Case Of Interstitial Lung Disease Research Articles

Role of sleep questionnaires in predicting obstructive sleep apnea amongst interstitial lung diseases patients.

The co-existence of obstructive sleep apnea (OSA) and interstitial lung diseases (ILD) results in significant morbidity and mortality. So screening for OSA is important for its early diagnosis among ILD patients. The commonly used questionnaires for screening of OSA are Epworth sleep score (ESS) and STOP-BANG. However, the validity of these questionnaires among ILD patients is not well studied. The aim of this study was to assess the utility of these sleep questionnaires in detection of OSA among ILD patients. It was a prospective observational study of one year in a tertiary chest centre in India. We enrolled 41 stable cases of ILD who were subjected to self-reported questionnaires (ESS, STOP-BANG, and Berlin questionnaire). The diagnosis of OSA was done by Level 1 polysomnography. The correlation analysis was done between the sleep questionnaires and AHI. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for all the questionnaires. The cutoff values of STOPBANG and ESS questionnaire were calculated from the ROC analyses. P value of <0.05 was considered to be significant. OSA was diagnosed in 32 (78%) patients with mean AHI of 21.8 ± 17.6.The mean age was 54.8 ± 8.9 years with majority being female (78%) and mean body mass index (BMI) was 29.7 ± 6.4 kg/m2. The mean ESS and STOPBANG score were 9.2 ± 5.4 and 4.3 ± 1.8, respectively, and 41% patients showed high risk for OSA with Berlin questionnaire. The sensitivity for detection of OSA was highest (96.1%) with ESS and lowest with Berlin questionnaire (40.6%). The receiver operating characteristics (ROC) area under curve for ESS was 0.929 with optimum cutoff point of 4, sensitivity of 96.9%, and specificity of 55.6%, while ROC area under curve for STOPBANG was 0.918 with optimum cutoff point of 3, sensitivity of 81.2% and specificity of 88.9%.The combination of two questionnaires showed sensitivity of >90%. The sensitivity also increased with the increasing severity of OSA. AHI showed positive correlation with ESS (r = 0.618, P < 0.001) and STOPBANG (r = 0.770, P < 0.001). The ESS and STOPBANG showed high sensitivity with positive correlation for prediction of OSA in ILD patients. These questionnaires can be used to prioritize the patients for polysomnography (PSG) among ILD patients with suspicion of OSA.

Incidence of interstitial lung disease and cardiotoxicity with trastuzumab-deruxtecan in patients with breast cancer: A systematic review and single-arm meta-analysis.

e13033 Background: The new antibody-drug conjugated directed to HER2, Trastuzumab-Deruxtecan (T-DXd), has shown the benefit of progression-free survival and overall survival in metastatic breast cancer (mBC) patients after progression to ≥1 HER2 targeted therapies. Interstitial lung disease (ILD) and cardiotoxicity are the most significant and concerning toxicities related to T-DXd. We performed a systematic review and meta-analysis to assess the incidence and severity of those adverse events (AE) in mBC patients treated with T-DXd. Methods: We comprehensively searched Pubmed, Cochrane, and Scopus databases for randomized clinical trials (RCT) and observational cohort studies, including mBC patients with HER2-low or -positive expression who have received at least one dose of T-DXd. The DESTINY-Breast02 study was also included after its presentation at the SABCS 2022. The statistical analysis was performed using R software, and the results are presented as pooled analysis in forest plots. Results: We included nine studies: three phase III RCTs, three phase II and two phase I non-RCTs, and one retrospective cohort comprising 1,443 patients with a mean follow-up of 14.9 months. The median age of our population ranged from 53 to 59 years. Most were non-Asian (40.5%) and presented with hormone-receptor positive mBC (66.8%). In a pooled analysis, the incidence of ILD was 13.0% (179 patients; 95%CI 11.0 to 13.0). Patients enrolled in phase III clinical trials had an ILD rate of 12.0%, while the observational cohort reported a numerically higher rate of 18.0%. Most ILD cases, 84.9% (152 patients), were mild (grade 1 or 2). Grade 3 or 4 AE were reported in 13 patients (7,3%), and grade 5 in 14 patients (7,8%). Decreased left ventricular ejection fraction (LVEF) was seen in 3.6% (95%CI 3.0 – 5.0%), and most patients were asymptomatic. Eleven patients developed prolonged QT interval, and four had left ventricular dysfunction and cardiac failure. Conclusions: Our meta-analysis reinforces the importance of close vigilance for pulmonary and cardiac toxicities in mBC patients on treatment with T-DXd. Early detection and management by a multidisciplinary team following the most recent guidelines may improve the patient outcomes. [Table: see text]

Interstitial Lung Disease in Systemic Lupus Erythematosus and Systemic Sclerosis: How Can We Manage the Challenge?

