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BACKGROUND: Limited research has investigated the relationship between small airway dysfunction (SAD) and static lung hyperinflation (SLH) in patients with post-acute sequelae of COVID-19 (PASC) especially dyspnea and fatigue. METHODS: 64 patients with PASC were enrolled between July 2020 and December 2022 in a prospective observational cohort. Pulmonary function tests, impulse oscillometry (IOS), and symptom questionnaires were performed two, five and eight months after acute infection. Multivariable logistic regression models were used to test the association between SLH and patient-reported outcomes. RESULTS: SLH prevalence was 53.1% (34/64), irrespective of COVID-19 severity. IOS parameters and circulating CD4/CD8 T-cell ratio were significantly correlated with residual volume to total lung capacity ratio (RV/TLC). Serum CD8 + T cell count was negatively correlated with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) with statistical significance. Of the patients who had SLH at baseline, 57% continued to have persistent SLH after eight months of recovery, with these patients tending to be older and having dyspnea and fatigue. Post-COVID dyspnea was significantly associated with SLH and IOS parameters R5-R20, and AX with adjusted odds ratios 12.4, 12.8 and 7.6 respectively. SLH was also significantly associated with fatigue. CONCLUSION: SAD and a decreased serum CD4/CD8 ratio were associated with SLH in patients with PASC. SLH may persist after recovery from infection in a substantial proportion of patients. SAD and dysregulated T-cell immune response correlated with SLH may contribute to the development of dyspnea and fatigue in patients with PASC.
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COVID-19 , Pulmón , Síndrome Post Agudo de COVID-19 , Pruebas de Función Respiratoria , Humanos , Masculino , Femenino , Persona de Mediana Edad , COVID-19/fisiopatología , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/diagnóstico , COVID-19/inmunología , Estudios Prospectivos , Pulmón/fisiopatología , Pruebas de Función Respiratoria/métodos , Anciano , Adulto , Recuperación de la Función , Factores de Tiempo , Disnea/fisiopatología , Disnea/epidemiología , Disnea/diagnóstico , Volumen Espiratorio Forzado/fisiologíaRESUMEN
BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.
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BACKGROUND AND OBJECTIVE: Correlations between the image analysis of CT scan, lung function and quality of life in patients with idiopathic pulmonary fibrosis (IPF) remain unclear. This study aimed to investigate the impacts of pulmonary blood-vessel distribution and the extent of fibrosis on the lung function and quality of life of patients with IPF. METHODS: Patients were enrolled in an IPF registry and had completed pulmonary function tests, chest HRCT, St. George Respiratory Questionnaire (SGRQ) and echocardiography. Pulmonary blood-vessel distribution, specific image-derived airway volume (siVaw) and fibrosis extent (siVfib) were quantitatively calculated by functional respiratory imaging on HRCT. RESULTS: The study subjects were categorized into DLco <40% pred. (n = 40) and DLco ≥40% pred. (n = 19) groups. Patients with DLco <40% pred. had significantly higher scores of SGRQ, composite physiologic index (CPI), exercise oxygen desaturation (∆SpO2), siVaw, lower FVC% pred. and 6-minute walking distance% pred. The proportion of small blood vessels in the upper lobes (BV5PR-UL) was significantly correlated with CPI, DLco % Pred., FVC% pred., SGRQ and ∆SpO2. Only BV5PR-UL had a significant impact on all indices but not BV5PR in the lower lobes (BV5PR-LL). siVfib was significantly negatively correlated with BV5PR-UL, DLco% pred. and FVC% pred., as well as positively correlated with CPI, ∆SpO2 and siVaw. CONCLUSION: BV5PR-UL and siVfib had significant correlations with lung function and may become important indicators to assess the severity of IPF and the impact on quality of life.
