Abstract 26-74% of microplastics are derived from tire rubber and is a large contributor to environmental pollution. While infrastructure contributes to environmental pollution, it equally contributes to pathogenesis of pulmonary disease. Industry workers, particularly in tire manufacturing plants, are susceptible to pulmonary fibrosis and interstitial lung disease (ILD), with studies showing almost half of ILD cases secondary to microplastics. This case highlights the effect of exposure in industry workers over time. A 63-year-old gentleman with remote history of smoking presented to the emergency department with worsening shortness of breath. He was diagnosed to have chronic obstructive pulmonary disease exacerbation, imaging revealed interstitial pattern. He was treated with steroids and with improvement in symptoms. High resolution computed tomography showed evidence of interstitial lung disease. Further questioning revealed that patient reported a 20+ year history of working in a tire shop with exposure to buffed tire dust and autoshop particulates without proper protection. Patient had multiple outpatient visits for 10 years due to recurrent sinusitis. Imaging in the past demonstrated atypical lung disease, which was attributed to chronic sinobronchitis. Pulmonary function test prior to admission demonstrated obstructive disease. While signs of ILD were noted for over 6 years, due to confounding factors, there was delay in further evaluation. He was discharged on 6L oxygen. He presented again to the ED for worsening dyspnea and acute on chronic hypoxia. During this admission, he was unable to be weaned off high flow nasal cannula and discharged to long term acute care for aggressive physical therapy and oxygen management. He was intubated at the facility and returned due to inability to wean from ventilator. He subsequently passed after family decided on compassionate extubation. Talc is commonly used in the tire industry; however, exposure to this substance can cause granuloma formation and subsequent ILD. Our patient was working in the tire industry for more than 20 years with recurrent symptoms of inflammatory processes. Based on imaging, his disease process started in the upper lobe and progressed diffusely throughout the parenchyma. The pathogenesis of microplastics resulting in ILD is not well understood, but is becoming more evident that chronic inflammation from microplastic inhalation can contribute to development of severe ILD over time. Our case highlights the role of environmental tire fiber exposure in the development of ILD. Regulations on occupational hazards of exposure to microplastics need to be further explored and education to workers to be further enhanced.
AB1192 PREVALENCE, RISK FACTORS, AND OUTCOMES OF SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE IN CHINESE: A MULTI-CENTRED COHORT STUDY
Background:Interstitial lung disease (ILD) is one of the leading causes of death in systemic sclerosis (SSc) and can have a significant impact on a patient’s quality of life [1]. Identification...
Read moreAssociation Between Single-Nucleotide Polymorphism and Trastuzumab Deruxtecan-Induced Interstitial Lung Disease in Breast Cancer Using the Japonica Array NEO.
Background/Objectives: Trastuzumab deruxtecan (T-DXd) is an effective antibody-drug conjugate for human epidermal growth factor receptor 2-expressing solid tumors; however, interstitial lung disease (ILD) remains a clinically significant adverse event. Although both clinical characteristics and genetic susceptibility have been implicated in drug-induced ILD, the factors specifically associated with T-DXd-induced ILD remain unclear. This study aimed to evaluate clinical and genetic factors associated with the development of ILD in patients treated with T-DXd. Methods: We retrospectively analyzed the clinical data of 54 patients treated with T-DXd. The baseline clinical and treatment-related characteristics of patients with ILD and those without were compared. Genome-wide single-nucleotide polymorphism (SNP) analyses with genotype imputation and targeted candidate SNP analyses were performed to evaluate genetic susceptibility. Results: ILD occurred in 15 patients (27.8%), with a median time to onset of 215 days (range, 48-1187). None of the baseline clinical or treatment-related factors were significantly associated with ILD development. Genome-wide analyses did not reveal any significant SNPs after correcting for multiple testing. Contrarily, a targeted analysis focusing on SNPs previously associated with drug-induced ILD identified one variant rs12625311 that was significantly associated with ILD in this cohort. Conclusions: In this exploratory study, baseline clinical characteristics alone were insufficient to discriminate the risk of ILD among patients treated with T-DXd. Although no high-penetrance genetic variants were identified, candidate-based genetic analyses suggested that host genetic factors may contribute to ILD susceptibility. Integrating genetic information with clinical assessment may help refine the risk stratification for T-DXd-induced ILD in future studies.
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2FRI0059 Interstitial lung disease in patients with rheumatoid arthritis of a cohort treated with methotrexate monotherapy
BackgroundDiffuse interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and an important cause of morbidity and mortality in this patient population. The predisposing and prognostic...
