Increased Levels of Hyaluronic Acid in Bronchoalveolar Lavage from Patients with Interstitial Lung Diseases, Relationship with Lung Function and Inflammatory Cells Recruitment

Purpose: Interstitial Lung Diseases (ILD) are characterized by inflammation and fibrosis. It described the role of hyaluronic acid (HA) as an immune-regulator. It is not known if HA contributes to the recruitment of inflammatory cells associated with ILD. If this hypothesis was correct, then concentrations of HA in bronchoalveolar lavage (BAL) should correlate with the severity of ILD. Methods: We collected BAL from 22 ILD patients and 15 control subjects. We determined HA and cytokine levels by ELISA. In vitro chemotaxis assays were performed by using a transwell system. Results: We found that ILD patients showed a significant increase in HA, IL-6 levels and the amount of cells in BAL compared to control subjects. We detected a significant positive correlation between HA and IL-6 levels (r = 0.53 and p In vitro, HA induced migration of macrophages and monocytes through a CD44-dependent process. BAL from patients with ILD stimulated macro-phage migration and this was abrogated by hyaluronidase. Conclusions: Our results support the hypothesis that HA contributes to the recruitment of monocytes towards the alveolar space, leading to exacerbation of lung inflammation in ILD patients.

Interstitial Lung Diseases Associated with Connective Tissue Pathologies: Radiologic Features

Introduction: The high resolution computed tomography (HRCT) is an important part in the diagnostic approach of interstitial lung disease (ILD) associated with connective tissue diseases (CTD) by providing detailed information on the elementary lesion and the radiological pattern of ILD. Aim: to point out the role of HRCT in the diagnosis of ILD associated with CTD (ILD-CTD). Methods: A Retrospective descriptive study was conducted between 2008 and 2017. Data of 24 patients presenting ILD-CTD were collected. A review of HRCT was performed by a radiologist without knowledge of the CTD. Results: Predominant elementary lesion of ILD associated with dermatomyositis (9 cases) was ground glass opacity (n = 9) followed by consolidation (n = 6). Non Specific Interstitial Pneumonia (NSIP) was the most reported pattern (5 cases). Ground glass opacity was also the predominant elementary lesion for the 2 cases of scleroderma and in Sj&#246gren’s syndrome (4 cases/5). NSIP was the predominant radiological presentation in these two CTD. Lymphoid interstitial pneumonia revealed Sj&#246gren’s syndrome in one case. In rheumatoid arthritis (6 cases), the elementary HRCT lesions were irregular interlobular septal thickening (n = 4) and honeycombing (n = 4) consistent with Usual Interstitial Pneumonia (UIP) in 2 cases. Similarly UIP has been described for the 2 patients with lupus and mixed connective tissue disease. Conclusion: HRCT plays an important role in the management of ILD-CTD. Description of the HRCT elementary lesions and the radiological pattern of ILD can be helpful for CTD’s diagnosis.

The Differences of Interstitial Lung Diseases in High-Resolution Computerized Tomography and Pulmonary Function Test among Different Connective Tissue Diseases, and the Correlated Factors

Objective. To study the difference of interstitial lung diseases (ILDs) in high-resolution computerized tomography and pulmonary function test among different connective tissue diseases (CTDs). Methods. 209 patients with different CTDs were recruited and underwent lung HRCT and PFT. Eerythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin (SF), anti-SSA, and so on were tested. Based on HRCT, a patient was classified into ILD group (CTD+ILD) or non-ILD group (CTD-ILD). HRCT, PFT, and laboratory markers were compared according to CTDs and CTD-associated ILDs. Results. The incidences of ILD were 79.6%, 82.0%, 89.7%, and 97.1% respectively for Rheumatoid arthritis (RA), primary Sjogren’s symptom (pSS), dermatomyositis/polymyositis (DM/PM), and systemic sclerosis (SSc) groups. RA and pSS patients exhibited more nodules, patching, ground-glass opacity, and cord shadow foci in HRCT, DM/PM and SSc patients exhibited more reticular opacity and honeycombing foci. RA and pSS patients exhibited more obstructive ventilatory disorder, small airway dysfunction and emphysema in PFT, and DM/PM and SSc patients exhibited more restrictive ventilatory disorder, mixed ventilatory disorder. ESR, CRP and SF were significantly higher in total CTD+ILD group than in total CTD-ILD group (P = 0.047, 0.006, 0.004, respectively), and higher in different CTD+ ILD groups than in comparable CTD-ILD groups (P = 0.049, 0.048, and 0.023, pSS+ILD, SSc+ILD and RA+ILD compared to pSS-ILD, SSc-ILD and RA-ILD, respectively for ESR, CRP, SF). The positive rate of anti-SSA was significantly higher in DM/PM+ILD group than in DM/PM-ILD group (P = 0.025). Conclusions. The manifestations and incidences of ILDs differ among different CTDs in HRCT and PFT, and inflammation and anti-SSA are positively correlated with ILDs in different CTDs, which provide important evidences for judging disease condition and prognosis.

