RESUMEN
Interstitial lung abnormalities (ILAs) are immune checkpoint inhibitor (ICI)-related pneumonitis (ICI-P) risk factors. However, the relationship between imaging patterns and immunotherapy outcomes, and treatment strategies remain unclear in patients with non-small cell lung cancer (NSCLC) and ILAs. We retrospectively evaluated patients with ILAs-complicated NSCLC who received ICI therapy. ILAs were subcategorized as non-subpleural, subpleural non-fibrotic, and subpleural fibrotic (SF) based on the 2020 position paper by the Fleischner Society. We investigated ICI-P incidence, ICI-P risk factors, lung cancer prognosis, and ILAs radiological progression. Of the 481 ICI-treated patients, 79 (16.4%) had ILAs (45 non-SF and 34 SF). The ICI-P cumulative incidence (hazard ratio, 4.57; 95% confidence interval [CI], 1.90-10.98; p = 0.001) and any grade and grade ≥ 3 ICI-P incidences were higher in patients with SF-ILAs than in those with non-SF-ILAs (all grades: 7/45 [15.6%)] vs. 18/34 [52.9%]; p < 0.001; grade ≥ 3: 1/45 [2.2%] vs. 10/34 [29.4%]; p = 0.001). According to multivariate analysis, SF-ILAs independently predicted ICI-P (odds ratio, 5.35; 95% CI 1.62-17.61; p = 0.006). Patients with SF-ILAs had shorter progression-free and overall survival and higher ICI-P-related respiratory failure death rates than those with non-SF-ILAs. Approximately 2.5 times more patients with SF-ILAs showed progression by the 2-year follow-up than those with non-SF-ILAs. SF-ILAs is an independent strong predictor of ICI-P development in patients with NSCLC, may increase ICI-P severity, worsen prognosis, and accelerate ILAs progression. ILAs subcategorization is an important treatment strategy for patients with lung cancer treated with ICIs.
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Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Masculino , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Anciano de 80 o más Años , Resultado del Tratamiento , AdultoAsunto(s)
Enfermedades Pulmonares Intersticiales , Ácido Micofenólico , Rituximab , Humanos , Ácido Micofenólico/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Rituximab/uso terapéutico , Femenino , Estudios de Seguimiento , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Inmunosupresores/uso terapéuticoRESUMEN
OBJECTIVE: To develop a multivariable model for predicting the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) over 52 weeks. METHODS: We used logistic regression models to analyse associations between candidate predictors assessed at baseline and progression of SSc-ILD (absolute decline in forced vital capacity (FVC) % predicted >5% or death) over 52 weeks in the placebo group of the SENSCIS trial. Analyses were performed in the overall placebo group and in a subgroup with early and/or inflammatory SSc and/or severe skin fibrosis (<18 months since first non-Raynaud symptom, elevated inflammatory markers, and/or modified Rodnan skin score (mRSS) >18) at baseline. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: In the overall placebo group (n=288), the performance of the final multivariable model for predicting SSc-ILD progression was moderate (apparent AUC: 0.63). A stronger model, with an apparent AUC of 0.75, was developed in the subgroup with early and/or inflammatory SSc and/or severe skin fibrosis at baseline (n=155). This model included diffusing capacity of the lung for carbon monoxide (DLco) % predicted, time since first non-Raynaud symptom, mRSS, anti-topoisomerase I antibody status and mycophenolate use. CONCLUSION: Prediction of the progression of SSc-ILD may require different approaches in distinct subgroups of patients. Among patients with SSc-ILD and early and/or inflammatory SSc and/or severe skin fibrosis, a nomogram based on a multivariable model may be of value for identifying patients at risk of short-term progression.
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Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/complicaciones , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Adulto , Curva ROC , Pronóstico , Capacidad Vital , Biomarcadores , Modelos LogísticosRESUMEN
BACKGROUND/AIMS: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. RESULTS: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. CONCLUSION: Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.
