Lung Disease In Patients Research Articles

The emerging role of ultrasound in detecting interstitial lung disease in patients with rheumatoid arthritis.

To investigate the potential role of US in the detection of ILD in a cohort of patients with RA. Patients with diagnosis of RA were consecutively enrolled. All patients underwent pulmonary examination, laboratory data, DLCO measure, chest HRCT and radiographs, and US examination. A healthy group was included as control group. US was performed according the 14-intercostal space scanning protocol using the following semiquantitative scale [0=normal (≤5 B-lines); 1=slight (≥6 and ≤15 B-lines); 2=moderate, (≤16 and ≥30 B-lines); 3=severe (≥30 B-lines)]. A total of 74 RA patients and 74 healthy controls were included. Thirty of 74 patients (40.5%) showed US signs of ILD with respect to the healthy controls (3 subjects, 4.1%) (P<0.001); whereas HRCT showed ILD in 27 (36.4%) of 74 patients. Among the 30 patients that showed US findings of ILD, 17 (56.6%) were asymptomatic from respiratory view-point. The sensitivity and specificity of US were 92% and 89% respectively. A positive correlation between US and HRCT findings were found (P<0.001) whereas no correlation was found with chest radiographs and DLCO findings. Positive association between US findings and DAS28-ESR, anti-CCP and RF (P<0.01 for each respectively) was found. Feasibility, represented by the mean time spent to perform the pulmonary US assessment was 7.8minutes (±SD 1.2, range 6 to 10minutes). Our results support the potential of US in detect accurately ILD in patients with RA and provide a rationale to consider it as a friendly screening tool to be implemented in early phases of the disease.

Nocardia spp. isolation in chronic lung diseases: Are there differences between patients with pulmonary nocardiosis and Nocardia colonization?

Chronic lung diseases are a recognized risk factor for Nocardia spp. Nocardia spp. isolation does not inevitably imply disease, and thus colonization must be considered. Here, we aimed to analyse the differences between pulmonary nocardiosis (PN) and Nocardia spp. colonization in patients with chronic lung diseases. A retrospective study of patients with laboratory confirmation of isolation of Nocardia spp. in at least one respiratory sample was performed. Patients with PN and Nocardia spp. colonization were compared. There were 71 patients with Nocardia spp. identification, 64.8% were male, with a mean age of 67.7 ± 11.2 years. All patients had ≥1 pre-existing chronic lung disease, and 19.7% of patients were immunocompromised. PN and Nocardia spp. colonization were considered in 26.8% and 73.2% of patients, respectively. Symptoms and chest CT findings were significantly more frequent in patients with PN (p < 0.001). During follow-up time, 12 (16.9%) patients died, 6 in PN group. Immunosuppression, constitutional symptoms, haematological malignancy and PN diagnosis were associated with significantly shorter survival times, despite only immunosuppression (HR 3.399; 95% CI 1.052-10.989) and PN diagnosis (HR 3.568; 95% CI 1.078-11.910) remained associated with a higher death risk in multivariate analysis. PN was associated with clinical worsening, more chest CT findings and worse clinical outcomes. Nocardia spp. isolation in chronic lung disease patients is more common than expected and the differentiation between colonization and disease is crucial.

Cultural Sensitivity of Sputum Bacteria Involved in Chronic Lung Disease and Type of Bacteria Involved in Chronic Lung Disease Sputum

Objective: To determine the type of bacterium involved in sputum of patients with chronic lung disease and to determine the culture sensitivity of bacterium involved in sputum of chronic lung disease patients Methodology: This Cross-sectional study, at Deptt of Pediatric Medicine, The Children’s Hospital, Lahore during 2020 to 2021. Total 160 children meeting the criteria of inclusion were the part of this trial. Then the children were given a petri dish to spit in and the samples were submitted to the medical lab to be analysed for bacteria. Penicillin, Ampicillin, Amoxicillin-clavulanic acid, Erythromycin, Tetracycline, Ciprofloxacin, Cefuroxime, Ceftazidime, Cefepime, Piperacillin-tazobactam, Amikacin, Gentamycin, and Vancomycin were tested on all cultured bacteria after they were identified. Results: we recorded 8.60±2.54 years mean age. The most frequent isolated organism was H-influenza (43.1%) followed by H-Parainfluenza (36.9%) and S. Pneumonia (20%). Sensitivity of Ciprofloxacin, Cefuroxime, Amikacin, Gentamycin, Piperacillin / Tazobactam, Ceftazidime, Cefepime and Vancomycin was significantly higher for H parainfluenza as compared to other isolated bacterium. Conclusion: Results of this study showed that among children with chronic lung disease the most frequency isolated bacterium was H-influenza (43.1%) followed by H-Parainfluenza (36.9%) and S. Pneumonia (20%). Antibiotic sensitivity was significantly higher for H-parainfluenza as compared to other isolated bacteria. Keywords: Bacterium, Sputum, Chronic, Lung disease, Culture, Sensitivity

Clinical, Functional, and Prognostic Evaluation of Idiopathic Pulmonary Fibrosis, Connective Tissue Disease-Associated Interstitial Lung Disease, Interstitial Pneumonia with Autoimmune Features: A Single-Center Prospective Study.

Our study aimed to evaluate clinical, functional, and prognostic features and to determine the prognosis of idiopathic pulmonary fibrosis, connective tissue disease-associated interstitial lung diseases, and interstitial pneumonia with autoimmune features. Sixty-nine cases with interstitial lung diseases were recruited in this study prospectively. Demographic features, symptoms, radiological findings, functional measurements, and immunological markers were recorded twice (at the time of initial admission and in the 12th month). Twenty-four of 69 cases were idiopathic pulmonary fibrosis, 32 were connective tissue diseaseassociated interstitial lung diseases, and 13 were interstitial pneumonia with autoimmune features . Most of the patients with idiopathic pulmonary fibrosis were male, while there were more female patients in connective tissue disease-associated interstitial lung diseases and interstitial pneumonia with autoimmune features groups. Female patients (65.0%) predominated in connective tissue disease-associated interstitial lung diseases group (P <.001). There was no significant difference in the mean ages of the disease groups, yet connective tissue disease-associated interstitial lung diseases patients were generally younger (min- max: 34-82 years). In the idiopathic pulmonary fibrosis group, only low titers of antinuclear antibody positivity were found. Antinuclear antibody positivity in the connective tissue disease-associated interstitial lung diseases group and interstitial pneumonia with autoimmune features group was high (P = .001). The long-term survival of idiopathic pulmonary fibrosis, connective tissue disease-associated interstitial lung diseases, and interstitial pneumonia with autoimmune features patients were 37%, 40 months (median) (95% CI, 5.193- 74.807), 48.6%, 80 months (median) (95% CI, 57.032-102.968), 30.8%, 46 months (median) (95% CI, 26.624-65.376), respectively. Although a consensus report describing interstitial lung diseases with autoimmune features has been published, diagnostic criteria for this group are still vague. Since the interstitial pneumonia with autoimmune features group had the worst results in terms of functional loss and survival rates, the follow-up parameters and follow-up algorithm should be established for this group. Clinical and immunological evaluation of the interstitial pneumonia with autoimmune features group should include detailed parameters because of follow-up and to estimate survival.

A Portable Servoregulation Controller to Automate CO2 Removal in Artificial Lungs.

Artificial lung (AL) systems provide respiratory support to patients with severe lung disease, but none can adapt to the changing respiratory needs of the patients. Precisely, none can automatically adjust carbon dioxide () removal from the blood in response to changes in patient activity or disease status. Because of this, all current systems limit patient comfort, activity level, and rehabilitation. A portable servoregulation controller that automatically modulates removal in ALs to meet the real-time metabolic demands of the patient is described. The controller is based on a proportional-integral-derivative (PID) based closed-loop feedback control system that modulates sweep gas (air) flow through the AL to maintain a target exhaust gas partial pressure (target or ). The presented work advances previous research by (1) using gas-side sensing that avoids complications and clotting associated with blood-based sensors, (2) incorporating all components into a portable, battery-powered package, and (3) integrating smart moisture removal from the AL to enable long term operation. The performance of the controller was tested in vitro for ∼12 h with anti-coagulated bovine blood and 5 days with distilled water. In tests with blood, the sweep gas flow was automatically adjusted by the controller rapidly (<2 min) meeting the specified tEG level when confronted with changes in inlet blood partial pressure of (p) levels at various AL blood flows. Overall, the removal from the AL showed a strong correlation with blood flow rate and blood p levels. The controller successfully operated continuously for 5 days when tested with water. This study demonstrates an important step toward ambulatory AL systems that automatically modulate removal as required by lung disease patients, thereby allowing for physiotherapy, comfort, and activity.

Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathways

MiRNAs are widely acknowledged as regulating gene expression and thus, being involved in broad biological functions, environmental responses, and the process of diseases. Epidemiology could provide exposure- or disease-relevant miRNAs, while toxicology could reveal the underlying mechanisms. Here, a new “Bottom-up” approach was proposed to identify miRNAs that are responsible for environmental exposure-induced adverse outcomes. In our previous study, 5 key toxicity pathways were established underlying BaP-induced lung diseases; further, genes from these 5 pathways that were responsive to BaP exposure in HBE-CYP1A1 cells were identified. In this study, we identified 26 miRNA:mRNA interactions during BaP exposure through RNA-sequencing using the same HBE-CYP1A1 cells. According to the expression alteration and regulatory mechanisms, we summarized 8 action patterns of miRNA:mRNA, which led to the induction of miRNAs that predominantly regulate target genes and responsible are for the pathway perturbations (as “drivers”), and miRNAs that subordinately regulate genes during pathway perturbations (as “symptoms”). 5 corresponding miRNAs: miR-3173-5p, miR-629-3p, miR-9-5p, miR-1343-3p and miR-219a-1-3p were identified as “drivers”, and were all validated with expression alteration in lung disease patients from published studies. In conclusion, this study offers a new approach to identification of epigenetic factors that may shed light on the causation of environment-related health outcomes.

Imaging biomarkers of lung ventilation in interstitial lung disease from 129Xe and oxygen enhanced 1H MRI

PurposeTo compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. Study typeProspective longitudinal. PopulationForty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. Field strength/sequenceMRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. AssessmentFive 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. Statistical testTo evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. ResultsThe global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. Data conclusionNeither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.

Effect of chronic lung diseases on mortality of prevariant COVID-19 pneumonia patients.

BackgroundThe aim of the study is to assess the effect of chronic lung disease on mortality in patients hospitalized with the diagnosis of prevariant COVID-19 Pneumonia compared to patients without chronic lung disease.Research design and methodsA cohort of 1,549 patients admitted to the pandemic clinic with a COVID-19 Pneumonia diagnosis was analyzed. Group 1 and Group 2 were compared in terms of the treatment they received, admission to intensive care, mortality and follow-up parameters.ResultsThe patient group with COVID-19 and lung disease consisted of 231 participants (14.91%) (Group 1). The patient group with COVID-19 but without lung disease had 1,318 participants (85.19%). Group 1 cases were found to receive more oxygen therapy and mechanical ventilation than Group 2 cases (p ≤ 0.001), Following univariate and multiple logistic regression analyses, it was determined that patients with chronic lung disease had a 25.76% higher mortality risk [OR: 25.763, 95% CI (Lower-Upper) (2.445–271.465), p = 0.007].ConclusionIt was found that chronic lung disease contributed significantly to mortality in this study. Among chronic lung diseases, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and interstitial lung diseases (ILDs) were shown to be more effective than other chronic lung diseases in patients with prevariant COVİD-19 population.

Epidemiology of interstitial lung disease in patients with metastatic breast cancer at baseline and after treatment with HER2-directed therapy: a real-world data analysis

PurposeUsing real-world data, interstitial lung disease (ILD) prevalence before and after HER2-directed therapy was estimated. Potential ILD risk factors in patients receiving HER2-directed therapy for metastatic breast cancer (mBC) were evaluated.MethodsAdults with HER2-directed therapy for mBC initiated between September 25, 1998, and February 22, 2020 were, included. ILD was defined broadly as one or more of 64 lung conditions. Patients were followed until incident ILD, death, last contact, or study end.ResultsIn total, 533 patients were identified with median age at mBC of 57, 51% had de novo mBC, 43% were ever smokers, 30% had lung metastases, 9% had thoracic radiation, 6% had chronic obstructive pulmonary disease, and 16% had prevalent ILD. ILD cumulative incidence at one year was 9% (95% CI 6%, 12%), with a median follow-up of 23 months. Smoking (HR 2.2, 95% CI 1.1, 4.8) and Black/African-American race (HR 3.4, 95% CI 1.6, 7.5) were significantly associated with ILD; HRs for preexisting lung conditions (HR 1.8, 95% CI 0.9, 3.8) and thoracic radiation (HR 2.3, 95% CI 0.8, 7.1) were not statistically significant. Prevalent ILD was associated with 13-fold greater occurrence of incident ILD. 85% of patients with prevalent or incident ILD were symptomatic.ConclusionsThis real-world population of patients with mBC had a high prevalence of ILD prior to HER2-directed therapy, reflecting the multifactorial causation of interstitial lung changes. The cumulative incidence of ILD in patients receiving HER2-directed therapy for mBC augments prior reports. Symptomatic presentation suggests an opportunity for early intervention.

Clinical impact of antineutrophil cytoplasmic antibody positivity on the occurrence of interstitial lung disease in patients with polymyositis/dermatomyositis.

This study investigated the clinical impact of antineutrophil cytoplasmic antibody (ANCA) positivity on the occurrence of interstitial lung disease (ILD) in patients with probable and definite polymyositis (PM)/dermatomyositis (DM) who met both the Bohan and Peter and the 2017 European League Against Rheumatism/American College of Rheumatology criteria. The medical records of 75 PM/DM patients were retrospectively reviewed. ANCA and anti-Jo 1 positivity at diagnosis were obtained, and pulmonary function test and chest high-resolution computed tomography results at ILD occurrence were collected. The follow-up duration based on ILD was defined as the period from the time of PM/DM diagnosis to the occurrence of ILD in PM/DM patients with ILD and to the last visit for those without ILD. The median age was 50.0 years and 21.3% were male. ANCA and anti-Jo 1 were detected in 12 (16.0%) and 26 patients (34.7%), respectively. ILD occurred in 32 patients, 24 of whom had ILD at the time of PM/DM diagnosis. Anti-Jo 1 was detected more often in PM/DM patients without ANCA than those with (39.7% vs. 8.3%). ILD occurred more frequently in PM/DM patients with ANCA than those without ANCA (75.0% vs. 36.5%). However, the occurrence of ILD was not affected by anti-Jo 1 positivity. Furthermore, ANCA-positive PM/DM patients exhibited a significantly lower cumulative ILD-free survival rate than ANCA-negative PM/DM patients (P=0.009). ANCA positivity at the time of PM/DM diagnosis might be an important risk factor for ILD in PM/DM patients.

Pulmonary hypertension in patients with interstitial lung disease: a tool for early detection.

Pulmonary hypertension (PH) complicates the treatment of interstitial lung disease (ILD) patients resulting in poor functional status and worse outcomes. Early recognition of PH in ILD is important for initiating therapy and considering lung transplantation. However, no standard exists regarding which patients to screen for PH‐ILD or the optimal method to do so. The aim of this study was to create a risk assessment tool that could reliably predict PH in ILD patients. We developed a PH‐ILD Detection tool that incorporated history, exam, 6‐min walk distance, diffusion capacity for carbon monoxide, chest imaging, and cardiac biomarkers to create an eight‐component score. This tool was analyzed retrospectively in 154 ILD patients where each patient was given a score ranging from 0 to 12. The sensitivity (SN) and specificity (SP) of the PH‐ILD Detection tool and an area‐under‐the‐curve (AUC) were calculated. In this cohort, 74 patients (48.1%) had PH‐ILD. A score of ≥6 on the PH‐ILD Detection tool was associated with a diagnosis of PH‐ILD (SN: 86.5%; SP: 86.3%; area‐under‐the‐curve: 0.920, p < 0.001). The PH‐ILD Detection tool provides high SN and SP for detecting PH in ILD patients. With confirmation in larger cohorts, this tool could improve the diagnosis of PH in ILD and may suggest further testing with right heart catheterization and earlier intervention with inhaled treprostinil and/or lung transplant evaluation.

OVARIAN RESERVE IN PATIENTS WITH INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS

OVARIAN RESERVE IN PATIENTS WITH INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS

Promising Neutrophil-Associated Biomarkers in Lung Diseases of Patients with Antisynthetase Syndrome and Dermatomyositis.

Objectives Antisynthetase syndrome (ASS) and dermatomyositis (DM) are serious autoimmune diseases, with lungs being the most frequently involved organ and sometimes fatal. This study is aimed at clarifying the role of neutrophil-associated biological markers in suggesting ASS and DM-associated respiratory infections and interstitial lung diseases. Methods We carried out a retrospective review of the medical records of 46 cases of ASS and DM diagnosed at the Second Hospital of Zhejiang University College of Medicine, between January 2017 and December 2020. Serum myeloperoxidase (MPO), neutrophil elastase (NE), α1 anti-trypsin (AAT), and interleukin-6 (IL-6) were also detected. Results Gottron's sign is characteristic of dermatomyositis, while polyarthritis is more characteristic of ASS. Pulmonary function is worse in ASS than in DM patients. Patients with ASS and DM had abnormal lymphocyte and neutrophil counts compared to healthy subjects, but not in relation to lung function and rapid progression of interstitial lung disease (RP-ILD). Elevated serum NE, MPO, and IL-6 levels are suggestive of respiratory infections, whereas decreased circulating IL-6 is predictive of RP-ILD. Conclusion Our study identified the neutrophil-associated biomarkers MPO, NE, and IL-6 as promising indicators with different suggestive roles in respiratory infections and interstitial lung diseases in patients with ASS and DM.

Comparison of physiological responses after incremental shuttle walking test and 6-minute walk test in patients with systemic sclerosis.

The 6‑minute walk test (6MWT) is acommonly used to evaluate exercise capacity in patients with systemic sclerosis (SSc), but there was no study using the incremental shuttle walking test (ISWT) for assessing exercise capacity and comparing the patient's cardiorespiratory responses to these tests. The aim was to investigate the usability and determinants of the ISWT in patients with SSc and compare the physiological responses after the ISWT and 6MWT. A total of thirty four female patients with SSc were included. Dyspnea during daily activities and knee extensor muscle strength was assessed, skin fibrosis and disease severity were recorded, and 6MWT and ISWT were carried out for the exercise capacity measurement. Pulmonary function test results were recorded from the individuals' medical records for SSc with interstitial lung disease (SSc-ILD) patients. The ISWT distance was significantly correlated with the 6MWT distance (p < 0.001). The 6MWT was correlated with age, modified Rodnan skin score, Medsger severity score, modified British Medical Research Council Questionnaire (mMRC) score, and knee extensor muscle strength (p < 0.05). The 6MWT was correlated with the forced expiratory volume in thefirstsecond (FEV1) (lt) and forced vital capacity (FVC) (lt) in patients with SSc-ILD (p < 0.05). The ISWT distance was correlated with age, modified Rodnan skin score, mMRC score, and knee extensor muscle strength (p < 0.05). Age, mMRC, and knee extensor muscle strength explained 33.8% of the variance in 6MWT distance, while age, mMRC, and knee extensor muscle strength explained 51.7% of the variance in the ISWT distance. Because of the higher cardiopulmonary responses, and having amore standardized procedure, the ISWT may be preferable for investigating symptom-limited exercise capacity in patients with SSc. Age, dyspnea, and knee extensor muscle strength were the determinants of exercise capacity in patients with SSc.

Longitudinal study of patients with antimelanoma differentiation-associated gene 5 antibody-positive dermatomyositis-associated interstitial lung disease.