Interstitial lung disease (ILD) is a severe and frequent manifestation of connective tissue diseases (CTD). Due to its debilitating potential, it requires serious evaluation and treatment. The prevalence of ILD in systemic lupus erythematosus (SLE) is still controversial. Therefore, in order to establish the diagnosis of ILD, an overlap syndrome must be excluded. Increasing the identification of SLE-associated ILD cases should become a target. To treat this complication, various therapies are now being proposed. To date, no placebo-controlled studies were conducted. Regarding another CTD, systemic sclerosis (SSc), SSc-associated ILD is considered one of the leading causes of mortality. The incidence of ILD varies among disease subtypes, being influenced by diagnostic method, but also by disease duration. Due to the high prevalence of this complication, all SSc patients should be investigated for ILD at the time of SSc diagnosis and during the course of the disease. Fortunately, progress was made in terms of treatment. Nintedanib, a tyrosine kinases inhibitor, showed promising results. It appeared to decrease the rate of progression of ILD compared to placebo. This review aimed to provide up-to-date findings related to SLE-associated ILD and SSc-associated ILD, in order to raise awareness of their diagnosis and management.

Interstitial lung disease in patients treated with poly (ADP-ribose) polymerase inhibitors (PARPi): analysis of results from clinical trials and the FDA Adverse Events Reporting System database

ObjectiveTo evaluate the risk of interstitial lung disease associated with poly (ADP-ribose) polymerase inhibitors (PARPi) and characterize its clinical features.MethodsWe systematically reviewed phase III randomized clinical trials of interstitial lung...

Tyrosine kinase inhibitors-associated interstitial lung disease used in non-small cell lung cancer: a pharmacovigilance analysis based on the FDA adverse event reporting system database

ABSTRACT Background Interstitial lung disease (ILD) was a relatively common cause of drug-induced mortality. However, the safety profile of the whole TKIs induced ILD was largely unknown. Research design and methods The reported cases of ILD associated with TKIs were downloaded from the FDA adverse event reporting system (FAERS) database between 1 January 2004 and 30 April 2022 to detect ILD signals by disproportionality analysis. Furthermore, the fatality rate and time to onset (TTO) of various TKIs were also calculated. Results The median age of total 2999 reported cases was 67. The largest reported cases came from osimertinib (n = 736, 24.5%). However, gefitinib had the highest ROR of 12.47 (11.4, 13.64) and IC of 3.53 (3.23, 3.86), means the strongest association with ILD. Trametinib, vemurafenib, larotectinib, selpercatinib, and cabozantinib did not show ILD signal. The median age of dead cases was 72 (Q1:62, Q3:83), and 53.02% (n = 579) were female and 41.11% (n = 449) were male. MET group showed the highest fatality rate of 55.17% with the shortest median TTO of 21 days (Q1: 8.5, Q3: 35.5). Conclusions TKIs were significantly associated with ILD. More attention should be paid to female, older, MET group with shorter TTO, as their prognosis might be worse.

Extracting patient-level data from the electronic health record: Expanding opportunities for health system research.

Epidemiological studies of interstitial lung disease (ILD) are limited by small numbers and tertiary care bias. Investigators have leveraged the widespread use of electronic health records (EHRs) to overcome these limitations, but struggle to extract patient-level, longitudinal clinical data needed to address many important research questions. We hypothesized that we could automate longitudinal ILD cohort development using the EHR of a large, community-based healthcare system. We applied a previously validated algorithm to the EHR of a community-based healthcare system to identify ILD cases between 2012-2020. We then extracted disease-specific characteristics and outcomes using fully automated data-extraction algorithms and natural language processing of selected free-text. We identified a community cohort of 5,399 ILD patients (prevalence = 118 per 100,000). Pulmonary function tests (71%) and serologies (54%) were commonly used in the diagnostic evaluation, whereas lung biopsy was rare (5%). IPF was the most common ILD diagnosis (n = 972, 18%). Prednisone was the most commonly prescribed medication (911, 17%). Nintedanib and pirfenidone were rarely prescribed (n = 305, 5%). ILD patients were high-utilizers of inpatient (40%/year hospitalized) and outpatient care (80%/year with pulmonary visit), with sustained utilization throughout the post-diagnosis study period. We demonstrated the feasibility of robustly characterizing a variety of patient-level utilization and health services outcomes in a community-based EHR cohort. This represents a substantial methodological improvement by alleviating traditional constraints on the accuracy and clinical resolution of such ILD cohorts; we believe this approach will make community-based ILD research more efficient, effective, and scalable.

Impact of a structured reporting template on the quality of HRCT radiology reports for interstitial lung disease

PurposeThis QI study compared the completeness of HRCT radiology reports before and after the implementation of a disease-specific structured reporting template for suspected cases of interstitial lung disease (ILD). Materials and methodsA pre-post study of radiology reports for HRCT of the thorax at a multicenter health system was performed. Data was collected in 6-month period intervals before (June 2019–November 2019) and after (January 2021–June 2021) the implementation of a disease-specific template. The use of the template was voluntary. The primary outcome measure was the completeness of HRCT reports graded based on the documentation of ten descriptors. The secondary outcome measure assessed which descriptor(s) improved after the intervention. Results521 HRCT reports before and 557 HRCT reports after the intervention were reviewed. Of the 557 reports, 118 reports (21%) were created using the structured reporting template. The mean completeness score of the pre-intervention group was 9.20 (SD = 1.08) and the post-intervention group was 9.36 (SD = 1.03) with a difference of −0.155, 95% CI [−0.2822, −0.0285, p < 0.0001]. Within the post-intervention group, the mean completeness score of the unstructured reports was 9.25 (SD = 1.07) and the template reports was 9.93 (SD = 0.25) with a difference of −0.677, 95% CI [−0.7871, −0.5671, p < 0.0001]. After the intervention, the use of two descriptors improved significantly: presence of honeycombing from 78.3% to 85.1% (p < 0.0039) and technique from 90% to 96.6% (p < 0.0001). DiscussionShifting to disease-specific structured reporting for HRCT exams of suspected ILD is beneficial, as it improves the completeness of radiology reports. Further research on how to improve the voluntary uptake of a disease-specific template is needed to help increase the acceptance of structured reporting among radiologists.

Abstract P6-10-03: Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple-Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study

