OBJECTIVE: Rheumatoid arthritis (RA) is sometimes complicated by interstitial lung disease (ILD) with a poor prognosis. A single nucleotide variant (SNV) in MUC5B was associated with ILD in European RA patients. However, associations of this SNV were not found in Japanese RA patients, because its frequency in Japanese populations is very low. We investigated the associations of candidate SNVs including the MUC5B variant with ILD in Japanese RA.
METHODS: Genotyping of MUC5B rs35705950, MUC2 rs7934606, MAD1L1 rs12699415, and PPFIBP2 rs6578890 in Japanese RA patients was conducted for association analyses.
RESULTS: MUC5B rs35705950 was associated with usual interstitial pneumonia (UIP) (p = 0.0039, Pc = 0.0156, odds ratio [OR] 10.66, 95% confidence interval [CI] 2.05-55.37) or ILD (p = 0.0071, Pc = 0.0284, OR 7.33, 95%CI 1.52-35.44) in Japanese RA under the allele model. MUC2 rs7934606 was associated with UIP (p = 0.0072, Pc = 0.0288, OR 29.55, 95%CI 1.52-574.57) or ILD (p = 0.0037, Pc = 0.0148, OR 22.95, 95%CI 1.27-416.13) in RA. Haplotype analyses suggested the primary association of MUC5B rs35705950 with UIP in Japanese RA. No significant association of MAD1L1 rs12699415 or PPFIBP2 rs6578890 with UIP, nonspecific interstitial pneumonia, or ILD in RA was observed.
CONCLUSIONS: MUC5B rs35705950 is associated with, and might be involved in the pathogenesis of ILD, especially UIP, in Japanese RA.

Idiopathic pulmonary fibrosis (IPF) has traditionally been considered the archetype of progressive fibrotic interstitial lung diseases (f-ILDs), but several other f-ILDs can also manifest a progressive phenotype. Integrating genomic signatures into clinical practice for f-ILD patients may help to identify patients predisposed to a progressive phenotype. In addition to the risk of progressive pulmonary fibrosis, there is a growing body of literature examining how pharmacogenomics influences treatment response, particularly regarding the efficacy and safety profiles of antifibrotic and immunomodulatory agents. In this narrative review, we discuss current studies in IPF and other forms of pulmonary fibrosis, including systemic autoimmune disorders associated ILDs, sarcoidosis and hypersensitivity pneumonitis. We also provide insights into the future direction of research in this complex field.

BACKGROUND: The presence of emphysema is common in patients with interstitial lung disease (ILD), which is designated as combined pulmonary fibrosis and emphysema (CPFE). This study aimed to examine the association between smoking, emphysema, and fibrosis in ILD patients.
METHODS: A total of 800 patients hospitalized for ILD at the affiliated hospital of Qingdao University, Shandong, Qingdao, China, from December 2012 to December 2020 were included in our retrospective cohort study. Participants were divided into CPFE and non-CPFE groups. The patients\' clinical presentations and radiographic and laboratory findings were reviewed and compared. The two groups were then divided and compared based on smoking status. Kaplan-Meier survival analysis with log-rank testing and multivariable Cox proportional hazards regression analysis were used to compare all-cause mortality.
RESULTS: Emphysema was present in 188 (23.5%) ILD patients. Smoking was associated with increased odds of CPFE (adjusted odds ratio, AOR=2.13; 95% CI: 1.33-3.41, p=0.002). The CPFE patients had a comparable risk of death to non-CPFE patients (adjusted hazard ratio, AHR=0.89; 95% CI: 0.64-1.24, p=0.493). Smoking was not a risk prognostic factor in the whole group (AHR=1.34; 95% CI: 0.90-1.99, p=0.152) or the CPFE group (AHR=0.90; 95% CI: 0.43-1.86, p=0.771). However, a significant prognostic difference between smokers and non-smokers was found in the non-CPFE group (AHR=1.62; 95% CI: 1.02-2.58, p=0.042). In ILD patients, smoking pack-years were weakly correlated with total centrilobular emphysema (CLE) scores and total fibrosis scores (TFS), but not with total emphysema scores (TES); TFS were weakly correlated with TES.
CONCLUSIONS: CPFE did not affect the prognosis of ILD. Smoking was a risk but not a prognostic factor for CPFE. However, smoking was associated with worse survival in non-CPFE patients. There was an intricate association among smoking, emphysema, and fibrosis in ILD patients.

Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.

Fibrotic interstitial lung diseases (fILDs) have poor survival rates and lack effective therapies. Despite evidence for immune mechanisms in lung fibrosis, immunotherapies have been unsuccessful for major types of fILD. Here, we review immunological mechanisms in lung fibrosis that have the potential to impact clinical practice. We first examine innate immunity, which is broadly involved across fILD subtypes. We illustrate how innate immunity in fILD involves a complex interplay of multiple cell subpopulations and molecular pathways. We then review the growing evidence for adaptive immunity in lung fibrosis to provoke a re-examination of its role in clinical fILD. We close with future directions to address key knowledge gaps in fILD pathobiology: (1) longitudinal studies emphasizing early-stage clinical disease, (2) immune mechanisms of acute exacerbations, and (3) next-generation immunophenotyping integrating spatial, genetic, and single-cell approaches. Advances in these areas are essential for the future of precision medicine and immunotherapy in fILD.

