Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Percent Predicted vs. Absolute Six-Minute Walk Distance as Predictors of Lung Transplant-Free Survival in Fibrosing Interstitial Lung Diseases.

INTRODUCTION: Fibrosing interstitial lung diseases (ILDs) often progress despite treatment and become life-threatening, with lung transplant (LTx) remaining the only curative option. Six-minute walk distance (6MWD) is increasingly recognized as reliable predictor of clinical course, especially when longitudinally considered. The use of reference equations to express 6MWD as percent predicted (6MWD%) has not been previously studied in fibrosing ILDs. We sought to investigate whether the prognostic power of 6MWD% is superior to that of 6MWD expressed in meters (6MWD-m). METHODS: A retrospective, multicenter cohort analysis was conducted on both idiopathic pulmonary (IPF) and non-IPF fibrosing ILD patients. Patients were divided into a discovery (n = 211) and a validation (n = 260) cohort. Longitudinal changes of 6MWD% and lung function parameters were simultaneously considered. LTx-free survival at 3 years from baseline was the endpoint. Competing risks of death and LTx were considered. RESULTS: Baseline 6MWD% and its longitudinal changes were significant predictors of LTx-free survival and independent from lung function variables. In both cohorts, on multivariate cox proportional hazard regression analysis, receiver operating characteristics analysis and Kaplan-Meier estimates, 6MWD% was consistently, but only slightly superior to 6MWD-m as a predictor of LTx-free survival. CONCLUSION: 6MWD% has only a slight, yet detectable advantage over 6MWD-m as a predictor of survival in fibrosing ILDs. Utilizing 6MWD% may aid in risk stratification, treatment monitoring, and LTx timing optimization. However, available reference equations do have predicting limitations. Refined predictive equations and standardizing reporting practices are therefore needed to further enhance the clinical utility of 6MWD% in fibrosing ILDs.

Interstitial lung disease presents with varying characteristics in patients with non-Hodgkin lymphoma undergoing rituximab-containing therapies.

Although the incidence and outcomes of rituximab-induced interstitial lung disease (RILD) have been partially reported, there are no systematic studies on the characteristics and types of RILD. This study aimed to investigate the clinical characteristics, bronchoalveolar lavage (BAL) findings, and treatment course of RILD in patients with non-Hodgkin lymphoma. We retrospectively analyzed the data from 321 patients with non-Hodgkin lymphoma who developed RILD between 2020 and 2022. The extent, distribution, and radiologic patterns of interstitial lung disease were determined using high-resolution computed tomography of the chest. BAL was performed in 299 (93.1%) patients to determine cellular distribution patterns and identify pathogenic microorganisms using metagenomic next-generation sequencing. All patients received combination therapy, with cyclophosphamide, doxorubicin, vincristine, and prednisone being the most commonly administered regimens. The median time from treatment to RILD development was 1.7 months. In the 217 patients who underwent metagenomic next-generation sequencing, 179 pathogenic microorganisms were detected, including 77 (43.0%) bacteria, 45 (25.1%) viruses, 28 (15.6%) Pneumocystis jirovecii strains, 17 (9.5%) fungi, 6 (3.5%) Mycobacterium tuberculosis, and 6 (3.5%) atypical pathogens. All RILD diagnoses were based on multidisciplinary team discussions and compliance with international standards. In conclusion, RILD exhibits a range of radiological and BAL patterns, reflecting different interstitial lung disease types. The most common patterns of RILD are infectious lung disease, organizing pneumonia, and nonspecific interstitial pneumonia. These findings enhance the understanding of RILD in patients with non-Hodgkin lymphoma and serve as a reference for best management guidelines in these patients.

Antibody-drug conjugates-related interstitial lung diseases: data mining of the FAERS database.

