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BACKGROUND: Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP. METHODS: This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis. RESULTS: In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters. INTERPRETATION: These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.
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Neumonías Intersticiales Idiopáticas , Enfermedades Pulmonares Intersticiales , Femenino , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Benralizumab is a promising drug for severe uncontrolled asthma. This study aimed to clarify the effectiveness of benralizumab in a real-life setting. METHODS: Subjects included 24 patients with severe type 2 asthma who received benralizumab between April 2018 and July 2019. Changes in parameters, exacerbation frequency, and oral corticosteroid (OCS) use after 4 and 24 weeks of administration were examined. The parameters included the Global Evaluation of Treatment Effectiveness (GETE) scale, Asthma Control Questionnaire (ACQ), Asthma Control Test (ACT), blood eosinophils, fractional exhaled nitric oxide (FeNO), and spirometry. The response to treatment was defined as follows: for patients with exacerbations or OCS use before treatment initiation, a reduction of ≥50% in exacerbation frequency or OCS use; and for patients without exacerbations or OCS use, an improvement of ≥0.5 in ACQ scores and ≥3 in ACT scores, or of ≥10.38% in FEV1. RESULTS: Twenty-one patients completed the treatment for 24 weeks. Excellent and good GETE scales and ACQ and ACT improvement were found in 67% of the patients at 4 weeks, and the effect continued until 24 weeks. The patients' rate with exacerbations was significantly reduced compared to the previous 24 weeks before administration. In 17 patients receiving OCS, the use could be reduced or quit in 14 patients. Overall, 16 patients (76.2%) met the responder definition and could be predicted by the baseline eosinophil count and FeNO levels with the best cutoff values of 100/µL and 40 ppb, respectively. CONCLUSIONS: Blood eosinophil and FeNO could predict benralizumab effectiveness.
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Antiasmáticos , Asma , Corticoesteroides/uso terapéutico , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Asma/inducido químicamente , Asma/tratamiento farmacológico , Progresión de la Enfermedad , Eosinófilos , Humanos , Recuento de LeucocitosRESUMEN
BACKGROUND AND OBJECTIVE: The efficacy of combination therapy with corticosteroids and CNI, TAC and CsA, for PM/DM-ILD has been described retrospectively. However, it remains unknown which CNI treatment regimens, TAC or CsA regimens, are more effective as initial treatments for patients with PM/DM-ILD. METHODS: We conducted a prospective multicentre, open-label, randomized, 52-week phase 2 trial. Patients with PM/DM-ILD were randomly allocated to receive PSL plus TAC (TAC group) or PSL plus CsA (CsA group). The primary endpoint was PFS rate in the intention-to-treat population at 52 weeks. The secondary endpoints were OS rate at 52 weeks, changes in pulmonary function tests from baseline to 52 weeks and AE. RESULTS: Fifty-eight patients were randomly assigned to the TAC group (n = 30) and the CsA group (n = 28). The PFS rates at 52 weeks were 87% in the TAC group and 71% in the CsA group (P = 0.16). The OS rates at 52 weeks were 97% in the TAC group and 93% in the CsA group (P = 0.50). The %FVC at 52 weeks in the per-protocol populations significantly increased in both groups. None of the patients discontinued the treatment due to AE. CONCLUSION: PSL plus TAC treatment may achieve a better short-term PFS rate compared with PSL plus CsA treatment. Further studies must be conducted to evaluate the long-term efficacy and safety of such treatment.
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Dermatomiositis , Enfermedades Pulmonares Intersticiales , Ciclosporina/uso terapéutico , Dermatomiositis/complicaciones , Dermatomiositis/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Prednisolona/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Tacrolimus/uso terapéuticoRESUMEN
BACKGROUND: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial. METHODS: To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case-control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department. RESULTS: There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12). CONCLUSION: This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.
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Vacunas Neumococicas/inmunología , Neumonía Neumocócica/prevención & control , Trastornos Respiratorios/complicaciones , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Vacunas Neumococicas/administración & dosificación , Neumonía Neumocócica/epidemiología , Vacunación , Potencia de la VacunaRESUMEN
BACKGROUND: Lung fibrosis is a serious life-threatening condition whose manifestation varies according to the localization and characteristics of fibroblasts, which are considered heterogeneous. Therefore, to better understand the pathology and improve diagnosis and treatment of this disease, it is necessary to elucidate the nature of this heterogeneity and identify markers for the accurate classification of human lung fibroblast subtypes. METHODS: We characterized distinct mouse lung fibroblast subpopulations isolated by fluorescence-activated cell sorting (FACS) and performed microarray analysis to identify molecular markers that could be useful for human lung fibroblast classification. Based on the expression of these markers, we evaluated the fibroblast-like cell subtype localization in normal human lung samples and lung samples from patients with idiopathic pulmonary fibrosis (IPF). RESULTS: Mouse lung fibroblasts were classified into Sca-1high fibroblasts and Sca-1low fibroblasts by in vitro biological analyses. Through microarray analysis, we demonstrated CD248 and integrin alpha-8 (ITGA8) as cell surface markers for Sca-1high fibroblasts and Sca-1low fibroblasts, respectively. In mouse lungs, Sca-1high fibroblasts and Sca-1low fibroblasts were localized in the collagen fiber-rich connective tissue and elastic fiber-rich connective tissue, respectively. In normal human lungs and IPF lungs, two corresponding major fibroblast-like cell subtypes were identified: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. CONCLUSION: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells were localized in an almost exclusive manner in human lung specimens. This human lung fibroblast classification using two cell surface markers may be helpful for further detailed investigations of the functions of lung fibroblast subtypes, which can provide new insights into lung development and the pathological processes underlying fibrotic lung diseases.
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Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Fibroblastos/metabolismo , Fibrosis Pulmonar Idiopática/patología , Cadenas alfa de Integrinas/metabolismo , Pulmón/citología , Anciano , Animales , Antígenos Ly/metabolismo , Tejido Conectivo/patología , Células del Tejido Conectivo , Tejido Elástico , Fibroblastos/clasificación , Citometría de Flujo , Humanos , Técnicas In Vitro , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Persona de Mediana Edad , Análisis de Matrices TisularesRESUMEN
The usefulness of the oscillometry, known as forced oscillation technique, for predicting exercise tolerance in subjects with COPD is unknown. To test the hypothesis, we investigated whether oscillometry could predict a 6-minute walking distance (6MWD) <350 m in the 6-minute walk test (6MWT).This was a prospective, observational study. Fifty-seven subjects with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between April 2015 and April 2016 (54 males; median age, 70 years; and %FEV1, 61.0%). Modified MRC dyspnea scale (mMRC), COPD Assessment Test (CAT), oscillometry, spirometry, and 6MWT were performed in a stable condition. The participants were classified into subjects with 6MWD ≥350 m or 6MWD <350 m, and the predictor of 6MWD <350 m was assessed.Of the 57 total subjects, 43 (75.4%) had a 6MWD ≥350 m, and 14 (24.6%) had a 6MWD <350 m. Between the two groups, there were significant differences in mMRC scale, GOLD stages, CAT scores, FEV1, IC, 6MWD, lowest SpO2, maximum Borg scale, respiratory resistance (Rrs), and reactance (Xrs). In multivariate regression analysis, a 6MWD <350 m was independently predicted by CAT scores (OR 1.15, 95% CI: 1.01-1.30) and inspiratory R5 (OR 6.01, 95% CI: 1.09-33.30). In receiver operating characteristic curves, the area under the curve was 0.76, 0.78, and 0.85 for CAT scores, R5, and CAT scores + R5, respectively, with the best cutoff value of 17 and 2.82 cmH20/L/s. In conclusion, the oscillatory parameter, inspiratory R5, predicted low exercise tolerance in COPD subjects.
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Tolerancia al Ejercicio/fisiología , Oscilometría , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Espirometría , Prueba de PasoAsunto(s)
Asma , Interleucina-5 , Humanos , Asma/tratamiento farmacológico , Interleucina-5/antagonistas & inhibidores , Interleucina-5/inmunología , Femenino , Antiasmáticos/uso terapéutico , Subunidad alfa del Receptor de Interleucina-5/antagonistas & inhibidores , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Adulto , Inducción de RemisiónAsunto(s)
Asma , Óxido Nítrico , Asma/diagnóstico , Pruebas Respiratorias , Espiración , Humanos , OscilometríaRESUMEN
BACKGROUND: Combination therapy with an inhaled corticosteroid (ICS) and a long-acting ß2-agonist (LABA) in a single inhaler is the mainstay of asthma management. We previously showed that switching from salmeterol/fluticasone combination (SFC) 50/250 µg bid to a fixed-dose formoterol/budesonide combination (FBC) 9/320 µg bid improved asthma control and pulmonary functions, but not fractional exhaled nitric oxide (FeNO), in patients with asthma not adequately controlled under the former treatment regimen. OBJECTIVE: To assess whether switching from SFC to FBC improves peripheral airway/alveolar inflammation in asthma (UMIN000009619). METHODS: Subjects included 66 patients with mild to moderate asthma receiving SFC 50/250 µg bid for more than 8 weeks. Patients were randomized into FBC 9/320 µg bid or continued the same dose of SFC for 12 weeks. Asthma Control Questionnaire, 5-item version (ACQ5) score, peak expiratory flow, spirometry, FeNO, alveolar NO concentration (CANO), and maximal NO flux in the conductive airways (J'awNO) were measured. RESULTS: Sixty-one patients completed the study. The proportion of patients with an improvement in ACQ5 was significantly higher in the FBC group than in the SFC group (51.6% vs 16.7%, respectively, p = 0.003). A significant decrease in CANO was observed in the FBC group (from 8.8 ± 9.2 ppb to 4.0 ± 2.6 ppb; p = 0.007) compared to the SFC group (from 7.4 ± 7.8 ppb to 6.4 ± 5.0 ppb; p = 0.266) although there was no significant difference in the changes in pulmonary functions between the 2 groups. Similar significant differences were found in the CANO corrected for the axial back diffusion of NO (FBC, from 6.5 ± 8.2 ppb to 2.3 ± 2.5 ppb; and SFC, from 4.3 ± 5.3 ppb to 3.9 ± 4.3 ppb). There was no difference in the changes in FeNO or J'awNO between the 2 groups. CONCLUSIONS: Switching therapy from SFC to FBC improves asthma control and peripheral airway/alveolar inflammation even though there is no improvement in pulmonary functions, and FeNO in asthmatic patients.
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Albuterol/análogos & derivados , Androstadienos/uso terapéutico , Asma/tratamiento farmacológico , Budesonida/uso terapéutico , Etanolaminas/farmacología , Administración por Inhalación , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Adulto , Anciano , Albuterol/administración & dosificación , Albuterol/uso terapéutico , Androstadienos/administración & dosificación , Asma/fisiopatología , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Budesonida/administración & dosificación , Combinación de Medicamentos , Etanolaminas/administración & dosificación , Femenino , Combinación Fluticasona-Salmeterol , Fumarato de Formoterol , Humanos , Inflamación/tratamiento farmacológico , Inflamación/patología , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Estudios Prospectivos , Alveolos Pulmonares/patología , Índice de Severidad de la Enfermedad , Espirometría , Encuestas y Cuestionarios , Resultado del TratamientoAsunto(s)
Corticoesteroides/uso terapéutico , Agonistas Adrenérgicos beta/uso terapéutico , Tos/diagnóstico , Tos/tratamiento farmacológico , Hipersensibilidad Respiratoria/diagnóstico , Hipersensibilidad Respiratoria/tratamiento farmacológico , Administración por Inhalación , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Tos/metabolismo , Tos/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/fisiopatología , Espirometría , Adulto JovenRESUMEN
Cite this article as: Okawa K, Shirai T, Akamatsu T, Hirai K. Comparison of 2005 and 2021 American Thoracic Society/European Respiratory Society criteria for bronchodilator response. Thorac Res Pract. 2024;25(4):168-170.
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Introduction: Solid organ malignancies rarely metastasize to the duodenal papilla. We describe a case of primary lung cancer with duodenal papillary metastasis in a patient who presented with melena. To the best of our knowledge, this is only the second report of duodenal papillary metastasis from lung cancer. Case Presentation: A 65-year-old woman presented with complaints of anorexia, weight loss, and black stool. Imaging studies led to a clinical diagnosis of stage IVB lung cancer, and anticoagulants were initiated to treat pulmonary artery thrombosis. However, endoscopic hemostasis was challenging because of bleeding from a duodenal papillary tumor. Fortunately, the patient was positive for the plasma epidermal growth factor receptor (EGFR) gene mutation, and osimertinib, an EGFR tyrosine kinase inhibitor, was administered, successfully achieving hemostasis. Subsequently, endoscopic ultrasonography-guided transbronchial needle aspiration of an enlarged mediastinal lymph node and duodenal papillary tumor biopsy confirmed duodenal papillary metastasis of the primary lung adenocarcinoma. Conclusion: Although duodenal papillary metastasis is extremely rare, a good clinical outcome was achieved in this case by considering duodenal papillary metastasis from lung cancer as the differential diagnosis and administering systemic osimertinib therapy.
