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While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322.
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Asma , Fibrosis Pulmonar Idiopática , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Pronóstico , Estudios Prospectivos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/terapia , Oxígeno/uso terapéuticoRESUMEN
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
Stimulator of interferon genes (STING) is a DNA sensor that responds to pathogens and induces type I interferon production. Herein, the role of STING in house dust mite extract (HDM)-induced allergic asthma was investigated. C57BL/6 wild-type (WT) and Sting-/- mice were intratracheally sensitized with HDM, and the bronchoalveolar lavage fluid (BALF), sera, lungs, and mediastinal lymph nodes (MLNs) were analyzed. The total and HDM-specific serum IgE levels were lower in Sting-/- mice than in WT mice. B cell and IgE-positive B cell proportion in BALF and MLNs, respectively, was significantly lower in Sting-/- mice than in WT mice. Additionally, cyclic GMP-AMP, a STING ligand, augmented total and HDM-specific serum IgE levels and B cell proportion in BALF when applied in combination with HDM. To elucidate the role of STING in IgE production, follicular helper T (Tfh) cells, which are involved in B cell maturation, were investigated. Tfh cell proportion in MLNs decreased in Sting-/- mice, and IL-4 and IL-13 production by HDM-restimulated MLN cells from HDM-sensitized mice was decreased in Sting-/- mice compared with WT mice. Thus, STING plays an important role in the maturation and class switching of IgE-producing B cells in allergic inflammation via Tfh cells.
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Alérgenos/inmunología , Asma/genética , Inmunoglobulina E/biosíntesis , Proteínas de la Membrana/fisiología , Extractos de Tejidos/inmunología , Animales , Asma/etiología , Asma/inmunología , Linfocitos B/inmunología , Líquido del Lavado Bronquioalveolar/citología , Femenino , Cambio de Clase de Inmunoglobulina , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Interleucina-13/biosíntesis , Interleucina-13/genética , Interleucina-4/biosíntesis , Interleucina-4/genética , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Nucleótidos Cíclicos/farmacología , Pyroglyphidae , Reacción en Cadena en Tiempo Real de la Polimerasa , Células T Auxiliares Foliculares/inmunologíaRESUMEN
IL-17A and IL-17F are both involved in the pathogenesis of neutrophilic inflammation observed in COPD and severe asthma. To explore this, mice deficient in both Il17a and Il17f and wild type (WT) mice were exposed to cigarette smoke or environmental air for 5 to 28 days and changes in inflammatory cells in bronchoalveolar lavage (BAL) fluid were determined. We also measured the mRNA expression of keratinocyte derived chemokine (Kc), macrophage inflammatory protein-2 (Mip2), granulocyte-macrophage colony stimulating factor (Gmcsf) and matrix metalloproteinase-9 (Mmp9 ) in lung tissue after 8 days, and lung morphometric changes after 24 weeks of exposure to cigarette smoke compared to air-exposed control animals. Macrophage counts in BAL fluid initially peaked at day 8 and again on day 28, while neutrophil counts peaked between day 8 and 12 in WT mice. Mice dual deficient with Il17a and 1l17f showed similar kinetics with macrophages and neutrophils, but cell numbers at day 8 and mRNA expression of Kc, Gmcsf and Mmp9 were significantly reduced. Furthermore, airspaces in WT mice became larger after cigarette smoke exposure for 24 weeks, whereas this was not seen dual Il17a and 1l17f deficient mice. Combined Il17a and Il17f deficiency resulted in significant attenuation of neutrophilic inflammatory response and protection against structural lung changes after long term cigarette smoke exposure compared with WT mice. Dual IL-17A/F signalling plays an important role in pro-inflammatory responses associated with histological changes induced by cigarette smoke exposure.