BACKGROUND: Interstitial lung diseases (ILD) is a serious adverse event (AE) associated with antibody-drug conjugates (ADCs). This study aims to delve deeply into the signals of AE associated with ILD linked to ADCs. RESEARCH DESIGN AND METHODS: The AE reports were extracted from the first quarter of 2004 to the fourth quarter of 2023 based on the FDA Adverse Event Reporting System (FAERS) database. Signal mining was performed using the reporting odds ratio (ROR) method and the multi-item gamma Poisson shrinker (MGPS) method. Data management, analysis, and visualization were carried out using Python, R software, and MySQL. RESULTS: A total of 1389 AE reports related to ILD with 11 types of ADCs as the primary suspected drugs were obtained. The age groups most represented were 61-80 age group. ILD-related AE signals were detected for 11 ADCs in the study. Trastuzumab deruxtecan showed the strongest signals in both for ROR and MGPS methods. The median onset time vary from 8 days to 207 days. CONCLUSIONS: The signals of ILD AE associated with ADCs are notably strong. ILD should be closely monitored and assessed in the clinical use of ADCs taking full account of the efficacy and risks of these drugs.

Utility of the 52-Gene Risk Score to Identify Patients with Idiopathic Pulmonary Fibrosis at Greater Risk of Mortality in the Era of Antifibrotic Therapy.

PURPOSE: We investigated whether a 52-gene signature was associated with transplant-free survival and other clinically meaningful outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry, which enrolled patients who were and were not taking antifibrotic therapy. METHODS: The 52-gene risk signature was implemented to classify patients as being at "high risk" or "low risk" of disease progression and mortality. Transplant-free survival and other outcomes were compared between patients with a low-risk versus high-risk signature. RESULTS: The 52-gene signature classified 159 patients as at low risk and 86 as at high risk; in these groups, respectively, 56.6% and 51.2% used antifibrotic therapy at enrollment. Among those taking antifibrotic therapy, patients with a low-risk versus high-risk signature were at decreased risk of death, a composite of lung transplant or death, and a composite of decline in DLco % predicted > 15%, lung transplant, or death. Similar results were observed in the overall cohort. CONCLUSIONS: These data suggest that the 52-gene signature can be used in patients with IPF treated with antifibrotic therapy to distinguish patients at higher risk of disease progression and mortality.

Association between acute exacerbation and progressive pulmonary fibrosis in interstitial lung disease: a retrospective cohort study.

BACKGROUND: Acute exacerbation (AE) refers to rapidly progressive respiratory deterioration in the clinical course of interstitial lung disease (ILD). Progressive pulmonary fibrosis (PPF) is the chronic progressive phenotype of ILD. No study has investigated the relationship between AE and PPF in ILD. OBJECTIVES: We aimed to determine the association between AE and PPF in ILD patients. DESIGN: A retrospective cohort study. METHODS: A total of 414 patients hospitalised for ILD were included in our study. The clinical presentations, radiographic features and laboratory findings of the patients were reviewed. RESULTS: AE was present in 120 (29.0%) ILD patients and was associated with a higher risk of death than non-AE patients in the whole cohort (HR 2.893; 95% CI, 1.847-4.529; p < 0.001). However, the significant difference disappeared when stratified by PPF (HR 1.192; 95% CI, 0.633-2.247; p = 0.586) and non-PPF (HR 1.113; 95% CI, 0.384-3.223; p = 0.844). In addition, the adverse effect of PPF on prognosis remained consistent in both AE and non-AE patients. Multivariable logistic regression analysis showed that compared with non-PPF patients, only age was a risk factor for PPF in AE-ILD, while the risk factors for PPF in the non-AE group were age, definite usual interstitial pneumonia and mediastinal lymph node enlargement. CONCLUSION: In the context of ILD, both AE and PPF were found to be associated with poor prognosis. However, the adverse effect of AE on prognosis disappeared when PPF was considered as a stratification feature, whereas the adverse effect of PPF on prognosis persisted in both AE and non-AE individuals. Therefore, it is important to investigate effective strategies to prevent disease progression after AE. Increased recognition and attention to PPF and early antifibrotic therapy at the appropriate time is also warranted.