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OBJECTIVE: Interferon-λ3 (IFNλ3) is a cytokine with antiviral functions on barrier surfaces, and it is associated with disease activity in autoimmune diseases. This study assessed the clinical significance of serum IFNλ3 levels in polymyositis/dermatomyositis (PM/DM)-associated interstitial lung disease (ILD). METHODS: We measured serum IFNλ3 levels in 221 patients with PM/DM-ILD (155 in the derivation cohort, 66 in the validation cohort) and 38 controls. We evaluated factors associated with mortality risk among 79 patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM-ILD. RESULTS: Serum IFNλ3 levels at diagnosis were significantly higher in patients with PM/DM-ILD than in healthy controls. Remarkably, serum IFNλ3 levels were specifically increased in patients with anti-MDA5 antibody-positive DM-ILD in both the derivation and validation cohorts. In anti-MDA5 antibody-positive DM-ILD, patients with high IFNλ3 levels (>120 pg/mL) had significantly lower survival rates than those with low IFNλ3 levels (≤120 pg/mL). A multivariate analysis revealed that high IFNλ3 levels, as well as old age and low Pao2, were significantly associated with poor prognoses in patients with anti-MDA5 antibody-positive DM-ILD. In a classification analysis of patients with anti-MDA5 antibody-positive DM-ILD based on age, IFNλ3 level, and Pao2, patients with old age (>53 years), high IFNλ3 levels (>120 pg/mL), and low Pao2 (<75 mm Hg) had the worst survival. In lung pathologic analyses, IFNλ3-positive staining was observed in macrophages, airway epithelial cells, the pleural region, and intrapulmonary veins in patients with anti-MDA5 antibody-positive DM-ILD. CONCLUSION: Serum IFNλ3 is a promising biomarker for identifying patients at high risk of poor outcomes in anti-MDA5 antibody-positive DM-ILD.
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Autoanticuerpos , Dermatomiositis , Interferón lambda , Helicasa Inducida por Interferón IFIH1 , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/inmunología , Dermatomiositis/inmunología , Dermatomiositis/complicaciones , Dermatomiositis/sangre , Masculino , Femenino , Persona de Mediana Edad , Helicasa Inducida por Interferón IFIH1/inmunología , Pronóstico , Anciano , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Interferones , Adulto , Interleucinas/sangre , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Patients with idiopathic interstitial pneumonia (IIP) have a favourable prognosis when they have interstitial pneumonia with autoimmune features (IPAF). However, precise IPAF-related findings from high-resolution computed tomography (HRCT) and lung histopathological specimens and the treatment response have not been fully determined. Therefore, this study was conducted to evaluate the relationship between findings on HRCT or lung histopathological specimens and the progression of interstitial pneumonia in patients with IPAF. METHODS: This multicentre cohort study prospectively enrolled consecutive patients with IIP. At the diagnosis of IIP, we systematically evaluated 74 features suggestive of connective tissue diseases and followed them up. HRCT, lung specimens, serum antibodies, and the clinical course were also evaluated. RESULTS: Among 222 patients with IIP, 26 (11.7%) fulfilled the IPAF criteria. During a median observation period of 36 months, patients with IPAF showed better survival than those without IPAF (p = 0.034). While histopathological findings were not related to IPAF, nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap was the most prevalent HRCT pattern (p < 0.001) and the consolidation opacity was the most common radiological finding in IPAF (p = 0.017). Furthermore, in patients with IPAF, the diagnosis of COP or NSIP with OP overlap was associated with a higher increase in %FVC in 1 year than in those with idiopathic pulmonary fibrosis, NSIP, or unclassifiable IIP (p = 0.002). CONCLUSIONS: This study shows the presence of consolidation opacity on HRCT and the diagnosis of COP or NSIP with OP overlap are associated with IPAF and its favourable treatment response in patients with IPAF.
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Enfermedades Autoinmunes , Enfermedades del Tejido Conjuntivo , Neumonías Intersticiales Idiopáticas , Enfermedades Pulmonares Intersticiales , Humanos , Estudios de Cohortes , Estudios Prospectivos , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico por imagen , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/diagnóstico , Neumonías Intersticiales Idiopáticas/diagnóstico , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico por imagenRESUMEN
BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.