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Fumar Cigarrillos , Regulación de la Expresión Génica/inmunología , Interleucina-17/deficiencia , Pulmón/inmunología , Enfermedad Pulmonar Obstructiva Crónica/prevención & control , Enfermedad Aguda , Animales , Enfermedad Crónica , Fumar Cigarrillos/genética , Fumar Cigarrillos/inmunología , Citocinas/genética , Citocinas/inmunología , Femenino , Interleucina-17/inmunología , Macrófagos/inmunología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Ratones Mutantes , Neutrófilos/inmunología , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/inmunologíaRESUMEN
ABSTRACT: Immune checkpoint inhibitors (ICIs) have emerged as evolutionary treatments for malignant diseases. Although ICIs can cause immune-related adverse events (irAEs) in various organs, precise timing after ICI initiation has been scarcely reported. Elucidating the effects of irAEs, such as time to onset, involvement of major organs, influence on progression-free survival (PFS), and overall survival (OS), are critical issues for physicians. Furthermore, lung-irAE as a whole is not well known.We conducted a retrospective study of 156 patients who were treated with ICIs and compared 82 irAE patients with 74 non-irAE patients.This study clearly demonstrated that the preferred period after induction of ICIs was significantly longer in lung-irAE than in other major organs (skin, digestive tract, and endocrine). The effect of irAEs on PFS and OS was evident PFS in the irAE group (nâ=â82) (median 128âdays, interquartile range [IQR] 62-269âdays, Pâ=â.002) was significantly longer than that in the non-irAE group (nâ=â74) (median 53âdays, IQR 33-151âdays). Similarly, OS was significantly longer in the irAE group (median 578âdays, IQR 274-1027âdays, Pâ=â.007) than in the non-irAE group (median 464âdays, IQR: 209-842âdays). However, this positive effect of irAEs in the lungs was not proportional to the extent of severity.Lung-irAEs can occur at a later phase than non-lung-irAEs and seemed not to prolong OS and PFS. However, further studies are needed to support these findings.
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Inhibidores de Puntos de Control Inmunológico/efectos adversos , Pulmón/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Anciano , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Pulmón/inmunología , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de TiempoRESUMEN
ABSTRACT: Carcinomatous meningitis (CM) is a critical issue for physicians. However, no study has reported a simple and useful diagnostic or predictive marker for CM.This study aimed to elucidate the potential markers for diagnosing CM derived from cerebrospinal fluid (CSF).We retrospectively enrolled 78 lung cancer patients with suspected CM during the clinical course, including 42 CM and 36 non-CM patients. We compared the clinical and CSF findings, including carcinoembryonic antigen (CEA), between CM and non-CM patients, and explored the diagnostic markers for early identification of CM as well as the contributing factors for mortality.On CSF analysis, with cutoff values of CEA ≥5âng/ml, total protein (TP) in CSF ≥45âg/dl, and total cell count (TCC) ≥7âcells/µL, the sensitivity, specificity, and area under the curve (AUC) for CM were 85.7%, 84.6%, and 0.887 (95% CI: 0.758-1.0, Pâ<â.001); 80.5%, 69.4%, and 0.755 (95% CI: 0.646-0.865, Pâ<â.001); and 56.1%, 100%, and 0.817 (95% CI: 0.722-0.912, Pâ<â.001), respectively. TP levels in CSF ≥the patients' age had a sensitivity, specificity, and an AUC of 48.8%, 77.8%, and 0.633 (95% CI: 0.722-0.912, Pâ=â.045) for CM, respectively. Among CM patients, patients with 'TP in CSF (>patients' age)" (nâ=â19, Pâ=â.008) showed significantly shorter 90-day survival probability than the residual patients (nâ=â20). None of the CSF parameters could predict the risk of mortality on Cox regression analysis.The cutoff value of CEA ≥5âng/ml in CSF is a simple and useful method with a high diagnostic value for CM diagnosis, but not a suitable predicting factor for mortality. 'TP in CSF >patients' age" might be a novel factor for assessing short-term mortality.
