RESUMEN
BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.
Asunto(s)
Absentismo , Asma/epidemiología , Eficiencia , Calidad de Vida , Lugar de Trabajo , Actividades Cotidianas , Adulto , Anciano , Asma/diagnóstico , Asma/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. AIMS: To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. METHODS: A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. RESULTS: Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). CONCLUSION: Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting.
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Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Omalizumab/administración & dosificación , Vigilancia de Productos Comercializados , Adolescente , Corticoesteroides/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antiasmáticos/efectos adversos , Australia , Dolor en el Pecho/inducido químicamente , Niño , Comorbilidad , Femenino , Cefalea/inducido químicamente , Humanos , Hipersensibilidad/etiología , Modelos Lineales , Masculino , Persona de Mediana Edad , Omalizumab/efectos adversos , Calidad de Vida , Sistema de Registros , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Rhinoviruses (RV) are the most common acute triggers of asthma, and airway epithelial cells are the primary site of infection. Asthmatic bronchial epithelial cells (BECs) have been found to have impaired innate immune responses to RV. RV entry and replication is recognized by pathogen recognition receptors (PRRs), specifically toll-like receptor (TLR)3 and the RNA helicases; retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). OBJECTIVE: Our aim was to assess the relative importance of these PRRs in primary bronchial epithelial cells (pBEC) from healthy controls and asthmatics following RV infection and determine whether deficient innate immune responses in asthmatic pBECs were due to abnormal signalling via these PRRs. METHODS: The expression patterns and roles of TLR3 and MDA5 were investigated using siRNA knock-down, with subsequent RV1B infection in pBECs from each patient group. We also used BX795, a specific inhibitor of TBK1 and IKKi. RESULTS: Asthmatic pBECs had significantly reduced release of IL-6, CXCL-8 and IFN-λ in response to RV1B infection compared with healthy pBECs. In healthy pBECs, siMDA5, siTLR3 and BX795 all reduced release of IL-6, CXCL-10 and IFN-λ to infection. In contrast, in asthmatic pBECs where responses were already reduced, there was no further reduction in IL-6 and IFN-λ, although there was in CXCL-10. CONCLUSION AND CLINICAL RELEVANCE: Impaired antiviral responses in asthmatic pBECs are not due to deficient expression of PRRs; MDA5 and TLR3, but an inability to later activate types I and III interferon immune responses to RV infection, potentially increasing susceptibility to the effects of RV infection.
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Asma/genética , Asma/metabolismo , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Transducción de Señal , Receptor Toll-Like 3/genética , Receptor Toll-Like 3/metabolismo , Adulto , Asma/inmunología , Asma/virología , Estudios de Casos y Controles , Proteína 58 DEAD Box , Células Epiteliales/metabolismo , Células Epiteliales/virología , Femenino , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Factor 3 Regulador del Interferón/antagonistas & inhibidores , Helicasa Inducida por Interferón IFIH1 , Interferones/biosíntesis , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Infecciones por Picornaviridae/genética , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/metabolismo , Receptores Inmunológicos , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/virología , Rhinovirus/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of hospital admission and clinical guidelines for optimised management are available. However, few data assessing concordance with these guidelines are available. We aimed to identify gaps and document variability in clinical practices for COPD admissions. METHODS: Medical records of all admissions over a 3-month period as COPD with non-catastrophic or severe comorbidities or complications at eight acute-care hospitals within the Hunter New England region were retrospectively audited. RESULTS: Mean (SD) length of stay was 6.3 (6.1) days for 221 admissions with mean age of 71 (10), 53% female and 34% current smokers. Spirometry was performed in 34% of admissions with a wide inter-hospital range (4-58%, P < 0.0001): mean FEV1 was 36% (18) predicted. Arterial blood gases were performed on admission in 54% of cases (range 0-85%, P < 0.0001). Parenteral steroids were used in 82% of admissions, antibiotics in 87% and oxygen therapy during admission in 79% (with oxygen prescription in only 3% of these). Bronchodilator therapy was converted from nebuliser to an inhaler device in 51% of cases early in admission at 1.6 (1.7) days. Only 22% of patients were referred to pulmonary rehabilitation (inter-hospital range of 0-50%, P = 0.002). Re-admission within 28 days was higher in rural hospitals compared with metropolitan (27% vs 7%, P < 0.0001). CONCLUSIONS: We identified gaps in best practice service provision associated with wide inter-hospital variations, indicating disparity in access to services throughout the region.