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For most patients, asthma can be effectively managed using inhaled medications. However, patients who have severe and/or uncontrolled asthma, or who experience exacerbations, may require systemic corticosteroids (SCSs) to maintain asthma control. Although SCS are highly effective in this regard, even modest exposure to these medications can increase the risk for long-term, adverse health outcomes, such as type 2 diabetes, renal impairment, cardiovascular disease and overall mortality. Clinical and real-world data from studies investigating asthma severity, control and treatment practices around the globe have suggested that SCS are overused in asthma management, adding to the already substantial healthcare burden experienced by patients. Throughout Asia, although data on asthma severity, control and SCS usage are limited and vary widely among countries, available data strongly suggest a pattern of overuse consistent with the broader global trend. Coordinated changes at the patient, provider, institutional and policy levels, such as increasing disease awareness, promoting better adherence to treatment guidelines and increasing availability of safe and effective alternatives to SCS, are likely necessary to reduce the SCS burden for patients with asthma in Asia.
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Antiasmáticos , Asma , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Asma/terapia , Corticoesteroides , Asia/epidemiología , Antiasmáticos/uso terapéuticoRESUMEN
BACKGROUND/PURPOSE: The application of the checkbox for identifying patients with traits of both chronic obstructive pulmonary disease (COPD) and asthma proposed by the 2015 Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations has not been well studied although such identification is important in clinical practice. Thus, we aimed to investigate the prevalence and features of COPD coexistent with asthma traits diagnosed based on the 2015 GINA/GOLD strategies, and explore the gap between guidelines and routine practice in the diagnosis and pharmacological management of such condition in a COPD cohort. METHODS: COPD subjects were enrolled retrospectively throughout Taiwan. A patient record form was completed for each participant and the data were analyzed. RESULTS: Of 340 participants, the prevalence of COPD coexistent with traits of asthma was 39.4% and 30.3% based on guidelines and physician's judgment, respectively. Coexistent patients were characterized by blood eosinophilia, higher total immunoglobulin E (IgE) levels, preserved lung function, and the presence of gastro-esophageal reflux disease and atopic disease while total IgE level > 100 kU/L and the presence of atopic disease were predictors for coexistent patients. Gaps existed in the diagnosis (a weak agreement with kappa = 0.53) and treatment (non-adherence to the preferred therapy in 18.4% of physician-judged coexistent patients) in COPD patients with asthma traits. The exacerbation history was similar between coexistent and non-coexistent patients. CONCLUSION: We found that measuring circulatory eosinophil and total IgE levels may raise clinicians' awareness of the presence of traits of asthma in the management of COPD.
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Asma , Enfermedad Pulmonar Obstructiva Crónica , Asma/epidemiología , Humanos , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Taiwán/epidemiologíaRESUMEN
Asthma imposes a significant burden on the health system and patients' quality of life. Within Asia, there is large variability in several cultural, social and economic factors ultimately influencing the management of asthma. Differences in risk factors and asthma management practices across Asia make asthma a truly 'mixed-bag' phenomenon. With the advent of biological agents and the consequent emphasis on asthma phenotyping and endotyping, it is more important than ever to understand the diverse nature of asthma as a disease. This is a collaborative review within Asia to highlight the differences in management of adult asthma, and the local modifications that are made to international guidelines. This review paves the way for a future Asian collaborative network in asthma epidemiological research.
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Asma , Carga Global de Enfermedades , Manejo de Atención al Paciente/métodos , Calidad de Vida , Adulto , Asia/epidemiología , Asma/economía , Asma/epidemiología , Asma/psicología , Asma/terapia , Salud Global , Humanos , Factores de RiesgoRESUMEN
Chronic obstructive pulmonary disease (COPD) is a major disease in Asia. However, how to manage specifically Asian COPD patients has not been proposed. Awareness of COPD is very low and underdiagnosis/undertreatment is common in Asian countries. Low utilization of pulmonary function test and inhalers is also a problem. Moreover, high smoking prevalence and air pollution are barriers to managing Asian patients with COPD. The relatively low body mass index of Asian patients with COPD can increase their risk for experiencing adverse effects from COPD drugs. Physicians should consider the unique features of Asian populations with COPD such as the high prevalence rates of bronchiectasis and tuberculosis-destroyed lungs, biomass smoke exposure and parasitic infection.