Transbronchial Lung Cryobiopsy in the Diagnosis of Interstitial Lung Diseases. Looking at the Holy Grail or Another Misleading Diagnostic Approach?

Interstitial lung diseases (ILD’s) are a group of heterogenous chronic, ferociously progressive lung diseases. The aetiology of the aforementioned diseases is not always recognisable. The diagnosis of these dismal diseases is a vivid challenge for the physicians. Through the intervening years different diagnostic algorithms have been implemented towards more accurate outcome. Different types of ILD’s demand diverse diagnostic approaches. In the latest years a novel diagnostic mini invasive approach seems to gain continuously terrain towards the diagnosis of ILD’s. Transbronchial cryobiopsy may be the Holy Grail in the diagnosis of these diseases or a misleading diagnostic tool in this challenging field.

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome:A case report

BACKGROUND This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome(AS)following coronavirus disease 2019(COVID-19)in a 33-year-old man diagnosed with Klinefelter syndrome(KS).CASE SUMMARY A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19.Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs,accompanied by signs of partial bronchial inflation.Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen.A biopsy specimen revealed organizing pneumonia with alveolar septal thickening.Additionally,extensive auto-antibody tests showed strong positivity for anti-SSA,anti-SSB,anti-Jo-1,and anti-Ro-52.Following multidisciplinary discussions,the patient received a final diagnosis of AS,leading to rapidly progressing respiratory failure.CONCLUSION This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Association between the Lung Immune Prognostic Index and mortality in patients with idiopathic inflammatory myopathy-associated interstitial lung disease

Objective:To explore the association between the Lung Immune Prognostic Index(LIPI)and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease(IIM-ILD).Methods:Patients who were diagnosed with IIM-ILD at West China Hospital,Sichuan University from January 2008 to December 2021 were retrospectively included and categorized into three groups based on LIPI.Univariable and multivariable Cox proportional hazards models were conducted to explore potential association between the LIPI and patients'mortality.Results:A total of 1116 patients were screened,and 830 were included in this study.The multivariable Cox analysis showed that,compared with patients with poor LIPI,the hazard ratio(HR)for all-cause 1-year mortality was 0.22(95%CI 0.05-0.93,P=0.04)for patients in the good LIPI group(LDH<250 IU/L and dNLR<3).After excluding patients lost to follow-up within one year,a similar result was found for LIPI(HR 0.20,95%CI 0.05-0.86;P=0.03).Conclusions:Good LIPI was independently associated with decreased risk of all-cause 1-year mortality in patients with IIM-ILD.This easy-to-obtain index might be served as a potential marker for assessing the prognosis of IIM-ILD.