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Abatacept , Antirreumáticos , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Humanos , Abatacept/uso terapéutico , Abatacept/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/diagnóstico , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Anciano , Resultado del Tratamiento , Progresión de la Enfermedad , Factores de Tiempo , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Factores de Riesgo , Adulto , República de Corea , Tomografía Computarizada por Rayos XRESUMEN
In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.
What did we find out from the INBUILD trial about progressive lung fibrosis?Lung fibrosis is a rare disease in which the lung tissue becomes scarred and hardened. This makes it more difficult for the lungs to inflate and for the lungs to exchange oxygen with the blood. In some patients, lung fibrosis gets worse over time. This is known as progressive lung fibrosis. In the INBUILD trial, researchers looked at the effects of a drug called nintedanib in patients with progressive lung fibrosis. In this trial, 663 patients were randomly allocated to receive either nintedanib or a placebo and then followed for approximately 19 months. The patients and the researchers did not know which patients were taking the active drug (nintedanib) and which patients were taking placebo. The results showed that the criteria used to find patients with progressive lung fibrosis to take part in the trial successfully identified patients whose disease would continue to worsen. These criteria were based on a decline in the volume (size) of the lungs, worsening symptoms such as shortness of breath, and worsening of changes seen on a scan of the chest. The trial results also showed that nintedanib slowed down loss of lung function and had a similar benefit in patients with different severities of disease at the start of the trial. The most common side-effects of nintedanib were gastrointestinal problems, particularly diarrhea, but most patients given nintedanib were able to cope with these side-effects without needing to stop treatment. Large trials like the INBUILD trial are important for helping us understand how diseases progress and in which patients particular drugs should be used.
Asunto(s)
Progresión de la Enfermedad , Indoles , Fibrosis Pulmonar , Tomografía Computarizada por Rayos X , Humanos , Indoles/efectos adversos , Indoles/uso terapéutico , Indoles/administración & dosificación , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/fisiopatología , Capacidad Vital , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/diagnóstico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/fisiopatología , Fibrosis Pulmonar Idiopática/diagnóstico , Masculino , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificaciónRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) infection is currently widespread throughout the world. Bismuth-containing quadruple therapy is widely used, but it has rarely been associated with interstitial lung disease. CASE PRESENTATION: We described six cases with similar clinical symptoms and typical pulmonary interstitial imaging changes during anti-H. pylori therapy, usually on Days 7-12 following treatment. Anti-H. pylori infection treatment was discontinued when it was suspected to be the cause of the clinical symptoms, and all of the patients accepted observation therapy. All of them had a favorable outcome, the clinical symptoms returned to normal almost 1 week later, and the chest computed tomography (CT) scan images showed remarkable absorption 4 weeks later. CONCLUSIONS: Drug interactions could be the cause, and the most likely drug was furazolidone. All of the patients recovered quickly after drug discontinuation, and low-dose steroid may help shorten the recovery time.
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Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Tomografía Computarizada por Rayos X , Adulto , Femenino , Humanos , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Quimioterapia Combinada , Furazolidona/uso terapéutico , Furazolidona/efectos adversos , Furazolidona/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Tomografía Computarizada por Rayos X/métodosRESUMEN
Rheumatoid arthritis is a chronic inflammatory disease, and interstitial lung disease is one of the important extra-articular manifestations. There is limited evidence comparing abatacept (ABA) and tumor necrosis factor inhibitors (TNFi) regarding the risk of mortality among patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD). The aim of this study is to investigate the risk of mortality in patients with RA-ILD treated with ABA compared to TNFi. This retrospective cohort study utilized TriNetX electronic health record database. We enrolled patients who were diagnosed with RA-ILD and had received a new prescription for either ABA or TNFi. Patients were categorized into two cohorts based on their initial prescription. The primary outcome was all-cause mortality, and secondary outcomes were healthcare utilizations, including hospitalization, critical care services, and mechanical ventilation. Subgroup analyses were performed on age, presence of anti-citrullinated peptide antibodies (ACPA), and cardiovascular risk. Among 34,388 RA-ILD patients, 895 were selected for each group (ABA and TNFi) following propensity score matching. The ABA group exhibited a higher all-cause mortality risk. (HR 1.296, 95% CI 1.006-1.671). Subgroup analysis showed a heightened risk of receiving mechanical ventilation in ABA-treated patients aged 18-64 years old (HR 1.853, 95% CI 1.002-3.426), and those with cardiovascular risk factors (HR 2.015, 95% CI 1.118-3.630). Another subgroup analysis indicated a higher risk of mortality among ABA-treated patients with positive-ACPA. (HR 4.138 95% CI 1.343-12.75). This real-world data research demonstrated a higher risk of all-cause mortality in RA-ILD patients treated with ABA compared to TNFi, particularly those aged 18-64 years, lacking cardiovascular risk factors, and positive-ACPA. ABA was associated with an increased risk of mechanical ventilation in patients aged 18-64 years and those with cardiovascular risk factors.
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Abatacept , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/mortalidad , Artritis Reumatoide/complicaciones , Abatacept/uso terapéutico , Anciano , Adulto , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Hospitalización/estadística & datos numéricosRESUMEN
Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.
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Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Receptor ErbB-2 , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , China , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Neumonía/tratamiento farmacológico , Femenino , Consenso , Trastuzumab/uso terapéutico , Trastuzumab/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Camptotecina/análogos & derivadosRESUMEN
Randomized controlled trials have recently shown that both the IL-6 inhibitor Tocilizumab and the antifibrotic Nintedanib are efficacious for Systemic Sclerosis (SSc)-associated progressive interstitial lung disease (ILD). Since real-world clinical data on Tocilizumab/Nintedanib combination are lacking, we report on their long-term safety and efficacy. Consecutive patients who received off-label Tocilizumab for SSc plus Nintedanib for progressive ILD were retrospectively studied. Adverse events, and changes in Forced Vital Capacity (FVC), Diffucing Capacity for Carbon Monoxide (DLCO) and high resolution chest tomography (HRCT) between baseline and 6 and 12 months were assessed. Tocilizumab/Nintedanib combination was well tolerated by all 20 patients [aged 52 ± 13 years (mean ± SD), 14 women, 15 diffuse SSc, disease duration of 5.7 ± 4.9 years]; 7 of 20 patients received concomitant mycophenolate mofetil safely. No serious adverse events or laboratory abnormalities were noted. Five patients developed persistent diarrhea and 2 of them reduced dosage of Nintedanib. Baseline FVC (74%±12%) and DLCO (45%±10%) remained overall stable both at 6 months (73.5%±13% and 46%±11%, respectively) and 12 months (73%±14% and 45%±11%, respectively), regardless of disease duration. The extent of fibrotic reticular pattern in available pairs of HRCTs (n = 12) remained also stable at 12 months, whereas proportion (%) of ground glass opacities decreased from 29%±16 to 21%±14% (p = 0.048); improvement in HRCTs by almost 75% was noted in 2 of these12 patients. Tocilizumab/Nintedanib combination for one year was safe and stabilized lung function in real-world SSc patients with progressive ILD. Additional studies of this combination treatment in SSc-ILD are warranted.
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Anticuerpos Monoclonales Humanizados , Quimioterapia Combinada , Indoles , Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Femenino , Persona de Mediana Edad , Indoles/uso terapéutico , Indoles/administración & dosificación , Indoles/efectos adversos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Masculino , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Adulto , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Progresión de la Enfermedad , Capacidad Vital , Pulmón/fisiopatología , Pulmón/efectos de los fármacos , Pulmón/diagnóstico por imagenRESUMEN
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.
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Líquido del Lavado Bronquioalveolar , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades Pulmonares Intersticiales , Humanos , Femenino , Líquido del Lavado Bronquioalveolar/microbiología , Masculino , Persona de Mediana Edad , Anciano , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Estudios Transversales , Estudios Retrospectivos , Inmunosupresores/administración & dosificación , Metagenómica/métodos , Metilprednisolona/administración & dosificación , Progresión de la EnfermedadRESUMEN
RATIONALE: The interstitial pneumonia (IP) linked to vedolizumab (VDZ) in patients with ulcerative colitis (UC) is rare. Prompt diagnosis and treatment can improve patient outcomes. PATIENT CONCERNS: A 39-year-old man with UC who received VDZ as sole therapy developed symptoms such as chest tightness, cough, and suffocation. DIAGNOSES: IP was confirmed through pulmonary function tests, chest computed tomography, and bronchoscopic biopsy. INTERVENTIONS: The patient was given methylprednisolone and VDZ cessation. OUTCOMES: The patient's symptoms improved and remained symptom-free after nearly 2 years. LESSONS: VDZ-induced IP should be considered when evaluating pulmonary infections in UC patients treated with VDZ.
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Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Fármacos Gastrointestinales , Enfermedades Pulmonares Intersticiales , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Masculino , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Metilprednisolona/uso terapéuticoRESUMEN
Anti-synthetase syndrome (ASyS) is an autoimmune disease characterized by the presence of autoantibodies to aminoacyl-tRNA synthetases accompanied with various organ involvements, including the lung, joints, and skin. The ASyS-related interstitial lung disease (ILD) can be seen in the vast majority of patients. The extent of lung involvement has a significant impact on patient prognosis; the occurrence of rapid-progressive ILD could prominently increase mortality. The mainstay of treatment is prednisone in combination with conventional synthetic disease-modifying anti-rheumatic drugs or some biologic disease-modifying anti-rheumatic drugs (DMARDs). Tocilizumab (TCZ), a recombinant humanized anti-interleukin (IL)-6 receptor monoclonal antibody, has also been used to treat some systemic autoimmune rheumatic diseases associated with ILD. Although the most recent American College of Rheumatology (ACR) Guideline for the Treatment of Interstitial Lung Disease conditionally recommends against the use of TCZ as a treatment option for people with idiopathic inflammatory myopathy (IIM)-ILD progression despite initial ILD treatment, the treatment effect of TCZ in ASyS patients remains obscure, particularly for refractory cases with anti-non-Jo1 antibodies. This report describes a case of Chinese ASyS patients with anti-EJ-positive antibodies who presented with typical proximal muscle weakness, elevated creatine kinase, and ILD with non-specific interstitial pneumonia (NSIP) pattern, along with typical skin involvement such as mechanic's hand. The patients were resistant to various treatments, including rituximab (RTX), but benefited from TCZ. In this case, TCZ shows good therapeutic efficacy in a fatal acute exacerbation of ILD with a hyperinflammatory status, resulting in a relative remission of the disease flare and full preservation of lung function with a positive long-term treatment outcome.
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Anticuerpos Monoclonales Humanizados , Enfermedades Pulmonares Intersticiales , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Miositis/tratamiento farmacológico , Persona de Mediana Edad , Autoanticuerpos/sangre , Femenino , MasculinoRESUMEN
PURPOSE OF REVIEW: Idiopathic pulmonary fibrosis (IPF) is the prototype of fibrosing interstitial lung diseases. It is mirrored by progressive pulmonary fibrosis (PPF), an umbrella term which characterizes disease behavior of various fibrotic interstitial lung diseases with irreversible progression, accounting for loss of lung function, exercise intolerance and respiratory failure leading to early mortality. Pirfenidone and nintedanib halve the decline in lung function but do not halt disease progression. RECENT FINDINGS: Since the publication in 2014 of pivotal pirfenidone and nintedanib studies, a number of clinical trials were conducted, many of them did not reach their primary endpoints. In IPF, promising phase 2 trials were followed by large phase 3 trials that did not confirm a favorable efficacy to tolerability favorable profile, including those with ziritaxestat, an autotaxin-1 inhibitor, zinpentraxin-alpha (human recombinant pentraxin-2), and the monoclonal antibody pamrevlumab targeting connective tissue growth factor. Nevertheless, newer compounds that hold promise are currently being evaluated in phase 3 or phase 2b randomized controlled trials, including: nerandomilast, a preferential phosphodiesterase 4B inhibitor; admilparant, a lysophosphatidic acid receptor antagonist; inhaled treprostinil, a prostacyclin agonist; and bexotegrast, a dual-selective inhibitor of αvß6 and αvß1 integrins. Nerandomilast, admilparant, inhaled treprostinil, and inhaled AP01 (pirfenidone), are currently studied in patients with PPF. SUMMARY: Despite recent frustrating negative results, there is a growing portfolio of candidate drugs developed in both IPF and PPF.