Abstract Background: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 mAb covalently linked to a highly potent topoisomerase I (Topo I) inhibitor payload via a stable, tumor selective, tetrapeptide-based cleavable linker. Dato-DXd has previously shown encouraging activity in heavily pretreated patients (pts) with metastatic TNBC (Krop, SABCS 2021). Here we report updated results from the TROPION-PanTumor01 study in pts with advanced/metastatic TNBC. Methods: TROPION-PanTumor01 (NCT03401385) is a phase 1, multicenter, open-label, 2-part dose-escalation/expansion study evaluating Dato-DXd in previously treated pts with solid tumors. Based on previous clinical and exposure-response results from pts with NSCLC, Dato-DXd 6 mg/kg IV Q3W is being evaluated in pts with advanced TNBC that relapsed/progressed on standard therapies; 2 pts received 8 mg/kg prior to selection of 6 mg/kg. The primary objectives were safety and tolerability. Tumor responses, including objective response rate (ORR; complete response [CR] + partial response [PR]) and disease control rate (DCR; CR + PR + stable disease [SD]), were assessed per RECIST v1.1 by blinded independent central review. Results: As of April 29, 2022, 44 pts received Dato-DXd (median follow-up, 16.6 mo [range, 13-22]) at the time of data cutoff. The primary cause of treatment discontinuation was disease progression (86%; PD or clinical progression), and 4 pts are still receiving therapy. Median age was 53 y (range, 32-82); 32% had de novo metastatic disease. Pts were heavily pretreated with a median of 3 (range, 1-10) prior regimens in the metastatic setting. Prior treatments included taxanes (91%), anthracyclines (75%), capecitabine (61%), platinum (52%), immunotherapy (43%), Topo I inhibitor–based ADC therapy (32%), and PARPi (18%). Treatment-emergent adverse events (TEAEs; all cause) occurred in 100% (any grade) and 50% (grade ≥3) of pts, respectively. Most common TEAEs (any grade, grade ≥3) were stomatitis (73%, 11%), nausea (66%, 2%), vomiting (39%, 5%), fatigue (34%, 7%), and alopecia (36%, 0%). One pt had grade 3 decreased neutrophil count; no cases of interstitial lung disease (ILD) or grade ≥3 diarrhea were observed. Serious TEAEs were reported in 9 pts (20%); no deaths associated with adverse events (AEs) were observed. Dose reductions occurred in 8 pts (18%) due to stomatitis (n=3), fatigue (n=2), dry eye (n=1), retinal exudates (n=1), and dysgeusia (n=1); 12 pts (27%) delayed treatment due to stomatitis (n=5), dry eye (n=1), keratitis (n=1), blurred vision (n=1), fatigue (n=1), bronchitis (n=1), skin infection (n=1), musculoskeletal chest pain (n=1), dysgeusia (n=1), chronic obstructive pulmonary disease (n=1), and dyspnea (n=1; &amp;gt;1 AE per pt). One pt (2%) discontinued treatment due to grade 1 pneumonitis (which was centrally adjudicated as not ILD). ORR in all pts was 32% (1 CR, 13 PRs), DCR was 80% (35/44), and clinical benefit rate (CR + PR + SD ≥6 mo) was 34% (15/44). Median duration of response was not yet reached; median progression-free survival (mPFS) was 4.3 mo (95% CI, 3.0-7.3), and median overall survival (mOS) was 12.9 mo (95% CI, 10.1-14.7). In the subset of pts without prior Topo I inhibitor–based ADC therapy and with measurable disease at baseline, ORR was 44% (12/27). Among all pts without prior Topo I inhibitor–based ADC therapy (n=30), mPFS was 7.3 mo (95% CI, 3.0-NE), and mOS was 14.3 mo (95% CI, 10.5-NE). Conclusions: Dato-DXd continues to demonstrate encouraging and durable antitumor activity, along with a manageable safety profile, in heavily pretreated pts with metastatic TNBC. Based on these findings, the phase 3 randomized TROPION-Breast02 (NCT05374512) trial comparing Dato-DXd vs chemotherapy as 1L therapy for pts with metastatic TNBC is currently underway. Citation Format: Aditya Bardia, Ian Krop, Funda Meric-Bernstam, Anthony W. Tolcher, Toru Mukohara, Aaron Lisberg, Toshio Shimizu, Erika Hamilton, Alexander I. Spira, Kyriakos P. Papadopoulos, Jonathan Greenberg, Wen Gu, Fumiaki Kobayashi, Hong Zebger-Gong, Yui Kawasaki, Rie Wong, Takahiro Kogawa. Datopotamab Deruxtecan (Dato-DXd) in Advanced Triple-Negative Breast Cancer (TNBC): Updated Results From the Phase 1 TROPION-PanTumor01 Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-03.

Abstract GS2-01: GS2-01 Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized, phase 3 study DESTINY-Breast02