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Bronquiectasia/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Contaminación del Aire/efectos adversos , Asia/epidemiología , Índice de Masa Corporal , Femenino , Humanos , Masculino , Enfermedades Parasitarias/complicaciones , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria/estadística & datos numéricos , Factores de Riesgo , Humo/efectos adversos , Fumar/efectos adversos , Tuberculosis Pulmonar/complicacionesRESUMEN
BACKGROUND: The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposed a new severity assessment system for emphasizing clinical symptom evaluation by COPD Assessment Test (CAT) or modified Medical Research Council (mMRC) dyspnea scores. The aim of the study was to evaluate the effectiveness of two scoring systems in evaluating COPD patients. METHODS: A population based cross-sectional study employing computer-assisted telephone interviewing system (CATI) for surveying the epidemiology of COPD in Taiwan. Among 6600 subjects recruited (age > 40), 404 subjects (6.1%) were diagnosed as COPD. The comorbidities, COPD-related symptoms, health care resources utilization were compared between CAT and mMRC. RESULTS: There were significant differences in all co-morbidities, symptom severity in favor of CAT as compared to mMRC. When comparing health care resources utilization, CAT and mMRC have equal effectiveness in evaluating patients with regular medical treatment. There were significant differences in emergency room visit and hospitalization in favor of mMRC. However, CAT was more effective in evaluating patients with ICU admission (P = 0.005). CONCLUSION: Compared with CAT and mMRC, there are individual benefits in the evaluation of clinical symptoms, co-morbidities and medical resources utilization for ER, hospitalization and ICU admission in COPD patients.
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Disnea/diagnóstico , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Índice de Severidad de la Enfermedad , Evaluación de Síntomas/normas , Adulto , Anciano , Área Bajo la Curva , Comorbilidad , Estudios Transversales , Disnea/fisiopatología , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Curva ROC , Encuestas y Cuestionarios , Taiwán , Capacidad VitalRESUMEN
BACKGROUND: The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients. METHODS: This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared. RESULTS: Among the 253 randomized subjects, 244 patients were evaluable (119 in the BDP/F group and 125 in the FP/S group). A significant improvement from baseline to the end of treatment period was observed in both BDP/F and FP/S groups in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), morning and evening peak expiratory flow (PEF), Asthma Control Test (ACT) score and the use of rescue medication. FVC increase from pre-dose was significant after 5 min post inhalation in the BDP/F group only, while statistically significant within group improvement was not achieved until 30 min post inhalation in the FP/S group. CONCLUSION: The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F.
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Asma/tratamiento farmacológico , Beclometasona/administración & dosificación , Combinación Fluticasona-Salmeterol/administración & dosificación , Fumarato de Formoterol/administración & dosificación , Administración por Inhalación , Adulto , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , TaiwánRESUMEN
Sleep disorders are common non-motor symptoms in patients with Parkinson's disease. Our study aims to explore the relationship between non-apnea sleep disorders and future Parkinson's disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91 273 adult patients who had non-apnea sleep disorders without pre-existing Parkinson's disease were enrolled. An age-, gender-, income-, urbanization- and Charlson comorbidity index score-matched control cohort consisting of 91 273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinson's disease, death or until the end of 2010, whichever came first. The Kaplan-Meier analyses revealed patients with non-apnea sleep disorders tended to develop Parkinson's disease (log-rank test, P < 0.001). After a multivariate adjustment in a Cox regression model, non-apnea sleep disorders was an independent risk factor for the development of Parkinson's disease [crude hazard ratio: 1.63, 95% confidence interval (CI): 1.54-1.73, P < 0.001; adjusted hazard ratio: 1.18, 95% CI: 1.11-1.26, P < 0.001]. In the subgroup analysis, patients with chronic insomnia (lasting more than 3 months) had the greatest risk (crude hazard ratio: 2.91, 95% CI: 2.59-3.26, P < 0.001; adjusted hazard ratio: 1.37, 95% CI: 1.21-1.55, P < 0.001). In conclusion, this study revealed that non-apnea sleep disorders, especially chronic insomnia, are associated with a higher risk for future Parkinson's disease.
