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OBJECTIVE: Dysfunctional breathing often coexists with asthma and complicates asthma control, especially in difficult-to-treat asthma. Voice bubbling therapy (VBT) by a specialized speech therapist may influence the breathing pattern. This pilot study investigated the effect of voice bubbling therapy (VBT) in participants with difficult-to-treat asthma, who fulfilled criteria for dysfunctional breathing pattern. METHOD: Twenty-four patients were randomized between VBT and usual care (UC). VBT is blowing into a glass (resonance) tube (28 cm in length, 0.9 cm inner diameter) which ends in a bowl of water (1.5 litre). Lung function, capillary blood gas and questionnaires were measured at baseline, at 6 and 18 weeks of follow up. RESULTS: No difference in ACQ and quality of life was found after VBT compared to UC group. However, after six weeks of bubbling therapy, pCO2 levels measured in capillary blood gas were higher (baseline median (IQR) pCO2 = 33.00 (17.25 - 38.6) mmHg; week 6 pCO2 = 36.00 (29.00 - 42.3) mmHg) p = 0.01. Moreover, ΔpCO2 (baseline - 18 weeks of follow up) was significantly correlated with ΔAQLQ (rs = 0.78, p = 0.02). CONCLUSION: VBT in participants with difficult-to-treat asthma resulted in a higher average pCO2 level, indicating the treatment may improve hyperventilation. However, this did not improve asthma control or quality of life. VBT may have value for a better management of asthma related symptoms.
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Asma , Disfunción de los Pliegues Vocales , Asma/diagnóstico , Humanos , Hiperventilación , Proyectos Piloto , Calidad de VidaRESUMEN
BACKGROUND: Coronavirus disease 2019 is a serious respiratory virus pandemic. Patient characteristics, knowledge of the COVID-19 disease, risk behaviour and mental state will differ between individuals. The primary aim of this study was to investigate these variables in patients visiting an emergency department in the Netherlands during the COVID-19 pandemic and to compare the "COVID-19 suspected" (positive and negative tested group) with the "COVID-19 not suspected" (control group) and to compare in the "COVID-19 suspected" group, the positive and negative tested patients. METHODS: Consecutive adult patients, visiting the emergency room at the Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands, were asked to fill out questionnaires on the abovementioned items on an iPad. The patients were either "COVID-19 suspected" (positive and negative tested group) or "COVID-19 not suspected" (control group). RESULTS: This study included a total of 159 patients, 33 (21%) tested positive, 85 (53%) negative and 41 (26%) were COVID-19 not suspected (control group). All patients in this study were generally aware of transmission risks and virulence and adhered to the non-pharmaceutical interventions. Working as a health care professional was correlated to a higher risk of SARS-Cov-2 infection (p- value 0.04). COVID-19 suspected patients had a significantly higher level of anxiety compared to COVID-19 not suspected patients (p-value < 0.001). The higher the anxiety, the more seriously hygiene measures were followed. The anxiety scores of the patients with (pulmonary) comorbidities were significantly higher than without comorbidities. CONCLUSION: This is one of the first (large) study that investigates and compares patient characteristics, knowledge, behaviour, illness perception, and mental state with respect to COVID-19 of patients visiting the emergency room, subdivided as being suspected of having COVID-19 (positive or negative tested) and a control group not suspected of having COVID-19. All patients in this study were generally aware of transmission risks and virulence and adhered to the non-pharmaceutical interventions. COVID-19 suspected patients and patients with (pulmonary) comorbidities were significantly more anxious. However, there is no mass hysteria regarding COVID-19. The higher the degree of fear, the more carefully hygiene measures were observed. Knowledge about the coping of the population during the COVID-19 pandemic is very important, certainly also in the perspective of a possible second outbreak of COVID-19.
