Anti-synthase syndrome associated with SARS-Cov-2 infection.

BACKGROUND: Anti-synthetase syndrome (AS) is a rare autoimmune idiopathic inflammatory myopathy (IIM) with diverse manifestations, including arthritis, interstitial lung disease (ILD), Raynaud's phenomenon, unexplained persistent fever, and mechanic's hands. CASE PRESENTATION: We present the case of a 72-year-old woman, previously healthy, who was admitted to our hospital for treatment of cough and rapid breathing. The patient had elevated white blood cells and C-reactive protein, and tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). She was initially diagnosed with community-acquired pneumonia and received tamoxifen for anti-infection treatment, but her dystonia worsened. She eventually required non-invasive ventilator support, tested positive for SARS-Cov-2 again, and started antiviral therapy, corticosteroids to reduce alveolar effusion, anticoagulation, and other treatments. However, her condition continued to deteriorate, with the lowest oxygenation index reaching only 80mmHg. Ultimately, she underwent tracheal intubation and mechanical ventilation. Chest CT revealed rapid progressive interstitial changes in her lungs, and her hands showed noticeable fraternization changes. At this point, we suspected that the novel coronavirus infection might be associated with autoimmune diseases. The patient's autoimmune antibody spectrum showed positive results for anti-recombinant RO-52 antibody and myositis-specific antibody anti-alanyl tRNA synthetase (anti-PL-12). The patient was treated with dexamethasone sodium phosphate for anti-inflammatory and anti-fibrotic effects. After successful extubation, the patient was discharged with only oral prednisone tablets at a dose of 30 mg. CONCLUSIONS: This case presents an early diagnosis and successful treatment of anti-synthetase syndrome combined with SARS-Cov-2 infection, emphasizing the importance of comprehensive physical examination. Additionally, it highlights the rapid progression of interstitial lung disease under SARS-Cov-2 infection, which is often difficult to distinguish on imaging. In cases where treatment for SARS-Cov-2 infection is ineffective, early screening for autoimmune diseases is recommended. As there is currently no standardized method for treating AS-ILD, the successful treatment of this case provides a reference for clinical research on anti-synthetase syndrome in the later stage.

Feasibility and acceptability of remotely monitoring spirometry and pulse oximetry as part of interstitial lung disease clinical care: a single arm observational study.

BACKGROUND: Remote monitoring of patient-recorded spirometry and pulse oximetry offers an alternative approach to traditional hospital-based monitoring of interstitial lung disease (ILD). Remote spirometry has been observed to reasonably reflect clinic spirometry in participants with ILD but remote monitoring has not been widely incorporated into clinical practice. We assessed the feasibility of remotely monitoring patients within a clinical ILD service. METHODS: Prospective, single-arm, open-label observational multi-centre study (NCT04850521). Inclusion criteria included ILD diagnosis, age ≥ 18 years, FVC ≥ 50% predicted. 60 participants were asked to record a single spirometry and oximetry measurement at least once daily, monitored weekly by their local clinical team. Feasibility was defined as ≥ 68% of participants with ≥ 70% adherence to study measurements and recording measurements ≥ 3 times/week throughout. RESULTS: A total of 60 participants were included in the analysis. 42/60 (70%) were male; mean age 67.8 years (± 11.2); 34/60 (56.7%) had idiopathic pulmonary fibrosis (IPF), Median ILD-GAP score was 3 (IQR 1-4.75). Spirometry adherence was achieved for ≥ 70% of study days in 46/60 participants (77%) and pulse oximetry adherence in 50/60 participants (83%). Recording ≥ 3 times/week every week was provided for spirometry in 41/60 participants (68%) and pulse oximetry in 43/60 participants (72%). Mean difference between recent clinic and baseline home spirometry was 0.31 L (± 0.72). 85.7% (IQR 63.9-92.6%) home spirometry attempts/patient were acceptable or usable according to ERS/ATS spirometry criteria. Positive correlation was observed between ILD-GAP score and adherence to spirometry and oximetry (rho 0.24 and 0.38 respectively). Adherence of weekly monitoring by clinical teams was 80.95% (IQR 64.19-95.79). All participants who responded to an experience questionnaire (n = 33) found remote measurements easy to perform and 75% wished to continue monitoring their spirometry at the conclusion of the study. CONCLUSION: Feasibility of remote monitoring within an ILD clinical service was demonstrated over 3 months for both daily home spirometry and pulse oximetry of patients. Remote monitoring may be more acceptable to participants who are older or have more advanced disease. TRIAL REGISTRATION: clinicaltrials.gov NCT04850521 registered 20th April 2021.

Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

A new definition and treatment options of allergic alveolitis.

In this review, we discuss a new definition and treatment options of allergic alveolitis (AA). AA is an immune-mediated interstitial lung disease triggered by inhaled antigens, it is defined as non-fibrotic (inflammatory) and/or fibrotic, and diagnosis relies on a multidisciplinary approach using clinical, radiological and sometimes histological assessments. Treatment involves early antigen elimination and may include corticosteroids or other immunosuppressants. Prognosis varies from reversible inflammation to irreversible fibrosis. Early detection is crucial for better outcomes.

Exploratory mass cytometry analysis reveals immunophenotypes of cancer treatment-related pneumonitis.

Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16+ T cell population, with the highest CD16+ T proportion in a fatal case. In ICI-ILD, we found an increase in CD57+ CD8+ T cells expressing immune checkpoints (TIGIT+ LAG3+ TIM-3+ PD-1+), FCRL5+ B cells, and CCR2+ CCR5+ CD14+ monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.

Lung adenocarcinoma discovered during the follow-up of lung-dominant connective tissue disease: a case report and literature review.

Interstitial lung disease (ILD) can lead to lung cancer, which brings great challenges to differential diagnosis and comprehensive treatment. However, the clinical features of lung-dominant connective tissue disease (LD-CTD) related ILD combined with lung cancer has not been validated. We report the case of an 80-year-old woman with LD-CTD treated regularly with nintedanib who presented progressive dyspnoea and hypoxemia after recurrent viral infections. Her chest computed tomography (CT) showed aggravated interstitial fibrosis in both lower lungs with moderate right pleural effusion. Clinicians should be alert to lung cancer in patients who are experiencing poor responsiveness to treatment or acute progression of ILD. The available literatures about the differential diagnosis of clinical manifestations, imaging, treatment and prognosis of LD-CTD are reviewed and discussed in this study.

Pembrolizumab-associated anti-MDA5 dermatomyositis in a patient with lung cancer: a first case report.

We report the first case of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis as a systemic immune-related adverse event in a 64-year-old man receiving pembrolizumab to treat advanced lung cancer. The patient experienced hypothyroidism, myalgia, skin involvement, dyspnoea and diarrhoea. Laboratory tests revealed raised inflammatory markers, hypercreatinekinasemia and anti-MDA5 autoantibodies. Electroneuromyography and pathognomonic signs on physical examination confirmed the diagnosis of pauci-myopathic dermatomyositis. Pembrolizumab was discontinued and immunosuppressive therapy led to rapid and progressive improvement, with complete remission of dermatomyositis. This case report widens the spectrum of systemic immune-related adverse events associated with pembrolizumab.

A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. CASE PRESENTATION: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal. CONCLUSIONS: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Prevalence and prognostic meaning of interstitial lung abnormalities in remote CT scans of patients with interstitial lung disease treated with antifibrotic therapy.

OBJECTIVES: To describe the prevalence and characteristics of interstitial lung abnormalities (ILA) in CT scans performed prior to the initiation of antifibrotics in a series of patients with interstitial lung disease (ILD), and to identify characteristics apparent on early CT scans that could help to predict outcomes. METHODS: We conducted a retrospective observational study. The original cohort consisted of 101 patients diagnosed with ILD and treated with antifibrotics in a tertiary hospital. Patients were included if they had a thoracic CT scan performed at least one year before initiation of therapy. They were classified radiologically in three groups: without ILA, with radiological ILA and extensive abnormalities. ILA were classified as subpleural fibrotic, subpleural non-fibrotic and non-subpleural. The initial scan and the latest CT scan performed before treatment were read for assessing progression. The relationship between CT findings of fibrosis and the radiological progression rate and mortality were analyzed. RESULTS: We included 50 patients. Only 1 (2%) had a normal CT scan, 25 (50%) had extensive alterations and 24 (48%) had radiological criteria for ILA, a median of 98.2 months before initiation of antifibrotics, of them 18 (75%) had a subpleural fibrotic pattern. Significant bronchiectasis and obvious honeycombing in the lower zones were associated with shorter survival (p = 0.04). Obvious honeycombing in the lower zones was also significantly (p < 0.05) associated with a faster progression rate. CONCLUSIONS: Fibrotic ILAs are frequent in remote scans of patients with clinically relevant ILD, long before they require antifibrotics. Findings of traction bronchiectasis and honeycombing in the earliest scans, even in asymptomatic patients, are related to mortality and progression later on.

Prevalencia de la enfermedad pulmonar esclerodermia-intersticial limitada frente a la extensa en el momento del diagnóstico de SSc-EPID según los criterios de Goh et al. Revisión sistemática y metaanálisis / Prevalence of the limited vs. extensive scleroderma-related interstitial lung disease at the time of diagnosis of SSc-ILD based on Goh et al. criteria. Systematic review and meta-analysis

Introducción: Goh et al. propusieron en 2008 un algoritmo clasificatorio de SSc-EPID limitada o extensa. La prevalencia de ambos en el momento del diagnóstico de SSc-EPID no se conoce con exactitud. Métodos: La revisión se realizó mediante MEDLINE y SCOPUS desde 2008 hasta 2023 y utilizando los términos: «sistémica», «esclerodermia» o «enfermedad pulmonar intersticial» [MesH]. Se utilizó la escala de Newcastle-Ottawa para la evaluación de la calificación de los estudios observacionales y la escala de Jadad para los ensayos clínicos. Se realizó el método inverso ponderado por la varianza. Resultados: Se incluyeron inicialmente 27 estudios en la revisión sistemática y metaanálisis (SRMA). De ellos, 17 estudios no tenían datos coincidentes. Comunicaron datos de 2.149 pacientes, 1.369 (81,2%) eran mujeres. La edad media era de 52,4 (DE 6,6) años. El 45,2% de los pacientes presentaban el subtipo difuso y el 54,8% el subtipo limitado o esclerodermia sinusal. El 38,7% de los pacientes presentaban anticuerpos antitopoisomerasa positivos y el 14,2% anticuerpos anticentrómero positivos. El porcentaje medio de capacidad vital forzada al inicio del estudio fue del 80,5% (DE 6,9) y de capacidad de difusión pulmonar para el monóxido de carbono fue del 59,1% (DE 9,6). Doce estudios presentaron datos de extensión de SSc-EPID ajustados por PFR y se incluyeron en el metaanálisis. Los 10 estudios observacionales de cohortes se analizaron por separado. El porcentaje global de afectación limitada se estimó en un 63,5% (IC del 95%: 55,3-73; p<0,001) utilizando el modelo de efectos aleatorios. La heterogeneidad entre estudios (I2) fue del 9,8% (IC del 95%: 0-68,2%). La afectación pulmonar extensa se estimó en 34,3% (IC del 95%: 26-45,4; p<0,001). La heterogeneidad entre estudios (I2) fue del 0% (IC del 95%: 0-61,6%) con el modelo de efectos aleatorios.(AU)

Introduction: Goh et al. proposed in 2008 a classificatory algorithm of limited or extensive SSc-ILD. The prevalence of both at the time of diagnosis of SSc-ILD is not known with exactitude. Methods: The review was undertaken by means of MEDLINE and SCOPUS from 2008 to 2023 and using the terms: “systemic”, “scleroderma” or “interstitial lung disease” [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment for observational studies and the Jadad scale for clinical trials. The inverse variance-weighted method was performed. Results: Twenty-seven studies were initially included in the systematic review and meta-analysis (SRMA). Of these, 17 studies had no overlapping data. They reported data from 2,149 patients, 1,369 (81.2%) were female. The mean age was 52.4 (SD 6.6) years. 45.2% of the patients had the diffuse subtype and 54.8% had the limited or sine scleroderma subtype. A total of 38.7% of the patients showed positive antitopoisomerase antibodies and 14.2% positive anticentromere antibodies. The mean percentage of forced vital capacity at baseline was 80.5% (SD 6.9) and of diffusing capacity of the lungs for carbon monoxide was 59.1% (SD 9.6). Twelve studies presented SSc-ILD extension data adjusted for PFTs and were included in the meta-analysis. The 10 observational cohort studies were analyzed separately. The overall percentage of limited extension was estimated at 63.5% (95%CI 55.3–73; p<0.001) using the random-effects model. Heterogeneity between studies (I2) was 9.8% (95%CI 0–68.2%) with the random-effects model. Extensive pulmonary involvement was estimated at 34.3% (95%CI 26–45.4; p<0.001). Heterogeneity between studies (I2) was 0% (95%CI 0–61.6%) with the random-effects model. Conclusion: The overall percentage of limited SSc-ILD at the time of diagnosis of SSc-ILD was estimated at 63.5% and extensive at 34.3%.(AU)

Neumomediastino espontáneo: una manifestación extramuscular de la dermatomiositis anti-MDA5. Reporte de 2 casos / Spontaneous pneumomediastinum: An extra muscular manifestation of anti-MDA5 dermatomyositis. Report of 2 cases

El uso de anticuerpos específicos en miopatías inflamatorias ha mejorado la caracterización de esta enfermedad identificando distintos fenotipos clínicos. Los pacientes con dermatomiositis y anticuerpos anti-MDA5 muestran síntomas típicos en la piel, un menor compromiso muscular y una prevalencia de enfermedad pulmonar intersticial de hasta el 91%. Además de la enfermedad pulmonar intersticial, se ha identificado el neumomediastino espontáneo como una manifestación pulmonar rara pero potencialmente mortal. Se reportan 2 casos de esta manifestación en pacientes con dermatomiositis anti-MDA5.(AU)

The use of specific antibodies in inflammatory myopathies has improved the characterization of this disease, identifying different clinical phenotypes. Patients with dermatomyositis and anti-MDA5 antibodies display typical skin symptoms, lesser muscular involvement, and a prevalence of interstitial lung disease of up to 91%. Beyond interstitial lung disease, spontaneous pneumomediastinum has been identified as a rare but potentially fatal pulmonary manifestation. Two cases of this complication in patients with anti-MDA5 dermatomyositis are reported.(AU)

Pulmonary manifestations and prognosis of a cohort of patients with interstitial lung disease and positive to anti-Th/To autoantibodies / Manifestaciones pulmonares y pronóstico de una cohorte de pacientes con enfermedad pulmonar intersticial y autoanticuerpos anti-Th/To positivos

Introduction: Th/To autoantibody may be relevant in evaluating patients with interstitial lung disease (ILD) because the clinical diagnosis of systemic sclerosis (SSc) may not be evident. The study's objective was to describe manifestations and evolution of pulmonary function in a cohort of ILD patients positive for Th/To autoantibodies. Methods: ILD patients positive for anti-Th/To autoantibody were enrolled in this protocol. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. Results: Fifty-two patients positive for anti-Th/To autoantibodies with ILD were included. Only 21% of the patients fulfilled the ACR/EULAR 2013 systemic sclerosis classification criteria, and 63.4% fulfilled the IPAF ATS/ERS 2015 criteria. Twenty-five percent of the patients died during follow-up. Respiratory failure was the principal cause of death. Twenty-nine patients (56%) were positive for other hallmark SSc autoantibodies. The most frequent HRCT pattern was nonspecific interstitial pneumonia (NISP). Survival was strongly associated to the systolic pulmonary arterial pressure (sPAP), male sex and the extent of fibrosis in HRCT; besides, patients positive for other hallmark SSc autoantibodies had worse survival compared to those positive only to anti-Th/To. Seventy-six percent of them behaved as fibrotic progressive pulmonary disease, with an absolute decline of the FVC of at least 5%. Conclusions: Only a small proportion of ILD patients positive for Th/To meet the criteria to be classified as SSc; however, most met criteria for IPAF. A high proportion of patients behave as progressive fibrotic pulmonary disease. Survival is associated with sPAP, the extent of lung disease, and the presence of other hallmark SSc autoantibodies. (AU)

Introducción: El autoanticuerpo Th/To puede ser relevante en la evaluación de pacientes con enfermedad pulmonar intersticial (EPI) debido a que el diagnóstico clínico de esclerosis sistémica (ES) puede no ser evidente. El objetivo del estudio fue describir las manifestaciones clínicas y la evolución de la función pulmonar en una cohorte de pacientes con EPI positivos para autoanticuerpos Th/To. Métodos: En este protocolo se inscribieron pacientes con EPI positivos para autoanticuerpos anti-Th/To. Se registraron las características clínicas iniciales y se realizó un análisis de supervivencia para identificar los factores de riesgo asociados con una peor supervivencia. Resultados: Se incluyeron 52 pacientes positivos para autoanticuerpos anti-Th/To con EPI. Solo el 21% de los pacientes cumplió los criterios de clasificación para esclerosis sistémica ACR/EULAR 2013 y el 63,4% cumplió los criterios de neumonía con características autoinmunes ATS/ERS 2015. El 25% de los pacientes falleció durante el seguimiento. La insuficiencia respiratoria fue la principal causa de muerte. Veintinueve pacientes (56%) dieron positivo para otros autoanticuerpos distintivos de ES. El patrón más frecuente en la tomografía computarizada de alta resolución (TCAR) fue la neumonía intersticial inespecífica. La supervivencia estuvo estrechamente asociada con la presión arterial pulmonar sistólica (PAPs), el sexo masculino y la extensión de fibrosis en la TCAR. Además, los pacientes positivos para otros autoanticuerpos distintivos de ES tuvieron una peor supervivencia en comparación con aquellos positivos solo para anti-Th/To. El 66% de ellos se comportaron como enfermedad pulmonar fibrótica progresiva, con una disminución absoluta de la capacidad vital forzada de al menos el 5%. Conclusiones: Solo una pequeña proporción de pacientes con EPI positivos para Th/To cumplieron con los criterios para ser clasificados como ES... (AU)

Relationship between idiopathic interstitial pneumonias (IIPs) and connective tissue disease-related interstitial lung disease (CTD-ILD): A narrative review.

While idiopathic interstitial pneumonia (IIP) centering on idiopathic pulmonary fibrosis (IPF) is the most prevalent interstitial lung disease (ILD), especially in the older adult population, connective tissue disease (CTD)-related ILD is the second most prevalent ILD. The pathogenesis of IPF is primarily fibrosis, whereas that of other ILDs, particularly CTD-ILD, is mainly inflammation. Therefore, a precise diagnosis is crucial for selecting appropriate treatments, such as antifibrotic or immunosuppressive agents. In addition, some patients with IIP have CTD-related features, such as arthritis and skin eruption, but do not meet the criteria for any CTD, this is referred to as interstitial pneumonia with autoimmune features (IPAF). IPAF is closely associated with idiopathic nonspecific interstitial pneumonia (iNSIP) and cryptogenic organizing pneumonia (COP). Furthermore, patients with iNSIP or those with NSIP with OP overlap frequently develop polymyositis/dermatomyositis after the diagnosis of IIP. Acute exacerbation of ILD, the most common cause of death, occurs more frequently in patients with IPF than in those with other ILDs. Although acute exacerbation of CTD-ILD occurs at a low rate of incidence, patients with rheumatoid arthritis, microscopic polyangiitis, or systemic sclerosis experience more acute exacerbation of CTD-ILD than those with other CTD. In this review, the features of each IIP, focusing on CTD-related signatures, are summarized, and the pathogenesis and appropriate treatments to improve the prognoses of patients with various ILDs are discussed.

Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis.

