Search

Abstract Background Multidisciplinary discussion (MDD), in which physicians, radiologists, and pathologists communicate and diagnose together, has been reported to improve diagnostic accuracy compared to diagnoses made solely by physicians. However, even among experts, diagnostic concordance of MDD is not always good, and some patients may not receive a specific diagnosis due to insufficient findings. A provisional diagnosis based on the ontology with a diagnostic confidence level has recently been proposed. Additionally, we developed an artificial intelligence model to differentiate idiopathic pulmonary fibrosis (IPF) from other chronic interstitial lung diseases (ILD)s, which needs validation in a broader population. Methods This prospective nationwide ILD registry has recruited patients with newly diagnosed ILD at the referral respiratory hospitals in Japan and provides rapid MDD diagnoses and treatment recommendations through a central online MDD platform with a 3-year follow-up period. A modified diagnostic ontology is used. If no diagnosis reaches more than 50% certainty, the diagnosis is unclassifiable ILD. If multiple diseases are expected, the diagnosis with a high probability takes precedence. If the confidence levels for the top two possible diagnoses are equal, the diagnosis can be unclassifiable. The registry uses tentative diagnostic criteria for nonspecific interstitial pneumonia with organising pneumonia and smoking-related ILD not otherwise specified as possible new entities. Central MDD diagnosticians review the clinical data, test results, radiology images, and pathological specimens on a dedicated website and conduct MDD diagnoses using online meetings with a cloud-based reporting system. This study aims to (1) provide MDD diagnoses with treatment recommendations; (2) determine the overall ILD rates in Japan; (3) clarify the reasons for unclassifiable ILDs; (4) evaluate possible new disease entities; (5) identify progressive phenotypes and create a clinical prediction model; (6) measure the agreement rate between institutional and central diagnoses in ILD referral and non-referral centres; (7) identify key factors for each specific ILD diagnosis; and (8) create a new disease classification system based on treatment strategies, including the use of antifibrotic drugs. Discussion This study will provide ILD frequencies, including new entities, using central MDD on dedicated online systems, and develop a machine learning model for ILD diagnosis and prognosis prediction. Trial registration UMIN-CTR Clinical Trial Registry (UMIN000040678).

Abstract Background Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury with high mortality; no approved medication exists. Efficacy and safety of bone marrow–derived, allogeneic, multipotent adult progenitor cells (invimestrocel) plus standard treatment in patients with ARDS caused by pneumonia was evaluated. Methods A randomized, open-label, standard therapy–controlled, phase 2 study (January 2019–September 2021) conducted in 29 centers in Japan. Patients with ARDS caused by pneumonia, with extensive early fibroproliferation on high-resolution computed tomography and low risk of systemic organ failure identified by an Acute Physiology and Chronic Health Evaluation (APACHE II) score were included. Patients were randomized 2:1 to receive a single intravenous infusion of 9.0 × 108 cells of invimestrocel (administered at a rate of up to 10 mL/min over 30–60 min by free flow) plus standard treatment (N = 20) or standard treatment (N = 10) consistent with the clinical practice guidelines of the Japanese Respiratory Society for the management of ARDS. Primary endpoint was ventilator-free days (VFDs) through day 28 after study treatment. Analysis of covariance was performed with treatment group, age, partial pressure arterial oxygen/fraction of inspired oxygen ratio, and APACHE II score as covariates. Results Median (interquartile range) number of VFDs was numerically higher in the invimestrocel group versus standard group (20.0 [0.0–24.0] vs 11.0 [0.0–14.0]) but was not statistically significantly different (least square [LS] means [95% confidence interval (CI)]: invimestrocel group, 11.6 [6.9–16.3]; standard group, 6.2 [− 0.4 to 12.8]; LS mean difference [95% CI], 5.4 [− 1.9 to 12.8]; p = 0.1397). Ventilator weaning rate at day 28 was 65% (13/20) versus 30% (3/10), and mortality rate was 21% (4/19) versus 29% (2/7) at day 28 and 26% (5/19 patients) versus 43% (3/7 patients) at day 180, for the invimestrocel and standard groups, respectively. No allergic or serious adverse reactions were associated with invimestrocel. Conclusions In Japanese patients with ARDS caused by pneumonia, invimestrocel plus standard treatment resulted in no significant difference in the number of VFDs but may result in improved survival compared with standard treatment. Invimestrocel was well tolerated. Trial registration: ClinicalTrials.gov, Identifier: NCT03807804; January 8, 2019; https://clinicaltrials.gov/ct2/show/NCT03807804 .