Association between acute exacerbation and progressive pulmonary fibrosis in interstitial lung diseaseWhy was the study done? Acute exacerbation (AE) is an acute respiratory worsening of interstitial lung disease (ILD). Progressive pulmonary fibrosis (PPF) is a chronic progressive-fibrosing form of ILD. The relationship between AE and PPF in ILD remained unclear. We aimed to determine the association between AE and PPF in ILD patients.What did the researchers do? The researchers studied 414 patients with ILD to see how AE and PPF affect the outcome of ILD and explored the risk factors for PPF in ILD.What did the researchers find? AE was present in 120 (29.0%) ILD patients and was associated with higher risk of death than non-AE patients in the whole cohort. However, the significant difference disappeared when stratified by PPF and non-PPF. In addition, the adverse effect of PPF on prognosis remained consistent in both AE and non-AE patients. In AE-ILD patients, age was the only risk factor for PPF. In the non-AE group, age, definite usual interstitial pneumonia and mediastinal lymph node enlargement were risk factors for PPF.What do the findings mean? The findings suggest that it is important to investigate effective strategies to prevent disease progression after AE. Increased recognition and attention to PPF and early antifibrotic therapy at the appropriate time is also necessary.

Pilot study of home-based monitoring for early prediction of acute exacerbations in patients with fibrosing interstitial lung diseases.

This study aimed to assess the potential of home monitoring using a monitoring application for the early prediction of acute exacerbations (AEs) in patients with fibrosing interstitial lung diseases (F-ILDs) by tracking symptoms, peripheral blood oxygen saturation (SpO2), and heart rate (HR). Data on symptoms, SpO2, and HR before and after a 1-min sit-to-stand test (1STST) were collected using an online home monitoring application. Symptoms were recorded at least 3 times a week, including cough intensity and frequency (Cough Assessment Test scale (COAT) score), breathlessness grade (modified Medical Research Council (mMRC) score), and SpO2 and HR before and after 1STST. Eighty-five patients with stable F-ILDs were enrolled. We observed a significant increase in COAT and mMRC scores, alongside a significant decrease in SpO2 before and after 1STST, 2 weeks before the first recorded AE. Furthermore, a combination of variables-an increase in COAT (≥ 4) and mMRC(≥ 1) scores, a decrease in SpO2 at rest (≥ 5%), and a decrease in SpO2 after 1STST (≥ 4%)- proved the most effective in predicting AE onset in patients with F-ILDs at 2 weeks before the first recorded AE. Home telemonitoring of symptoms, SpO2 holds potential value for early AE detection in patients with F-ILDs.

Use of pirfenidone in fibrotic interstitial lung diseases and beyond: a review.

The pathophysiological mechanisms involved in fibrotic interstitial lung diseases (FILDs) are akin to those observed in idiopathic pulmonary fibrosis (IPF), implying the potential for shared therapeutic approaches. Pirfenidone exhibits antifibrotic and anti-inflammatory properties, making it the first small-molecule drug approved for treating IPF. Pirfenidone has been utilized in IPF treatment for more than one decade. However, guidelines for progressive pulmonary fibrosis (PPF) treatment suggest that further research and evidence are needed to fully comprehend its efficacy and safety across various PPF subtypes. In recent years, numerous studies have explored the use of pirfenidone in treating non-IPF FILD. Herein, we provide an overview of the latest research data on application of pirfenidone in occupational-related ILD, connective tissue disease-associated ILD, post-coronavirus disease-2019 pulmonary fibrosis, and other conditions. We summarize the level of evidence and highlight challenges associated with using pirfenidone in different FILDs to offer clinical guidance.

Value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in acute exacerbation of fibrosing interstitial lung disease: an individualized treatment protocol based on microbiological evidence.