To describe the 8-year longitudinal study and long-term prognosis of a large inception cohort of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) DM-interstitial lung disease (ILD) patients. In total, 216 patients diagnosed with MDA5+ DM-ILD were enrolled and followed up to analyse long-term survival rate. Demographic and clinical variables were collected at baseline and each temporal end point. Seventy patients who survived the first year were analysed for the long-term serological and respiratory outcomes. A total of 85 patients (39.3%) died during the follow-up period up to 96 months, with 89% of the deaths occurring in the first year after diagnosis. Long-term outcome was reported in 70 patients. Serological markers including anti-MDA5 antibody showed significant improvement with time. Radiographic findings and pulmonary function also improved notably in the follow-up period, especially in rapidly progressive ILD group, as measured by high-resolution computed tomography imaging scores, the estimated forced vital capacity, estimated diffusing capacity of lung carbon monoxide and dyspnoea scores. Early application of anti-fibrosis therapy helped to improve long-term pulmonary function. MDA5+ DM-ILD patients had a high mortality rate despite aggressive treatment. Patients who survived the first year usually showed a significant improvement in serological markers and pulmonary function during the long-term follow-up.

242P Investigating the risk of drug-induced interstitial lung disease in patients with metastatic breast cancer treated with antiHER2 regimens through a network meta-analysis approach

The advent of antibody-drug conjugates such as trastuzumab deruxtecan (T-Dxd), has significantly increased the awareness towards drug-induced Interstitial Lung Disease (ILD), a pulmonary disorder caused by several conditions including drugs, which may cause a wide range of pathological processes, from inflammation to interstitial fibrosis. However, the differential magnitude of risk among the available treatments is still unknown. This network meta-analysis (NMA) aims to provide first preliminary data on the risk of ILD across antiHER2 regimens. After a systematic literature review, a Bayesian NMA using a Markov-Chain Monte Carlo simulation was performed using STATA software (Stata Corp, version 17). Treatments were classified as: Trastuzumab (T) + chemotherapy (CT), T/Pertuzumab (P)+CT, Everolimus (Eve)/T+CT, T-DM1, T-DM1/P, T-DM1+Atezolizumab (Atezo) and T-Dxd. Outcomes were reported with corresponding 95% credible intervals (CrIs). Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). BOLERO-1, BOLERO-3, CLEOPATRA, KATE2, MARIANNE and DESTINY-Breast03 were the main trials included in the NMA. In the experimental arm, ILD of any grade was detected in 10.5% of patients for DESTINY-Breast03, 4.5% and 3.6% respectively for BOLERO-1 and BOLERO-3, 0.7% in KATE2, 0.5% in CLEOPATRA and 0.3% in MARIANNE. In terms of tolerability, T-DM1 ranked first (SUCRA 80.1%), followed by TDM1/P/T + CT (SUCRA 77.5%). Instead, T-Dxd and Eve/T + CT were the most prone to ILD development (respectively SUCRA 18.7% and 11.1%). No significant differences were shown between T+CT and T-DM1 or T-DM1+Atezo in NMA, while a significantly lower risk ratio was observed for T+CT when compared to T/P+ CT (RR 0.04, 95%CrI 0.01-0.34), T-Dxd (RR 0.03, 95%CrI 0.00 - 0.56) and Eve/T+CT (RR 0.02, 95%CrI 0.00 - 0.08). Our NMA showed how drug induced ILD could differentially affect antiHER2 treatments for MBC patients. Further investigations are needed to understand the underlying pathological mechanisms causing drug induced ILD and to identify predictive biomarkers focused on the early identification of patients at higher risk.

1148P The effects of statin use on lung cancer development in patients with idiopathic pulmonary fibrosis using clinical data warehouse

Statin use was associated with reduced all-cause mortality in interstitial lung disease and idiopathic pulmonary fibrosis (IPF) patients. To further investigate the potential preventive effects of statins on lung cancer development in IPF patients, we used clinical data warehouse (CDW) for electronic medical record (EMR)-based clinical research.

Clinical Predictors of Lung-Function Decline in Systemic-Sclerosis-Associated Interstitial Lung Disease Patients with Normal Spirometry.

Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Progressive pulmonary fibrosis (PPF) is defined as progression in 2 domains including clinical, radiological or lung-function parameters. Our aim was to assess predictors of functional decline in SSc-ILD patients and compare disease behavior to that in idiopathic pulmonary fibrosis (IPF) patients. Patients with normal forced vital capacity (FVC > 80% predicted; SSc-ILD: n = 31; IPF: n = 53) were followed for at least 1 year. Predictors of functional decline including clinical symptoms, comorbidities, lung-function values, high-resolution CT pattern, and treatment data were analyzed. SSc-ILD patents were significantly younger (59.8 ± 13.1) and more often women (93 %) than IPF patients. The median yearly FVC decline was similar in both groups (SSc-ILD = −67.5 and IPF = −65.3 mL/year). A total of 11 SSc-ILD patients met the PPF criteria for functional deterioration, presenting an FVC decline of −153.9 mL/year. Cough and pulmonary hypertension were significant prognostic factors for SSc-ILD functional progression. SSc-ILD patients with normal initial spirometry presenting with cough and PH are at higher risk for showing progressive functional decline.

Functional clinical impairments and frailty in interstitial lung disease patients.

BackgroundPatients with interstitial lung disease (ILD) often present with persistent dyspnoea and reduced exercise capacity and quality of life (QoL), but their functional limitation in relation to their frailty status remains unclear. We thus aimed to compare exercise tolerance, functional mobility, and muscle function and composition between ILD participants and healthy subjects and according to their frailty status.MethodsA total of 36 ILD participants and 15 heathy subjects performed a 6-min walk test, a 1-min sit-to-stand test, a Short Physical Performance Battery test, a hand grip test and complete quadriceps function testing. Patient-related impacts were assessed via questionnaires. Muscle composition was obtained using noncontrast computed tomography scans. The frailty status of patients with ILD was determined using the Fried frailty phenotype assessment.ResultsCompared with control subjects, ILD participants exhibited significantly lower performance in every exercise and functional capacity test, higher dyspnoea and depression scores, and worse QoL. In ILD participants, the same observations were noted for the frail subgroup compared with the robust subgroup. No differences in muscle function and composition were observed between the ILD and control group, but mid-thigh muscle cross-sectional area and skeletal muscle index were significantly reduced in frail ILD participants.ConclusionsILD patients present reduced exercise tolerance and functional capacity, and have decreased health-related QoL, when compared with healthy subjects. Physical frailty seems to be associated with worse clinical status, exercise tolerance, muscle and functional impairment, and decreased QoL. The 1-min sit-to-stand test may be a good discriminatory test for frailty status in ILD patients.

Reduction of Emphysema Severity by Human Umbilical Cord-Derived Mesenchymal Stem Cells in Mice.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in chronic lung disease patients throughout the world. Mesenchymal stem cells (MSCs) have been shown to regulate immunomodulatory, anti-inflammatory, and regenerative responses. However, the effects of human-umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) on the lung pathophysiology of COPD remain unclear. We aimed to investigate the role of hUC-MSCs in emphysema severity and Yes-associated protein (Yap) phosphorylation (p-Yap) in a porcine-pancreatic-elastase (PPE)-induced emphysema model. We observed that the emphysema percentages (normalized to the total lung volume) measured by chest computed tomography (CT) and exercise oxygen desaturation were significantly reduced by hUC-MSCs at 107 cells/kg body weight (BW) via intravenous administration in emphysematous mice (p < 0.05). Consistently, the emphysema index, as assessed by the mean linear intercept (MLI), significantly decreased with hUC-MSC administration at 3 × 106 and 107 cells/kg BW (p < 0.05). Changes in the lymphocytes, monocytes, and splenic cluster of differentiation 4-positive (CD4+) lymphocytes by PPE were significantly reversed by hUC-MSC administration in emphysematous mice (p < 0.05). An increasing neutrophil/lymphocyte ratio was reduced by hUC-MSCs at 3 × 106 and 107 cells/kg BW (p < 0.05). The higher levels of tumor necrosis factor (TNF)-α, keratinocyte chemoattractant (KC), and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) were significantly decreased by hUC-MSC administration (p < 0.05). A decreasing p-Yap/Yap ratio in type II alveolar epithelial cells (AECII) of mice with PPE-induced emphysema was significantly increased by hUC-MSCs (p < 0.05). In conclusion, the administration of hUC-MSCs improved multiple pathophysiological features of mice with PPE-induced emphysema. The effectiveness of the treatment of pulmonary emphysema with hUC-MSCs provides an essential and significant foundation for future clinical studies of MSCs in COPD patients.