BACKGROUND: The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can potentially result in interstitial lung disease (ILD), which can substantially impact a patient's quality of life, subsequently leading to the interruption or discontinuation of EGRF-TKI treatment. Clinicians, therefore, need to thoroughly assess patients to determine if they are at risk for ILD. METHODS: We searched for observational study in the following databases: MEDLINE via the PubMed, CENTRAL, and IchushiWeb. The primary outcome was risk factors for the development of ILD, while the secondary outcome was risk factors for the severity of ILD. Of the 1602 studies returned, we selected 11 for meta-analysis, performed using a random-effects model. RESULTS: Risk factors for developing ILD were sex (odds ratio (OR), 1.87; 95% confidence interval (CI), 1.08-3.22; I2 = 0%; P = 0.02), smoking history (OR, 2.13; 95% CI, 1.51-3.00; I2 = 3 4%; P = 0.0001), and history of ILD (OR = 5.95; 95% CI, 3.34-10.59; I2 = 67%; P = 0.0009). Age, previous thoracic surgery or radiotherapy, performance status, histological type of lung cancer, and treatment line were not statistically significant risk factors for ILD. Risk factors identified in one study were serum albumin level, history of nivolumab use, radiographic residual lung volume, and history of pulmonary infection. CONCLUSIONS: We identified risk factors for developing ILD in patients with non-small cell lung cancer treated with EGFR-TKIs.

Incidence, etiology, and outcome of hospital-acquired pneumonia in patients with acute exacerbation of fibrotic idiopathic interstitial pneumonia.

BACKGROUND: Acute exacerbations (AEs) of fibrotic idiopathic interstitial pneumonia (fIIP) that require hospitalization occur in some patients. During hospitalization, these patients can develop hospital-acquired pneumonia (HAP), a common hospital-acquired infection with a high mortality rate. However, the characteristics of HAP in AE-fIIP remain unknown. The purpose of this study was to determine the incidence, causative pathogens, and outcomes of HAP in patients with AE-fIIP. METHODS: The medical records of consecutive patients who were hospitalized with AE-fIIP from January 2008 to December 2019 were analyzed for the incidence, causative pathogen, and survival of HAP. The records of patients with an obvious infection-triggered AE were excluded from analysis. RESULTS: There were 128 patients with AE-fIIP (89 with idiopathic pulmonary fibrosis [IPF] and 39 with non-IPF fIIP) who were hospitalized a total of 155 times (111 with IPF and 44 with non-IPF fIIP). HAP occurred in 49 patients (40 with IPF and 9 with non-IPF fIIP). The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP were high, at 32.2% and 48.9%, respectively. Corynebacterium spp. was the most common causative pathogen, which was followed by human cytomegalovirus (HCMV). CONCLUSIONS: The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP are high. To improve their survival, patients with fIIP who had AEs and HAP should receive prompt empirical treatment for possible infections with Corynebacterium spp. and testing for HCMV.

Autoimmunity against melanoma differentiation-associated gene 5 induces interstitial lung disease mimicking dermatomyositis in mice.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) is characterized by amyopathic DM with interstitial lung disease (ILD). Patients with anti-MDA5 antibody-associated ILD frequently develop rapidly progression and present high mortality rate in the acute phase. Here, we established a murine model of ILD mediated by autoimmunity against MDA5. Mice immunized with recombinant murine MDA5 whole protein, accompanied with complete Freund's adjuvant once a week for four times, developed MDA5-reactive T cells and anti-MDA5 antibodies. After acute lung injury induced by intranasal administration of polyinosinic-polycytidylic acid [poly (I:C)] mimicking viral infection, the MDA5-immunized mice developed fibrotic ILD representing prolonged respiratory inflammation accompanied by fibrotic changes 2 wk after poly (I:C)-administration, while the control mice had quickly and completely recovered from the respiratory inflammation. Treatment with anti-CD4 depleting antibody, but not anti-CD8 depleting antibody, suppressed the severity of MDA5-induced fibrotic ILD. Upregulation of interleukin (IL)-6 mRNA, which was temporarily observed in poly (I:C)-treated mice, was prolonged in MDA5-immunized mice. Treatment with anti-IL-6 receptor antibody ameliorated the MDA5-induced fibrotic ILD. These results suggested that autoimmunity against MDA5 exacerbates toll-like receptor 3-mediated acute lung injury, and prolongs inflammation resulting in the development of fibrotic ILD. IL-6 may play a key role initiating ILD in this model.

Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis.

BACKGROUND: Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5+DM patients. METHODS: Serums were collected from 39 patients with anti-MDA5+DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay. RESULTS: Serum BAFF level was higher in anti-MDA5+DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5+DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5+DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609-54.769; p = 0.013). CONCLUSIONS: Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5+DM patients.

Factors influencing the therapeutic failure of high-flow nasal cannula oxygen humidification in patients with interstitial pneumonia complicated by respiratory failure.

OBJECTIVE: The aim of this study was to explore the factors influencing the treatment failure of high-flow nasal cannula (HFNC) therapy in patients with interstitial pneumonia (IP) complicated by respiratory failure. PATIENTS AND METHODS: A total of 158 patients with IP and respiratory failure treated with HFNC in our hospital from January 2020 to August 2023 were selected as the study population. Based on treatment efficacy, they were categorized into the HFNC treatment failure group and the HFNC treatment success group. Clinical data were compared between the two groups. Multiple logistic regression analysis was employed to identify independent factors influencing treatment failure, and the predictive value of these factors for HFNC treatment failure was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: After 7 days of HFNC treatment, among the 158 patients with IP and respiratory failure, 25 (15.8%) declared treatment failure, while the remaining 133 (84.2%) showed treatment success. Patients in the HFNC treatment failure group had significantly higher age, duration of IP, pre-treatment respiratory rate, C-reactive protein (CRP), and controlling nutritional status (CONUT) scores compared to the HFNC treatment success group. The PaO2/FiO2 ratio, left ventricular ejection fraction, and Glasgow Coma Scale (GCS) were significantly lower in the HFNC treatment failure group (p<0.05). Multiple logistic regression analysis revealed that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores were independent factors influencing HFNC treatment failure in patients with IP and respiratory failure (p<0.05). Lower PaO2/FiO2 ratio and GCS scores, and higher CRP and CONUT scores were associated with an increased risk of HFNC treatment failure. ROC curve analysis indicated that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores in patients with IP and respiratory failure had a high predictive value for HFNC treatment failure (p<0.05). CONCLUSIONS: The HFNC failure rate in patients with IP and respiratory failure is 15.8%. Pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores are independent factors associated with HFNC treatment failure and warrant clinical attention.

[A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies].

OBJECTIVE: To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies (IIMs) patients receiving conventional treatment. METHODS: Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were included. The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics, laboratory features, peripheral blood lymphocytes, immunological indicators, and therapeutic drugs. RESULTS: Among the 635 patients included, 518 patients finished the follow-up, with an average time of 36.8 months. The total complete clinical response rate of IIMs was 50.0% (259/518). The complete clinical response rate of dermatomyositis (DM), anti-synthetase syndrome (ASS) and immune-mediated necrotizing myopathy (IMNM) were 53.5%, 48.9% and 39.0%, respectively. Fever (P=0.002) and rapid progressive interstitial lung disease (RP-ILD) (P=0.014) were observed much more frequently in non-complete clinical response group than in complete clinical response group. The aspartate transaminase (AST), lactate dehydrogenase (LDH), D-dimer, erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group. As for the treatment, the percentage of glucocorticoid received and intravenous immunoglobin (IVIG) were significantly higher in non-complete clinical response group than in complete clinical response group. Risk factor analysis showed that IMNM subtype (P=0.007), interstitial lung disease (ILD) (P=0.001), eleva-ted AST (P=0.012), elevated serum ferritin (P=0.016) and decreased count of CD4+T cells in peripheral blood (P=0.004) might be the risk factors for IIMs non-complete clinical response. CONCLUSION: The total complete clinical response rate of IIMs is low, especially for IMNM subtype. More effective intervention should be administered to patients with ILD, elevated AST, elevated serum ferritin or decreased count of CD4+T cells at disease onset.