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Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Piridonas , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/fisiopatología , Piridonas/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Indoles/uso terapéutico , Progresión de la Enfermedad , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos como AsuntoRESUMEN
Objetivo: Describir los hallazgos imagenológicos en radiografías de tórax y ecografías pulmonares de pacientes con síndrome post-COVID-19. Métodos: estudio descriptivo, prospectivo y transversal que incluyó pacientes con síndrome post-COVID-19, sometidos a radiografías de tórax y ecografías pulmonares en el Servicio de Neumonología Clínica del Hospital Dr. José Ignacio Baldo, entre enero y octubre de 2022, con la finalidad de establecer su evolución imagenológica pulmonar. Se utilizó estadística descriptiva, chi-cuadrado de Pearson y prueba kappa de concordancia, considerando significativo un valor de p < 0,05. Resultados: La muestra consistió en 58 pacientes con una edad media de 55 ± 13 años, predominando el sexo femenino (58,6%). El 60,3% mostró alteraciones en la radiografía de tórax; un 74,3% con patrón intersticial bilateral y un 25,7% con patrón intersticial unilateral. La ecografía reveló patrón intersticial en el 43,1% de los casos y se observaron dos microconsolidaciones subpleurales. Conclusiones: Las radiografías de tórax y las ecografías pulmonares son herramientas imagenológicas eficaces, accesibles y económicas para detectar alteraciones en pacientes con síndrome post-COVID-19. (AU)
Objective: To describe imaging findings in chest radiographs and lung ultrasounds of patients with post-COVID-19 syndrome. Methods: A descriptive, prospective, and cross-sectional study was carried out that included patients with post-COVID-19 syndrome, who underwent chest radiographs and lung ultrasounds at the Clinical Pneumonology Service of Dr. José Ignacio Baldo Hospital, between January and October 2022. Descriptive statistics, Pearson's chi-square, and kappa concordance test were used, considering a p-value < 0.05 significant. Results: The sample consisted of 58 patients with an average age of 55 ± 13 years, with a predominance of females (58.6%). 60.3% showed alterations in the chest radiograph; 74.3% with a bilateral interstitial pattern and 25.7% with a unilateral interstitial pattern. The ultrasound revealed an interstitial pattern in 43.1% of the cases and two subpleural microconsolidations were observed. Conclusions: Chest radiographs and lung ultrasounds are effective, accessible, and economical imaging tools to detect alterations in patients with post-COVID-19 syndrome. (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Radiografía Torácica , COVID-19/diagnóstico , Síndrome Post Agudo de COVID-19/tratamiento farmacológico , Neumonía/patología , Calidad de Vida , Estudios Prospectivos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológicoRESUMEN
BACKGROUND: Interstitial lung disease (ILD) is a common complication of rheumatoid arthritis (RA) that plays a significant role in the morbidity and mortality of individuals with this condition. In clinical settings, Si Miao Wan (SMW), a traditional Chinese medicine, is often utilized for the management of RA, as it is believed to possess properties that aid in reducing inflammation, eliminating excess moisture, and alleviating joint pain. PURPOSE: The primary objective of this investigation was to elucidate the potential mechanism of RA-ILD prevention from the perspective of ferroptosis mediated by SMW. METHODS: UPLC-Q-TOF/MS and network pharmacology were employed to forecast the potential targets of SMW for the early prevention of RA-ILD. Following this, HE staining, metabolomics, and RT-PCR were utilized to investigate the mechanism by which SMW prevents RA-ILD at an early stage. RESULTS: Following six weeks of continuous administration of SMW extract at a dosage of 2.16 g/kg/day, it was observed that SMW exhibited early preventive effects against RA-ILD. Metabolomics analysis revealed seven potential biomarkers linked to the pharmacological efficacy of SMW in the early prevention of RA-ILD. Additionally, network pharmacology analysis suggested that SMW may exert its therapeutic effects on RA-ILD by modulating signaling pathways associated with lipid metabolism, atherosclerosis, TNF, and IL-17. Ultimately, through the integration of metabolomics and network pharmacology analysis, along with subsequent verification, it was determined that the early prevention of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) by Shenmai injection (SMW) is associated with the ferroptosis pathway. CONCLUSION: This research offers preliminary insights into the potential mechanism by which traditional Chinese medicine Shen Mai Wan (SMW) may mitigate the early onset of Rheumatoid Arthritis-Interstitial Lung Disease (RA-ILD) via the process of ferroptosis. Furthermore, it establishes a theoretical framework for the development of innovative SMW-based pharmaceuticals for the management of RA-ILD. The signal proteins implicated in this process are anticipated to emerge as crucial targets for the prevention of RA-ILD.