BACKGROUND: Acute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD. METHODS: We conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission. RESULTS: Patients with a variety of ILD classification were included. Connective-tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p < 0.001). After treatment, the GGO score and the consolidation score were significantly lower during follow up in survivors (1.57 ± 0.53 vs. 2.38 ± 0.83 with p < 0.001, 1.11 ± 0.24 vs. 1.49 ± 0.47 with p < 0.001, respectively). Some detected microorganisms, such as Tropheryma whipplei, Mycobacterium, Aspergillus, and mixed infections were difficult to be fully covered by empirical medication. BALF mNGS was also very helpful for excluding infections and early administration of methylprednisolone and/or ISA. CONCLUSIONS: mNGS has been shown to be a useful tool to determine pathogens in patients with AE-ILD, the results should be fully analyzed. The comprehensive treatment protocol based on mNGS has been shown crucial in AE-ILD patients.

Evaluation of progressive pulmonary fibrosis in non-idiopathic pulmonary fibrosis-interstitial lung diseases: a cross-sectional study.

BACKGROUND: Progressive pulmonary fibrosis is the symptomatic, physiological, and radiological progression of interstitial lung diseases. The aim of this study was to examine the relationship between progressive pulmonary fibrosis and demographic characteristics and to evaluate the effect on clinical outcomes and mortality. METHODS: This cross-sectional study included 221 patients diagnosed with non-idiopathic pulmonary fibrosis interstitial lung diseases who were followed in the last 5 years. Patient symptoms, clinical, radiological, and demographic data were examined. Risk factors for the development of progressive pulmonary fibrosis and the relationship with clinical outcomes and mortality were examined. RESULTS: Of the patients, 33.0% (n = 73) had fibrotic idiopathic nonspecific interstitial pneumonia (iNSIP), 35.7% (n = 79) had fibrotic hypersensitivity pneumonia (HP), 18.1% (n = 40) had fibrotic connective tissue disease (CTD) interstitial lung diseases (ILD), and 13.1% (n = 29) had postinfectious fibrotic ILD. The progressive pulmonary fibrosis development rates of the subtypes were 46.5% iNSIP (n = 34), 86.0% fibrotic HP (n = 68), 42.5% fibrotic CTD-ILD (n = 17), and 20.7% postinfectious ILD (n = 6). The presence of progressive pulmonary fibrosis was associated with the development of respiratory failure and mortality (odds ratio [OR]: 2.70, 95% CI: 1.04-7.05 and OR: 2.13, 95% CI: 1.23-3.69). Progressive pulmonary fibrosis development was higher in hypersensitivity pneumonia patients with farmer's lung (OR: 5.06, 95% CI: 1.02-25.18). CONCLUSION: Progressive pulmonary fibrosis was more prevalent in older patients. Farming was an important risk factor in the development of hypersensitivity pneumonia-progressive pulmonary fibrosis. Respiratory failure and mortality were higher in those who developed progressive pulmonary fibrosis.

Association of rare single nucleotide variant MUC5B rs35705950 with interstitial lung disease in Japanese rheumatoid arthritis.

OBJECTIVES: 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.

Childhood interstitial lung diseases: current understanding of the classification and imaging findings.

Childhood interstitial lung diseases (chILDs) encompass a diverse group of disorders with a high mortality rate and severe respiratory morbidities. Recent investigations have revealed that the classification of adult ILDs is not valid for chILDs, particularly for ILDs of early onset. Therefore, Children's Interstitial Lung Disease Research Cooperative of North America proposed a new classification of chILDs for affected children under 2 years of age, and later another classification for affected individuals between 2 and 18 years of age. In this review, we provide an overview of the imaging findings of chILDs by classification. Most infantile ILDs have unique clinical, radiological, and molecular findings, while the manifestation of pediatric ILDs overlaps with that of adult ILDs.

Knowledge, attitude, and practice toward interstitial lung disease among patients: a cross-sectional study.

Objective: To explore the knowledge, attitude, and practice (KAP) toward interstitial lung disease (ILD) among patients and analyze the factors affecting KAP. Methods: 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. Results: 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 (ß = 0.842, p < 0.001) and practice (ß = 0.363, p < 0.001), and their attitude also affected their practice (ß = 0.347, p = 0.014). Conclusion: 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.

