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Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the reality that airflow obstruction assessed by spirometry only partially reflects disease severity, a thorough clinical evaluation of the patient should include assessment of symptom burden and risk of exacerbations that permits the implementation of evidence-informed pharmacologic and nonpharmacologic interventions. This guideline provides recommendations from a comprehensive systematic review with a meta-analysis and expert-informed clinical remarks to optimize maintenance pharmacologic therapy for individuals with stable COPD, and a revised and practical treatment pathway based on new evidence since the 2019 update of the Canadian Thoracic Society (CTS) Guideline. The key clinical questions were developed using the Patients/Population (P), Intervention(s) (I), Comparison/Comparator (C), and Outcome (O) model for three questions that focuses on the outcomes of symptoms (dyspnea)/health status, acute exacerbations, and mortality. The evidence from this systematic review and meta-analysis leads to the recommendation that all symptomatic patients with spirometry-confirmed COPD should receive long-acting bronchodilator maintenance therapy. Those with moderate to severe dyspnea (modified Medical Research Council ≥ 2) and/or impaired health status (COPD Assessment Test ≥ 10) and a low risk of exacerbations should receive combination therapy with a long-acting muscarinic antagonist/long-acting áº2-agonist (LAMA/LABA). For those with a moderate/severe dyspnea and/or impaired health status and a high risk of exacerbations should be prescribed triple combination therapy (LAMA/LABA/inhaled corticosteroids) azithromycin, roflumilast or N-acetylcysteine is recommended for specific populations; a recommendation against the use of theophylline, maintenance systemic oral corticosteroids such as prednisone and inhaled corticosteroid monotherapy is made for all COPD patients.
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Agonistas de Receptores Adrenérgicos beta 2 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Quimioterapia Combinada , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Broncodilatadores/uso terapéutico , Canadá , Antagonistas Muscarínicos/uso terapéutico , Administración por Inhalación , Disnea/tratamiento farmacológico , Corticoesteroides/uso terapéuticoRESUMEN
BACKGROUND: Infections are considered as leading causes of acute exacerbations of chronic obstructive pulmonary disease (COPD). Non-infectious risk factors such as short-term air pollution exposure may play a clinically important role. We sought to estimate the relationship between short-term air pollutant exposure and exacerbations in Canadian adults living with mild to moderate COPD. METHODS: In this case-crossover study, exacerbations ('symptom based': ≥48 hours of dyspnoea/sputum volume/purulence; 'event based': 'symptom based' plus requiring antibiotics/corticosteroids or healthcare use) were collected prospectively from 449 participants with spirometry-confirmed COPD within the Canadian Cohort Obstructive Lung Disease. Daily nitrogen dioxide (NO2), fine particulate matter (PM2.5), ground-level ozone (O3), composite of NO2 and O3 (Ox), mean temperature and relative humidity estimates were obtained from national databases. Time-stratified sampling of hazard and control periods on day '0' (day-of-event) and Lags ('-1' to '-6') were compared by fitting generalised estimating equation models. All data were dichotomised into 'warm' (May-October) and 'cool' (November-April) seasons. ORs and 95% CIs were estimated per IQR increase in pollutant concentrations. RESULTS: Increased warm season ambient concentration of NO2 was associated with symptom-based exacerbations on Lag-3 (1.14 (1.01 to 1.29), per IQR), and increased cool season ambient PM2.5 was associated with symptom-based exacerbations on Lag-1 (1.11 (1.03 to 1.20), per IQR). There was a negative association between warm season ambient O3 and symptom-based events on Lag-3 (0.73 (0.52 to 1.00), per IQR). CONCLUSIONS: Short-term ambient NO2 and PM2.5 exposure were associated with increased odds of exacerbations in Canadians with mild to moderate COPD, further heightening the awareness of non-infectious triggers of COPD exacerbations.