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OBJECTIVE: This meta-analysis aimed to examine the prognosis of patients with acute exacerbation of interstitial lung disease (AE-ILD) treated with lung transplantation compared to those with stable interstitial lung disease (ILD).
METHODS: We conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library, with the primary outcomes being overall survival (OS), acute cellular rejection (ACR), primary graft dysfunction (PGD), and length of stay (LOS).
RESULTS: Five cohort studies were included in this meta-analysis, with 183 patients enrolled in the AE-ILD group and 337 patients in the stable-ILD group. The results showed that in regard to perioperative outcomes, the AE-ILD group did not differ from the stable-ILD group in the incidence of ACR (relative risks [RR] = 0.34, p = 0.44) and the incidence of PGD Ⅲ (RR = 0.53, p = 0.43), but had a longer LOS (mean difference = 9.15, p = 0.02). Regarding prognosis, the two also did not differ in 90-day OS (RR = 0.97, p = 0.59), 1-year OS (RR = 1.05, p = 0.66), and 3-year OS (RR = 0.91, p = 0.76).
CONCLUSIONS: Our study concluded that the efficacy of lung transplantation in patients with AE-ILD is not inferior to that of patients with stable ILD. Lung transplantation is one of the potential treatments for patients with AE-ILD.

UNASSIGNED: To explore the knowledge, attitude, and practice (KAP) toward interstitial lung disease (ILD) among patients and analyze the factors affecting KAP.
UNASSIGNED: This cross-sectional study enrolled patients with ILD treated at the Respiratory Department of Shanghai Pulmonary Hospital between January 2023 and June 2023. A self-administered questionnaire was developed to evaluate their KAP toward ILD through convenient sampling. Multivariate regression analysis and structural equation model (SEM) were used to analyze the factors influencing KAP and their interactions.
UNASSIGNED: A total of 397 patients were enrolled, with 61.71% male. The mean KAP scores were 4.60 ± 3.10 (possible range: 0-12), 16.97 ± 2.16 (possible range: 5-25), and 32.60 ± 7.16 (possible range: 9-45), respectively. Multivariate logistic regression analysis showed that junior high school [OR = 2.003, 95%CI: 1.056-3.798, p = 0.033], high school and above [OR = 2.629, 95%CI: 1.315-5.258, p = 0.006], and duration of disease ≥5 years [OR = 1.857, 95%CI: 1.132-3.046, p = 0.014] were independently associated with adequate knowledge. The knowledge [OR = 1.108, 95%CI: 1.032-1.189, p = 0.005] and duration of disease ≥5 years [OR = 0.525, 95%CI: 0.317-0.869, p = 0.012] were independently associated with a positive attitude. The knowledge [OR = 1.116, 95%CI: 1.036-1.202, p = 0.004], attitude [OR = 1.180, 95%CI: 1.061-1.312, p = 0.002], and the age of >70 years [OR = 0.447, 95%CI: 0.245-0.817, p = 0.009] were independently associated with the proactive practice. SEM showed that patients\' knowledge of ILD directly affected their attitude (β = 0.842, p < 0.001) and practice (β = 0.363, p < 0.001), and their attitude also affected their practice (β = 0.347, p = 0.014).
UNASSIGNED: Patients with ILD in China had poor knowledge, intermediate attitude, and proactive practice toward ILD, which suggests that the health education of patients should be further strengthened.

BACKGROUND: Pulmonary rehabilitation is widely recommended to improve functional status and as secondary and tertiary prevention in individuals with chronic pulmonary diseases. Unfortunately, access to timely and appropriate rehabilitation remains limited. To help close this inaccessibility gap, telerehabilitation has been proposed. However, exercise testing is necessary for effective and safe exercise prescription. Current gold-standard tests, such as maximal cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT), are poorly adapted to home-based or telerehabilitation settings. This was an obstacle to the continuity of services during the COVID-19 pandemic. It is essential to validate tests adapted to these new realities, such as the 6-minute stepper test (6MST). This test, strongly inspired by 6MWT, consists of taking as many steps as possible on a \"stepper\" for 6 minutes.
OBJECTIVE: This study aims to evaluate the metrological qualities of 6MST by (1) establishing concurrent validity and agreement between the 6MST and CPET, as well as with the 6MWT; (2) determining test-retest reliability in a home-based setting with direct and remote (videoconferencing) monitoring; and (3) documenting adverse events and participant perspectives when performing the 6MST in home-based settings.
METHODS: Three centers (Centre de recherche de l\'Institut universitaire de cardiologie et de pneumologie de Québec in Québec, Groupement des Hôpitaux de l\'Institut Catholique de Lille in France, and FormAction Santé in France) will be involved in this multinational project, which is divided into 2 studies. For study 1 (objective 1), 30 participants (Québec, n=15; France, n=15) will be recruited. Two laboratory visits will be performed to assess anthropometric data, pulmonary function, and the 3 exercise tolerance tests (CPET, 6MWT, and 6MST). Concurrent validity (paired sample t tests and Pearson correlations) and agreement (Bland-Altman plots with 95% agreement limits) will be evaluated. For study 2 (objectives 2 and 3), 52 participants (Québec, n=26; France, n=26) will be recruited. Following a familiarization trial (trial 1), the 6MST will be conducted on 2 separate occasions (trials 2 and 3), once under direct supervision and once under remote supervision, in a randomized order. Paired sample t test, Bland-Altman plots, and intraclass correlations will be used to compare trials 2 and 3. A semistructured interview will be conducted after the third trial to collect participants\' perspectives.
RESULTS: Ethical approval was received for this project (October 12, 2023, in Québec and September 25, 2023, in France) and the first participant was recruited in February 2024.
CONCLUSIONS: This study innovates by validating a new clinical test necessary for the development and implementation of new models of rehabilitation adapted to home and telerehabilitation contexts. This study also aligns with the United Nations Sustainable Development Goals by contributing to augmenting health care service delivery (goal 3) and reducing health care access inequalities (goal 11).
BACKGROUND: ClinicalTrials.gov NCT06447831; https://clinicaltrials.gov/study/NCT06447831.
UNASSIGNED: DERR1-10.2196/57404.

High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility.