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STUDY OBJECTIVES: Poor adherence to continuous positive airway pressure (CPAP) has been a critical issue in treating obstructive sleep apnea. Because long-term CPAP adherence may be established shortly after treatment begins, early intervention is essential. This study aimed to identify the potential factors affecting CPAP therapy adherence during diagnostic polysomnography and auto CPAP titration polysomnography. METHODS: This retrospective observational study included 463 patients with obstructive sleep apnea who underwent consecutive diagnostic polysomnography and titration polysomnography. We recorded their demographic, anthropometric, and lifestyle factors and obtained self-reported comments regarding their sleep status following both polysomnography evaluations. CPAP adherence was evaluated following 3 months of treatment. RESULTS: A total of 312 patients (67.4%) fulfilled the criteria for good adherence. Each patient's CPAP adherence was categorized as "poor" (< 4 hours/night or <70% of nights), "good" (≥ 4 hours/night and ≥ 70% of nights), or "excellent" (≥ 6 hours/night and ≥ 80% of nights). There were no significant differences in arterial oxyhemoglobin saturation measured by pulse oximetry and apnea-hypopnea index during diagnostic polysomnography among 3 groups. The polysomnographic evaluations indicated that patients with better adherence displayed more significant improvements in sleep parameters, including apnea-hypopnea index, sleep efficacy, sleep latency, and sleep architecture, which were correlated with an improvement in self-reported sleep quality. CONCLUSIONS: Polysomnographic evaluations enabled CPAP adherence prediction and a comparison of self-reported sleep quality with and without CPAP; CPAP adherence led to improvements in polysomnographic parameters. Our findings suggest that titration polysomnography and self-reported sleep improvement with CPAP could be used for adherence prediction in clinical practice. CITATION: Shirahata T, Uchida Y, Uchida T, et al. Improvement of sleep parameters by titration polysomnography could predict adherence to positive airway pressure therapy in obstructive sleep apnea. J Clin Sleep Med. 2023;19(8):1465-1473.
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Apneia Obstrutiva do Sono , Sono , Humanos , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Pressão Positiva Contínua nas Vias Aéreas , Oximetria , Cooperação do PacienteRESUMO
PURPOSE: Inferior vena cava filter fracture (FF) may cause life-threatening complications, including cardiac tamponade, although the actual prevalence remains unclear. Therefore, we investigated the incidence of FF. MATERIALS AND METHODS: Data on fracture incidence with filter brands, filter positions [suprarenal (SR) vs. infrarenal (IR)], and follow-up durations were collected from the databases of eight hospitals. RESULTS: Of 532 patients, Günther Tulip (GT), Trap/OptEase (TE/OE), ALN and VenaTech (VT) were implanted in 345, 147, 38 and 2 patients, respectively. Of these, filter retrieval was attempted in 110 (21.7%) patients and was successful in 106 (96.4%). Of the remaining 426 patients, FFs were observed in two (0.7%) of 270 GT filters and 19 (14.1%) of 135 TE/OE filters. Fragment embolization occurred in one patient with a GT filter (50.0%) and three with a TE/OE filter (15.8%) with a total follow-up interval of 718.0 ± 1019.4 days. FF occurred more frequently in TE/OE than in GT filters (p < 0.001). Kaplan-Meier estimates showed significantly higher fracture-free rates for GT than TE/OE (p < 0.001) and IR-TE/OE than SR-TE/OE (p < 0.05). CONCLUSIONS: TE/OE filters are not suitable for permanent implantation due to the relatively early and high fracture rates.