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Enfermedad de Parkinson/epidemiología , Medición de Riesgo , Trastornos del Sueño-Vigilia/epidemiología , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Taiwán/epidemiologíaRESUMEN
BACKGROUND: While Candida pneumonia is life-threatening, biomarker measurements to early detect suspected Candida pneumonia are lacking. This study compared the diagnostic values of measuring levels of (1, 3)-ß-D-glucan in endotracheal aspirate, bronchoalveolar lavage fluid, and serum to detect suspected Candida pneumonia in immunocompromised and critically ill patients. METHODS: This prospective, observational study enrolled immunocompromised, critically ill, and ventilated patients with suspected fungal pneumonia in mixed intensive care units from November 2010 to October 2011. Patients with D-glucan confounding factors or other fungal infection were excluded. Endotracheal aspirate, bronchoalveolar lavage fluid and serum were collected from each patient to perform a fungal smear, culture, and D-glucan assay. RESULTS: After screening 166 patients, 31 patients completed the study and were categorized into non-Candida pneumonia/non-candidemia (n = 18), suspected Candida pneumonia (n = 9), and non-Candida pneumonia/candidemia groups (n = 4). D-glucan levels in endotracheal aspirate or bronchoalveolar lavage were highest in suspected Candida pneumonia, while the serum D-glucan level was highest in non-Candida pneumonia/candidemia. In all patients, the D-glucan value in endotracheal aspirate was positively correlated with that in bronchoalveolar lavage fluid. For the detection of suspected Candida pneumonia, the predictive performance (sensitivity/specificity/D-glucan cutoff [pg/ml]) of D-glucan in endotracheal aspirate and bronchoalveolar lavage fluid was 67%/82%/120 and 89%/86%/130, respectively, accounting for areas under the receiver operating characteristic curve of 0.833 and 0.939 (both P < 0.05), respectively. Measuring serum D-glucan was of no diagnostic value (area under curve =0.510, P = 0.931) for the detection of suspected Candida pneumonia in the absence of concurrent candidemia. CONCLUSIONS: D-glucan levels in both endotracheal aspirate and bronchoalveolar lavage, but not in serum, provide good diagnostic values to detect suspected Candida pneumonia and to serve as potential biomarkers for early detection in this patient population.
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Líquido del Lavado Bronquioalveolar , Candidiasis/diagnóstico , Neumonía/diagnóstico , beta-Glucanos/análisis , Adulto , Anciano , Biomarcadores/análisis , Candidemia/diagnóstico , Enfermedad Crítica , Diagnóstico Precoz , Femenino , Humanos , Huésped Inmunocomprometido , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Neumonía/microbiología , Estudios Prospectivos , Proteoglicanos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: We examined the physician perspectives on asthma management in Asia. METHODS: An online/face-to-face, questionnaire-based survey of respiratory specialists and primary care physicians from eight Asian countries/region was carried out. The survey explored asthma control, inhaler selection, technique and use; physician-patient communications and asthma education. Inclusion criteria were >50% of practice time spent on direct patient care; and treated >30 patients with asthma per month, of which >60% were aged >12 years. RESULTS: REALISE Asia (Phase 2) involved 375 physicians with average 15.9(±6.8) years of clinical experience. 89.1% of physicians reporting use of guidelines estimated that 53.2% of their patients have well-controlled (GINA-defined) asthma. Top consideration for inhaler choice was asthma severity (82.4%) and lowest, socio-economic status (32.5%). Then 54.7% of physicians checked their patients' inhaler techniques during consultations but 28.2(±19.1)% of patients were using their inhalers incorrectly; 21.1-57.9% of physicians could spot improper inhaler techniques in video demonstrations. And 79.6% of physicians believed combination inhalers could increase adherence because of convenience (53.7%), efficacy (52.7%) and usability (18.9%). Initial and follow-up consultations took 16.8(±8.4) and 9.2(±5.3) minutes, respectively. Most (85.1%) physicians used verbal conversations and least (24.5%), video demonstrations of inhaler use; 56.8% agreed that patient attitudes influenced their treatment approach. CONCLUSION: Physicians and patients have different views of 'well-controlled' asthma. Although physicians informed patients about asthma and inhaler usage, they overestimated actual usage and patients' knowledge was sub-optimal. Physician-patient interactions can be augmented with understanding of patient attitudes, visual aids and ancillary support to perform physical demonstrations to improve treatment outcomes.