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Artritis Reumatoide , Medicamentos Herbarios Chinos , Ferroptosis , Enfermedades Pulmonares Intersticiales , Metabolómica , Farmacología en Red , Ferroptosis/efectos de los fármacos , Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Animales , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/prevención & control , Masculino , Biomarcadores , Medicina Tradicional China , RatonesRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH)-specific therapies are generally ineffective in patients with pulmonary hypertension associated with lung disease (PH-LD). The aim of this preliminary study was to evaluate the potential efficacy of selexipag, titrated according to individual tolerance, in patients with PH-LD. METHODS: Consecutive patients diagnosed with PH-LD between October 2016 and March 2019, who received selexipag treatment, were retrospectively evaluated. Specific parameters, including changes in hemodynamic parameters, 6-min walk distance (6MWD), and partial pressure of atrial oxygen/fraction of inspiratory oxygen (PaO2/FiO2) were evaluated. Patients whose 6MWD improved ≥20 m were defined as responders. RESULTS: Eight patients with PH-LD were included, comprising four with chronic obstructive pulmonary disease (COPD), two with interstitial lung disease (ILD) related to rheumatoid arthritis, one with ILD related to systemic sclerosis, and one with pulmonary Langerhans cell histiocytosis. No statistically significant improvements in hemodynamic parameters and 6MWD were noted following selexipag treatment. However, four patients showed improvements in 6MWD ≥20 m at follow-up and were considered responders. They had a higher body mass index (BMI) and lower PaO2/FiO2 at baseline than non-responders (p = 0.02 and p = 0.04, respectively). No Grade 3 or 4 adverse events were observed. CONCLUSIONS: Selexipag was effective in half of the PH-LD cases, emphasizing higher BMI and lower PaO2/FiO2 as possible indicators for favorable response. Since selexipag starting at a low dose with subsequent titration may reduce the risk of early adverse events, it can be considered a treatment option for PH-LD. Further large-scale studies are warranted to confirm these findings.
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Acetamidas , Hipertensión Pulmonar , Pirazinas , Humanos , Masculino , Femenino , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Anciano , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos , Acetamidas/administración & dosificación , Resultado del Tratamiento , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/tratamiento farmacológico , Prueba de Paso , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/complicacionesRESUMEN
Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed 2 distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug-related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing patients with ILD, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a noninvasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes.