Read more2Exhaustion of NK cells and interferon activation in anti-MDA5+ dermatomyositis are associated and determine the development of ILD
ObjectivesThis study aimed to investigate the role of natural killer (NK) cell and interferon (IFN) signaling in the peripheral circulation of anti-MDA5+ dermatomyositis (DM) patients, particularly in the context of interstitial lung disease (ILD) development.MethodsPeripheral blood mononuclear cells (PBMCs) from six newly diagnosed, active anti-MDA5+ DM patients (3 with ILD, 3 without ILD) were analyzed using single-cell RNA sequencing (scRNA-seq), focusing on NK cell features. The correlation between serum cytokine levels and ILD severity assessed by HRCT scores was further analyzed. Flow cytometry in an independent cohort validated NK cell apoptosis, and in vitro experiments evaluated IFN-induced apoptosis in NK-92 cells.ResultsScRNA-seq revealed widespread activation of IFN responses in PBMCs from anti-MDA5+ DM-ILD patients, with pronounced upregulation in innate immune cells (e.g., NK cells and monocytes). A reduction in circulating NK cell proportions was observed in ILD patients. Serum levels of cytokines (IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12P70, TNF-α, and IFN-α) positively correlated with the radiologic severity of ILD as quantified by HRCT scores. Flow cytometry confirmed significantly decreased NK cell counts and increased apoptosis in the ILD group. PBMCs from healthy donors exposed to an ILD-like cytokine milieu exhibited upregulated IFN pathway genes (ISG15, MX2, IFIT3), EIF2AK2 (encoding protein kinase R), and apoptosis-related genes (BCL2, BAX2). In vitro, IFN stimulation directly induced apoptosis in NK-92 cells.ConclusionExcessive IFN activation drives NK cell apoptosis in anti-MDA5+ DM-ILD, contributing to NK cell depletion and ILD development. IFN-related biomarkers may serve as valuable indicators for assessing ILD severity in these patients.
Read moreRheumatoid arthritis and interstitial lung disease: the role of comorbidities-a retrospective analysis of two RA inception cohorts in the UK.
The objective of this study was to assess the role of comorbidities measurements in interstitial lung disease (ILD) in patients with RA. The data were from two consecutive multicentre, prospective RA inception cohorts, including baseline socio-demographic, clinical, treatment, laboratory and functional features. Comorbidity burden was assessed using a count of major comorbidities, the Rheumatic Disease Comorbidity Index (RDCI) and the Charlson Comorbidity Index (CCI). Associations between comorbidities and the development of ILD were explored, adjusted for clinical factors using multivariable logistic regression analyses. The data from 2701 patients were included, and the median follow-up time was 6 years. In total, 101 patients (3.7%) were diagnosed with ILD. Twelve (0.44%) had the diagnosis at baseline, 46 were diagnosed during follow-up, and 43 were identified from death certificates. In multivariable analyses, age at onset [adjusted odds ratio (aOR) 1.03, 95% CI 1.01-1.05], seropositivity (aOR 2.58, 95% CI 1.38-4.81) and ever smoking (aOR 1.70, 95% CI 1.04-2.79) were associated with ILD diagnosis. Higher lung comorbidity burden measured using the lung disease component of the RDCI (aOR 4.59, 95% CI 2.68-7.88) was associated, as was using the entire index (aOR 1.32, 95% CI 1.07-1.63). The association did not remain when assessing comorbidity with alternative measures. The method chosen to assess the comorbidity burden affected whether baseline comorbidity was associated with subsequent ILD development. This study demonstrates that a specific Rheumatic Disease Comorbidity Index reveals associations not detected by generic tools or simple counts. Baseline lung comorbidities should be added to the known list of risk factors for ILD and aid targeted screening in the context of RA.