Risk factors of interstitial lung diseases in clinically amyopathic dermatomyositis

Background:Clinically amyopathic dermatomyositis(CADM)is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease(ILD).Poor prognosis of the patients was strongly associated with rapid progressive ILD.The aim of this study was to identify risk factors for prediction of different types of ILD in CADM.Methods:In this study,data of 108 inpatients with CADM were collected,including 87 with ILD.The baseline clinical data and laboratory parameters,including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis(A/SIP)and chronic interstitial pneumonitis(CIP).Results:In 87 patients with CADM-ILD,39(36.1%)were A/SIP,and 48(44.4%)were CIP.There were 22(20.4%)patients with asymptomatic ILD who were detected by routine high resolution computed tomography.Cytokeratin-19 fragment(CYFRA21-1)was significantly higher in CADM-ILD than that in CADM patients without ILD;carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP.Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5(MDA5),while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52.Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD,higher titer of anti-MDA5 indicated increased likelihood for A/SIP,and higher titer of anti-Ro-52 was also clearly associated with CIP.Conclusions:This study indicated that the prevalence of ILD was high in CADM.Asymptomatic ILD has been previously underestimated.Anti-MDA5 was a risk factor for the presence of A/SIP,and CYFRA21-1 was a risk factor for ILD.

Systemic juvenile idiopathic arthritis–associated lung disease: A retrospective cohort study

BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease

Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Acute exacerbation of interstitial lung disease in the intensive care unit:Principles of diagnostic evaluation and management

Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis,etc.Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation,while almost all patients will benefit from early palliative care.This review focused on the types of ILD,diagnosis,and management pathways for this challenging condition.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Interstitial lung disease in rheumatoid arthritis:Current concepts in pathogenesis,diagnosis and therapeutics

Rheumatoid arthritis(RA) is the most common chronic autoimmune inflammatory joint disease. RA-associated interstitial lung disease(RA-ILD) is a major extraarticular complication and causes symptoms that lead to a deterioration in the quality of life, high utilization of health resources, and an increased risk of earlier mortality. Early in the course of RA-ILD, symptoms are highly variable, making the diagnosis difficult. Therefore, a rational diagnostic strategy that combines an adequate clinical assessment with the appropriate use of clinical tests, including pulmonary function tests and high-resolution computed tomography, should be used. In special cases, lung biopsy or bronchioalveolar lavage should be performed to achieve an early diagnosis. Several distinct histopathological subtypes of RA-ILD are currently recognized. These subtypes also have different clinical presentations, which vary in therapeutic response and prognosis. This article reviews current evidence about the epidemiology of RA-ILD and discusses the varying prevalence rates observed in different studies. Additionally, aspects of RA-ILD pathogenesis, including the role of cytokines and other molecules such as autoantibodies, as well as the evidence linking several drugs used to treat RA with lung damage will be discussed. Some aspects of the clinical characteristics of RA-ILD are noted, and diagnostic strategies are reviewed. Finally, this article analyzes current treatments for RA-ILD, including immunosuppressive therapies and biologic agents, as well as other therapeutic modalities. The prognosis of this severe complication of RA is discussed. Additionally, this paper examines updated evidence from studies identifying an association between drugs used for the treatment of RA and the development of ILD.

Application of the COPD Assessment Test (CAT) to Patients with Interstitial Lung Disease

The COPD Assessment Test was recently developed to assess health status in patients with COPD. However, little was known about its application to patients with interstitial lung disease, so we examined the relationship between the COPD Assessment Test score and respiratory impairment including the clinical picture in subjects with interstitial lung disease. Data were collected retrospectively from 52 consecutive subjects with interstitial lung disease on admission to our facility. All subjects completed the COPD Assessment Test, in which a higher score represented a worse health status. They were also assessed by pulmonary function test, SpO2 during 6-min walk test, and arterial blood gases. The COPD Assessment Test score was negatively correlated with the percentage of predicted forced vital capacity, forced expiratory volume in 1 second, total lung capacity, diffusion capacity of the lung for carbon monoxide, and PaO2 (p = 0.0005, 0.005, 0.0002, 0.0005, and 0.002, respectively). Breathlessness was detected as the high scoring item, while phlegm and sleep were the last affected items. The COPD Assessment Test score was higher in subjects with oxygen desaturation in SpO2 (≥4%) during 6-min walk test (p = 0.0001) and in subjects on home oxygen therapy (p = 0.0007). More than 75% of subjects with oxygen desaturation during walking were classified into a medium or severer impact level of the COPD Assessment Test score, and subjects on home oxygen therapy were classified into a high or severer impact level. PaCO2 in room air and SpO2 at rest did not correlate with the COPD Assessment Test score. The reliability of items in the COPD Assessment Test was 0.87 by Cronbach’s α coefficient. Our results suggest that the COPD Assessment Test may be a candidate for evaluating the health status and impact of disease on patients with interstitial lung disease.