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Antígeno Carcinoembrionario/líquido cefalorraquídeo , Proteínas del Líquido Cefalorraquídeo/líquido cefalorraquídeo , Neoplasias Pulmonares/patología , Carcinomatosis Meníngea/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/líquido cefalorraquídeo , Estudios de Casos y Controles , Recuento de Células/métodos , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Carcinomatosis Meníngea/líquido cefalorraquídeo , Carcinomatosis Meníngea/mortalidad , Carcinomatosis Meníngea/secundario , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
RATIONALE: Severe eosinophilic asthma is characterized by airway eosinophilia and corticosteroid-resistance, commonly overlapping with type 2 inflammation. It has been reported that chemokine (C-C motif) ligand 5 (CCL5) is involved in the exacerbation of asthma by RNA virus infections. Indeed, treatment with a virus-associated ligand and a T helper type 2 cell (Th2) cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells. We aimed to evaluate the mechanisms underlying CCL5 production in this in vitro model and to assess the potential of Janus kinase 1 (JAK1) as a novel therapeutic target via the use of ruxolitinib. METHODS: We stimulated primary normal human bronchial epithelial (NHBE) cells and BEAS-2B cells with poly(I:C) along with interleukin-13 (IL-13) or IL-4, and assessed CCL5 production. We also evaluated the signals involved in virus- and Th2-cytokine-induced CCL5 production and explored a therapeutic agent that attenuates the CCL5 production. RESULTS: Poly(I:C) stimulated NHBE and BEAS-2B cells to produce CCL5. Poly(I:C) and IL-13 increased CCL5 production. Poly(I:C)-induced CCL5 production occurred via the TLR3-IRF3 and IFNAR/JAK1-phosphoinositide 3-kinase (PI3K) pathways, but not the IFNAR/JAK1-STATs pathway. In addition, IL-13 did not augment poly(I:C)-induced CCL5 production via the canonical IL-13R/IL-4R/JAK1-STAT6 pathway but likely via subsequent TLR3-IRF3-IFNAR/JAK1-PI3K pathways. JAK1 was identified to be a potential therapeutic target for severe eosinophilic asthma. The JAK1/2 inhibitor, ruxolitinib, was demonstrated to more effectively decrease CCL5 production in BEAS-2B cells than fluticasone propionate. CONCLUSION: We have demonstrated that JAK1 is a possible therapeutic target for severe corticosteroid-resistant asthma with airway eosinophilia and persistent Th2-type inflammation, and that ruxolitinib has potential as an alternative pharmacotherapy.
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Asma , Citocinas , Asma/tratamiento farmacológico , Bronquios , Quimiocina CCL5 , Células Epiteliales , Humanos , Nitrilos , Fosfatidilinositol 3-Quinasas , Pirazoles , PirimidinasRESUMEN
BACKGROUND: A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown. METHODS: This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4â mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide (D LCO) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability. RESULTS: 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was -300â mL and -123â mL, respectively (difference -178â mL, 95% CI -324--31 mL; p=0.018). Serial change in D LCO, 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups. CONCLUSIONS: Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.
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Acetilcisteína , Fibrosis Pulmonar Idiopática , Acetilcisteína/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Japón , Piridonas/uso terapéutico , Resultado del Tratamiento , Capacidad VitalRESUMEN
During bronchoscopy, discomfort is mainly caused by an unavoidable cough; however, there are no reports of any predictive factors for strong cough during bronchoscopy identified before the procedure. To clarify the factors underlying the discomfort status and predictive factors for strong cough during bronchoscopy, we prospectively evaluated patients who underwent bronchoscopy at Kyorin University Hospital between March 2018 and July 2019. Before and after bronchoscopy, the enrolled patients answered a questionnaire regarding the procedure. At the same time, bronchoscopists evaluated cough severity using a four-grade cough scale. We evaluated patient characteristics and predictive factors associated with bronchoscopy from the perspective of discomfort and strong cough. A total of 172 patients were ultimately enrolled in this study. On multivariate logistic regression analysis, comparison of the subjective data between the discomfort and comfort groups revealed that factors that were more common in the former group were younger age (OR = 0.96, p = 0.002), less experienced bronchoscopist (OR = 2.08, p = 0.047), and elevation of cough score per 1 point (OR = 1.69, p < 0.001). Furthermore, the predictive factors for strong cough prior to performing bronchoscopy were female sex (OR = 2.57, p = 0.009), EBUS-TBNA (OR = 2.95, p = 0.004), and prolonged examination time of more than 36 min (OR = 2.32, p = 0.022). Regarding patients' discomfort, younger age, less experienced bronchoscopist, and the elevation of cough score per 1 point were important factors for discomfort in bronchoscopy. On the other hand, female sex, EBUS-TBNA, and prolonged examination time were crucial factors for strong cough.
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Broncoscopía/efectos adversos , Tos/etiología , Satisfacción del Paciente/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Broncoscopía/psicología , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Caracteres Sexuales , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
A 39-year-old man was admitted to our university hospital because of diffuse pulmonary infiltrates on chest X-ray. He had been diagnosed with T-acute lymphoblastic leukaemia/lymphoblastic lymphoma three years before and had been treated with chemotherapy and cord blood stem cell transplantation twice. Although he had neither blast cells in the peripheral blood nor leucocytosis, urgent bronchoscopy findings demonstrated blast cells invading both the alveolar spaces/alveolar septa and the vein walls. These pathological findings corresponded to ground-glass opacities and thickening of the interlobular septa on thoracic computed tomography (CT). In acute lymphoblastic leukaemia/lymphoblastic lymphoma patients presenting with infiltrates on thoracic CT, leukaemic pulmonary involvement should be considered in the differential diagnoses, even in the absence of hyperleucocytosis or blast cells in the blood, similar to pulmonary involvement in myeloid leukaemias.
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An 82-year-old man was presented to our hospital due to epigastric and right hypochondrial pain 17 weeks after the initiation of intravenous treatment with nivolumab for recurrent lung adenocarcinoma as multiple lung and sternal metastases. Urgent gastroscopy revealed macroscopic duodenitis such as severe erythema, oedema, black-coloured erosions, and ulcers located throughout the second portion of the duodenum, which was confirmed by abdominal computed tomography as circumferential thickening of the duodenal wall. Those lesions were pathologically considered as non-specific inflammation and spontaneously disappeared within a month, suggesting nivolumab-induced immune-related adverse events.
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BACKGROUND AND OBJECTIVE: Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). However, the clinical significance of the positivity of Aspergillus precipitating antibody (APAb), a serodiagnostic test for pulmonary aspergillosis (PA), at the time of MAC-LD diagnosis is unknown. The objective of this study was to investigate the effects of APAb test results on the clinical outcomes of patients with MAC-LD. METHODS: We retrospectively analyzed patients who were newly diagnosed as having MAC-LD between 2007 and 2014 in our hospital and checked for APAb at the time of diagnosis. RESULTS: We enrolled 131 patients in this study. Of these patients, 20 (15.3%) tested positive for APAb at the diagnosis of MAC-LD. The APAb-positive patients were more frequently male (70.0% vs. 37.8%, P = 0.013) and more frequently had pulmonary emphysema (60.0% vs. 13.5%, P < 0.001) and interstitial pneumonia (15.0% vs. 1.8%, P = 0.025) compared with the APAb-negative patients. During a median follow-up period of 4.0 years, PA developed in 12 of the APAb-positive patients (60.0%, CPA: 9 and allergic bronchopulmonary aspergillosis: 3) and 12 APAb-negative patients (10.8%, CPA: 12) (P < 0.001). The APAb-positive patients had a significantly higher rate of mortality than did the APAb-negative patients (P = 0.004). A multivariate analysis indicated that older age, lower albumin, fibrocavitary or fibrocavitary and nodular/bronchiectatic radiographic features, and APAb positivity were negative prognostic factors. CONCLUSIONS: APAb-positive patients with MAC-LD more frequently develop PA and may have an unfavorable prognosis.