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Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Nebulizadores y Vaporizadores , Educación del Paciente como Asunto/organización & administración , Relaciones Médico-Paciente , Administración por Inhalación , Adolescente , Adulto , Antiasmáticos/uso terapéutico , Asia , Asma/fisiopatología , Recursos Audiovisuales , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Índice de Severidad de la Enfermedad , Factores Socioeconómicos , Especialización , Adulto JovenRESUMEN
PURPOSE: Epidemiological studies have identified a trend in the development of depressive and anxiety disorders following a diagnosis of sleep apnea. The relationship between sleep apnea and subsequent panic disorder, however, remains unclear. METHODS: Using a nationwide database, the Taiwan National Health Insurance Research Database, patients with sleep apnea and age-, sex-, income-, and urbanization-matched control patients who did not have sleep apnea were enrolled between 2000 and 2010. Patients with a prior diagnosis of panic disorder before enrollment were excluded. The 2 cohorts were observed until December 31, 2010. The primary endpoint was occurrence of newly diagnosed panic disorder. RESULTS: A total of 8,704 sleep apnea patients and 34,792 control patients were enrolled. Of the 43,496 patients, 263 (0.60%) suffered from panic disorder during a mean follow-up period of 3.92 years, including 117 (1.34%) from the sleep apnea cohort and 146 (0.42%) from the control group. The Kaplan-Meier analysis revealed a predisposition of patients with sleep apnea to develop panic disorder (log-rank test, P <.001). After multivariate adjustment, the hazard ratio for subsequent panic disorder among the sleep apnea patients was 2.17 (95% confidence interval, 1.68-2.81; P <.001). CONCLUSIONS: Sleep apnea appears to confer a higher risk for future development of panic disorder.
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Trastorno de Pánico/epidemiología , Síndromes de la Apnea del Sueño/epidemiología , Adulto , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVE: The efficacy of budesonide/formoterol maintenance and reliever therapy (BFMRT) in asthma control is well documented in large randomized controlled trials. However, the acute reliever effects and real-life effectiveness are seldom reported. METHODS: This multicenter trial enrolled steroid-naïve, symptomatic asthmatics with baseline exhaled nitric oxide (eNO) of ≥ 40 ppb. There were 120 eligible patients who were randomized and received a dose of inhaled budesonide/formoterol 320/9 µg (lower dose budesonide/formoterol), 640/18 µg (higher dose budesonide/formoterol (HDBF)), or terbutaline (TERB) 1 mg. Inflammatory cells and mediators in induced sputum, eNO and lung function were measured at baseline and 6 h (acute phase). Subsequently, all patients used BFMRT as real-life practice for 24 weeks (maintenance phase). RESULTS: In the acute phase, the degree of post-treatment reduction in total eosinophil counts, interleukin-8 and matrix metalloproteinase-9 in induced sputum were significantly greater in group HDBF (vs TERB, P < 0.05). The increase in forced expiratory volume in first second (FEV1 ) in group HDBF was significantly higher (vs LDBF and TERB, P < 0.05) 3 h after dosing. In the maintenance phase, significant improvement of asthma control (presented by eNO, FEV1 and a five-item asthma control questionnaire) in real-life settings was observed at 4 weeks and sustained to the end of study. The rate of patients who followed scheduled visits declined over time (87% at week 4 and 42% at week 24). CONCLUSIONS: Budesonide/formoterol as reliever exerts acute, dose-related anti-inflammatory effects and FEV1 improvement in symptomatic asthmatics. BFMRT is effective in asthma control. However, the decrease in long-term follow-up rate remains an issue to overcome in real-life settings.
