46 per 100,000 according to several studies. Thus, chILDs are 10 times less common than in adults. The chILD disease spectrum differs significantly from that seen in older children and adults. Interest in the topic of chILD has increased over the past 20 years, as evidenced by the published results of numerous studies and reviews. Also, multidisciplinary groups and respiratory societies have been established, such as the American Thoracic Society (ATS), the European Research Collaboration for Children’s Interstitial Lung Disease (ERS CRC chILD-EU), the French National Reference Center for Rare Respiratory Diseases in Children (RESPIRARE), etc. This article discusses recent advances in the study and diagnosis of chILD, with a special focus on rare and ultra-rare types of chILD. In addition, the stages of the diagnostic search and the increasing role of computed tomography are discussed.

Volume changes of diseased and normal areas in progressive fibrosing interstitial lung disease on inspiratory and expiratory computed tomography.

The diagnosis of progressive fibrosing interstitial lung disease (PF-ILD) using computed tomography (CT) is an important medical practice in respiratory care, and most imaging findings for this disease have been obtained with inspiratory CT. It is possible that some characteristic changes in respiration may be seen in normal and diseased lung in PF-ILD, which may lead to a new understanding of the pathogenesis of interstitial pneumonia, but it has never been examined. In this study, we collected and selected inspiratory and expiratory CT scans performed in pure PF-ILD cases, and evaluated the volumes of diseased and normal lung separately by manual detection and 3-dimensional volumetry to characterize the dynamic features of PF-ILD. Cases were collected retrospectively from a total of 753 inspiratory and expiratory CT scans performed at our hospital over a 3-year period. Sixteen cases of pure PF-ILD, excluding almost all other diseases, were included. We measured their diseased, normal, and the whole lung volumes manually and evaluated the correlation of their values and their relationship with respiratory function tests (FVC, FVC%-predicted, and DLCO%-predicted). The relative expansion rate of the diseased lung is no less than that of the normal lung. The "Expansion volume of total lung" divided by the "Expansion volume of normal lung" was found to be significantly associated with DLCO%-predicted abnormalities (p = 0.0073). The diseased lung in PF-ILD retained expansion capacity comparable to the normal lung, suggesting a negative impact on respiratory function.

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.

Transbronchial cryobiopsy followed by as-needed surgical lung biopsy versus immediate surgical lung biopsy for diagnosing interstitial lung disease (the COLD study): a randomised controlled trial.

An adequate diagnosis for interstitial lung disease (ILD) is important for clinical decision making and prognosis. In most patients with ILD, an accurate diagnosis can be made by clinical and radiological data assessment, but in a considerable proportion of patients, a lung biopsy is required. Surgical lung biopsy (SLB) is the most common method to obtain tissue, but it is associated with high morbidity and even mortality. More recently, transbronchial cryobiopsy has been introduced, with fewer adverse events but a lower diagnostic yield than SLB. The aim of this study is to compare two diagnostic strategies: a step-up strategy (transbronchial cryobiopsy, followed by SLB if the cryobiopsy is insufficiently informative) versus immediate SLB. The COLD study was a multicentre, randomised controlled trial in six hospitals across the Netherlands. We included patients with ILD with an indication for lung biopsy as assessed by a multidisciplinary team discussion. Patients were randomly assigned in a 1:1 ratio to the step-up or immediate SLB strategy, with follow-up for 12 weeks from the initial procedure. Patients, clinicians, and pathologists were not masked to the study treatment. The primary endpoint was unexpected chest tube drainage, defined as requiring any chest tube after transbronchial cryobiopsy, or prolonged (>24 h) chest tube drainage after SLB. Secondary endpoints were diagnostic yield, in-hospital stay, pain, and serious adverse events. A modified intention-to-treat analysis was performed. This trial is registered with the Dutch Trial Register, NL7634, and is now closed. Between April 8, 2019, and Oct 24, 2021, 122 patients with ILD were assessed for study participation; and 55 patients were randomly assigned to the step-up strategy (n=28) or immediate SLB (n=27); three patients from the immediate SLB group were excluded. Unexpected chest tube drainage occurred in three of 28 patients (11%; 95% CI 4-27%) in the step-up group, and the number of patients for whom the chest tube could not be removed within 24 h was 11 of 24 patients (46%; 95% CI 2-65%) in the SLB group, with an absolute risk reduction of 35% (11-56%; p=0·0058). In the step-up strategy, the multidisciplinary team diagnostic yield after transbronchial cryobiopsy alone was 82% (64-92%), which increased to 89% (73-96%) when subsequent SLB was performed after inconclusive transbronchial cryobiopsy. In the immediate surgery strategy, the multidisciplinary team diagnostic yield was 88% (69-97%). Total in-hospital stay was 1 day (IQR 1-1) in the step-up group versus 5 days (IQR 4-6) in the SLB group. One (4%) serious adverse event occurred in step-up strategy versus 12 (50%) in the immediate SLB strategy. In ILD diagnosis, if lung tissue assessment is required, a diagnostic strategy starting with transbronchial cryobiopsy, followed by SLB when transbronchial cryobiopsy is inconclusive, appears to result in a significant reduction of patient burden and in-hospital stay with a similar diagnostic yield versus immediate SLB. Netherlands Organisation for Health Research and Development (ZonMW) and Amsterdam University Medical Centers.

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.

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.