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Anticuerpos Antifúngicos/sangre , Aspergillus/inmunología , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/diagnóstico , Infección por Mycobacterium avium-intracellulare/mortalidad , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/etiología , Pruebas Serológicas/métodos , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/epidemiología , Masculino , Persona de Mediana Edad , Infección por Mycobacterium avium-intracellulare/complicaciones , Infección por Mycobacterium avium-intracellulare/epidemiología , Pronóstico , Aspergilosis Pulmonar/epidemiología , Aspergilosis Pulmonar/mortalidad , Enfisema Pulmonar/epidemiología , Estudios Retrospectivos , Factores SexualesRESUMEN
BACKGROUND: Airway obstruction due to decreased airway diameter and increased incidence of mucus plugs has not been directly observed in asthma exacerbation. We studied the changes in the inner diameter of the airway (Din) and the frequency of mucus plugs by airway generation in patients with asthma exacerbation. We compared these patients to those in a stable phase using high-resolution computed tomography (HRCT). METHODS AND FINDINGS: Thirteen patients with asthma were studied by HRCT during asthma exacerbation and in a stable period. The HRCT study was performed on patients who could safely hold their breath for a short while in a supine position 1 hour after initial treatment for asthma exacerbation. Using a curved multiplanar reconstruction (MPR) software, we reconstructed the longitudinal airway images and the images exactly perpendicular to the airway axis to measure the Din and mucus plugs from the second- (segmental) to sixth-generation bronchi in all segments of the lungs.The ratios of Din (exacerbation/stable) were 0.91(P = 0.016), 0.88 (P = 0.002), 0.83 (P = 0.001), 0.80 (P = 0.001), and 0.87 (NS) in the second-, third-, fourth-, fifth-, and sixth-generation bronchi, respectively. The percentages of airway obstruction due to mucus plugs were notably higher in the fourth- and fifth-generation bronchi (17.9%/18.1% in stable phase and 43.2%/45.9% in the exacerbation phase, respectively) than in the other generations of bronchi. CONCLUSIONS: Among the bronchi examined, the fourth- and fifth-generation bronchi were significantly obstructed during asthma exacerbation compared with the stable phase in terms of a decreased airway diameter and mucus plugs.
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Obstrucción de las Vías Aéreas/etiología , Asma/complicaciones , Bronquios/patología , Moco/metabolismo , Obstrucción de las Vías Aéreas/diagnóstico por imagen , Obstrucción de las Vías Aéreas/patología , Asma/diagnóstico por imagen , Bronquios/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moco/química , Moco/diagnóstico por imagen , Pronóstico , Tomografía Computarizada por Rayos X/métodosRESUMEN
Most patients with liver cysts are asymptomatic and require no treatment. In this patient with symptoms and restrictive ventilatory impairment, percutaneous needle aspiration with injection of minocycline hydrochloride was effective.
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Human respirovirus 3 (HRV3) is a major causative agent of acute respiratory infections in humans. HRV3 can manifest as a recurrent infection, although exactly how is not known. In the present study, we conducted detailed molecular evolutionary analyses of the major antigen-coding hemagglutinin-neuraminidase (HN) gene of this virus detected/isolated in various countries. We performed analyses of time-scaled evolution, similarity, selective pressure, phylodynamics, and conformational epitope prediction by mapping to HN protein models. In this way, we estimated that a common ancestor of the HN gene of HRV3 and bovine respirovirus 3 diverged around 1815 and formed many lineages in the phylogenetic tree. The evolutionary rates of the HN gene were 1.1 × 10-3 substitutions/site/year, although the majority of these substitutions were synonymous. Some positive and many negative selection sites were predicted in the HN protein. Phylodynamic fluctuations of the gene were observed, and these were different in each lineage. Furthermore, most of the predicted B cell epitopes did not correspond to the neutralization-related mouse monoclonal antibody binding sites. The lack of a link between the conformational epitopes and neutralization sites may explain the naturally occurring HRV3 reinfection.