Abstract Background Interstitial lung abnormalities (ILAs) are subtle or mild parenchymal abnormalities observed in more than 5% of the lungs on computed tomography (CT) scans in patients in whom interstitial lung disease was not previously clinically suspected and is considered. ILA is considered to be partly undeveloped stages of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). This study aims to clarify the frequency of subsequent IPF or PPF diagnosis, the natural course from the preclinical status of the diseases, and the course after commencing treatment. Methods This is an ongoing, prospective, multicentre observational cohort study of patients with ILA referred from general health screening facilities with more than 70,000 annual attendances. Up to 500 participants will be enrolled annually over 3 years, with 5-year assessments every six months. Treatment intervention including anti-fibrotic agents will be introduced in disease progression cases. The primary outcome is the frequency of subsequent IPF or PPF diagnoses. Additionally, secondary and further endpoints are associated with the efficacy of early therapeutic interventions in cases involving disease progression, including quantitative assessment by artificial intelligence. Discussion This is the first prospective, multicentre, observational study to clarify (i) the aetiological data of patients with ILA from the largest general health check-up population, (ii) the natural course of IPF or PPF from the asymptomatic stage, and (iii) the effects and outcomes of early therapeutic intervention including anti-fibrotic agents for progressive cases of ILA. The results of this study could significantly impact the clinical practice and treatment strategy for progressive fibrosing interstitial lung diseases. Trial registration number UMIN000045149.

Abstract Background Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF. Methods In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering. Results The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22–0.76] and 0.65 [0.36–1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14–0.99] and 0.27 [0.094–0.83] in the multi-center and administrative cohorts, respectively). Conclusion Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Abstract Background The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. Methods The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. Results Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). Conclusions This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

BackgroundThere is no existing reliable and practical method for predicting the prognosis of acute respiratory distress syndrome (ARDS).ObjectiveWe aimed to clarify the association between the ROX index, which is calculated as the ratio of peripheral oxygen saturation divided by the fraction of inspired oxygen to the respiratory rate, and the prognosis of patients with ARDS under ventilator support.MethodsIn this single-center retrospective cohort study from prospectively collected database, eligible patients were categorized into three groups based on ROX tertiles. The primary outcome was the 28-day survival, and the secondary outcome was 28-day liberation from ventilator support. We performed multivariable analysis using the Cox proportional hazards model.ResultsAmong 93 eligible patients, 24 (26%) patients died. The patients were divided into three groups according to the ROX index (< 7.4, 7.4-11, ≥ 11), with 13, 7, and 4 patients dying in the groups, respectively. A higher ROX index was associated with lower mortality; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 0.54[0.21-1.41], 0.23[0.074-0.72] (P = 0.011 for trend) and a higher rate of successful 28-day liberation from ventilator support; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 1.41[0.68-2.94], 2.80[1.42-5.52] (P = 0.001 for trend).ConclusionsThe ROX index at 24 h after initiating ventilator support is a predictor of outcomes in patients with ARDS and might inform initiation of more advanced treatments.