Genomic Profiling for Predictive Treatment Strategies in Fibrotic Interstitial Lung Disease.

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.

Treatment with low-dose nintedanib and tacrolimus in patients with progressive fibrosing interstitial lung diseases with anti-ARS antibody-positive dermatomyositis.

Nintedanib has been demonstrated to inhibit the rate of forced vital capacity decline in patients with progressive fibrosing interstitial lung diseases (PF-ILD) at a dose of 200 or 300 mg/day in the INBUILD trial. Although concomitant use of nintedanib with P-glycoprotein inhibitors reportedly increases the plasma concentrations of the former, tacrolimus, a P-glycoprotein inhibitor, is often used to treat connective tissue diseases-related interstitial lung diseases. The optimal dose of nintedanib in combination with tacrolimus for the treatment of PF-ILD with connective tissue disease is unknown. We herein present two patients with PF-ILD with anti-aminoacyl-tRNA synthetase antibody-positive dermatomyositis who were successfully treated with low-dose nintedanib (<200 mg/day) in combination with tacrolimus.

Prognosis of Lung Transplantation in Patients with Acute Exacerbations of Interstitial Lung Disease: A Meta-Analysis Based on Cohort Studies.

PURPOSE: 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). CONCLUSION: 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.

Baricitinib and Pulse Steroids Combination Treatment in Hyperinflammatory COVID-19: A Rheumatological Approach in the Intensive Care Unit.

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.

Relationship between nailfold capillaroscopy findings and the etiology and prognosis of interstitial lung disease.

OBJECTIVES: Connective tissue-associated interstitial lung diseases (CTD-ILD) are believed to be caused by microvascular damage. The objective of this study was to assess the nailfold capillaroscopy (NFC) pattern in patients diagnosed with both CTD-ILD and non-CTD-ILD to identify microvascular changes and determine the relation between capillaroscopic parameters, clinical variables, and disease-related measurements. PATIENTS AND METHODS: This cross-sectional study included 95 patients with interstitial lung disease who applied to our Rheumatology and Chest Clinics between September 2021 and July 2023. The patients were divided into two groups based on their diagnosis: non-CTD-ILD (group 1) and CTD-ILD (group 2). Nailfold capillaroscopy was performed. RESULTS: Ninety-five patients, 49 (51% female, mean age 62.31 ± 11.027 years) in group 1 and 46 (69.6% female, mean age 62.09 ± 10.887 years) in group 2, were included in the study. Abnormal capillary morphologies were both detected in the CTD-ILD group and the non-CTD-ILD groups. In patients with a usual interstitial pneumonia (UIP) pattern on chest computed tomography (CT), tortuosity was higher than in patients with non-specific interstitial pneumonia (NSIP) (P = 0.041), and the proportion of tortuosity increased significantly as the duration of the disease increased (P = 0.016). CONCLUSION: Our study highlights capillaroscopic abnormalities alone may not be sufficient to differentiate CTD-ILD (other than systemic sclerosis) from non-CTD-ILD. The presence of NFC abnormalities in non-CTD-ILD may suggest that fibrotic lung disease could potentially play a role in the deterioration of the microvascular structure or abnormal angiogenesis. Our study demonstrated that a multidisciplinary approach, incorporating clinical, morphological, pathological, and serological evaluations, is necessary for interpreting ILD. Key Points • Capillaroscopic abnormalities can also be seen in non-CTD-ILD. • Capillaroscopy findings do not distinguish the non-Ssc etiology of ILD. • Nailfold capillaroscopy may have the potential to serve as a useful tool in predicting prognosis and monitoring the disease progression in patients with idiopathic pulmonary fibrosis (IPF).

The link between smoking, emphysema, and fibrosis: A retrospective cohort study.

INTRODUCTION: 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.

Immune mechanisms in fibrotic interstitial lung disease.

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.