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Evolución Molecular , Proteína HN/genética , Virus de la Parainfluenza 3 Humana/genética , Filogenia , Teorema de Bayes , Biología Computacional , Mapeo Epitopo , Epítopos/genética , Proteína HN/química , Humanos , Cadenas de Markov , Método de MontecarloRESUMEN
A 60-year-old woman with a 20-year history of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis visited our hospital due to productive cough and a low-grade fever for several weeks. Thoracic computed tomography demonstrated scattered tiny nodules, patchy consolidation, ground glass opacities, and thickening interlobular septa. On video-assisted thoracic surgery, those abnormalities were found to correspond to the accumulation of hemosiderin-laden alveolar macrophages (AMs) in the alveolar spaces and alveolar septa due to MPO-ANCA vasculitis. The radiological findings persisted for a further two years, indicating the possibility of persistent vasculitis in the lung or evidence of incomplete clearance of hemosiderin-laden AMs.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico por imagen , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Hemosiderosis/diagnóstico , Hemosiderosis/terapia , Enfermedades Pulmonares/terapia , Peroxidasa/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Femenino , Hemosiderosis/fisiopatología , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/fisiopatología , Persona de Mediana Edad , Radiografía/métodos , Tomografía Computarizada por Rayos X/métodosAsunto(s)
Fístula/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Enfisema Mediastínico/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Enfisema Subcutáneo/diagnóstico por imagen , Pared Torácica/diagnóstico por imagen , Anciano , Diagnóstico Diferencial , Fístula/cirugía , Humanos , Enfermedades Pulmonares/cirugía , Masculino , Pared Torácica/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Background and purpose of the study:Pseudomonas aeruginosa commonly colonizes the airway of patients with chronic obstructive pulmonary disease (COPD) and exacerbates their symptoms. P. aeruginosa carries flagellin that stimulates toll-like receptor (TLR)-5; however, the role of flagellin in the pathogenesis of COPD remains unclear. The aim of the study was to evaluate the mechanisms of the flagellin-induced innate immune response in bronchial epithelial cells, and to assess the effects of anti-inflammatory agents for treatment. Materials and methods: We stimulated BEAS-2B cells with P. aeruginosa-derived flagellin, and assessed mRNA expression and protein secretion of interleukin (IL)-6 and IL-8. We also used mitogen-activated protein kinases (MAPK) inhibitors to assess the signaling pathways involved in flagellin stimulation, and investigated the effect of clinically available anti-inflammatory agents against flagellin-induced inflammation. Results: Flagellin promoted protein and mRNA expression of IL-6 and IL-8 in BEAS-2B cells and induced phosphorylation of p38, ERK, and JNK; p38 phosphorylation-induced IL-6 production, while IL-8 production resulted from p38 and ERK phosphorylation. Fluticasone propionate (FP) and dexamethasone (DEX) suppressed IL-6 and IL-8 production in BEAS-2B cells, but clarithromycin (CAM) failed to do so. Conclusions:P. aeruginosa-derived flagellin-induced IL-6 and IL-8 production in bronchial epithelial cells, which partially explains the mechanisms of progression and exacerbation of COPD. Corticosteroids are the most effective treatment for the suppression of flagellin-induced IL-6 and IL-8 production in the bronchial epithelial cells.
Asunto(s)
Bronquios/inmunología , Células Epiteliales/inmunología , Flagelina/inmunología , Interleucina-6/inmunología , Interleucina-8/inmunología , Pseudomonas aeruginosa/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Antiinflamatorios/farmacología , Bronquios/efectos de los fármacos , Bronquios/microbiología , Línea Celular , Progresión de la Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/microbiología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/microbiología , Fosforilación/efectos de los fármacos , Fosforilación/inmunología , Pseudomonas aeruginosa/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Receptor Toll-Like 5/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/inmunologíaRESUMEN
BACKGROUND: Aspiration pneumonia is a serious problem among elderly patients; it is caused by many risk factors including dysphagia, poor oral hygiene, malnutrition, and sedative medications. The aim of this study was to define a convenient procedure to objectively evaluate the risk of aspiration pneumonia in the clinical setting. METHODS: This prospective study included an aspiration pneumonia (AP) group, a community-acquired pneumonia (CAP) group, and a control (Con) group (patients hospitalized for lung cancer chemotherapy). We used the Oral Health Assessment Tool (OHAT), which assesses oral hygiene, and evaluated performance status, body mass index, serum albumin levels, substance P values in plasma, and oral bacterial counts. RESULTS: The oral health as assessed by the OHAT of the aspiration pneumonia group was significantly impaired compared with that of the CAP group and the control (5.13 ± 0.18, 4.40 ± 0.26, 3.90 ± 0.22, respectively; p < 0.05). The oral bacterial count in the aspiration pneumonia group (7.20 ± 0.11) was significantly higher than that in the CAP group (6.89 ± 0.12), consistent with the OHAT scores. Oral bacterial count was significantly reduced by oral care. CONCLUSIONS: OHAT and oral bacterial counts can be a tool to assess the requirement of taking oral care and other preventive procedures in patients at high risk of aspiration pneumonia.