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Contaminantes Atmosféricos , Contaminación del Aire , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Humanos , Estudios Cruzados , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Canadá/epidemiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Material Particulado/efectos adversos , Material Particulado/análisis , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisisRESUMEN
Background: Patients with asthma use short-acting ß-agonists (SABA) to relieve symptoms but SABA alone does not treat underlying inflammation. Thus, over-reliance on SABA may result in poor asthma control and negative health outcomes. Objective: To describe use of SABA and characterise the relationship with severe exacerbations in the Canadian provinces of Nova Scotia (NS) and Alberta (AB). Methods: In this longitudinal Canadian SABA In Asthma (SABINA) study, patients with an asthma diagnosis were identified between 2016 and 2020 within two provincial administrative datasets (Health Data Nova Scotia and Alberta Health Services). All patients were followed for ≥24â months, with the first 12â months used to measure baseline asthma severity. Medication use and the relationship of SABA overuse (three or more canisters per year) with severe asthma exacerbations were characterised descriptively and via regression analysis. Results: A total of 115 478 patients were identified (NS: n=8034; AB: n=107 444). SABA overuse was substantial across both provinces (NS: 39.4%; AB: 28.0%) and across all baseline disease severity categories. Patients in NS with SABA overuse had a mean±sd annual rate of 0.46±1.11 exacerbations, compared to 0.30±1.36 for those using fewer than three canisters of SABA. Patients in AB had mean±sd exacerbation rates of 0.31±0.86 and 0.17±0.62, respectively. The adjusted risk of severe exacerbation was associated with SABA overuse (NS: incidence ratio rate 1.36, 95% CI 1.18-1.56; AB: incidence ratio rate 1.32, 95% CI 1.27-1.38). Conclusion: This study supports recent updates to Canadian Thoracic Society and Global Initiative for Asthma guidelines for asthma care. SABA overuse is associated with increased risk of severe exacerbations and can be used to identify patients at a higher risk for severe exacerbations.
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Studies assessing dyspnoea and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) have focussed on patients in clinical settings, not the general population. The aim of this analysis was to compare the prevalence and severity of dyspnoea and impaired HRQoL in individuals with and without COPD from the general population, focussing on mild-moderate COPD. Analysis of the 3-year Canadian Cohort Obstructive Lung Disease (CanCOLD) study included four subgroups: mild COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1); moderate COPD (GOLD 2); non-COPD smokers; and non-COPD never-smokers. The primary outcome was dyspnoea (Medical Research Council (MRC) scale), and the secondary outcome was HRQoL (COPD Assessment Test (CAT) score; Saint George's Respiratory Questionnaire (SGRQ) score). Subgroups were analysed by sex, physician-diagnosed COPD status and exacerbations. 1443 participants (mild COPD (n=397); moderate COPD (n=262(; smokers (n=449) and never-smokers (n=335)) were studied. People with mild COPD were more likely to report more severe dyspnoea (MRC 2 versus 1) than those without COPD (OR (95% CI) 1.42 (1.05-1.91)), and non-COPD never-smokers (OR (95%CI) 1.64 (1.07-2.52)). Among people with mild COPD, more severe dyspnoea was reported in women versus men (MRC2 versus 1; OR (95% CI) 3.70 (2.23-6.14)); people with, versus without, physician-diagnosed COPD (MRC2 versus 1; OR (95% CI) 3.27 (1.71-6.23)), and people with versus without recent exacerbations (MRC2 versus 1; ≥2 versus 0 exacerbations: OR (95% CI) 3.62 (1.02-12.86); MRC ≥3 versus 1; 1 versus 0 exacerbation: OR (95% CI): 9.24 (2.01-42.42)). Similar between-group differences were obtained for CAT and SGRQ scores. Careful assessment of dyspnoea and HRQoL could help identify individuals for earlier diagnosis and treatment.
