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.

Effect of N-Acetylcysteine Combined with Lung Rehabilitation Therapy on Exercise Endurance and Quality of Life of Patients with Rheumatoid Arthritis-Related Interstitial Lung Disease

Objective:To explore the effect of N-acetylcysteine combined with lung rehabilitation therapy on exercise endurance and quality of life in patients with rheumatoid arthritis-related interstitial lung disease(RA-ILD).Methods:Fifty-six patients with RA-ILD admitted to Xijing Hospital from May 2022 to January 2024 were randomly divided into two groups:a non-rehabilitation group and a pulmonary rehabilitation group,with 28 patients in each group.Both groups received routine treatment.Additionally,the non-rehabilitation group received N-acetylcysteine treatment,while the lung rehabilitation group received lung rehabilitation treatment in addition to N-acetylcysteine.The improvement in exercise endurance and dyspnea between the two groups after treatment was compared and the quality of life of the patients was observed.Results:After treatment,the exercise endurance score in the lung rehabilitation group(335.67±45.29)was higher than that in the non-rehabilitation group(P<0.05).The dyspnea score in the lung rehabilitation group(0.72±0.16)was lower than that in the non-rehabilitation group(P<0.05).Additionally,FVC(3.18±0.58 L),FEV1(2.28±0.56 L),FEV1/FVC(69.69±5.56),and DLCO(60.53±5.92 mL/mmHg/min)were higher in the lung rehabilitation group compared to the non-rehabilitation group after treatment(P<0.05).Conclusion:Lung rehabilitation therapy combined with N-acetylcysteine treatment can effectively improve dyspnea symptoms,lung function,and exercise endurance in patients with RA-ILD.This approach helps to improve patient’s quality of life and is beneficial for their prognosis.

Microvascular alterations of the ocular surface and retina in connective tissue disease-related interstitial lung disease

AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.

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.

Nodular Pulmonary Amyloidosis with Interstitial Lung Disease—Case Report and Literature Review

Amyloidosis is a rare spectrum of disease which involves deposition of misfolded extracellular proteins (amyloids) in various body organs leading to progressive organ dysfunction. Clinical presentation can be variable depending on the organ involved and type of protein. Amyloidosis can be classified based on quantity, type, and location of these proteins. Amyloid light-chain amyloidosis develops in the bone marrow, producing abnormal forms of light-chain proteins, which cannot be broken down. These proteins transform into amyloid fibrils and form amyloid deposits in different organs. Pulmonary amyloidosis is uncommonly diagnosed since it is rarely symptomatic. Diagnosis of pulmonary amyloidosis is usually made in the setting of systemic amyloidosis;however, it may present as localised pulmonary disease. Localized pulmonary Amyloidosis can present as nodular, cystic, or tracheobronchial amyloidosis. Depending on the degree of the interstitial involvement, it may affect alveolar gas exchange and cause respiratory symptoms. This is a case of a 47-year-old female with background history of interstitial lung disease presenting with progressive shortness of breath. Computed tomography scan revealed bilateral pulmonary nodules. The patient was referred to our thoracic surgery team with the suspicion of bronchogenic malignancy with metastasis. Diagnostic video assisted wedge resection was performed for this patient, and histology confirmed pulmonary amyloidosis of nodular type. Amyloid deposition simulates both inflammatory and neoplastic conditions. Definitive diagnosis requires biopsy confirmation therefore early detection and commencing the patient on appropriate treatment pathway may help in symptomatic relief and better outcome.

Correlation Analysis Between Changes of D-Dimer Level and Rheumatoid Arthritis Complicated with Interstitial Lung Disease

Objective:To explore the correlation between the change of D-dimer level and rheumatoid arthritis complicated with interstitial lung disease.Methods:From January 2022 to February 2024,20 rheumatoid arthritis patients complicated with interstitial lung disease(interstitial lung disease group),20 rheumatoid arthritis patients without interstitial lung disease(without interstitial lung disease group),and 20 healthy people(control group)in Xijing Hospital were selected for this study.The fasting venous blood of the three groups of subjects was collected and their D-dimer,C-reactive protein(CRP),rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)were detected.Subsequently,the correlation between each index and rheumatoid arthritis complicated with interstitial lung disease was analyzed.Results:The D-dimer level of the interstitial lung disease group was significantly higher than the other two groups(P<0.05).The D-dimer level of the group without interstitial lung disease was significantly higher than the control group(P<0.05).CRP levels in the interstitial lung disease group and the group without interstitial lung disease were significantly higher than those of the control group(P<0.05).The ESR and RF levels of the interstitial lung disease group were significantly higher than the other two groups(P<0.05).The levels of ESR and RF levels of the group without interstitial lung disease were significantly higher than the control group(P<0.05).Conclusion:D-dimer levels of rheumatoid arthritis patients are higher than those of healthy individuals,and those complicated with interstitial lung disease present even higher levels.This finding shows that there is a correlation between D-dimer levels and rheumatoid arthritis with interstitial lung disease,which may facilitate the evaluation and diagnosis of this disease.

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.

Reliability and validity of Chinese version of a tool to assess the quality of life in idiopathic pulmonary fibrosis in patients with interstitial lung disease

Objective:This paper aims to determine the reliability and validity of the Chinese version of a tool that assesses the quality of life in idiopathic pulmonary fibrosis(cATAQ-IPF)in patients with interstitial lung disease(ILD).Methods:We used the process of scale introduction to establish cATAQ-IPF.The content validity of the scale was evaluated by six experts.A total of 92 patients with ILD completed the cATAQ-IPF,St.George's respiratory questionnaire(SGRQ),and The Medical Research Council dyspnoea scale at the baseline,and 15 patients completed cATAQ-IPF at the follow-up period 2 weeks later.Thus,yielding data were used to assess various psychometric properties of cATAQ-IPE Intraclass correlation coefficient(ICC),Cronbach'sαcoefficient,content validity index(CVI),item-level CVI(I-CVI),Pearson's coefficients,criterion-relation validity,and known-group validity were used for data analysis.Results:The cATAQ-IPF showed excellent test-retest reliability(ICC=0.95),except for the therapy domain(Cronbach'sα=0.60)and acceptable internal consistency(Cronbach'sα=0.96 for the total).The scale-level CVI was 0.80,and the I-CVI was in the range of 0.78-1.00.The total cATAQ-IPF score was strongly correlated with the SGRQ total score(r=0.71,P<0.01).The cATAQ-IPF score of patients with ILD was 250.74±47.39,and that of patients with IPF was 287.90±22.56.Patients with IPF possessed considerable impairments in health-related quality of life according to the cATAQ-IPF score(t=4.94,P<0.01).Conclusions:The cATAQ-IPF is a reliable and valid instrument for the evaluation of quality of life of Chinese patients with various forms of ILD.

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.

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.