Abstract There have been no report of objective clinical characteristics or prognostic factors that predict fatal outcome of acute respiratory distress syndrome (ARDS) since the Berlin definition was published. The aim of this study is to identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia. In total, 104 cases of Japanese patients with pneumonia-induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (

Background Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO.Methods We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO.Results Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22–56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted 20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

Abstract Background The use of baseline tumor burden (TB) as a prognostic factor for non‐small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) and associations between TB and other prognostic biomarkers remain unclear. In this study, we investigated the association between TB and survival in NSCLC patients treated with ICIs in comparison with other biomarkers. Methods We retrospectively evaluated 83 NSCLC patients with ICIs administered between February 2016 and December 2018. TB was measured as the sum of the unidimensional diameters of up to five target lesions. Results The median observation period was 14.2 months. A total of 42 patients died during the follow‐up. Univariate Cox regression analysis showed that baseline TB was associated with OS. Cox regression analysis adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) alone or with addition of programmed cell death ligand 1 expression and treatment line showed that TB was a prognostic factor for OS. Using time‐dependent receiver operating characteristic curve analysis, the optimal TB cutoff for predicting OS was 12 cm, and patients were divided into a high TB group (n = 21) and a low TB group (n = 62). The low TB group achieved significantly longer OS than the high TB group (median OS: 18.5 months, [95% CI = 11.7‐not reached] vs. 2.3 months [95% CI = 1.3–2.9], P

Introduction Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown aetiology with a poor prognosis. Several clinical trials of nintedanib in patients with IPF have reported its inhibitory effect on reduced lung function, incidence of acute exacerbation of IPF and worsened health-related quality of life. Although nintedanib has a manageable safety and tolerability profile over long-term use, it was discontinued in over 20% of patients because of adverse events such as diarrhoea and liver dysfunction. This might explain why nintedanib use in patients with IPF is not widespread, especially among patients with early-stage IPF. In the present study, we aimed to clarify the efficacy, safety and tolerability of nintedanib in patients with stage I/II IPF, based on the Japanese IPF disease severity staging classification system.Methods and analysis This is an ongoing, prospective, multicentre observational cohort study of patients with stage I/II IPF who will start receiving nintedanib. Totally, 215 patients at 35 sites in Kyushu and Okinawa, Japan will be enrolled and followed up for 3 years. Nintedanib therapy would be initiated at the discretion of the investigator. The primary endpoint, change in forced vital capacity (FVC) at 156 weeks, will be shown as the mean change in FVC from baseline to week 156 with 95% CIs estimated using the Wald method. The safety endpoint—occurrence of adverse events—will be assessed in each system organ class/preferred term.Ethics and dissemination The study protocol and informed consent documents were approved by the Institutional Review Board at Nagasaki University Hospital (approval number 19102146) and each participating site. Written informed consent was obtained from all participants. Patient recruitment has begun. The results will be disseminated through scientific peer-reviewed publications and national and international conferences.Trial registration number UMIN000038192.

Abstract Background and objective Here, we present real-world data on the incidence and risk factors of acute exacerbation (AE) in patients with chronic fibrotic interstitial pneumonia (CFIP) treated with antifibrotic agents, which has been previously poorly documented. Methods We retrospectively examined clinical characteristics, incidence and risk factors of AE in a cohort of 100 patients with CFIP (n = 75, idiopathic pulmonary fibrosis [IPF]; n = 25, other conditions), all of whom received antifibrotic agents in a real-world setting. Results The median follow-up was 17.4 months (interquartile range [IQR], 6.6 to 26.7 months). During the follow-up periods, 21 patients experienced AE after starting antifibrotic agents. The estimated 1-, 2-, and 3-year AE incidence rates were 11.4% (95% confidence interval [95%CI], 6.2–20.3%), 32% (95%CI, 20.7–47.4%), and 36.3% (95%CI 23.5–53.1%), respectively. Decreased baseline lung function (forced vital capacity and carbon monoxide diffusing capacity of the lung), existence of pulmonary hypertension estimated from an echocardiogram, higher Interstitial Lung Disease-Gender, Age, and Physiology (ILD-GAP) score, supplementary oxygen, and concomitant corticosteroid and proton-pump inhibitor (PPI) use upon starting the antifibrotic agent were risk factors of AE. Concomitant corticosteroid and PPI use and corticosteroid dose were risk factor of AE in a multivariate Cox regression hazard model adjusting for ILD-GAP score. Conclusion AE of CFIP is more common in patients with physiologically and functionally advanced disease under antifibrotic agents. Prudent use of corticosteroids and PPIs when initiating antifibrotic agents may be recommended. Further studies are warranted.