Abstract In DESTINY-Breast01 (NCT03248492) and DESTINY-Breast03 (NCT03529110), trastuzumab deruxtecan (T-DXd) demonstrated unprecedented activity in patients (pts) with HER2+ (immunohistochemistry 3+; immunohistochemistry 2+/in situ hybridization+) advanced metastatic breast cancer (mBC), leading to regulatory approvals in several countries for HER2+ unresectable/mBC after a prior anti–HER2-based regimen. DESTINY-Breast02 (NCT03523585) is a phase 3 trial of T-DXd vs treatment of physician’s choice (TPC) in patients with centrally confirmed HER2+ mBC previously treated with trastuzumab emtansine (T-DM1). It acts as a confirmatory study for the pivotal phase 2 DESTINY-Breast01 trial. Here we report the primary results of DESTINY-Breast02. Methods: Pts with HER2+ mBC were randomized 2:1 to receive T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine) and stratified by hormone receptor (HR) status (HR+/HR-), prior pertuzumab treatment, and history of visceral disease. The primary endpoint of this time-driven primary analysis was progression-free survival (PFS) as determined by blinded independent central review (BICR). The powered secondary endpoint was overall survival (OS). Other secondary endpoints included confirmed objective response rate (ORR) by BICR, duration of response (DoR) by BICR, PFS by investigator assessment, safety, and others. Results: 608 pts were randomized to receive T-DXd (n = 406) or TPC (n = 202). Pts receiving T-DXd and TPC had a median age of 54.2 years (range, 22.4-88.5 years) and 54.7 years (range, 24.7-86.5 years), respectively, with a median of 2 (range, 0-10 and range,1-8) prior lines of systemic therapy (excluding hormone therapy) in the metastatic setting. Median treatment duration was 11.3 mo in the T-DXd arm and ~4.5 mo in the TPC arm. Efficacy and safety results are shown in the table below. T-DXd significantly improved PFS (HR, 0.36; 95% CI, 0.28-0.45; P &amp;lt;0.000001) and OS (HR, 0.66; 95% CI, 0.50-0.86; P = 0.0021) compared with TPC. Confirmed ORR was 69.7% (14% complete response) with T-DXd and 29.2% (5.0% complete response) with TPC. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 52.7% and 44.1% of pts receiving T-DXd and TPC, respectively. Adjudicated drug-related interstitial lung disease (ILD) occurred in 10.4% of pts with T-DXd vs 0.5% of pts with TPC. In pts receiving T-DXd, most ILD cases (88.1%) were grade 1/2 and grade 5 ILD was reported in 2 (0.5%) pts. Conclusions: Results from DESTINY-Breast02 confirmed the clinical benefit and superiority of T-DXd over conventional chemotherapy-based regimens in pts with HER2+ mBC previously treated with T-DM1, as evidenced by significant and clinically meaningful improvements in PFS and OS. These data, together with earlier reported results from the DESTINY-Breast03 study of T-DXd vs T-DM1 solidify T-DXd as an optimal treatment option in pts with progressive HER2+ mBC across broad settings. Editorial Acknowledgment Under guidance of the authors, assistance in medical writing and editorial support was provided by Caylin Bosch, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table. Summary of Efficacy and Safety Results for T-DXd and TPC in Patients With HER2+ mBC Previously Treated With T-DM1 Citation Format: Ian Krop, Yeon H. Park, Sung-Bae Kim, Giuliano Borges, Sercan Aksoy, Joaquin Gavila Gregori, Rebecca Roylance, Elgene Lim, Rinat Yerushalmi, Flora Zagouri, Francois P. Duhoux, Tanja Fehm, Toshimi Takano, Anton Egorov, Iris Wu, Jillian Cathcart, Changan Chu, Fabrice Andre. GS2-01 Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized, phase 3 study DESTINY-Breast02 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS2-01.

Immune cell profiles and patient clustering in complex cases of interstitial lung disease

Interstitial lung disease comprises numerous clinical entities posing significant challenges towards a prompt and accurate diagnosis. Amongst the contributing factors are intricate pathophysiological mechanisms, an overlap between conditions, and interobserver disagreement. We developed a model for patient clustering offering an additional approach to such complex clinical cases. The model is based on surface phenotyping of over 40 markers on immune cells isolated from bronchoalveolar lavage in combination with clinical data. Based on the marker expression pattern we constructed an individual immune cell profile, then merged these to create a global profile encompassing various pathologies. The contribution of each participant to the global profile was assessed through dimensionality reduction tools and the ensuing similarity between samples was calculated. Our model enables two approaches. First, assessing the immune cell population landscape similarity between patients within a diagnostic group allows rapid identification of divergent profiles, which is particularly helpful for cases with uncertain diagnoses. Second, sample clustering is based exclusively on the calculated similarity of the immune cell profiles, thereby removing physician bias and relying on cellular nearest neighbors.

Descriptive study of the role of ultrasound in the evaluation of patients with interstitial lung disease associated with autoimmune connective tissue disorders