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COVID-19/epidemiología , Servicios Médicos de Urgencia/tendencias , Conocimientos, Actitudes y Práctica en Salud/etnología , Adulto , Anciano , Ansiedad/epidemiología , Trastornos de Ansiedad/epidemiología , Estudios de Casos y Controles , Depresión/epidemiología , Brotes de Enfermedades , Servicio de Urgencia en Hospital/tendencias , Miedo , Femenino , Personal de Salud , Conductas de Riesgo para la Salud/fisiología , Humanos , Masculino , Salud Mental/tendencias , Persona de Mediana Edad , Países Bajos/epidemiología , Pandemias/prevención & control , Asunción de Riesgos , SARS-CoV-2/patogenicidadRESUMEN
Introduction: Severe eosinophilic asthma is an incapacitating disease. Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, proved to be effective as an add-on therapy in patients with severe eosinophilic asthma. However, only data from randomized controlled trials are available and real world data are lacking.Methods: A retrospective observational longitudinal study was conducted in a real world cohort of patients with severe eosinophilic asthma treated with mepolizumab. The primary objective was to determine response rate, based on a global evaluation of treatment effectiveness by the treating pulmonologist. Secondary objectives were to assess exacerbation frequency, systemic maintenance glucocorticoid usage, Asthma Control Questionnaire (ACQ), lung function, and adverse events.Results: Seventy-eight patients were included. Treatment with mepolizumab was considered beneficial and was therefore continued in 75.6% of patients 12 months from the initiation of mepolizumab. The most common reason for drop-out was insufficient response. Secondary objectives: 12 months from the initiation of mepolizumab there was a decrease of 3.2 (CI 2.5-4.1; p < 0.001) severe asthma exacerbations per year, a decrease of ACQ of 0.80 points (CI 0.49-1.12; p < 0.001), and an increase of 3.7 (CI 0.3-7.2; p = 0.034) percent of predicted FEV1 compared to baseline. At baseline 51.3% of patients were treated with systemic glucocorticoid maintenance therapy, compared to 15.4% (p < 0.001) of patients 12 months from the initiation of mepolizumab. No serious adverse events considered to be related to mepolizumab were reported.Conclusion: This study confirms that mepolizumab add-on therapy is effective and safe in a real world cohort of patients with severe eosinophilic asthma.
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Antiasmáticos/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Asma/tratamiento farmacológico , Eosinofilia Pulmonar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antiasmáticos/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Asma/fisiopatología , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Volumen Espiratorio Forzado , Glucocorticoides/administración & dosificación , Hospitalización/estadística & datos numéricos , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Many asthmatics in primary care have mild symptoms and lack airflow obstruction. If variable expiratory airflow limitation cannot be determined by spirometry or peak expiratory flow, despite a history of respiratory symptoms, a positive bronchial challenge test (BCT) can confirm the diagnosis of asthma. However, BCT is traditionally performed in secondary care. In this observational real-life study, we retrospectively analyze 5-year data of a primary care diagnostic center carrying out BCT by histamine provocation. In total, 998 primary care patients aged ≥16 years underwent BCT, without any adverse events reported. To explore diagnostic accuracy, we examine 584 patients with a high pretest probability of asthma. Fifty-seven percent of these patients have a positive BCT result and can be accurately diagnosed with asthma. Our real-life data show BCT is safe and feasible in a suitably equipped primary care diagnostic center. Furthermore, it could potentially reduce diagnostic referrals to secondary care.
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Asma/diagnóstico , Pruebas de Provocación Bronquial , Atención Primaria de Salud/métodos , Adolescente , Adulto , Anciano , Pruebas de Provocación Bronquial/efectos adversos , Pruebas de Provocación Bronquial/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
Since there is no adequate treatment for COVID-19, prevention of the transmission of SARS-CoV2 is the best way to cope with the pandemic. National guidelines for non-pharmaceutical interventions focus mainly on the interference with viral transmission via droplets and surface by hygiene measures, limitation of human contact, and social distancing. There is growing evidence that a third route of transmission by aerosols - exhaled tiny particles with viable infectious virus that remain airborne for hours - may be relevant. This route may even be the predominant way of viral transmission in the case of so-called superspreading events. It implies the need for adequate ventilation at indoor spaces without recirculation of virus containing aerosols. Here, the use of face-masks might be of added value too. These measures appear to be especially pivotal during episodes of colder weather, when people spend significantly more time indoors.
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Microbiología del Aire , Betacoronavirus , Infecciones por Coronavirus/transmisión , Neumonía Viral/transmisión , Aerosoles , COVID-19 , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Humanos , Pandemias/prevención & control , Equipo de Protección Personal , Neumonía Viral/prevención & control , Neumonía Viral/virología , SARS-CoV-2 , VentilaciónRESUMEN
A 19-year-old woman presented with a productive cough, fever and chest pain. Clinical and chest X-ray findings prompted us to do a CT-scan, which revealed a mediastinal mass extending in the left thoracic cavity, suggestive of a teratoma with an obstructive pneumonia. The patient was successfully treated with intravenous antibiotics and surgical removal of the tumour.