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Inhaled medications are critical in the pharmaceutical management of respiratory conditions, however, the majority of patients demonstrate at least one critical error when using an inhaler. Since community pharmacists can be instrumental in addressing this care gap, we aimed to determine the rate and type of critical inhaler errors in community pharmacy settings, elucidate the factors contributing to inhaler technique errors, and identify instances when community pharmacists check proper inhaler use. Fourth year pharmacy students on community practice placement (n = 53) identified 200 patients where at least one error was observed in 78% of participants when demonstrating inhaler technique. Prevalent errors of the users were associated with metered dose inhaler (MDI) (55.6%), Ellipta® (88.3%), and Discus® (86.7%) devices. Overall, the mean number of errors was 1.09. Possession of more than one inhaler, use of rescue inhaler, and poor control of asthma were found to be significant predictors of having at least one critical error. In all participating pharmacies, inhaler technique is mainly checked on patient request (93.0%) and for all new inhalers (79.0%).
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BACKGROUND: Previous studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear. METHODS: We determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1â s (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1 in a subset of 1285 males and females, aged ≥40â years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20â pack-years and >20â joint-years, respectively. RESULTS: â¼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55-3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV1 by 29.5â mL·year-1 (p=0.0007) and 21.1â mL·year-1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31â mL·year-1 (p<0.0001). INTERPRETATION: Heavy marijuana smoking increases the risk of COPD and accelerates FEV1 decline in concomitant tobacco smokers beyond that observed with tobacco alone.
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Fumar Marihuana/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar/epidemiología , Adulto , Factores de Edad , Anciano , Canadá , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Espirometría , Factores de TiempoRESUMEN
BACKGROUND: COPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations. METHODS: Data were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed. RESULTS: A total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P = .01), and they were more likely to have baseline PSQI scores > 5 (50.3% vs 37.3%; P = .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P = .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P = .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03). CONCLUSIONS: Higher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up.
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Progresión de la Enfermedad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Sueño , Anciano , Estudios de Cohortes , Disnea/fisiopatología , Femenino , Servicios de Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Esputo , Factores de TiempoRESUMEN
BACKGROUND: Patients with psychiatric disorders (depression, anxiety) are more likely to have poor health behaviours, including higher smoking and lower physical activity (PA) levels. Smoking is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD), and PA is critical for COPD management. However, no studies have assessed associations between psychological distress and these behaviours among patients with vs without COPD. This is a sub-analysis of the CanCOLD study that assessed the relationships between psychological disorders (depression, anxiety) and poor health behaviours (smoking, PA). METHODS: 717 COPD and 797 matched non-COPD individuals from the CanCOLD study, completed the Hospital Anxiety Depression Scale (HADS) to assess anxiety and depression. Smoking behaviour was self-reported pack-years smoking. The CHAMPS PA questionnaire determined calorific expenditure as a PA measure. Regressions determined relationships between anxiety/depression and health behaviours, adjusting for age, sex, BMI, GOLD stage and COPD status. RESULTS: Across the whole sample, we observed relationships between depression (ßâ¯=â¯1.107⯱â¯0.197; 95%CIâ¯=â¯0.691-1.462; pâ¯<â¯.001) and anxiety (ßâ¯=â¯0.780⯱â¯0.170; 95%CIâ¯=â¯0.446-1.114; pâ¯<â¯.001) and pack years. Higher depression (ßâ¯=â¯-0.220⯱â¯0.028; 95%CIâ¯=â¯-0.275 to -0.165; pâ¯<â¯.001) and anxiety (ßâ¯=â¯-0.091⯱â¯0.025; 95%CIâ¯=â¯-0.139 to -0.043; pâ¯<â¯.001) scores were related to lower PA. These associations were comparable across COPD and non-COPD patients. CONCLUSIONS: Results showed that higher levels of anxiety and depression were related to higher cumulative smoking and lower levels of PA in patients with and without COPD, suggesting symptoms of psychological distress is similarly associated with poorer health behaviours in COPD and non-COPD individuals. Future studies need to determine if treating symptoms of psychological distress can improve health behaviours and outcomes in this population.