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Falha de Prótese , Embolia Pulmonar/terapia , Filtros de Veia Cava , Adulto , Idoso , Idoso de 80 Anos ou mais , Remoção de Dispositivo/efeitos adversos , Desenho de Equipamento , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Veia Cava Inferior/cirurgia , Adulto JovemRESUMO
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP. CASE PRESENTATION: The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage. She tested negative for GM-CSF autoantibodies, with no underlying disease. Her serum GM-CSF level was elevated (91.3 pg/mL), indicating GM-CSF signaling impairment and genetic defects in the GM-CSF receptor. GM-CSF-stimulated phosphorylation in signal transducer and activator of transcription 5 (STAT5) was not observed, and GM-CSF-Rα expression was defective in her blood cells. Genetic screening revealed a homozygous, single-base C > T mutation at nt 508-a nonsense mutation that yields a stop codon (Q170X)-in exon 7 of CSF2RA. High-resolution analysis of single nucleotide polymorphism array confirmed a 22.8-Mb loss of heterozygosity region in Xp22.33p22.11, encompassing the CSF2RA gene. She was successfully treated with whole lung lavage (WLL), which reduced the serum levels of interleukin (IL)-2, IL-5, and IL-17, although IL-3 and M-CSF levels remained high. CONCLUSIONS: This is the first known report of elderly-onset hPAP associated with a CSF2RA mutation, which caused defective GM-CSF-Rα expression and impaired signaling. The analyses of serum cytokine levels during WLL suggested that GM-CSF signaling might be compensated by other signaling pathways, leading to elderly-onset PAP.
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Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Proteinose Alveolar Pulmonar/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Idade de Início , Idoso , Autoanticorpos/sangue , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Humanos , Interleucinas/sangue , Macrófagos Alveolares/imunologia , Mutação , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Radiografia Torácica , Transdução de Sinais , Tomografia Computadorizada por Raios XRESUMO
Cerebral and cerebellar symptoms are frequently associated with Legionnaires' disease. However, corresponding brain lesions are difficult to demonstrate using either computed tomography (CT) or magnetic resonance imaging (MRI). We report here two patients with Legionella pneumophila pneumonia accompanied by prolonged neurologic symptoms. In contrast to brain CT and MRI, which failed to detect any abnormalities, single-photon emission computed tomography (SPECT) showed multiple sites of hypoperfusion within the brains of both patients. These cases suggest that vasculopathy, which is detectable by SPECT, might be one of the causes of neurologic symptoms in patients with Legionnaires' disease.
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BACKGROUND: Eosinophilic esophagitis (EoE) is related to allergic diseases such as bronchial asthma (BA), atopic dermatitis, and allergic rhinitis. The aim of this study was to examine the eosinophil infiltration in the upper gastrointestinal (GI) tract in patients with BA using esophagogastroduodenoscopy. METHODS: Patients with BA who had upper GI tract symptoms were enrolled. Patients who received systemically administered steroids were excluded. Eosinophil infiltrations in the esophagus, stomach, and duodenum were examined with regard to the endoscopic findings and pathological findings of biopsy specimens (UMIN000010132). RESULTS: Ninety patients were enrolled from October in 2012 to September in 2014. Thirty-six were male, 54 were female, and the mean age was 57.5 years. Eighty-one (90%) used inhaled corticosteroids. Fourteen patients (15.6%) had reflux esophagitis, 8 of whom had grade A and 6 had grade B. No patient with EoE was observed. One female patient who had marked eosinophil infiltration in the esophagus, stomach, and duodenum was diagnosed as having eosinophilic gastroenteritis, but endoscopy showed only mucosal edema in the antrum. Another female patient who had marked eosinophil infiltration in the esophagus, stomach, and duodenum was diagnosed as having eosinophilic granulomatosis with polyangiitis, and endoscopy showed erosions in the antrum and the duodenum. Three patients had eosinophil infiltration in the stomach, but none of them had severe symptoms. CONCLUSIONS: Patients with asthma who had upper gastrointestinal symptoms rarely had eosinophilic gastrointestinal disorders. Biopsy specimens are of high importance in the diagnosis of eosinophilic gastrointestinal disorders even if there is no remarkable endoscopic finding.
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Asma/patologia , Eosinófilos/patologia , Trato Gastrointestinal Superior/patologia , Adolescente , Adulto , Idoso , Asma/complicações , Edema/patologia , Endoscopia Gastrointestinal , Enterite/complicações , Enterite/patologia , Eosinofilia/complicações , Eosinofilia/patologia , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/patologia , Feminino , Gastrite/complicações , Gastrite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/patologia , Adulto JovemRESUMO
Invasive tracheobronchial aspergillosis that is entirely limited or predominantly confined to tracheobronchial lesions is a relatively rare form of invasive pulmonary aspergillosis. Extended parenchymal opacities that are radiological manifestations of invasive aspergillosis sometimes occur following invasive tracheobronchial aspergillosis. However, it remains unclear whether or not invasive tracheobronchial aspergillosis is the initial stage of invasive pulmonary aspergillosis. A 61-year-old woman was admitted because of severe diarrhea and dehydration. Three days after admission, she complained of dyspnea. A computed tomography (CT) scan of the chest showed bronchial wall thickening. She developed respiratory failure despite antibiotic therapy. A CT scan showed obstructions of bronchial lumens and bronchiectasis in the right upper lobe. A spergillus fumigatus was identified from samples obtained in bronchoscopic examination. Bronchial lesions rapidly progressed to be extended. A spergillus infection with multiple parenchymal opacities was observed on CT scan. She responded to treatment with antifungal drugs.
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BACKGROUND: Underdiagnosis is a critical problem in the management of chronic obstructive pulmonary disease (COPD). It is important to screen patients at risk for COPD among those with lifestyle-related diseases such as hypertension, diabetes mellitus, and dyslipidemia, since these diseases promote the development of cardiovascular diseases closely associated with increased COPD mortality. METHODS: Thirteen primary care clinics in a suburb of Tokyo participated in the current study. A total of 950 patients from these clinics were enrolled in the study between 2010 and 2012; the patients ranged in age from 40 to 79 years, and they had no diagnosed respiratory diseases at the time of enrollment. Patients fulfilling the selection criteria were recruited to undergo spirometry and then completed a self-report questionnaire about comorbid diseases and smoking habits. Spirometry was performed 15 min after inhalation of 200 µg of salbutamol sulfate. RESULTS: The prevalence of airflow limitation was 12.7% in the 950 primary care clinic patients. Lifelong cigarette consumption was the most significant risk factor for airflow limitation, e.g., patients who smoked 60 pack-years or more had a 40% likelihood of airflow limitation. Among common lifestyle-related diseases, hypertension was associated with the severity of airflow limitation (p=0.03), whereas dyslipidemia appeared to be inversely correlated with the severity of airflow limitation (p=0.004) on multiple regression analysis including lifelong cigarette consumption as a factor. CONCLUSIONS: Undiagnosed airflow limitation was detected in 12.7% of outpatients at the primary care clinics. Since most patients with lifestyle-related diseases are treated by primary care physicians, it is essential for the physicians to obtain an accurate history of smoking and comorbid diseases to screen patients for COPD.
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Instituições de Assistência Ambulatorial/estatística & dados numéricos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Pacientes Ambulatoriais/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Fumar/efeitos adversos , Fumar/epidemiologia , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Hipertensão/etiologia , Japão/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etiologia , Ventilação Pulmonar , RiscoRESUMO
The nontuberculous mycobacteria (NTM) cause miscellaneous disorders in humans, especially in the lungs, which present with a variety of radiological features. To date, knowledge of the pathogenic role of the Mycobacterium avium-intracellulare complex (MAC) in the human lung and the definitive criteria for initiating multidrug therapy are still lacking. However, there is little doubt that clarithromycin is the most efficacious drug among the various treatment regimens for lung NTM. In this study, with the use of a bridged nucleic acid (BNA) probe a detection system based on a real-time PCR (BNA-PCR) for the identification of the point mutations at position 2058 or 2059 in domain V of the 23S rRNA gene responsible for clarithromycin resistance was developed and has been assessed using MAC isolates from clinical samples. Out of 199 respiratory specimens, the drug susceptibility test demonstrated 12 strains resistant to clarithromycin, while the BNA-PCR showed 8 strains carrying the point mutation at position 2058 or 2059 of the 23S rRNA gene. This system revealed that there were mycobacterial strains resistant to clarithromycin which do not carry previously identified resistance genes. This paper documents a novel system for detecting clarithromycin-resistant strains and demonstrates that although these mutations are tacitly assumed to account for >90% of the reported resistant mutants, there is a significant fraction of resistant mutants that do not harbor these mutations. Therefore, unknown mechanisms affecting clarithromycin resistance remain to be elucidated.
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Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/genética , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Complexo Mycobacterium avium/classificação , Reação em Cadeia da Polimerase , RNA Ribossômico 23S/genética , Sensibilidade e Especificidade , Escarro/microbiologiaRESUMO
BACKGROUND: Nontuberculous mycobacteria are well known to be a cause of hot tub lung, however, to our knowledge, there exists no case report of humidifier lung induced by mycobacteria. CASE PRESENTATION: A case of a nonimmunocompromised female patient with Mycobacterium gordonae-induced humidifier lung is described. She spontaneously recovered after discontinuing ultrasonic humidifier use. When subjected to a provocation test, she demonstrated acute respiratory distress with signs and symptoms, consistent with hypersensitivity pneumonitis. Before and after the provocation test, water in the humidifier reservoir revealed only Mycobacterium gordonae by the microbiologic analyses. CONCLUSION: To our knowledge, this is the first report of humidifier lung induced by nontuberculous mycobacteria. Although nontuberculous mycobacteria are well-known to be agents of hot tub lung or metal working fluid lung, physicians should also consider the pathogen as a cause of hypersensitivity lung reaction associated with humidifier use.
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Alveolite Alérgica Extrínseca/diagnóstico por imagem , Umidificadores , Pulmão/diagnóstico por imagem , Micobactérias não Tuberculosas/imunologia , Microbiologia da Água , Idoso de 80 Anos ou mais , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/imunologia , Testes de Provocação Brônquica , Feminino , Humanos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Most but not all data from different ethnic groups fit the Global Lung Function Initiative (GLI) spirometric reference model. This study investigates to what extent discrepancies are caused by secular changes in body proportions. METHODS: FEV1 and FVC from 20,336 healthy Japanese subjects (13,492 women) aged 17 to 95 years were compared with GLI-2012 reference values for Europeans. Data on the sitting height/standing height ratio (Cormic index) in 17-year-old students, collected from 1949 to 2012 in successive birth cohorts, were used to assess secular changes in body frame. The cohort-specific Cormic index was used to assess how variation in body frame affected pulmonary function. RESULTS: FEV1 and FVC were lower than GLI-2012 reference values, with values progressively falling until age 35 to 40 years and then rising to European levels in the elderly. The Cormic index rose until 1942, then fell, with a nadir in the 1970s, before rising again until 1995. Nearly one-half of the spirometric variability from predicted values could be explained by differences in the Cormic index between birth cohorts. CONCLUSIONS: In low-income countries, improving health conditions are likely to drive increases in height and changes in relative leg length similar to those observed in Japan and, thus, to a change in body frame. This implies that height-based prediction equations for such populations will need to be periodically updated.
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Povo Asiático , Estatura/fisiologia , Perna (Membro)/anatomia & histologia , Pulmão/fisiologia , Espirometria/normas , População Branca , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Valores de Referência , Estudos Retrospectivos , Capacidade Vital/fisiologia , Adulto JovemRESUMO
BACKGROUND: Reference values for lung function tests should be periodically updated because of birth cohort effects and improved technology. This study updates the spirometric reference values, including vital capacity (VC), for Japanese adults and compares the new reference values with previous Japanese reference values. METHODS: Spirometric data from healthy non-smokers (20,341 individuals aged 17-95 years, 67% females) were collected from 12 centers across Japan, and reference equations were derived using the LMS method. This method incorporates modeling skewness (lambda: L), mean (mu: M), and coefficient of variation (sigma: S), which are functions of sex, age, and height. In addition, the age-specific lower limits of normal (LLN) were calculated. RESULTS: Spirometric reference values for the 17-95-year age range and the age-dependent LLN for Japanese adults were derived. The new reference values for FEV(1) in males are smaller, while those for VC and FVC in middle age and elderly males and those for FEV(1), VC, and FVC in females are larger than the previous values. The LLN of the FEV(1)/FVC for females is larger than previous values. The FVC is significantly smaller than the VC in the elderly. CONCLUSIONS: The new reference values faithfully reflect spirometric indices and provide an age-specific LLN for the 17-95-year age range, enabling improved diagnostic accuracy. Compared with previous prediction equations, they more accurately reflect the transition in pulmonary function during young adulthood. In elderly subjects, the FVC reference values are not interchangeable with the VC values.
