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Background: Interstitial lung disease (ILD) is one of the significant complications of dermatomyositis (DM), but the mechanisms by which it occurs remain incompletely elucidated. This study aimed to explore further the possible genetic mechanisms by which this complication occurs. Methods: Gene expression profiles for DM (GSE39454, GSE46239, GSE143323) and ILD (GSE32537, GSE110147, GSE150910) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying common differentially expressed genes (DEGs) to DM and ILD using the "limma" R package and the "VennDiagram" R package, functional annotation, relationship to immune cell infiltration, identification of transcription factors (TFs), we also collected clinical cases of DM-associated ILD (DM-ILD), including 3 cases of rapidly progressive ILD (RP-ILD) and 3 cases of none-RP-ILD, and explored whether there were differences in serum lymphocyte subpopulations. Results: A total of 4 common DEGs (SLAMF7, SPP1, TDO2, and VCAM1) were screened and Gene Ontology (GO) enrichment analysis showed that these genes were mainly enriched in T cell activation, regulation of lymphocyte activation, lymphocyte differentiation, leukocyte proliferation and regulation of T cell activation. In terms of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the three significantly enriched pathways were the PI3K-Akt signaling pathway, MAPK signaling pathway, and Cytokine-cytokine receptor interaction. In lung and muscle tissues, 21 and 3 TFs may regulate the expression of these genes, respectively. Finally, by analysing the serum lymphocyte subpopulations, we also found a decrease in the absolute number of CD8+ T cells and an increase in the CD4+ /CD8+ T cell ratio in DM combined with RP-ILD. Conclusion: These common pathways and key genes may provide new ideas for further research into DM-ILD. [ABSTRACT FROM AUTHOR]

To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM). Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared. Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P 0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all< 0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all< 0.05). Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors. [ABSTRACT FROM AUTHOR]

Objectives To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS). Methods Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods. Results 91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P  < 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P  < 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P  < 0.001). Conclusion PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of bronchoalveolar lavage (BAL) in DM-associated interstitial lung disease (ILD). Methods We retrospectively reviewed the medical records of patients with DM-ILD who underwent bronchoscopy between October 2015 and September 2019. We then collated clinical features, laboratory data and bronchoscopy findings. The follow-up study was terminated on the 1 May 2020. Results A total of 113 DM-ILD patients were included in this study, including 27 patients with acute/subacute interstitial pneumonia (A/SIP) and 86 patients with chronic interstitial pneumonia (CIP). The A/SIP group had significantly lower proportions of lymphocytes and eosinophils in the bronchoalveolar lavage fluid (BALF) than the CIP group, but had a significantly higher proportion of neutrophils. Pathogens were discovered in BALF from 28 (24.8%) patients. Twenty-five (22.1%) patients commenced or changed antibiotic therapy on the basis of their bronchoscopy results. Lymphopenia and intensive care unit care were significantly associated with pathogen-positive BALF findings. Complications of bronchoscopy occurred in nine (8.0%) patients; fever (5.3%) was the most common complication. Twenty-five deaths (25/106, 23.6%) were observed during a mean follow-up of 22 months. Age, A/SIP and anti-MDA5 antibody were identified as independent predictors of a poor outcome, while mechanic's hands was an independent protective factor. However, cellular and pathogen findings in BALF had no significant influence on 30-day or overall mortality. Conclusion Bronchoscopy is a relatively useful instrument to evaluate ILD in patients with DM, and BAL can improve the diagnosis of infection. However, cellular and pathogen findings from BALF had no significant influence on prognosis. [ABSTRACT FROM AUTHOR]

Objectives: To determine the efficacy and safety of nintedanib in patients with anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5+ DM-ILD)., Methods: The study was a retrospective cohort design that evaluated patients with anti-MDA5+ DM who either received or did not receive nintedanib. Clinical symptoms, laboratory tests, and survival were compared in the two groups using a propensity score-matched analysis. The primary endpoint was mortality, while adverse events were recorded descriptively., Results: After propensity score matching, 14 patients who received nintedanib (nintedanib+ group) and matched 56 patients who did not receive nintedanib (nintedanib- group) were enrolled. Compared with the nintedanib- group, the nintedanib+ group had a lower incidence of heliotrope and arthritis, higher lymphocyte counts, lower serum ferritin levels, and greater 12-month survival (all p<0.005). Although lung function, HRCT score, and lung VAS were not statistically different between the two groups, the longitudinal study showed significant improvement in HRCT scores (p=0.028) and pulmonary VAS (p=0.019) in the nintedanib+ group. Adverse events occurred in 28.6% of patients, with the most common adverse event with nintedanib being diarrhoea., Conclusions: Nintedanib may be effective for improving clinical symptoms, laboratory parameters, lung lesions, and survival in anti-MDA5+ DM. Diarrhoea was the most common adverse event associated with nintedanib, although the drug was well tolerated by most patients.