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Antibacterianos/administración & dosificación , Neoplasias del Mediastino/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Teratoma/diagnóstico por imagen , Administración Intravenosa , Dolor en el Pecho/diagnóstico por imagen , Tos/diagnóstico por imagen , Disnea/etiología , Femenino , Fiebre/diagnóstico por imagen , Humanos , Neoplasias del Mediastino/cirugía , Neumonía/tratamiento farmacológico , Neumonía/cirugía , Teratoma/cirugía , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
OBJECTIVE: Assessment of the effectiveness of the Assessment of Burden of COPD (ABC) tool on disease-specific quality of life in patients with Chronic Obstructive Pulmonary Disease (COPD). DESIGN: Cluster-randomised controlled trial. METHOD: This concerned a trial in 39 Dutch primary care practices and 17 hospitals, involving 357 patients with COPD (postbronchodilator FEV1/FVC ratio < 0.7) aged ≥ 40 years. Healthcare providers were randomized to an intervention or control group. Patients in the intervention group were treated with the ABC tool. This innovative tool consists of a short validated questionnaire and a number of objective parameters, which collectively give a visual overview of the combined integral health; the tool subsequently produces an individualized treatment plan by means of a treatment algorithm. Patients in the control group received usual care. The primary outcome measure was the proportion of patients with a clinically relevant improvement in disease-specific quality of life measured, as measured by means of the St. George's Respiratory Questionnaire (SGRQ) score, between baseline and 18 months follow-up. Secondary outcomes included the SGRQ total score and the Patient Assessment of Chronic Illness Care (PACIC) score. RESULTS: At 18-month follow-up, a significant and clinically relevant improvement in the SGRQ score was seen in 34% of the patients (N=49) in the intervention group, and in the control group this figure was 22% (N=33). This difference between the two groups was significant (OR 1.85, 95% CI 1.08 to 3.16). Patients in the intervention group experienced a higher quality of care than patients in the control group (0.32 points difference in PACIC, 95% CI 0.14 to 0.50). CONCLUSION: Use of the ABC tool increases the disease-specific quality of life and the quality of care for COPD patients; it may therefore offer a valuable contribution to improvements in the daily care of COPD. Replication of this study in other (non-Dutch) health-care settings is recommended.
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Atención Primaria de Salud/métodos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Mejoramiento de la Calidad , Calidad de Vida , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Severe asthma in the elderly places a high burden on affected individuals and society. Emerging therapies target specific phenotypes of the asthma disease spectrum, and can be beneficial for older asthmatics, albeit their response might be altered due to age-related characteristics. Paradoxically, these characteristics are often ground for exclusion from clinical trials. The question thus arises how the senior asthmatic population can successfully enter the era of targeted therapy. Therefore, we highlight characteristics of this population relevant to effective treatment, and review the evidence for targeted therapy in elderly patients. For targeted therapy it is important to account for aging, as this affects the distribution of phenotypes (e.g. late-onset asthma, non-eosinophilic asthma) and may alter biomarkers and drug metabolism. Elderly asthmatics suffer from age-related comorbidities and subsequent polypharmacy. A systematic search into targeted asthma therapy yielded no randomized clinical trials dedicated to older asthmatics. Post hoc analyses of the anti-immunoglobulin E agent omalizumab indicate similar efficacy in both younger and older adults. Conference abstracts on anti-interleukin-5 and anti-interleukin-13 therapy suggest even more pronounced effects of targeted treatments in late-onset disease and in asthmatic patients 65 years or older, but full reports are lacking. For non-eosinophilic asthma in the elderly, there is not yet high-level evidence for targeted therapy, but macrolides may offer a viable option. In conclusion, there is a gap in knowledge regarding the effect of older age on the safety and efficacy of targeted asthma therapy. Further investigations in the elderly are needed, with special emphasis on both late-onset asthma and therapeutics for non-eosinophilic asthma.
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Envejecimiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Interleucina-13/antagonistas & inhibidores , Interleucina-5/antagonistas & inhibidores , Terapia Molecular Dirigida/métodos , Adulto , Anciano , Envejecimiento/inmunología , Anticuerpos Monoclonales Humanizados/efectos adversos , Asma/diagnóstico , Asma/inmunología , Biomarcadores , Humanos , Inmunoglobulina E/metabolismo , Omalizumab/administración & dosificación , Omalizumab/efectos adversos , Omalizumab/uso terapéutico , Fenotipo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To describe the number of ratings and the corresponding scores given to medical specialists on the Dutch healthcare assessment website 'Zorgkaart Nederland.nl', and evaluation of this website as tool for evaluation of quality. DESIGN: Explorative descriptive study. METHOD: In July 2015, data were gathered from the public section of the healthcare assessment website 'ZorgkaartNederland.nl'. The number of specialists, the mean ratings per department (group mark), the number of evaluations, the number of medical specialists without a rating and the number of specialists with at least 9 ratings were registered per speciality, per hospital. Outcomes measures were the median number of ratings per speciality and the group score. Data were analysed using descriptive and non-parametric statistics. RESULTS: Each month, 763,000 unique visitors access ZorgkaartNederland.nl; on average, 0.08% of these registers a vote. There were 15,337 medical specialists, spread across 97 hospitals and 2,060 specialities on ZorgkaartNederland.nl, with a total of 45,548 evaluations. Of these, 6,682 (43.4%) specialists were not rated, and 1.165 (7.6%) had ≥ 9 ratings. Additionally, 327 (15.9%) departments were unrated. Surgical departments were evaluated more often, and their grades were significantly higher, than those of non-surgical departments. CONCLUSION: The website ZorgkaartNederland.nl shows ratings for 56.6% of all medical specialists. When the lower limit of at least 9 evaluations per specialist introduced by ZorgkaartNederland.nl was applied, only the grades for 7.6% of all specialists are valid. On average, 0.08% of unique visitors cast a vote. Surgical specialities have a higher number of evaluations and a higher score than non-surgical ones. ZorgkaartNederland.nl in its current form does not constitute a valid tool for evaluation of the quality of medical specialist care in the Netherlands. This article provides recommendations for improvement.
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Servicios de Información/normas , Internet , Satisfacción del Paciente , Médicos/normas , Adulto , Femenino , Humanos , Masculino , Países Bajos , Médicos/psicologíaRESUMEN
Asthma exacerbations are frequently linked to rhinovirus infections. However, the associated inflammatory pathways are poorly understood, and treatment of exacerbations is often unsatisfactory. In the present study we investigated whether antiinflammatory treatment with inhaled corticosteroids prevents any rhinovirus-induced worsening of lower airway inflammation. To that end, we selected 25 atopic patients with mild asthma who underwent experimental rhinovirus 16 (RV16) infection, while receiving double-blind, placebo-controlled treatment with the inhaled corticosteroid budesonide (800 microg twice a day) throughout the study period, starting 2 wk before infection. We assessed inflammatory cell numbers in the bronchial mucosa as obtained by bronchial biopsies 2 d before and 6 d after RV16 infection, and analyzed those in relation to cold symptoms, changes in blood leukocyte counts, airway obstruction, and airway hyperresponsiveness. RV16 colds induced an increase in CD3(+) cells in the lamina propria (p = 0.03) and tended to decrease the numbers of epithelial eosinophils (p = 0.06) in both groups analyzed as a whole. The T cell accumulation was positively associated with cold symptoms. Budesonide pretreatment improved airway hyperresponsiveness (p = 0.02) and eosinophilic airways inflammation (p = 0.04). Yet it did not significantly affect the RV16-associated changes in the numbers of any of the inflammatory cell types. We conclude that RV16 infection by itself induces only subtle worsening of airway inflammation in asthma, which is not improved (or worsened) by inhaled corticosteroids. The latter finding is in keeping with the limited protection of inhaled corticosteroids against acute asthma exacerbations.
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Antiinflamatorios/administración & dosificación , Asma/complicaciones , Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Budesonida/administración & dosificación , Resfriado Común/tratamiento farmacológico , Resfriado Común/virología , Rhinovirus/efectos de los fármacos , Administración por Inhalación , Adulto , Resistencia de las Vías Respiratorias/efectos de los fármacos , Antiinflamatorios/farmacología , Asma/clasificación , Asma/inmunología , Asma/patología , Biopsia , Pruebas de Provocación Bronquial , Broncodilatadores/farmacología , Budesonida/farmacología , Resfriado Común/clasificación , Método Doble Ciego , Eosinófilos/efectos de los fármacos , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Recuento de Leucocitos , Masculino , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Beta-2 adrenoceptor agonists have been associated with sudden death in asthma patients but the cause and underlying mechanism are unclear. Animal experiments indicate that the combination of hypoxia and beta2 agonists may result in detrimental cardiovascular effects. A study was undertaken to investigate the effect of hypoxia on the systemic vascular effects of salbutamol in patients with asthma who are hypoxic by assessing forearm blood flow (FBF) as a measure of peripheral vasodilatation. METHODS: Eight men with mild asthma underwent the following treatments: normoxia + placebo (NP), normoxia + salbutamol (NS), hypoxia + placebo (HP), and hypoxia + salbutamol (HS). The period of mask breathing started at t=0 minutes, lasted for 60 minutes, and at 30 minutes 800 microg salbutamol was inhaled. The experiment was completed 30 minutes after the inhalation (t=60 minutes). For the hypoxia treatment the SpO2 level was 82%. Differences between treatments were sought using factorial ANOVA on percentage change from the pretreatment value. RESULTS: There were no significant differences in blood pressure and potassium levels between the treatments. After 60 minutes the increase in FBF was 13% (95% CI -12 to 39) more for HP treatment than for NP, 21% (95% CI -5 to 46) more for NS than for NP, and 32% (95% CI 7 to 58) more for HS than for HP (p=0.016). The inhalation of salbutamol during hypoxia resulted in a significant increase in FBF of 45% (95% CI 20 to 71) compared with NP (p=0.001). CONCLUSION: Patients with asthma who are hypoxic and inhale beta2 agonists have serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death.
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Agonistas Adrenérgicos beta/efectos adversos , Albuterol/efectos adversos , Asma/tratamiento farmacológico , Enfermedades Cardiovasculares/inducido químicamente , Hipoxia/complicaciones , Administración por Inhalación , Agonistas Adrenérgicos beta/administración & dosificación , Adulto , Albuterol/administración & dosificación , Análisis de Varianza , Asma/complicaciones , Estudios Cruzados , Método Doble Ciego , Antebrazo/irrigación sanguínea , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Resistencia Vascular/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
Excessive airway narrowing is a cardinal feature of asthma, and results in closure of airways. Therefore, asthmatic patients in whom airway closure occurs relatively early during expiration might be prone to severe asthma attacks. To test this hypothesis, we compared closing volume (CV) and closing capacity (CC) in a group of asthmatic patients with recurrent exacerbations (more than two exacerbations in the previous year; difficult-to-control asthma), consisting of 11 males and two females, aged 20 to 51 yr, with those in a group of equally severely asthmatic controls without recurrent exacerbations (stable asthma) consisting of 13 males and two females aged 18 to 52 yr. Both groups used equivalent doses of inhaled corticosteroids and were matched for sex, age, atopy, postbronchodilator FEV(1), and provocative concentration of methacholine causing a 20% decrease in FEV(1). They were studied during a clinically stable period of their disease. The patients inhaled 400 microg salbutamol via a spacer device, after which TLC and RV were measured by multibreath helium equilibration, together with the slope of Phase 3 (dN(2)), CV, and CC, by single-breath nitrogen washout. CV and CC were expressed as ratios of VC and TLC, respectively, and all data are presented as % predicted (mean +/- SEM). There was no difference in TLC in patients with difficult-to-control asthma and those with stable asthma (106.7 +/- 4.0% predicted versus 101.7 +/- 4.3% predicted, p = 0.40), RV (113.1 +/- 7.8% predicted versus 100.9 +/- 7.1% predicted, p = 0.26), or dN(2) (142.7 +/- 16.3% predicted versus 116.0 +/- 20.2% predicted, p = 0.23). In contrast, CV and CC were increased in the patients with difficult-to-control asthma as compared with the group with stable asthma (CV: 159.5 +/- 26.8% predicted versus 98.8 +/- 12.5% predicted, p = 0.024; CC: 114.0 +/- 6.4% predicted versus 99.9 +/- 3. 6% predicted, p = 0.030). These findings show that asthmatic individuals with recurrent exacerbations have increased CV and CC as compared with equally severely asthmatic but stable controls, even after bronchodilation during well-controlled episodes. The findings imply that airway closure at relatively high lung volumes under clinically stable conditions might be a risk factor for severe exacerbations in asthmatic patients.