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Ansiedad/psicología , Depresión/psicología , Enfermedad Pulmonar Obstructiva Crónica/psicología , Fumar/efectos adversos , Anciano , Ansiedad/epidemiología , Canadá/epidemiología , Estudios Transversales , Depresión/epidemiología , Progresión de la Enfermedad , Ejercicio Físico/psicología , Femenino , Conductas de Riesgo para la Salud , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Distrés Psicológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria/métodos , Factores de Riesgo , Autoinforme , Fumar/epidemiologíaAsunto(s)
Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Internacionalidad , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , EspirometríaRESUMEN
BACKGROUND: The COPD Assessment Test (CAT) is a valid disease-specific questionnaire measuring health status. However, knowledge concerning its use regarding patient and disease characteristics remains limited. Our main objective was to assess the degree to which the CAT score varies and can discriminate between specific patient population groups. METHODS: The Canadian Cohort Obstructive Lung Disease (CanCOLD) is a random-sampled, population-based, multicenter, prospective cohort that includes subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] classifications 1 to 3). The CAT questionnaire was administered at three visits (baseline, 1.5 years, and 3 years). The CAT total score was determined for sex, age groups, smoking status, GOLD classification, exacerbations, and comorbidities. RESULTS: A total of 716 subjects with COPD were included in the analysis. The majority of subjects (72.5%) were not previously diagnosed with COPD. The mean FEV1/FVC ratio was 61.1 ± 8.1%, with a mean FEV1 % predicted of 82.3 ± 19.3%. The mean CAT scores were 5.8 ± 5.0, 9.6 ± 6.7, and 16.1 ± 10.0 for GOLD 1, 2, and 3+ classifications, respectively. Higher CAT scores were observed in women, current smokers, ever-smokers, and subjects with a previous diagnosis of COPD. The CAT was also able to distinguish between subjects who experience exacerbations vs those who had no exacerbation. CONCLUSIONS: These results suggest that the CAT, originally designed for use in clinically symptomatic patients with COPD, can also be used in individuals with mild airflow obstruction and newly diagnosed COPD. In addition, the CAT was able to discriminate between sexes and subjects who experience frequent and infrequent exacerbations. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00920348; Study ID No.: IRO-93326.
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Evaluación de la Discapacidad , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Acute hypoxia increases cerebral blood flow (CBF) and ventilation (VÌe). It is unknown if these responses are impacted with normal aging, or in patients with enhanced oxidative stress, such as (COPD). The purpose of the study was to 1) investigate the effects of aging and COPD on the cerebrovascular and ventilatory responses to acute hypoxia, and 2) to assess the effect of vitamin C on these responses during hypoxia. In 12 Younger, 14 Older, and 12 COPD, we measured peak cerebral blood flow velocity (VÌp; index of CBF), and VÌe during two 5-min periods of acute isocapnic hypoxia, under conditions of 1) saline-sham; and 2) intravenous vitamin C. Antioxidants [vitamin C, superoxide dismutase (SOD), glutathione peroxidase, and catalase], oxidative stress [malondialdehyde (MDA) and advanced protein oxidation product], and nitric oxide metabolism end products (NOx) were measured in plasma. Following the administration of vitamin C, vitamin C, SOD, catalase, and MDA increased, while NOx decreased. VÌp and VÌe sensitivity to hypoxia was reduced in Older by â¼60% (P < 0.02). COPD patients exhibited similar VÌp and VÌe responses to Older (P > 0.05). Vitamin C did not have an effect on the hypoxic VÌe response but selectively decreased the VÌp sensitivity in Younger only. These findings suggest a reduced integrative reflex (i.e., cerebrovascular and ventilatory) during acute hypoxemia in healthy older adults. Vitamin C does not appear to have a large influence on the cerebrovascular or ventilatory responses during acute hypoxia.