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Disparidades en Atención de Salud/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Enfermedad Pulmonar Obstructiva Crónica/terapia , Anciano , Anciano de 80 o más Años , Auditoría Clínica , Comorbilidad , Femenino , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , New England , Estudios Retrospectivos , Espirometría , Resultado del TratamientoRESUMEN
The receptor for advanced glycation end-products (RAGE) is a pattern-recognition receptor involved in the host response to injury, infection and inflammation. It is a membrane receptor, but also has soluble forms (sRAGE). Deficiencies in sRAGE are linked to heightened inflammation in various chronic conditions. We determined whether airway and systemic levels of sRAGE and the RAGE ligands HMGB1 (high-mobility group box-1) and serum amyloid A (SAA) are related to neutrophilic inflammation in asthma and chronic obstructive pulmonary disease (COPD). Bronchial lavage fluid from subjects with moderate-to-severe persistent asthma (n = 16) or COPD (n = 37), or from healthy controls (n = 18), was analysed for neutrophils, total sRAGE, endogenous secretory RAGE (esRAGE), HMGB1 and SAA. We also determined systemic levels of sRAGE in a separate group of asthmatic (n = 101) and COPD (n = 34) subjects. Subjects with neutrophilic asthma or COPD had undetectable levels of lung sRAGE, while levels of sRAGE in asthma/COPD without neutrophilia were similar to those in controls. Systemic sRAGE was significantly decreased in subjects with neutrophilic asthma or COPD compared with those without airway neutrophilia. There was significant positive correlation between total sRAGE and esRAGE in the lung and systemically. HMGB1 levels were similar in all subject groups, while SAA was below detectable levels. Neutrophilic airway inflammation in asthma and COPD is associated with reduced sRAGE.
Asunto(s)
Asma/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Receptores Inmunológicos/deficiencia , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Femenino , Proteínas del Grupo de Alta Movilidad/análisis , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/análisis , Proteínas Represoras/análisis , Proteína Amiloide A Sérica/análisisRESUMEN
BACKGROUND: The role of toll-like receptors (TLRs) and innate immune activation in clinical asthma exacerbations and their relationship to virus infection are unclear. OBJECTIVE: This study aimed to characterize TLR expression and innate immune activity during virus infection in acute asthma. METHODS: Subjects with acute asthma, stable asthma and healthy controls were recruited and underwent spirometry and sputum induction with isotonic saline. Selected sputum was dispersed with dithiothreitol and total and differential leucocyte counts were performed. Selected sputum was also used for quantitative real-time PCR for TLR2, TLR3, TLR4, IL-10 and IP-10mRNA expression. Sputum supernatant was used for the measurement of innate immune markers, including IL-8, matrix metalloproteinase-9 and neutrophil elastase activity. Viruses were detected using real-time and gel-based PCR. RESULTS: Sputum TLR2 mRNA expression was up-regulated in both acute and stable asthma compared with healthy controls and decreased 4-6 weeks after acute exacerbation. Sputum TLR2 mRNA expression was elevated in viral, compared with non-viral, acute asthma. Sputum TLR3 mRNA expression was similar in controls, stable and acute asthma. However, in acute asthma, subjects with virus-induced acute asthma had significantly higher sputum TLR3 mRNA expression. Induced sputum gene expression for IP-10 and IL-10 were increased in viral, compared with non-viral, acute asthma. In virus-induced acute asthma, levels of IP-10 and IL-10 mRNA expression were correlated with the mRNA expression of TLR2 and TLR3. CONCLUSIONS AND CLINICAL RELEVANCE: Virus-induced acute asthma leads to specific induction of TLR2, TLR3, IP-10 and IL-10, suggesting that signalling via TLRs may play an important role in mediating airway inflammation, via both innate and adaptive pathways, in virus-induced exacerbations. These mediators may provide potential treatment targets for virus-induced asthma. They may also be useful in diagnosing the nature of acute asthma exacerbations and monitoring treatment responses, which would be useful in the clinical management of asthma exacerbations.