Background and Aim: High-resolution computed tomography (HRCT) of the chest has been the conventionally accepted modality of radiological investigation utilized in the evaluation and management of interstitial lung diseases (ILDs). The aim of this study was to compare the utilization of lung ultrasound (LUS) as a radiological modality versus HRCT scan of the chest, in the diagnosis of cases of ILD in autoimmune connective tissue disease (AICTD) patients at a tertiary care center in Northern India. Methods: In this descriptive study, 42 consecutive diagnosed cases of AICTD with clinical risk of ILD were included, between July 2016 and March 2019, attending the rheumatology outpatient department of CH WC. They were assessed with lung ultrasonography and HRCT chest. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LUS were estimated considering HRCT as the reference method. Results: Of these 42 patients, 30 (71.4%) had abnormal LUS findings. HRCT findings suggestive of ILD were seen in 31 (73.8%). Considering HRCT as gold standard, LUS resulted in 01 false-positive and 02 false-negative results. Sensitivity and specificity of LUS with respect to HRCT were 93.55% and 90.91%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of LUS were calculated at 89.38% and 94.51%, respectively. In 91.6% (11/12) patients with nonspecific interstitial pneumonitis pattern on HRCT, B-lines were found to be numerous and compact (<3 mm distance between B lines). On the other hand, compact B lines were seen in only 21.1% (4/19) cases showing HRCT patterns suggestive of usual interstitial pneumonitis (UIP)/likely UIP, with a significant difference between the two (P = 0.0002). Conclusions: LUS is as nearly sensitive and specific as HRCT chest in the detection of ILD and has the distinct advantage of being without radiation exposure.

Correlation between the Clinical, Etiological, Radiological, and Histopathological Pattern in Patients of Interstitial Lung Disease

Abstract Background and Objective: Interstitial lung diseases (ILDs) include a large number of conditions that primarily involve space between the alveolar epithelium, the capillary endothelium, and adjoining structures such as alveoli and small airways. This study has been conceived to generate the data on the clinical, etiological, radiological, and histopathological pattern of patients of ILD. Methods: This prospective study was conducted from January 1, 2018 to October 31, 2019 enrolling 43 patients of ILD who presented as outpatient/in patients to a tertiary care hospital in North India. Based on the clinical presentation and chest X-ray, the suspected patients were subjected to high-resolution computerised tomography (HRCT) chest and pulmonary function test for confirmation. The confirmed cases were then subjected to bronchoscopy and histopathological study. Results: There were 26 (60%) male patients and 17 (40%) female patients in the study population. The mean (±standard deviation) age was 56.9 ± 13.02 years. A diagnosis of ILD was made based on the history and clinical findings in 35 (81.5%) cases. The most common finding on chest radiography was reticular opacities in 20 (46%). Usual interstitial pneumonia pattern 20 (46%) was the most common abnormality on HRCT. Etiological profile was mainly found to be idiopathic pulmonary fibrosis in 19 (45%). Clinicoradiological correlation was seen in 35 cases, clinicohistological in 23 cases, and historadiological in 28 cases. Overall correlation between all the three modalities was established in 20 (46%) cases. Conclusion: The clinical suspicion of ILD is very important due to the varied etiologies and diseases with similar clinical presentations. Given the limitations of chest radiography, HRCT chest is the best noninvasive modality, while bronchoscopy is the most useful minimally invasive investigation tool to establish a diagnosis. Hence, multidisciplinary correlation is the best approach to evaluate a case of interstitial lung disease.

Rituximab for connective tissue disease-associated interstitial lung disease

Interstitial lung disease (ILD) is one of the most frequent and severe visceral complications of connective tissue diseases (CTDs).1 Despite the recent approval of nintedanib for the treatment of fibrosing progressive ILDs other than idiopathic pulmonary fibrosis,2 management of CTD-ILDs remains challenging. While fibrosing ILD represents at least 50% of ILD cases in patients with rheumatoid arthritis, the frequency of fibrosing subsets in CTDs is significantly lower.1,3 Therefore, immunosuppressants continue to be the most commonly adopted therapy for CTD-ILDs.

Interstitial lung disease in autoinflammatory disease in childhood: A systematic review of the literature.

The lung is one of the target organs in the systemic involvement of autoinflammatory disease (AID), and interstitial lung disease (ILD) is the primary phenotype of lung involvement in AID. In this review, we aimed to conduct a systematic review of the available literature to highlight ILD in AID. We conducted a systematic literature search in PubMed/MEDLINE and Scopus from the inception of the databases to January 2022. References were first screened by title and then by abstract by two authors. Eighteen original papers were selected for full-text review. During the literature search, we identified 18 relevant articles describing 52 cases of AID and ILD. Of those, 44 patients had stimulator of interferon genes-associated vasculopathy with onset in infancy (SAVI), six had coatomer protein complex (COPA) syndrome, one had haploinsufficiency of A20, and one had mevalonate kinase deficiency. Pulmonary fibrosis, cyst formation, and ground glass areas were the most common findings in chest tomography of patients with COPA syndrome and SAVI. Janus kinase inhibitors were used to treat most of the patients with SAVI, which stabilized ILD. ILD should be considered carefully in children with AID, especially those with interferonopathy.