Abstract Background Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, is a key drug for ALK rearranged lung adenocarcinoma. Interstitial lung disease (ILD) is an important adverse effect of alectinib, which generally requires termination of treatment. However, we treated two patients with drug-induced ILD who continued to receive alectinib. Case presentation Patient 1 was a 57-year-old male with an ALK-rearranged Stage IV lung adenocarcinoma who was administered alectinib as first-line therapy. Computed tomography (CT) detected asymptomatic ground-glass opacity (GGO) on day 33 of treatment. Alectinib therapy was therefore discontinued for 7 days and then restarted. GGO disappeared, and the progression of ILD ceased. Patient 2 was a 64-year-old woman with an ALK-positive lung adenocarcinoma who was administered alectinib as third-line therapy. One year later, CT detected GGO; and she had a slight, nonproductive cough. Alectinib therapy was continued in the absence of other symptoms, and GGO slightly diminished after 7 days. Two months later, CT detected increased GGO, and alectinib therapy was continued. GGO diminished again after 7 days. The patient has taken alectinib for more than 2 years without progression of ILD. Conclusions Certain patients with alectinib-induced ILD Grade 2 or less may continue alectinib therapy if they are closely managed.

Abstract Background Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition without an established pharmaceutical treatment. Most patients are treated with high-dose corticosteroids and broad-spectrum antibiotics. Azithromycin is a macrolide with immunomodulatory activity and may be beneficial for treatment of acute lung injury. The objective of this study was to determine the effect of azithromycin on survival of patients with idiopathic AE of IPF. Methods We evaluated 85 consecutive patients hospitalized in our department for idiopathic AE of IPF from April 2005 to August 2016. The initial 47 patients were treated with a fluoroquinolone-based regimen (control group), and the following 38 consecutive patients were treated with azithromycin (500 mg/day) for 5 days. Idiopathic AE of IPF was defined using the criteria established by the 2016 International Working Group. Results Mortality in patients treated with azithromycin was significantly lower than in those treated with fluoroquinolones (azithromycin, 26% vs. control, 70%; p

Abstract Background The efficacy of corticosteroid use in acute respiratory distress syndrome (ARDS) remains controversial. Generally, short-term high-dose corticosteroid therapy is considered to be ineffective in ARDS. On the other hand, low-dose, long-term use of corticosteroids has been reported to be effective since they provide continued inhibition of the systemic inflammatory response syndrome (SIRS) that accompanies ARDS. Thus far, no reports have been published on the efficacy of initiating treatment with a high-dose corticosteroid regimen with tapering. Methods We conducted a retrospective observational study involving 186 patients treated at a teaching hospital (68% had sepsis, pneumonia, or aspiration pneumonia). ARDS was diagnosed according to the Berlin definition. Patients were divided into a high-dose (n = 21) or low-dose corticosteroid group (n = 165) to compare the effectiveness of a down-titration regimen. The primary medical team chose which treatment a patient would receive. We were careful to conduct a differential diagnosis of interstitial pneumonia (e.g., acute eosinophilic pneumonia) since corticosteroid treatment has been proven effective in that patient population. The primary outcome was the 60-day mortality rate. The secondary outcome was the number of ventilator-free days (VFD). Results Those started on a high-dose regimen had a significantly higher 60-day mortality rate (P = 0.031) with significantly fewer VFD (P = 0.021). Propensity scores were used to adjust patient backgrounds in a variable analysis that also showed the high-dose regimen was a factor in decreasing VFD (OR, 95.63; 95% CI, 1.74–5271.07; P = 0.026) and worsening the 60-day mortality rate (OR, 2.54; 95% CI, 0.92–7.02; P = 0.072). Conclusions A tapering regimen after high-dose corticosteroids is likely to increase ventilator dependency and might aggravate the prognosis of patients with ARDS diagnosed according to the Berlin definition.