Read more276Gastroesophageal Reflux and Pulmonary Fibrosis in Scleroderma
Interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) is associated with increased morbidity and mortality. Gastroesophageal reflux (GER) is considered a contributing factor in the pathogenesis of ILD. To characterize GER (acid and nonacid) in patients with SSc with and without ILD. Patients with SSc underwent pulmonary high-resolution computer tomography (HRCT) scan and 24-hour impedance-pH monitoring off-proton pump inhibitor therapy. The presence of pulmonary fibrosis was assessed using validated HRCT-scores. Reflux monitoring parameters included number of acid and nonacid reflux episodes, proximal migration of the refluxate, and distal esophageal acid exposure. Unless otherwise specified, data are presented as median (25th-75th percentile). Forty consecutive patients with SSc (35 female; mean age, 53 yr; range, 24-71; 15 patients with diffuse and 25 with limited SSc) were investigated; 18 (45%) patients with SSc had pulmonary fibrosis (HRCT score >or= 7). Patients with SSc with ILD had higher (P < 0.01) esophageal acid exposure (10.3 [7.5-15] vs. 5.2 [1.5-11]), higher (P < 0.01) number of acid (41 [31-58] vs. 19 [10-23]) and nonacid (25 [20-35] vs. 17 [11-19]) reflux episodes, and higher (P < 0.01) number of reflux episodes reaching the proximal esophagus (42.5 [31-54] vs. 15 [8-22]) compared with patients with SSc with normal HRCT scores. Pulmonary fibrosis scores (HRCT score) correlated well with the number of reflux episodes in the distal (r(2) = 0.637) and proximal (r(2) = 0.644) esophagus. Patients with SSc with ILD have more severe reflux (i.e., more reflux episodes and more reflux reaching the proximal esophagus). Whether or not the development of ILD in patients with SSc can be prevented by reflux-reducing treatments needs to be investigated.
Read moreNasal High Flow Therapy in Chronic Obstructive Pulmonary Disease
<p>Background: In acute exacerbations of chronic obstructive pulmonary disease (AECOPD), hypercapnia (raised arterial partial pressure of carbon dioxide, PₐCO₂) is associated with worse clinical outcomes, including death. Nasal high flow (NHF) therapy is a common method of administering oxygen therapy in hypoxic respiratory failure, yet its effect on PₐCO₂ in COPD are uncertain. Aims: To investigate the effects of NHF therapy in people with COPD. Methods: Two randomised controlled trials (RCTs) were undertaken to investigate the effect of NHF on transcutaneous partial pressure of carbon dioxide (PtCO₂) in COPD: one comparing different flow rates (45 L/min, 30 L/min and 15 L/min) to breathing room air as a control in 48 participants with stable COPD, and another comparing NHF against non-invasive ventilation (NIV) in 24 stable COPD patients with chronic hypercapnia. Two further studies tested the feasibility of undertaking multicentre RCTs utilising different applications of NHF in COPD: one in 100 patients (20 in New Zealand, 80 in the United States) using NHF at home for 30 days following hospital discharge to determine patterns of use and rates of hospital readmission, and another in the Emergency Department (ED) to test whether a pre-specified standard protocol for managing acute hypercapnic respiratory failure (AHRF) could be followed. Finally, another RCT compared the tolerability and change in PtCO₂ of a dual NHF/NIV device to a standard NIV device in people with chronic respiratory disorders including COPD. Results: In stable COPD, the mean (95% CI) change in PtCO₂ at 20 min was −0.6 mm Hg (−1.1 to 0.0), P = 0.06; −1.3 mm Hg (−1.9 to 0.8), P < 0.001; and −2.4 mm Hg (−2.9 to −1.8), P < 0.001; for NHF at 15 L/min, 30 L/min and 45 L/min, respectively, compared with room air. In stable COPD with chronic hypercapnia, the mean (SD) reduction in PtCO₂ at 60 min from baseline with NHF was -2.5 mmHg (3.5) compared to -5.3 mm Hg (5.0) with NIV. The PtCO₂ change when analysed across all time points was lower using NIV than with NHF: -2.5mmHg (95% CI -4.5 to -0.5), P=0.016. In the international outpatient feasibility study, mean (SD) NHF use at home following hospital discharge was 1.6 (1.6) hours/day in the 20 NZ participants. The 30-day hospital readmission rate was 10% (95% CI 1.8 to 33.1). Recruitment in the US was unsuccessful, despite a 12-month extension, and no data was available. In the second feasibility study, 120 patients with AECOPD were reviewed over a 4-month period in ED. All 3 patients with AHRF received the standard of care protocol and in one there was significant deviation from the agreed protocol. There was no difference in tolerability between the dual NHF/NIV device and a standard NIV device on a 100mm visual analogue scale: mean difference - 1.3mm (95% CI -7.9 to 5.2, P=0.69), and a lower PtCO2 with the standard NIV device, mean difference -0.61mm Hg (95% CI -1.05 to -0.17, P=0.01). Conclusion: The small, flow-dependent reduction in PtCO₂ observed with the currently available NHF device across the range of flows used in clinical practice indicates that it is safe to use in COPD from a physiological perspective. The reduction on PtCO₂ with NHF was smaller than with NIV, however the difference was of uncertain clinical significance, suggesting NHF represents an alternative therapy for COPD patients with hypercapnia who cannot tolerate NIV, or during breaks from NIV. In NZ, it would be feasible to undertake an RCT using NHF in AECOPD patients discharged from hospital, but not those presenting to ED with AHRF. The recently developed dual NHF/NIV device had similar tolerability as a standard NIV device and there was no clinically significant difference in PtCO2. These findings suggest that NHF represents a therapeutic option for patients with COPD, with the dual NHF/NIV device demonstrating potential as a modality for delivering NHF in COPD patients with AHRF.</p>
Read more12High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial pneumonia: a retrospective observational study.