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Indoles , Proteómica , Fibrosis Pulmonar , Animales , Indoles/uso terapéutico , Indoles/farmacología , Ratones , Humanos , Proteómica/métodos , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/patología , Antifibróticos/farmacología , Antifibróticos/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Masculino , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/metabolismo , Matriz Extracelular/metabolismoRESUMEN
BACKGROUND: Immunosuppressants, biologic agents, antifibrotic drugs, and other drugs can be used to treat autoimmune disease-associated interstitial lung disease (ILD), but the preferred treatment is uncertain. We aimed to evaluate the efficacy and safety of multiple drugs in the treatment of autoimmune disease-associated ILD. METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to July 2023. Primary outcomes were percentage of predicted forced vital capacity (FVC% predicted) and discontinuations for adverse events (AEs). We estimated summary mean differences (MDs) and odds ratios (ORs) using network meta-analysis with fixed effects. RESULTS: The analysis is based on 15 RCTs involving 1832 patients. In terms of FVC% predicted, mycophenolate mofetil (MMF) (MD 1.27, 95 % credible interval [CrI] 0.08 to 2.43), cyclophosphamide (1.89, 0.10 to 3.68), rituximab (9.29, 2.79 to 15.80), tocilizumab (6.30, 3.27 to 9.34), nintedanib (1.71, 0.54 to 2.88), pirfenidone (2.03, 0.65 to 3.40) and nintedanib+MMF (2.43, 0.95 to 3.89) were more effective than placebo. Analysis based on a small sample size showed that riociguat also had good therapeutic potential when compared with placebo. By contrast, bosentan and pomalidomide showed no significant difference compared with placebo. Regarding discontinuations for AEs, nintedanib (OR 2.09, 95 %CrI 1.20 to 3.73) and pirfenidone (3.46, 1.31 to 10.56) were associated with higher dropout rates than placebo, and the combination therapy of nintedanib+MMF did not increase the risk of AEs compared with nintedanib monotherapy. CONCLUSIONS: MMF, cyclophosphamide, rituximab, tocilizumab, nintedanib and pirfenidone are effective in the treatment of autoimmune disease-associated ILD. The efficacy of riociguat and the superiority of combination therapy need to be demonstrated in more RCTs. The tolerance of nintedanib and pirfenidone is a concern, but most of their AEs are mild and controllable.
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Enfermedades Autoinmunes , Inmunosupresores , Enfermedades Pulmonares Intersticiales , Metaanálisis en Red , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Piridonas/uso terapéutico , Piridonas/efectos adversos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Resultado del Tratamiento , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Ácido Micofenólico/uso terapéutico , Indoles/uso terapéutico , Indoles/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Evidence on abatacept (ABA) utility for rheumatoid arthritis (RA) - associated interstitial lung disease (ILD) is growing. Clinical trials have shown equivalence in subcutaneous (SC) and intravenous (IV) administration of ABA for articular manifestations. However, this has not been studied in respiratory outcomes. OBJECTIVE: To compare the effectiveness of ABA in RA-ILD patients according to the route of administration. METHODS: National retrospective multicentre study of RA-ILD patients on treatment with ABA. They were divided into 2 groups: a) IV, and b) SC. The following outcomes were analysed from baseline to final follow-up using linear mixed models: a) forced vital capacity (FVC), b) diffusing capacity of the lungs for carbon monoxide (DLCO), c) chest high resolution computed tomography (HRCT), d) dyspnoea, e) RA activity, and f) sparing corticosteroids effect. RESULTS: A total of 397 patients were included (94 IV-ABA and 303 SC-ABA), median follow-up of 24 [10-48] months. After adjustment for possible confounders, FVC and DLCO remained stable during the first 24 months without differences between IV-ABA and SC-ABA (p = 0.6304 and 0.5337). Improvement/ stability of lung lesions in HRCT was observed in 67 % of patients (75 % IV-ABA, 64 % SC-ABA; p = 0.07). Dyspnoea stabilized/ improved in 84 % of patients (90 % IV-ABA, 82 % SC-ABA; p = 0.09). RA - disease activity improved in both groups. No statistically significant differences regarding any of the variables studied between the two groups were found. ABA was withdrawn in 87 patients (21.9 %), 45 % IV-ABA and 37 % SC-ABA (p = 0.29). ILD worsening and articular inefficacy were the most common reasons for ABA discontinuation. CONCLUSION: In patients with RA-ILD, ABA seems to be equally effective regardless of the route of administration.