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Espirometria/métodos , Espirometria/normas , Capacidade Vital , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Estudos Retrospectivos , Adulto JovemRESUMO
UNLABELLED: Identification of the causative pathogen(s) of pneumonia would allow the selection of effective antibiotics and thus reduce the mortality rate and the emergence of drug-resistant pathogens. To identify such pathogens and to obtain these benefits, it is necessary that a clinical test is rapid, accurate, easily performed, and cost-effective. Here, we devised a PCR-based test, named HIRA-TAN, which is able to discriminate therapeutic targets from commensal organisms (e.g. Streptococcus pneumoniae or Haemophilus influenzae) and to detect foreign organisms (e.g. Mycoplasma pneumoniae or Legionella pneumophila) in the sputum. The utility of this system was validated in a prospective study, using sputum samples from patients with pneumonia. 568 patients were enrolled and the HIRA-TAN assay identified the causative pathogens with an accuracy of 96.7% for H. influenzae; 93.2% for Pseudomonas aeruginosa; 80.6% for Klebsiella pneumoniae; 90.9% for Moraxella catarrhalis; 87.5% for Escherichia coli; 78.1% for MRSA and 91.6% for S. pneumoniae. Overall the HIRA-TAN procedure was able to identify the causative pathogens of pneumonia in 60% of the cases. Additionally, this procedure was able to determine when the pneumonia-causing organism was a commensal organism or a foreign organism in a single assay. The HIRA-TAN approach yielded reproducible results and provided valuable information to plan the course of treatment of pneumonia. Through the rapid identification of the causative pathogens, the HIRA-TAN will promote targeted treatments for pneumonias. CLINICAL TRIALS REGISTRATION: UMIN000001694.
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Bactérias/isolamento & purificação , Pneumonia Bacteriana/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Escarro/microbiologia , Simbiose , Triacetonamina-N-Oxil , Adulto JovemAssuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/diagnóstico , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/diagnóstico , Lesão Pulmonar Aguda/epidemiologia , Lesão Pulmonar Aguda/terapia , Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Antineoplásicos/efeitos adversos , Antirreumáticos/efeitos adversos , Biomarcadores/sangue , Testes de Provocação Brônquica , Diagnóstico por Imagem , Medicamentos de Ervas Chinesas/efeitos adversos , Testes Hematológicos , Humanos , Imunossupressores/efeitos adversos , Interferons/efeitos adversos , Japão/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/terapia , Ativação Linfocitária , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To assess clinical, laboratory and radiographic findings associated with outcomes and to clarify more practical ways to predict hospital mortality in patients with acute exacerbation (AE) of chronic fibrosing interstitial pneumonia (CFIP). DESIGN: Single-centre retrospective cohort study. SETTING: University Hospital in Japan. PARTICIPANTS: We identified 51 consecutive patients with AE of idiopathic CFIP through multidisciplinary discussion. Patients who had connective tissue disease, drug-induced lung disease, pneumoconiosis, hypersensitivity pneumonitis, sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis and eosinophilic pneumonia were excluded. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: The main outcome was determination of in-hospital mortality predictors. Other outcomes included clinical, laboratory and radiographic differences between non-survivors and survivors in patients with AE of CFIP. RESULTS: The mean age of the patients with AE of CFIP was 71 years. Compared with survivors, non-survivors had a significantly shorter duration of symptoms before admission, lower prevalence of peripheral distribution of ground-glass opacity and centrilobular emphysema (CLE) on thin-section CT, lower peripheral lymphocyte count, higher brain natriuretic peptide titre, lower Pao2:Fio2 (P:F) ratio, higher prevalence of systemic inflammatory response syndrome (SIRS) and higher SIRS score on admission (p=0.0069, 0.0032, 0.015, 0.040, 0.0098, 0.012, 9.9×10(-7) and 5.4×10(-6), respectively). Multivariate analysis revealed SIRS (HR=6.2810, p=0.015), CLE (HR=0.0606, p=3.6×10(-5)) and serum procalcitonin level (HR=2.7110, p=0.022) to be independent predictors of in-hospital mortality. A Kaplan-Meier estimate on the basis of stratification according to the presence or absence of SIRS and CLE demonstrated a distinct survival curve for each subset of patients. CONCLUSIONS: Distinct survival curves documented by stratification according to the presence or absence of SIRS and CLE may provide basic information for a rational management strategy for patients with AE of CFIP on admission.