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Envejecimiento , Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Circulación Cerebrovascular/efectos de los fármacos , Hipoxia/tratamiento farmacológico , Pulmón/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Ventilación Pulmonar/efectos de los fármacos , Adaptación Fisiológica , Administración Intravenosa , Adulto , Factores de Edad , Anciano , Alberta , Biomarcadores/sangre , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Hipoxia/sangre , Hipoxia/diagnóstico , Hipoxia/fisiopatología , Pulmón/metabolismo , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Especies Reactivas de Oxígeno/sangre , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Patients with chronic obstructive pulmonary disease (COPD) have decreased ventilatory and cerebrovascular responses to hypercapnia. Antioxidants increase the ventilatory response to hypercapnia in healthy humans. Cerebral blood flow is an important determinant of carbon dioxide/hydrogen ion concentration at the central chemoreceptors and may be affected by antioxidants. It is unknown whether antioxidants can improve the ventilatory and cerebral blood flow response in individuals in whom these are diminished. Thus, we aimed to determine the effect of vitamin C administration on the ventilatory and cerebrovascular responses to hypercapnia during healthy ageing and in COPD. Using transcranial Doppler ultrasound, we measured the ventilatory and cerebral blood flow responses to hyperoxic hypercapnia before and after an intravenous vitamin C infusion in healthy young (Younger) and older (Older) subjects and in moderate COPD. Vitamin C increased the ventilatory response in COPD patients (mean (95% CI) 1.1 (0.9-1.1) versus 1.5 (1.1-2.0)â L·min-1·mmHg-1, p<0.05) but not in Younger (2.5 (1.9-3.1) versus 2.4 (1.9-2.9)â L·min-1·mmHg-1, p>0.05) or Older (1.3 (1.0-1.7) versus 1.3 (1.0-1.7)â L·min-1·mmHg-1, p>0.05) healthy subjects. Vitamin C did not affect the cerebral blood flow response in the young or older healthy subjects or COPD subjects (p>0.05). Vitamin C increases the ventilatory but not cerebrovascular response to hyperoxic hypercapnia in patients with moderate COPD.
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Human rhinovirus (HRV) infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE) modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.
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Bronquios/patología , Células Epiteliales/metabolismo , Células Epiteliales/virología , Interacciones Huésped-Patógeno/genética , Infecciones por Picornaviridae/genética , Rhinovirus/fisiología , Fumar/efectos adversos , Adulto , Antivirales/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Regulación hacia Abajo/genética , Células Epiteliales/patología , Femenino , Humanos , Interferones/genética , Interferones/metabolismo , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/virología , Reproducibilidad de los Resultados , Transducción de Señal/genéticaRESUMEN
Recent advances in our understanding of the immune-mediated inflammatory pathways in asthma and other allergic diseases have resulted in the development of novel biological compounds for the treatment of these conditions. These compounds offer an advantage over glucocorticosteroid therapy by specifically targeting components of the immunologic cascade, thereby allowing patients to reduce or discontinue their glucocorticosteroid treatment. Another potential advantage of biological compounds is that they may provide additional anti-inflammatory benefits, over and above those provided by glucocorticosteroid therapy, for patients who continue to have evidence of refractory asthma. The anti-IgE monoclonal antibody omalizumab is already being used for the treatment of allergic asthma and a number of other biological therapies are currently in various stages of clinical development. The purpose of this review is to summarize the data from these studies and to provide a rationale for the use of these compounds in asthma and related allergic airway diseases.
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OBJECTIVE: This study was undertaken to assess the role of p97 (also known as melanotransferrin) in the transfer of iron into the brain, because the passage of most large molecules is limited by the presence of the blood-brain barrier, including that of the serum iron transporter transferrin. METHODS: To study the function of the soluble form of p97, we followed the uptake of radioiodinated and 55Fe loaded p97 and transferrin by the brain during a 24-hour period. RESULTS: We show that the soluble form of p97 has the ability to transcytose across the murine blood-brain barrier, and its transcytosis can be inhibited in a specific manner. We also provide evidence that p97 transports iron into the brain more efficiently than transferrin. CONCLUSIONS: These data support the idea that p97 is an important iron transporter across the blood-brain barrier in normal physiology and possibly in neurodegenerative diseases, such as Alzheimer disease, in which iron homeostasis in the brain becomes disrupted.