Characteristics and Prognosis of Microscopic Polyangiitis Patients with Diffuse Alveolar Hemorrhage and Interstitial Lung Disease

Objective To evaluate the clinical characteristics and prognostic predictors of patients with diffuse alveolar hemorrhage(DAH)and/or interstitial lung disease(ILD)secondary to microscopic polyangiitis(MPA)in a Chinese general hospital.Methods We retrospectively reviewed the medical records of MPA patients admitted to internal medicine departments between the year 2002 and 2012.The patients were divided into the ILD,DAH,DAH combined with ILD(DAHILD),and no pulmonary involvement(NPI)groups according to pulmonary involvement patterns.The clinical characteristics at diagnosis were analyzed.The risk factors associated with short-term death and long-term death were identified with Logistic regression and Cox analysis.Results Of 193 newly diagnosed MPA patients,181 patients were enrolled in the research,of which 19 had DAH alone,96 had ILD alone,18 had DAH and DAH concurrently,and 48 had NPI.The median of serum creatine level in the DAH group was 449μmol/L,significantly higher than that in the ILD group(123μmol/L,Nemenyi=-35.215,P=0.045)and DAHILD group(359μmol/L,Nemenyi=-43.609,P=0.007).The median follow-up time was 67(range:1-199)months.Patients in the ILD group were older than those in the DAH group(median:69 years vs.57 years,Nemenyi=43.853,P=0.005).The patients with both DAH and ILD had combined features of the two subtypes,and the highest mortality(72.2%at the end of follow-up).The elevated white blood cell count was a risk factor for short-term death(OR=1.103,95%CI:1.008-1.207,P=0.032 for one month;OR=1.103,95%CI:1.026-1.186,P=0.008 for one year).Old age(HR=1.044,95%CI:1.023-1.066,P<0.001),cardiovascular system involvement(HR=2.093,95%CI:1.195-3.665,P=0.010),poor renal function(HR=1.001,95%CI:1.000-1.002,P=0.032)were risk factors for long-term death.Pulmonary infections(38/54)were the leading causes of death,especially for the patients with ILD.Besides,49 patients suffered from pulmonary infections in the first year after diagnosis.Conclusions MPA patients who presented with different pulmonary involvement patterns have completely different clinical features.These subtypes probably have different pathogenesis and should be studied separately.

Vedolizumab-associated diffuse interstitial lung disease in patients with ulcerative colitis:A case report

BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are refractory to traditional therapies and tumor necrosis factor antagonists.However,some rare but lifethreatening adverse effects warrant pharmacovigilance.We describe the first fatal case of vedolizumab-associated severe diffuse interstitial lung disease in China.CASE SUMMARY We present a case of new-onset diffuse parenchymal lung disease developing under treatment with vedolizumab in a patient with UC.After two doses of vedolizumab,he developed persistent fever and progressively worsening dyspnea.Extensive workups,including bronchoalveolar lavage,transbronchial lung biopsy and metagenomic next-generation sequencing,identified no infectious causes,and other potential causes(such as tumors and cardiogenic pulmonary edema)were also excluded.As a result,a diagnosis of vedolizumabrelated interstitial lung disease was established.Unfortunately,although corticosteroids and empiric antibiotics were administered,the patient eventually died of respiratory failure.CONCLUSION Vedolizumab-related interstitial lung disease in patients with UC is rare but potentially lethal.Gastroenterologists and pulmonologists should be aware of vedolizumab-related adverse drug reactions.