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Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Combinación Budesonida y Fumarato de Formoterol/administración & dosificación , Administración por Inhalación , Adulto , Asma/fisiopatología , Pruebas Respiratorias , Recuento de Células , Combinación de Medicamentos , Eosinófilos , Etanolaminas/uso terapéutico , Espiración , Femenino , Volumen Espiratorio Forzado , Humanos , Interleucina-8/análisis , Quimioterapia de Mantención , Masculino , Metaloproteinasa 9 de la Matriz/análisis , Persona de Mediana Edad , Óxido Nítrico/análisis , Esputo/química , Esputo/citología , Terbutalina/uso terapéutico , Capacidad Vital , Adulto JovenRESUMEN
BACKGROUND: The association between amyloidosis and cancer remains unclear. PARTICIPANTS AND METHODS: Using the Taiwan National Health Insurance Research Database we conducted a population-based cohort study. Patients newly diagnosed with amyloidosis between 1997 and 2009 were enrolled. Patients with antecedent cancer were excluded. Standardized incidence ratios (SIR) of cancers were calculated for the study cohort and compared with cancer incidence among the general population. We used a multivariate Cox regression model to evaluate the predictors of cancer development for patients with amyloidosis. RESULTS: The study included 1,693 subjects with median follow-up of 5.63 years. A total of 68 patients developed cancer. The incidence of kidney cancer (SIR 3.42; 95 % CI 1.11-7.97; p = 0.034) and hematologic malignancies (SIR 3.88; 95 % CI 1.86-7.14; p < 0.001) were significantly higher for patients with amyloidosis. CONCLUSION: This is currently the largest study to evaluate cancer risk among patients with amyloidosis. The results indicate that amyloidosis may be associated with an increased risk of kidney cancer and hematologic malignancies.
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Amiloidosis/epidemiología , Neoplasias Hematológicas/epidemiología , Neoplasias Renales/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Taiwán/epidemiología , Adulto JovenRESUMEN
The mechanism underlying the inflammatory role of TRPA1 in lung epithelial cells (LECs) remains unclear. Here, we show that cigarette smoke extract (CSE) sequentially induced several events in LECs. The Ca(2+) influx was prevented by decreasing extracellular reactive oxygen species (ROS) with the scavenger N-acetyl-cysteine, removing extracellular Ca(2+) with the chelator EGTA, or treating with the TRPA1 antagonist HC030031. NADPH oxidase activation was abolished by its inhibitor apocynin, EGTA, or HC030031. The increased intracellular ROS was halted by apocynin, N-acetyl-cysteine, or HC030031. The activation of the MAPKs/NF-κB signaling was suppressed by EGTA, N-acetyl-cysteine, or HC030031. IL-8 induction was inhibited by HC030031 or TRPA1 siRNA. Additionally, chronic cigarette smoke (CS) exposure in wild-type mice induced TRPA1 expression in LECs and lung tissues. In CS-exposure trpa1 (-/-) mice, the increased BALF level of ROS was similar to that of CS-exposure wild-type mice; yet lung inflammation was lessened. Thus, in LECs, CSE may initially increase extracellular ROS, which activate TRPA1 leading to an increase in Ca(2+) influx. The increased intracellular Ca(2+) contributes to activation of NADPH oxidase, resulting in increased intracellular ROS, which activate the MAPKs/NF-κB signaling leading to IL-8 induction. This mechanism may possibly be at work in mice chronically exposed to CS.