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BACKGROUND: Neutrophils are often increased in the airways of either chronic severe asthma or acute exacerbations. Neutrophils that have migrated in response to interleukin-8 (IL-8) may lead eosinophils to accumulate in the airways of patients with asthma and possibly aggravate the disease. In this study, we investigated whether formoterol modified the trans-basement membrane migration (TBM) of eosinophils stimulated with neutrophils and IL-8. METHODS: Neutrophils and eosinophils were isolated from peripheral blood obtained from healthy donors. Eosinophil TBM was examined using a modified Boyden's chamber technique. Neutrophils were preincubated with or without formoterol (0.1 µM) at 37°C for 30 min. Eosinophils were added to the upper compartment of a chamber with a Matrigel-coated transwell insert. Medium containing preincubated neutrophils and IL-8 was added to the lower compartment of the chamber. After a 90-minute incubation, the eosinophils that had migrated into the lower chamber were calculated using eosinophil peroxidase assays. RESULTS: A combination of neutrophils and IL-8 significantly induced the eosinophil TBM; formoterol alone had no effect. However, formoterol modestly but significantly attenuated the TBM of eosinophils stimulated with neutrophils and IL-8. CONCLUSION: These results suggest that formoterol may act as a therapeutic agent on enhanced eosinophilic inflammation in acute exacerbation or persistent, severe asthma. The effect of formoterol likely involves the inhibition of neutrophil activation.
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Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Etanolaminas/farmacologia , Interleucina-8/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Migração Transendotelial e Transepitelial/imunologia , Membrana Basal , Células Cultivadas , Quimiotaxia de Leucócito/efeitos dos fármacos , Fumarato de Formoterol , Humanos , Ativação de Neutrófilo/efeitos dos fármacos , Ativação de Neutrófilo/imunologiaRESUMO
BACKGROUND: Omalizumab, an anti-immunoglobulin E monoclonal antibody, has shown an inhibitory effect on airway inflammation, which may be associated with clinical improvement of severe asthma. This study evaluated changes in airway inflammation and cytokine release by the peripheral blood mononuclear cells (PBMCs) of Japanese patients with severe asthma after administration of omalizumab. METHODS: Sixteen Japanese patients with severe asthma who were allergic to house-dust mites were enrolled in this study. Eight received omalizumab every 2 or 4 weeks for 16 weeks, and 8 control subjects were treated with conventional drug treatment. Changes in clinical scores for sputum eosinophils and levels of fraction of exhaled nitric oxide (FeNO) were measured at the time of enrollment and at week 16. Cytokines from PBMCs stimulated by house-dust mite (Dermatophagoides farinae) or ionomycin/phorbol myristate acetate (PMA) were measured at baseline and at week 16. RESULTS: In the omalizumab-treated group, decreases in sputum eosinophils and FeNO were observed following treatment. Furthermore, the ex vivo production of interleukin (IL)-5 by PBMCs in response to both mite allergen and ionomycin/PMA decreased significantly. In contrast, interferon (IFN)-γ production was unchanged. There were no changes in any of the parameters observed in the control group. CONCLUSION: Omalizumab exerts inhibitory effects on airway inflammation in Japanese patients with severe allergic asthma. This treatment attenuates production of IL-5 by PBMCs stimulated with both a specific allergen and a nonspecific activator. Reduction of the Th2 inflammatory cascade likely contributes to clinical benefits; however, further studies are required to clarify these results due to the small sample size in this study.