Asunto(s)
Asma/inmunología , Asma/virología , Inmunidad Innata , Transducción de Señal/inmunología , Receptores Toll-Like/inmunología , Enfermedad Aguda , Adolescente , Adulto , Asma/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Interleucina-10/genética , Interleucina-10/inmunología , Masculino , Persona de Mediana Edad , Receptores de Citocinas/genética , Receptores de Citocinas/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esputo/química , Esputo/inmunología , Esputo/virología , Receptores Toll-Like/genética , Adulto JovenRESUMEN
Asthma exacerbations are an exaggerated lower airway response to an environmental exposure. Respiratory virus infection is the most common environmental exposure to cause a severe asthma exacerbation. Airway inflammation is a key part of the lower airway response in asthma exacerbation, and occurs together with airflow obstruction and increased airway responsiveness. The patterns of airway inflammation differ according to the trigger factor responsible for the exacerbation. The reasons for the exaggerated response of asthmatic airways are not completely understood, but recent studies have identified a deficient epithelial type 1 interferon response as an important susceptibility mechanism for viral infection.
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Asma/patología , Bronquiolitis/patología , Enfermedad Aguda , Alérgenos/efectos adversos , Asma/etiología , Susceptibilidad a Enfermedades , Contaminantes Ambientales/toxicidad , Humanos , Moco/microbiología , Exposición Profesional/efectos adversos , Infecciones del Sistema Respiratorio/patología , Fumar/efectos adversos , Virosis/patologíaRESUMEN
BACKGROUND: Lung disease in cystic fibrosis is characterised by impaired mucociliary clearance. Hypertonic saline has been shown to enhance mucociliary clearance in vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To investigate the effects of treatment with nebulised hypertonic saline on people with cystic fibrosis compared to placebo and or other treatments that enhance mucociliary clearance. SEARCH STRATEGY: 'We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Most recent search of the Trials Register: September 2004. SELECTION CRITERIA: All controlled trials assessing the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with cystic fibrosis of any age or severity. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all identified trials and all data collected. Trial quality was assessed along with allocation concealment. MAIN RESULTS: Fourteen controlled trials were identified. Nine trials met the inclusion criteria involving 235 participants with an age range of 6 years to 46 years. Two short-term trials of immediate effect on mucociliary clearance demonstrated that hypertonic saline increased isotope clearance compared to control. Lung function, measured by improvement in forced expiratory volume at one second (FEV1 litre per minute), was observed in four trials. When 3% to 7% saline was used in a volume of 10 ml twice-a-day, in comparison to placebo, hypertonic saline led to a significant increase in FEV1, weighted mean difference 12.20 (95%CI 4.28 to 20.10). Two further trials compared a similar concentration and volume of hypertonic saline to recombinant deoxyribonuclease. Over a three-week period one trial showed a non-significant difference, mean difference 1.60 (95% CI -7.96 to 11.16). However, in a further trial, after 12 weeks treatment in participants with moderate to severe lung disease, recombinant deoxyribonuclease led to a greater increase in FEV1 than hypertonic saline (5 ml twice-daily), mean difference 8.00 (95%CI 2.00 to 14.00). No serious adverse events were noted. AUTHORS' CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance in short-term clinical trials and appears to increase lung function compared to control. In comparison to recombinant deoxyribonuclease it may be less effective at improving lung function after three months. Currently there is insufficient evidence to support the use of hypertonic saline as routine treatment for people with cystic fibrosis.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Solución Salina Hipertónica/uso terapéutico , Administración por Inhalación , Ensayos Clínicos Controlados como Asunto , Humanos , Depuración Mucociliar , Nebulizadores y Vaporizadores , Ensayos Clínicos Controlados Aleatorios como Asunto , Solución Salina Hipertónica/administración & dosificaciónRESUMEN
BACKGROUND: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January 2003. SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15). REVIEWERS' CONCLUSIONS: Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.