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Canales de Calcio/metabolismo , Calcio/metabolismo , Pulmón/patología , Proteínas del Tejido Nervioso/metabolismo , Humo/efectos adversos , Canales de Potencial de Receptor Transitorio/metabolismo , Acetanilidas/química , Acetofenonas/química , Animales , Biomarcadores/metabolismo , Líquido del Lavado Bronquioalveolar , Canales de Calcio/genética , Quelantes/química , Quimiocina CXCL2/metabolismo , Ácido Egtácico/química , Activación Enzimática , Regulación Neoplásica de la Expresión Génica , Humanos , Inflamación , Interleucina-8/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , NADPH Oxidasas/metabolismo , Proteínas del Tejido Nervioso/genética , Estrés Oxidativo , Purinas/química , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Canal Catiónico TRPA1 , Canales de Potencial de Receptor Transitorio/genéticaRESUMEN
BACKGROUND: Patients with obstructive sleep apnoea (OSA) experience repetitive cessation of breathing during sleep, leading to intermittent hypoxaemia, excessive oxidative stress and systemic inflammation. These insults may damage the vasculature and provoke the corresponding repair response, such as stem cell mobilization to peripheral blood. This study aimed to investigate nocturnal mobilization of stem cells in OSA. METHODS: Thirty-five patients with OSA and thirteen healthy controls were enrolled. Polysomnography was performed, and severity of OSA was defined by apnoea-hypopnoea index (AHI). Peripheral venous blood was drawn after and before sleep for measurement of CD34+ cell and SDF-1α level. Stem cell mobilization was gauged by ratios of the CD34+ level in the morning to that at night or by their difference. Correlation analysis was performed to identify factors related to stem cell mobilization. RESULTS: Compared to controls, the nocturnal ratios and difference of CD34+ cell levels were larger in patients with OSA (ratios: 1·141 vs. 0·896, P = 0·036; difference: 340 vs. -166/cc blood, P = 0·036), suggestive of stem cell mobilization. The mobilization ratios were related to AHI, body mass index (BMI), SpO2 nadir, oxygen desaturation index and time sustaining hypoxaemia. After adjusting age, gender and BMI, AHI (r = 0·357, P = 0·016) and hypoxaemia-related parameter remained significant. Paired nocturnal differences in CD34+ cell count (P = 0·009) and SDF-1α (P = 0·001) were also significant in patients with OSA, but not in controls. After CPAP therapy for 6 months, the elevated mobilization ratios in patients with OSA tended to decline (P = 0·059). CONCLUSION: CD34+ stem cell mobilization during sleep was observed in OSA.
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Apnea Obstructiva del Sueño/terapia , Células Madre/fisiología , Adulto , Estudios de Casos y Controles , Ritmo Circadiano , Presión de las Vías Aéreas Positiva Contínua/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Proyectos Piloto , PolisomnografíaRESUMEN
BACKGROUND: Sleep is essential for the maintenance of an intact immune function. Patients with sleep apnoea experience frequent sleep interruption due to apnoea-related arousals, possibly adversely impacting their immunity and affecting their outcomes when confronting sepsis. This case-control study aimed to compare the outcomes of sepsis patients with and without sleep apnoea. METHODS: From 2000 to 2009, 168 sleep apnoea patients who were first admitted for sepsis were identified from the Taiwan National Health Insurance Research Database. Also, 672 sepsis patients without sleep apnoea, who were matched by age, gender and Charlson's comorbidity index scores, served as controls. Hospital outcomes of the two groups were compared. Binary logistic regression was employed for multivariate analysis. RESULTS: The mortality rates of sepsis patients with and without sleep apnoea were 60.1% and 47.9%, respectively (P = 0. 005). After multivariate adjustment, sleep apnoea (OR: 1.805, 95% CI: 1.227-2.656, P = 0.003), presence of shock (OR: 3.600, 95% CI: 2.144-6.046, P < 0.001) and number of organs with dysfunction (OR: 1.591, 95% CI: 1.087-2.329, P = 0.017) were found to be independently associated with mortality. Sleep apnoea patients who needed continuous positive airway pressure treatment had an even higher risk of mortality. CONCLUSIONS: Sepsis patients with sleep apnoea may have poorer hospital outcomes than those without sleep apnoea.