ABSTRACTHigh-flow nasal cannula (HFNC) oxygen is a therapy that has demonstrated survival benefits in acute respiratory failure (ARF). However, the role of HFNC in ARF due to interstitial pneumonia (IP) is unknown. The aim of this study was to compare the effects of HFNC therapy and non-invasive positive pressure ventilation (NPPV) in ARF due to IP. This retrospective observational study included 32 patients with ARF due to IP who were treated with HFNC (n = 13) or NPPV (n = 19). The clinical characteristics, intubation rate and 30-day mortality were analyzed and compared between the HFNC group and the NPPV group. Predictors of 30-day mortality were evaluated using a logistic regression model. HFNC group showed higher mean arterial blood pressure (median 92 mmHg; HFNC group vs 74 mmHg; NPPV group) and lower APACHEII score (median 22; HFNC group vs 27; NPPV group) than NPPV group. There was no significant difference in the intubation rate at day 30 between the HFNC group and the NPPV group (8% vs 37%: p = 0.069); the mortality rate at 30 days was 23% and 63%, respectively. HFNC therapy was a significant determinant of 30-day mortality in univariate analysis, and was confirmed to be an independent significant determinant of 30-day mortality in multivariate analysis (odds ratio, 0.148; 95% confidence interval, 0.025–0.880; p = 0.036). Our findings suggest that HFNC therapy can be a possible option for respiratory management in ARF due to IP. The results observed here warrant further investigation of HFNC therapy in randomized control trials.
Read moreTHU0089 Il-17a+gm-csf+ neutrophils are the major infiltrating cells in interstitial lung disease in an autoimmune arthritis model
BackgroundInterstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Discrepancy in the effect of biologic agents on synovial and lung inflammation exists, indicating that the nature...
Read more84Efficacy and Tolerability of High-Flow Nasal Cannula Oxygen Therapy for Hypoxemic Respiratory Failure in Patients with Interstitial Lung Disease with Do-Not-Intubate Orders: A Retrospective Single-Center Study
Efficacy and Tolerability of High-Flow Nasal Cannula Oxygen Therapy for Hypoxemic Respiratory Failure in Patients with Interstitial Lung Disease with Do-Not-Intubate Orders: A Retrospective Single-Center Study
Read more3Effect of pre-treatment with EGFR-TKIs on immune checkpoint inhibitor-associated interstitial lung disease in lung cancer patients: Analysis using a Japanese claims database.
Immune checkpoint inhibitors (ICI) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) are key drugs for the treatment of EGFR mutation-positive lung cancer. While previous studies reported that the concomitant use of these drugs increases the risk of interstitial lung disease (ILD), the impact of sequential treatment on ILD risk is unknown. This study aimed to analyze the impact of EGFR-TKI pre-treatment on the risk of developing ILD after subsequent ICI administration. We conducted a retrospective study using a Japanese health insurance claims database. ILD-naive lung cancer patients who had first ICI administration during the screening period from July 2014 to February 2019 were selected. Patients who had ILD within 1 year of receiving the first ICI dose were included in the ILD group. Multivariate logistic regression analysis was conducted to evaluate the effect of pre-treatment with EGFR-TKI on the development of ICI-associated ILD. A total of 353 patients were included, of which 61 were included in the ILD group. The median time to onset of ILD after ICI administration was 3 months. Multivariate logistic regression analysis revealed that pre-treatment with EGFR-TKI was not associated with ICI-associated ILD (odds ratio: 0.26, 95% confidence interval: 0.033-2.01). Although further analyses are required to confirm our findings, this study indicated that pre-treatment with EGFR-TKI might not increase the ILD risk after ICI treatment.
Read moreRoentgenographic Underestimation of Early Asbestosis
Roentgenographic Underestimation of Early Asbestosis
80Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti-melanoma differentiation-associated gene 5 dermatomyositis.
Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) is a distinctive subtype of DM that carries a significant risk of interstitial lung disease (ILD). The mechanisms remain elusive. To explore the role of the type I interferon (IFN) system in the pathogenesis of anti-MDA5 DM. Twenty patients with anti-MDA5 DM were studied and compared with patients with anti-aminoacyl-tRNA synthetase (ARS) DM (n = 10) and autoantibody-negative patients with DM (n = 20). The levels of inflammatory cytokines, B-cell-activating factor (BAFF) and Krebs von den Lungen (KL)-6 in blood were tested by enzyme-linked immunosorbent assay and multiplex assays. Expressions of transcripts for IFN-associated sensors and type I IFN-inducible genes in peripheral blood mononuclear cells (PBMCs) were detected by real-time polymerase chain reaction. Expressions of the signal transducer and activator of transcription (STAT)1, interferon-stimulated gene (ISG)15 and MxA proteins in skin lesions were analysed by immunohistochemistry. Plasma IFN-α levels were significantly increased in patients with anti-MDA5 DM. PBMCs from patients with anti-MDA5 DM showed significant upregulation of the TLR3, TLR7, IFIH1 and DDX58 genes, as well as serial IFN-inducible genes. Skin biopsies from patients with anti-MDA5 DM were characterized by strong expression of the STAT1, ISG15 and MxA proteins. In the patients with anti-MDA5 DM and ILD with high IFN-α production, there was a positive quantitative correlation between IFN-α and BAFF (rs = 0·63, P = 0·044). In addition, the higher levels of BAFF paralleled the higher concentrations of KL-6 (rs = 0·86, P = 0·0012). Our data confirm the aberrant activation of the type I IFN system in anti-MDA5 DM. Overproduction of IFN-α linked with BAFF may be implicated in the development of ILD.
Read moreNasopharyngeal hyperbaric oxygen therapy in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease
Objective To investigate the effect of humidified high flow nasal cannula on the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A total of 68 patients with AECOPD treated in our hospital from August 2017 to January 2018 were selected as study subjects and divided into control group and study group according to random number table method, 34 cases in each group.Both groups received routine general treatment.The control group received conventional nasal cannula oxygen therapy on the basis of routine treatment.The study group was given HHFNC treatment on the basis of routine treatment.The results of blood gas analysis, respiratory rate (RR), PaO2/FiO2 improvement and treatment outcome were compared before and 2 h, 6 h, 12 h, 24 h and 48 h after treatment. Results After two hour treatment, pH, PaO2, RR and PaO2/FiO2 in the study group were significantly different from those in the control group (t=6.375, 3.524, 9.295, 2.206, P 0.05). Conclusions Transnasal high-flow wet oxygen therapy can significantly improve the clinical symptoms of patients with AECOPD and promote the prognosis of patients, it is worth clinical application. Key words: Humidified high flow nasal cannula; Acute exacerbation of chronic obstructive pulmonary disease; Effect
Read more4Nailfold Capillaroscopic Changes as a Marker of Interstitial Lung Disease in Systemic Sclerosis: A Cross-Sectional Study in a Tertiary Care Hospital in Eastern India.
Background:Systemic sclerosis (SSc) is an autoimmune connective tissue disorder causing microvascular abnormality leading to Raynaud's phenomenon, skin tightening, and nailfold capillary changes. The patient may have systemic involvement, among them interstitial lung disease (ILD) and pulmonary arterial hypertension are mainly associated with disease-related mortality.Aims:To find out an association between nailfold capillaroscopic changes with ILD severity.Materials and Methods:An institution based cross-sectional study was performed among the patients of SSc above 18 years. Detailed history was taken. Clinical examinations, nailfold capillaroscopy (NFC) with a dermatoscope and high-resolution computed tomography (HRCT) scan of thorax were done. Data were analyzed in MedCalc statistical software version 20.Results:Out of total 43 patients, 74.4% (n = 32) were female. Mean age was 35.05 ± 7.24 years and mean duration 4.28 ± 2.81 years. Diffuse SSc was found in 88.37% (n = 38). On NFC, early, active, and late patterns were found in 30.2% (n = 13), 25.6% (n = 11), and 44.2% (n = 19) cases, respectively. On HRCT, early, active, and late ILD were present in 18.6% (n = 8), 37.2% (n = 16), and 30.2% (n = 13) cases, respectively. ILD changes were absent in 14% (n = 6) though NFC changes were present in them. Respiratory symptoms were absent in 20.93% (n = 9) patients though all had features of early NFC and among them 9.3% (n = 4) showed early ILD changes on HRCT. Significant associations were found between NFC changes and ILD severity (P = 0.0003), NFC changes and respiratory symptoms (P < 0.0001) and between ILD changes and respiratory symptoms (P < 0.0001).Discussion:NFC, an inexpensive procedure, can be performed in all patients of SSc to detect development of early ILD even before appearance of respiratory symptoms to prevent further progression.
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