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Antifúngicos/uso terapéutico , Aspergilosis Broncopulmonar Alérgica/tratamiento farmacológico , Asma/complicaciones , Antifúngicos/efectos adversos , Humanos , Itraconazol/efectos adversos , Itraconazol/uso terapéutico , Cetoconazol/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January 2003. SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15). REVIEWER'S CONCLUSIONS: Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.
Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis Broncopulmonar Alérgica/tratamiento farmacológico , Asma/complicaciones , Ensayos Clínicos Controlados como Asunto , Humanos , Itraconazol/uso terapéutico , Cetoconazol/uso terapéuticoRESUMEN
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus, causing severe asthma that may progress to bronchiectasis. Sputum neutrophilia can occur in association with sputum eosinophilia and correlates with the degree of bronchiectasis. The mechanisms of sputum neutrophilia in ABPA are not known. The aim of this study was to investigate the role of the chemokine interleukin (IL)-8 in sputum neutrophilia in ABPA. Induced sputum was obtained from subjects with ABPA (n=29), and compared to nonsensitised asthma (n=9) and healthy controls (n=21). Semiquantitative polymerase chain reaction was used to assess IL-8 gene expression in induced sputum and IL-8 protein was measured by enzyme-linked immunosorbent assay. Sputum IL-8 protein was significantly higher in ABPA compared to asthma and controls. IL-8 messenger ribonucleic acid/glyceraldehyde-3-phosphate dehydrogenase ratio was elevated in ABPA compared to asthma and controls. Sputum IL-8 correlated with sputum neutrophils, matrix metalloproteinase-9 levels and forced expiratory volume in one second. Interleukin-8 gene expression and protein release were increased in allergic bronchopulmonary aspergillosis and correlated with airway neutrophilia and airway obstruction. The interleukin-8-mediated neutrophil influx in allergic bronchopulmonary aspergillosis may induce lung damage via release of matrix metalloproteinase-9, potentially leading to bronchiectasis.
Asunto(s)
Aspergilosis Broncopulmonar Alérgica/enzimología , Aspergilosis Broncopulmonar Alérgica/inmunología , Aspergillus fumigatus , Asma/inmunología , Interleucina-8/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Neutrófilos/inmunología , Esputo/inmunología , Adulto , Análisis de Varianza , Aspergilosis Broncopulmonar Alérgica/diagnóstico por imagen , Aspergillus fumigatus/inmunología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Ensayo de Inmunoadsorción Enzimática , Eosinófilos/inmunología , Femenino , Expresión Génica , Humanos , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos XRESUMEN
Infection with Chlamydia pneumoniae can trigger acute asthma and is associated with severe chronic asthma. The aim of the present study was to examine the relationship between airway inflammation and serological response to C. pneumoniae in acute severe asthma. Subjects (n=54) were recruited within 4 h of presentation to the emergency department with an acute exacerbation of asthma. Clinical history taking, sputum induction (0.9% saline), spirometry and acute and convalescent serology for C. pneumoniae immunoglobulins A and G were performed. At presentation, 47% of subjects had antibodies directed against C. pneumoniae, and 38% (20) demonstrated an increase in C. pneumoniae antibody levels, with 15 demonstrating a rise in immunoglobulin A concentration. C. pneumoniae responders exhibited significantly higher sputum neutrophil levels (4.6 x 10(6) cells x mL(-1)) compared to nonresponders (1.2 x 10(6) cells x mL(-1), p=0.02) and elevated sputum eosinophil cationic protein concentration (3,981 versus 1,122 ng x mL(-1), p=0.02). An acute antibody response to Chlamydia pneumoniae is common in exacerbations of asthma. The serological features suggest that Chlamydia pneumoniae reactivation may trigger neutrophilic airway inflammation in acute asthma.