Asunto(s)
Sepsis/mortalidad , Apnea Obstructiva del Sueño/terapia , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Presión de las Vías Aéreas Positiva Contínua/estadística & datos numéricos , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Sepsis/complicaciones , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/terapia , Apnea Obstructiva del Sueño/complicaciones , TaiwánRESUMEN
BACKGROUND: Evidence evaluating the risk of pneumonia in patients with obstructive sleep apnea is limited and mostly focuses on patients who receive continuous positive airway pressure (CPAP) therapy or on pediatric patients. We aimed to explore the risk of incident pneumonia among adults with sleep apnea, either with or without the need of CPAP therapy. METHODS: From Jan. 1, 2000, we identified adult patients with sleep apnea from the Taiwan National Health Insurance Research Database. A control cohort without sleep apnea, matched for age, sex and comorbidities, was selected for comparison. The 2 cohorts were followed until Dec. 31, 2010, and observed for occurrence of pneumonia. RESULTS: Of the 34,100 patients (6816 study patients and 27,284 matched controls), 2757 (8.09%) had pneumonia during a mean follow-up period of 4.50 years, including 638 (9.36%) study patients and 2119 (7.77%) controls. Kaplan-Meier analysis showed a higher incidence of pneumonia among patients with sleep apnea (log rank test, p < 0.001). After multivariate adjustment, patients with sleep apnea experienced a 1.20-fold (95% confidence interval 1.10-1.31) increase in incident pneumonia. The risk was even higher among patients who received CPAP therapy. INTERPRETATION: Sleep apnea appeared to confer a higher risk for future pneumonia, possibly in a severity-dependent manner.
Asunto(s)
Neumonía/epidemiología , Neumonía/terapia , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapia , Adulto , Distribución por Edad , Anciano , Estudios de Casos y Controles , Comorbilidad , Presión de las Vías Aéreas Positiva Contínua/métodos , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neumonía/diagnóstico , Pronóstico , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Apnea Obstructiva del Sueño/diagnóstico , Tasa de Supervivencia , Taiwán/epidemiologíaRESUMEN
PURPOSE: Chronic obstructive pulmonary disease (COPD) with eosinophilic airway inflammation may represent a unique phenotype, possibly with shared features of COPD and asthma. The role of exhaled nitric oxide (eNO) in identifying COPD patients with sputum eosinophilia was examined in this study. METHODS: Ninety COPD patients without past medical history of asthma or allergic diseases were prospectively enrolled, and their eNO, lung function, and cellular profile of induced sputum were measured. Eosinophil cationic protein and IgE in sputum and venous blood also were determined. Subjects with and without sputum eosinophilia (>3 %) were compared. The role of eNO in the prediction of sputum eosinophilia was assessed in a logistic regression model. RESULTS: Patients with sputum eosinophilia had significantly higher levels of eNO (29 vs. 18 ppb, p = 0.01) than those without. The difference in serum total IgE (168 vs. 84.9 IU/ml, p = 0.057) and percentages of positive allergen test results (48.3 vs. 29.5 %, p = 0.082) showed a trend toward significance. The sputum eosinophil level was significantly correlated to the eNO level (r = 0.485, p < 0.001). The eNO level at the cutoff of 23.5 ppb had the maximum sum of sensitivity (62.1 %) and specificity (70.5 %). The unadjusted and adjusted odds ratios of a higher eNO level (>23.5 ppb) in the prediction of sputum eosinophilia were 3.909 (confidence interval (CI) 1.542-9.91, p = 0.004) and 4.329 (CI 1.306-14.356, p = 0.017), respectively. CONCLUSIONS: eNO is a good marker to identify COPD patients with eosinophilic airway inflammation.