Evaluation of lung adverse events with trastuzumab using the Japanese pharmacovigilance database.

The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 4362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary edema, pleural effusion, lung disorder, acute pulmonary edema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease.

External quality assessment of flow cytometric bronchoalveolar lavage cellular analysis: 20 years' experience in The Netherlands.

Bronchoalveolar (BAL) cellular analysis can be supportive in the diagnosis of interstitial lung disease. The flow cytometric analysis of BAL fluid cells is complicated by cell fragility and adherence and autofluorescence of macrophages, making conventional analysis of BAL fluid cells as done in external quality schemes (EQA) for blood lymphocyte subsets, not representative. Following a procedure for stabilized BAL cells, a separate EQA was set up. The results of 20 years' experience are presented. From each round between 2000 and 2020 the following flow cytometric parameters were recorded from each participant: total lymphocyte population (TLY), CD3+ lymphocytes, CD3+ CD4+ lymphocytes, CD3+ CD8+ lymphocytes, CD3- CD16+/56+ lymphocytes, CD19+ lymphocytes and CD103 + CD3+ lymphocytes. In addition, the eosinophils and neutrophils were recorded. The mean and standard deviation of each parameter per round were calculated. The 40 rounds were divided in four respective groups of 10 in order to compare the results as function of time. In addition the interpretation of the results of participants was scored. The median SD in the four groups was below 10% for all parameters except for TLY and the CD103+ CD3+ lymphocytes. No improvement in time was observed for any (sub)population except for the CD3+ CD4+ subset. Interpretation of the results varied based on disease, with greatest consensus for sarcoidosis cases and lowest for nonspecific interstitial lung disease cases. A dedicated EQA for BAL fluid cellular analysis appears to be justified as the test material is substantially different from that of peripheral blood. We show that adequate analytical and post-analytical quality control can be achieved.

Clinical and Diagnostic Profile of Interstitial Lung Disease

Background: Interstitial lung disease are clinically challenging and diverse group of over 300 disorders. Theseheterogeneous group of disorders share few common clinical radiological and pathological profiles.Objective: To analyse these Clinical, spirometric, laboratory, radiological and bronchoscopic profile of various ILDs.Methods: It is an Institutional based prospective study of 50 cases of Interstitial Lung Disease presenting to pulmonologydepartment. After Obtaining Informed Consent patients were subjected to detailed Clinical, spirometric, laboratory,radiological and bronchoscopic examination. Initially a total of 60 patients were enrolled in the study .Out of which 4patients were excluded based on exclusion criteria and 6 patients were lost to follow up.Results: After Analysing 50 ILD patients, it showed a female preponderance, presenting mostly in 36-55 year age groupwith shortness of breath and cough as the predominant complaints. Majority of the patients showed exercise oxygendesaturation and a restrictive abnormality in spirometric evaluation. Radiologically, reticulonodular pattern was the mostcommon presentation on CXR and reticular opacities on HRCT. Most common HRCT pattern was UIP pattern with basalpredominance. The most common cause of ILD was IPF (30%) followed by LDCTD which comprised 28% of the cases.Conclusion: Patients, in their third to fifth decade, especially females, presenting with complaints of breathlessness andcough, with exercise oxygen desaturation, should be evaluated for ILD with complete profile to identify the disease at anearly stage.

Interstitial lung disease in ANCA-associated vasculitis: associated factors, radiographic features and mortality.