Asunto(s)
Asma/fisiopatología , Hiperreactividad Bronquial/inmunología , Infecciones por Chlamydophila/diagnóstico , Chlamydophila pneumoniae/inmunología , Inmunoglobulina A/análisis , Neumonía Bacteriana/diagnóstico , Adulto , Análisis de Varianza , Anticuerpos Antibacterianos/análisis , Asma/diagnóstico , Asma/inmunología , Hiperreactividad Bronquial/microbiología , Pruebas de Provocación Bronquial , Distribución de Chi-Cuadrado , Infecciones por Chlamydophila/inmunología , Cuidados Críticos , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/inmunología , Probabilidad , Pronóstico , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Espirometría , Esputo/citologíaRESUMEN
Acute exacerbations of asthma are frequently caused by viral infections, but the inflammatory mechanisms in virus-induced asthma are poorly understood. The aim of the present study was to determine whether viral infection in acute asthma was associated with increased sputum neutrophil degranulation and increased cellular lysis and whether these changes are related to clinical severity. Adults (n=49) presenting to the emergency department with acute asthma were examined for infection by means of sputum direct-fluorescence antigen detection, sputum culture, and sputum polymerase chain reaction for Mycoplasma, Chlamydia and Legionella pneumophila, and all common respiratory viruses. Subjects infected with one of these agents were classed as having an infective exacerbation. Spirometry and sputum induction were performed on presentation and 4-5 weeks later. Thirty-seven subjects (76%) had virus infection and acute asthma. Those with virus infection had increased sputum neutrophils (p<0.05) and increased neutrophil elastase (p<0.05), this was related to increased elevated sputum lactate dehydrogenase (LDH). Subjects with noninfective asthma had an increase in the proportion of sputum eosinophils. Both groups had elevated sputum eosinophil cationic protein (ECP) concentrations. Higher levels of sputum LDH and ECP were associated with a longer hospital stay. Virus infection and acute asthma is associated with neutrophilic inflammation, cell lysis and more severe clinical disease.
Asunto(s)
Asma/etiología , Asma/fisiopatología , Neutrófilos/fisiología , Ribonucleasas , Virosis/complicaciones , Adolescente , Adulto , Anciano , Proteínas Sanguíneas/análisis , Degranulación de la Célula/fisiología , Proteínas en los Gránulos del Eosinófilo , Femenino , Humanos , Inflamación , L-Lactato Deshidrogenasa/análisis , Masculino , Persona de Mediana Edad , Esputo/química , Esputo/citologíaRESUMEN
BACKGROUND: Epidemics of acute asthma associated with thunderstorms occur intermittently worldwide, though airway inflammation during these acute episodes has not been characterized. The aim of this study was to characterize airway inflammation in thunderstorm asthma. METHODS: Cases were recruited after presentation to the emergency room with acute asthma immediately following a thunderstorm (n = 6). They were compared to two control groups: a group of atopic asthmatics that had presented with acute asthma to the emergency room prior to the thunderstorm (n = 12), and a second group of corticosteroid naive asthmatics who presented to the emergency room in the prior 12 months (n = 6). Subjects had spirometry, sputum induction and allergy skin tests acutely and at review 4 weeks later. RESULTS: Thunderstorm (TS) cases were more likely to have a history of hay fever and grass pollen allergy, and less likely to be on inhaled corticosteroids (ICS) prior to presentation. Cases and control groups had a similar degree of moderate to severe acute airway obstruction (P = 1.0). TS cases had elevated sputum eosinophils (14.8% of total cell count) compared to controls (1%, 2.6%, P < 0.01). TS cases had higher sputum eosinophil cationic protein (ECP; 11,686 ng/mL) compared to controls (1,883, 3,300, P = 0.02) acutely. TS cases had more cells positive for IL-5 (30%) compared to controls (1, 1.5%, P = 0.02). When adjusted for ICS use, TS cases had a risk ratio for elevated sputum eosinophils of 2.4 (1.23-4.69). CONCLUSION: Thunderstorm asthma is characterized by airway inflammation with IL-5-mediated sputum eosinophilia and eosinophil degranulation. These results are consistent with allergen exposure as the cause of the exacerbation, and are consistent with the thunderstorm-induced grass pollen deluge as the cause of epidemic asthma after thunderstorms.