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Antiasmáticos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Asma/metabolismo , Interleucina-5/biossíntese , Leucócitos Mononucleares/metabolismo , Adulto , Antiasmáticos/administração & dosagem , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Asma/imunologia , Citocinas/biossíntese , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Omalizumab , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the efficacy and safety of golimumab 50 and 100 mg monotherapy in Japanese patients with active rheumatoid arthritis (RA) despite treatment with disease-modifying antirheumatic drugs (DMARDs). METHODS: A total of 316 patients were randomised to receive subcutaneous injections every 4 weeks of placebo (group 1), golimumab 50 mg (group 2) or golimumab 100 mg (group 3); group 1 crossed over to golimumab 50 mg at week 16. The primary end point was the proportion of patients achieving ≥20% improvement in the American College of Rheumatology criteria (ACR20) at week 14. ACR50 and ACR70 response rates were also measured. Adverse events (AEs) were monitored throughout the study. RESULTS: Demographics were similar across groups; the mean age was 52 years and 81.8% of patients (252/308) were female. Week 14 ACR20 response rates were significantly greater in groups 2 (51/101 (50.5%)) and 3 (60/102 (58.8%)) than in group 1 (20/105 (19.0%); p<0.0001 for both), as were ACR50 and ACR70 response rates. After placebo crossover at week 16, week 24 ACR response rates were similar in groups 1 and 2. Through week 16, 63.8% of patients in group 1, 62.4% in group 2 and 60.8% in group 3 had AEs and 1.9%, 1.0% and 2.0% had serious AEs. After week 16, one malignancy was reported (breast cancer, group 3). Infections were the most common AEs. No deaths or cases of tuberculosis were reported through week 24. CONCLUSIONS: Golimumab monotherapy (50 and 100 mg) was effective in reducing the signs and symptoms of RA in Japanese patients with active disease despite DMARD treatment.
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Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Resistência a Medicamentos , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
A 40-year-old woman, who was born in Thailand and moved to Japan 20 years previously, was admitted to our university hospital because of eosinophilia and abnormal chest radiography findings over a 6-month period. The chest CT showed multiple cavitary nodules in the subpleural area and a tubular structure that extended from each cavity to the pleura. Immunological examination revealed an elevation of antibody titers against Ancylostoma duodenale, Paragonimiasis miyazakii and Paragonimiasis westermanii based on an ELISA assay. In addition, hookworm eggs were found in the stool. We firstly administered pyrantel pamoates, following which the eggs become undetectable. Nevertheless, eosinophilia and abnormal chest CT findings persisted. We diagnosed the patient as having a superinfection with paragonimiasis and hookworm, then administered praziquantel. Subsequently, the number of eosinophils returned to a normal level and the abnormal shadow in the chest CT images diminished without scarring. The final diagnosis was a superinfection of paragonimiasis and hookworm.
Assuntos
Infecções por Uncinaria/complicações , Pneumopatias Parasitárias/complicações , Paragonimíase/complicações , Adulto , Feminino , Infecções por Uncinaria/diagnóstico , Humanos , Pneumopatias Parasitárias/diagnóstico , Paragonimíase/diagnósticoRESUMO
BACKGROUND: ImmunoCAP® Rapid is a rapid test kit to measure the allergen-specific IgE to the eight major inhalation allergen (cat, mite, orchard grass, ragweed, wormwood, dog, cockroach, Japan cedar). METHODS: We performed ImmunoCAP® Rapid 83 patients with allergic disease (26 males, 57 females, median aged 43 years, 53 of asthma, 43 of allergic rhinitis) in our allergy center. ImmunoCAP® Rapid results were compared with those of skin prick test (SPT). RESULTS: Although total positive allergens of SPT were higher than that of ImmunoCAP® Rapid (26.5% vs 22.5%, p<0.05), there was no significantly difference of each positive allergen between two tests. The rate of ImmunoCAP® Rapid to Japan cedar was almost equivalent to SPT in all patients (68.7% vs 55.4%, p=0.07). In contrast, the rate of ImmunoCAP® Rapid to Japan cedar was higher than SPT in patients with rhinitis (90.4% vs 71.4%, p<0.05). Efficiency between ImmunoCAP® Rapid and SPT was 86.4%, sensitivity was 66.9%, and specificity was 93.4%. The reactivity of ImmunoCAP® Rapid to allergens significantly correlated with sizes of SPT (erythema: r=0.645, urticaria: r=0.657). CONCLUSION: Although identification rate in the screening ImmunoCAP® Rapid slightly inferior to SPT, this test system was useful for diagnosis of Japan cedar and mite.