Few studies have reported the diagnostic variability in patients with a possible usual interstitial pneumonia (UIP) pattern on high-resolution CT (HRCT) who underwent surgical lung biopsy (SLB), and the prognostic factors for these patients have not been fully evaluated. We retrospectively investigated the frequency of idiopathic pulmonary fibrosis (IPF) and prognostic factors in patients with possible UIP pattern on HRCT.Consecutive patients who had a possible UIP pattern on HRCT, underwent SLB, and had a diagnosis of IIPs before SLB were retrospectively recruited from 10 hospitals. Diagnoses were made based on multidisciplinary discussion using the criteria for current IPF guidelines and multidisciplinary classification for IIPs in each hospital.179 patients who underwent SLB were enrolled. The diagnoses were IPF in 91 patients (51%), unclassifiable IIPs in 47 (26%), idiopathic NSIP in 18 (10%), and chronic hypersensitivity pneumonia in 17 (9%). One-year FVC changes showed significant differences between IPF and non-IPF (-138.6 mL versus 18.2 mL, p = 0.014). Patients with IPF had a worse mortality than those with non-IPF (Logrank test, p = 0.025). Multivariable Cox regression analysis demonstrated that diagnoses of IPF (HR, 2.961; 95% CI, 1.183-7.410; p = 0.02), high modified MRC score (HR, 1.587; 95% CI, 1.003-2.510; p = 0.049), and low %FVC (HR, 0.972; 95% CI, 0.953-0.992; p = 0.005).About a half of patients with a possible UIP pattern on HRCT had diagnoses other than IPF, and patients with IPF had a worse mortality than those with an alternative diagnosis. We reaffirmed that multidisciplinary discussion is crucial in patients with possible UIP pattern on HRCT.

Orbital metastasis of lung cancer is rare. It often causes visual disorder. To date, there are only a few case reports. Crizotinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that leads to responses in most patients with ALK-positive non-small-cell lung cancer. Visual disorder is one of the popular adverse events of crizotinib, but the symptom almost decreases over time. We report a case of orbital metastasis as the disease progression of ALK-positive lung cancer treated with crizotinib. It should be kept in mind that orbital metastasis can be the disease progression of lung adenocarcinoma with ALK translocation treated with crizotinib. When physicians encounter a patient receiving crizotinib with visual disorder, we must distinguish between adverse events and orbital metastasis.

Background: Amiodarone is a useful antiarrhythmic drug, especially in patients with serious heart diseases, but amiodarone-induced interstitial pneumonia (AMD-IP) is sometimes lethal. Methods and results: We retrospectively analyzed the clinical characteristics of 280 patients who were treated with daily oral amiodarone. Among the patients, 29 (10.2%) developed AMD-IP during the follow-up period of 66.0±38.2 months. The average dose of amiodarone in the AMD-IP group (173±10 mg) was significantly higher than that in the non-AMD-IP group (150±3 mg). The prevalence of smoking history (AMD-IP group: 70.0%; non-AMD-IP group: 42.2%; P5 years, 10.2% of patients receiving low-dose amiodarone therapy developed AMD-IP. Higher maintenance doses, smoking history, and preexisting lung disease were related to the development of AMD-IP. The AMD-IP patients with COPD had a poor prognosis.

Alkaline phosphatase (ALP) flare phenomenon documented as scintigraphic flare phenomenon due to elevated serum ALP levels produced by osteoblasts reflects an osteoblastic reaction in response to the effective therapy of non-small cell lung cancer (NSCLC). Here, we report a case of ALP flare following gefitinib treatment for NSCLC. We also retrospectively analyzed the prevalence of ALP flare in lung cancer patients treated via epidermal growth factor receptor-tyrosine kinase inhibitor in our hospital. Recognition of this phenomenon is important for physicians treating NSCLC patients to avoid discontinuation of a potentially beneficial treatment because of misdiagnosis for refractory multiple bone metastasis or adverse effect.