To evaluate the prevalence, clinical and radiographic features, and long-term outcomes of interstitial lung disease (ILD) in a United States-based ANCA-associated vasculitis (AAV) cohort. In this retrospective cohort study, we identified cases of ILD within the 2002-2019 Mass General Brigham AAV Cohort, a consecutive inception cohort of PR3- or MPO-ANCA+ AAV patients. ILD diagnosis and classification as fibrotic or non-fibrotic were confirmed by review of available chest imaging by two board-certified radiologists. Cox proportional hazard models, with age as the time scale, were used to estimate the association of AAV-ILD with all-cause mortality. Of 684 patients in the MGB AAV Cohort, 91 (13%) had ILD which preceded the diagnosis of AAV by a mean of 2.2 years. AAV-ILD patients were older (67 vs 60 years, P < 0.001) than patients without ILD but the distribution of sex and race was similar. AAV-ILD patients were more often MPO-ANCA+ (93% vs 65%, P < 0.001); among MPO-ANCA+ patients (n = 470), 85 (18%) had ILD. The majority of ILD was fibrotic (76%) and UIP was the most common ILD pattern (42%). The baseline forced vital capacity (FVC) % predicted among ILD patients was 81 ± 20%. Fibrotic AAV-ILD was associated with a 58% higher risk of death (aHR 1.58, 95% CI 1.06, 2.37) compared with AAV patients without ILD. ILD is a frequent complication of AAV, especially MPO-ANCA+ AAV, often preceding recognition of AAV. Fibrotic AAV-ILD is associated with a higher risk of death than AAV without ILD.

Interstitial lung disease with anti-melanoma differentiation-associated gene 5 antibody after allogeneic hematopoietic stem cell transplantation.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is one of auto-immune antibodies which is associated with a rare subtype of dermatomyositis (DM), and MDA5-DM is well-characterized by rapid progressive interstitial lung disease (ILD) which in part resembles pulmonary complications after allogeneic hematopoietic cell transplantation (allo-HCT). However, previous studies about anti-MDA5 antibody after allo-HCT were extremely limited. Here, we present 4 cases of ILD with anti-MDA5 antibody after allo-HCT. All of the cases showed rapidly progressive clinical course and 3 of 4 cases died despite intensive immunosuppressive therapies which included prednisolone, cyclophosphamide and calcineurin inhibitor. Additionally, 3 of 4 cases had tested positive for anti-MDA5 antibody by using cryopreserved plasma which were collected about 2–3 months before the diagnosis of MDA5-DM-ILD. It suggests that an inflammatory condition due to MDA5-DM-ILD might have sub-clinically occurred before the development of respiratory failure. The current cases suggest that the clinical feature was relatively similar to classical MDA5-DM-ILD, although it is difficult to distinguish MDA5-DM-ILD from chronic GVHD and other pulmonary complications after allo-HCT. Since clinical courses of MDA5-DM-ILD is considerably aggressive, it is important to discriminate MDA5-DM-ILD from other complications after allo-HCT.

Chronic fibrosing interstitial lung diseases according to the register of Irkutsk (Russia)

The Interstitial lung diseases (ILD) are a wide heterogeneous group of disorders, different in many parameters, however having similar pathophysiological mechanisms. Idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), chronic hypersensitivity pneumonitis (CHP), ILD associated with autoimmune disorders (predominantly systemic sclerosis (SSc ILD) and rheumatoid arthritis (RA ILD), and other diseases may be accompanied by the formation of pulmonary fibrosis. Currently there are no generally accepted criteria for the fibrosing and progressive fibrosing ILD, and the information on the frequency of these conditions is limited.The study aims to research the structure of fibrosing ILD and the frequency of the progressive fibrosing phenotype (PFP) according to the register of patients with ILD in Irkutsk, Russia.Methods. At the first stage information letters were sent to all medical institutions of Irkutsk with recommendations on all referral patients with ILD for further examination. At the second stage, each ILD case was verified collegially (n = 270). All patients’ data were analysed in terms of clinical, functional, radiological and histological aspects. A register of ILD patients was formed based on this analysis. The follow-up period was 1 to 5 years.Results. According to the results of a comprehensive assessment, HRCT signs of pulmonary fibrosis were detected by 104 patients (38.5%). fibrosing course was observed in 100% IPF and SSc ILD, in 90.9% of CHP, 71.4% of NSIP and 60% of RA ILD. 61 patients (22.6% of all ILD cases, 58.6% of fibrosing ILD) was diagnosed with PFP. The 5-year mortality for PFP ILD was 55.5%.Conclusion. In the case of a PFP development, the evolution of ILD loses its nosological specificity, acquiring similarity with IPF. Due to the high mortality rate, it is necessary to actively identify the progressive fibrosing course of a wide range of ILD and to prescribe an antifibrotic therapy in a timely manner.