Anti-Aminoacyl tRNA Synthetases Antibodies in Japanese Patients with Interstitial Lung Disease

Objectives: In the present study, we have sought to establish the clinical and immunological characteristics of Japanese patients with interstitial lung disease (ILD). Methods: Serum samples from 35 patients of ILD were screened for autoantibodies using RNA and protein immunoprecipitation assays. Patients with or without serum antibodies to aminoacyl tRNA synthetases (ARS) were assessed clinically and compared. Results: Sera from 12 of 35 (34%) patients with ILD (mean age at onset = 49.7 yrs;range 27 - 65 yrs) were found to contain anti-ARS antibodies (anti-EJ: 3 patients;anti-OJ: 2 patients;anti-PL-12: 3 patients;anti-KS: 4 patients). Nine of the 12 (75%) were female. Six (50%) had Raynaud’s phenomenon, 5 (42%) had arthralgia/arthritis and four (33%) had rheumatoid factor. Lung biopsy specimens of 8 patients with anti-ARS antibodies were examined histologically in detail. The following was determined: Two patients had usual interstitial pneumonia;3 had non-specific interstitial pneumonia;one had organizing pneumonia;one had lymphocyte interstitial pneumonia and the remaining patient had desquamative interstitial pneumonia. Age at disease onset was significantly lower and the frequency of Raynaud’s phenomenon was significantly greater in these patients compared to anti-ARS-negative patients (49.7 yrs vs. 62.6 yrs, p = 0.004;50% vs. 4%, p = 0.003, respectively). Conclusions: These results indicate that the presence of anti-ARS autoantibodies correlates with ILD without definite diagnosis of connective tissue diseases as well as polymyositis/dermatomyositis (PM/DM) with ILD in Japanese patients.

EFFECTS OF ALVEOLAR MACROPHAGE CONDITIONED MEDIA FROM INTERSTITIAL LUNG DISEASE PATIENTS ON THE PROCOLLAGEN mRNA EXPRESSION I

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Changes and clinical significance of serum tumor markers in patients with rheumatoid arthritis combined with interstitial lung disease

Objective: To investigate the changes and clinical significance of serum tumor markers in patients with rheumatoid arthritis (RA) combined with interstitial lung disease. Methods:A total of 50 healthy volunteers were chosen as the normal control group, 47 patients with rheumatoid arthritis alone were chosen as the RA group, and 28 patients with rheumatoid arthritis combined with interstitial lung disease were chosen as combined disease group. The differences in the levels of serum tumor markers, RA markers and inflammatory mediators were compared among the three groups, and Pearson test was used to evaluate the correlation of serum tumor marker levels with RA markers and inflammatory mediators in patients with RA combined with interstitial lung disease. Results: Serum tumor markers CA199, CA153 and CEA levels of combined disease group were higher than those of RA group;RA markers RF and GPI levels were higher than those of RA group whereas CCP and AKA levels were not significantly different from those of RA group;inflammatory mediators HMGB1, GM-CSF, IL-6, IL-17 and IL-27 levels were higher than those of RA group. Correlation analysis showed that serum tumor markers CA199, CA153 and CEA levels in patients with RA combined with interstitial lung disease were positively correlated with RF, GPI, HMGB1, GM-CSF, IL-6, IL-17 and IL-27 levels. Conclusion: Serum tumor markers CA199, CA153 and CEA levels abnormally increase in patients with RA combined with interstitial lung disease, and the specific levels were directly correlated with the disease severity.

Acute exacerbation of interstitial lung disease in the intensive care unit

Acute exacerbations of interstitial lung disease(AE-ILD)represent an acute,frequent and often highly morbid event in the disease course of ILD patients.Admission in the intensive care unit(ICU)is very common and the need for mechanical ventilation arises early.While non-invasive ventilation has shown promise in staving off intubation in selected patients,it is unclear whether mechanical ventilation can alter the exacerbation course unless it is a bridge to lung transplantation.Risk stratification using clinical and radiographic findings,and early palliative care involvement,are important in ICU care.In this review,we discuss many of the pathophysiological aspects of AE-ILD and raise the hypothesis that ventilation strategies used in acute respiratory distress syndrome might be implemented in AE-ILD.We present possible decision-making and management algorithms that can be used by the intensivist when caring for these patients.