Recent studies have suggested that an increased peripheral monocyte count predicts a poor outcome in fibrosing interstitial lung disease (ILD). However, the association between an increased monocyte count and acute exacerbations (AEs) of fibrosing ILD remains to be elucidated. Our retrospective cohort study aimed to assess the impact of peripheral monocyte count on AEs of fibrosing ILD. We analyzed the electronic medical records of 122 consecutive patients with fibrosing ILD and no prior history of an AE, who were treated with anti-fibrotic agents from August 2015 to December 2018. We determined their peripheral monocyte counts at anti-fibrotic agent initiation and performed univariate and multivariate Cox regression analyses of time-to-first AE after anti-fibrotic agent initiation to assess the impact of monocyte count on AEs of fibrosing ILD. Twenty-six patients developed an AE during the follow-up period, and there was an increased monocyte count at anti-fibrotic agent initiation in these patients compared to those who did not develop an AE. There was also a significantly shorter time-to-first AE of fibrosing ILD in patients with a higher absolute monocyte count. Subgroup analyses indicated similar results regardless of the idiopathic pulmonary fibrosis diagnoses. This association was independently significant after adjusting for the severity of the fibrosing ILD. Using our results, we developed a simple scoring system consisting of two factors—monocyte count (<>380 µL−1) and ILD-gender, age, physiology score (<>4 points). Our findings suggest that the absolute monocyte count is an independent significant risk factor for AE in patients with fibrosing ILD. Our simple scoring system may be a predictor for AEs of fibrosing ILD, although further studies are needed to verify our findings. [ABSTRACT FROM AUTHOR]

Objectives To report the clinical features and prognosis of drug-associatedacute respiratory distress syndrome (ARDS). Design A retrospective analysis of data collected during a prospective cohort study. Setting Intensive care unit in a teaching hospital. Participants A total of 197 Japanese patients with ARDS diagnosed by the Berlin definition who were admitted to the Division of Respiratory Medicine from October 2004 to December 2015 were enrolled in the study and were classified as two groups according to their causes: a drug-associated ARDS group (n=27) and a non-drugassociated ARDS group (n=170). Primary outcome measure is 28-day mortality, and the secondaryoutcome measure is ventilator-free days. Results The Acute Physiology and Chronic Health Evaluation II scores were significantly lower in the drug-associated ARDS group than in the non-drug-associated ARDS group (median (IQR): 18.0 (16.5-21.0) vs 23.0 (18.0-26.0), p<0.001), and the arterial oxygen tension/fractional inspired oxygen ratio was higher (148.0 (114.1-177.5) vs 101.0 (71.5-134.0), p=0.003). In the drug-associated ARDS group, although high-resolution CT scores indicative of the extent of fibroproliferation (301.6 (244.1-339.8) vs 208.3 (183.4-271.6), p<0.001), serum lactate dehydrogenase levels (477 (365-585) vs 322 (246-434), p=0.003) and the McCabe scores (score 1/2/3, n (%): 20 (74)/4 (15)/3 (11)vs154 (91)/7 (4)/9 (5), p=0.04) were significantly higher, ventilator weaning was earlier (p<0.001) and 28-day mortality was better (p=0.043). After adjusting for potentially confounding covariates, drug-associated ARDS group was associated with lower 28-day mortality (adjusted HR (HR) 0.275; 95% CI 0.106 to 0.711; p=0.008). Conclusions Although more severe lung damage with fibroproliferation was observed in patients with drug-associated ARDS, ventilator weaning was earlier, and their prognosis was better than the others. Further well-designed prospective studies are needed. [ABSTRACT FROM AUTHOR]

The differential diagnosis of multinodular lung disease includes miliary tuberculosis, pneumoconiosis, sarcoidosis and metastases. In many cases, high-resolution computed tomography can help the diagnosis, but sometimes, tissue diagnosis may be necessary. We report a case of malignant lymphoma on a background of pre-existing silicosis, distinguished from miliary tuberculosis by percutaneous needle lung biopsy. [ABSTRACT FROM AUTHOR]

The article discusses the medical case of a 52-year-old man with rapidly progressive interstitial lung disease (RP-ILD) with clinically amyopathic dermatomyositis (CADM). The case showed the usefulness of determining the anti-CADM-140/MDA45 antibody levels by enzyme-linked immunosorbent assay to monitor the disease activity in patients with RP-ILD. Plymyxin-B direct hemoperfusion (PMX-DHP) helped reduce the antibody concentration.