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Asma/diagnóstico , Hiperreactividad Bronquial/diagnóstico , Broncoconstricción/fisiología , Hipersensibilidad Respiratoria/diagnóstico , Adolescente , Adulto , Asma/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Volumen de Cierre/fisiología , Femenino , Humanos , Mediciones del Volumen Pulmonar , Masculino , Persona de Mediana Edad , Recurrencia , Hipersensibilidad Respiratoria/fisiopatología , Factores de RiesgoRESUMEN
Some patients with severe asthma are difficult to control and suffer from frequent exacerbations, whereas others remain stable with anti-inflammatory therapy. To investigate mechanisms of exacerbations, we compared 13 patients 20 to 51 yr of age (11 female, two male) with difficult-to-control asthma (two or more exacerbations during the previous year) and 15 patients 20 to 47 yr of age (13 female, two male) with severe but stable asthma (no exacerbations) after matching for sex, age, atopy, lung function, airway responsiveness, and medication. Exacerbations were induced by double-blind, controlled tapering of inhaled corticosteroids (fluticasone propionate) at weekly intervals. FEV1, airway responsiveness for methacholine (PC20MCh) and hypertonic saline (HYP slope), eosinophils and soluble markers (ECP, albumin, IL-6, IL-8) in induced sputum were assessed at baseline and during exacerbation (peak flow < 60% of personal best), or after 5 wk if no exacerbation occurred. Steroid tapering caused a decrease (mean +/- SEM) in FEV1 (12.1 +/- 3.1% pred; p = 0.045), PC20MCh (2.1 +/- 0.4 doubling dose; p = 0.004) and HYP slope (1.7 +/- 0.3 doubling dose; p = 0.001), and an increase in sputum eosinophils (10 +/- 3%; p = 0.008) and soluble markers for the two groups combined, without significant differences between the groups. Patients with difficult-to-control asthma had more exacerbations than did the stable asthmatics during both steroid tapering (7 versus 2; p = 0.022) and corticosteroid treatment (6 versus 0; p = 0.003). Exacerbations during steroid treatment in the patients with difficult-to-control asthma were associated with a decrease in FEV1 and PC20MCh, but not in HYP slope or increase in sputum eosinophils. We conclude that tapering of inhaled corticosteroids induces a rapid, reversible flare-up of eosinophilic airway inflammation. Patients with difficult-to-control asthma may develop exacerbations despite treatment with inhaled corticosteroids, which appear to have an eosinophil-independent mechanism. This implies that assessment of the nature of exacerbations may contribute to improved treatment for these patients.
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Androstadienos/efectos adversos , Antiasmáticos/efectos adversos , Antiinflamatorios/efectos adversos , Asma/tratamiento farmacológico , Esputo , Síndrome de Abstinencia a Sustancias/diagnóstico , Administración por Inhalación , Adulto , Resistencia de las Vías Respiratorias/efectos de los fármacos , Resistencia de las Vías Respiratorias/fisiología , Androstadienos/administración & dosificación , Antiasmáticos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/diagnóstico , Asma/fisiopatología , Pruebas de Provocación Bronquial , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Eosinófilos/efectos de los fármacos , Eosinófilos/fisiología , Femenino , Fluticasona , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Síndrome de Abstinencia a Sustancias/fisiopatologíaRESUMEN
BACKGROUND: Patients with asthma show altered surface expression of the adhesion molecules CD11b and L-selectin on airway granulocytes compared with blood granulocytes. OBJECTIVE: To investigate whether this modulation is related to disease activity or due to transendothelial migration, we compared the CD11b and L-selectin expression on blood and induced sputum eosinophils and neutrophils between patients with asthma and normal subjects. METHODS: Eleven normal subjects (21-43 years), nine patients (21-34 years) with mild atopic asthma and 10 patients (20-47 years) with moderate to severe atopic asthma on regular treatment with inhaled steroids underwent sputum induction by inhalation of nebulized hypertonic saline (4.5%). CD11b and L-selectin expression on granulocytes from blood and DTT-homogenized sputum were analysed by flow cytometry. Eosinophils could be discriminated from neutrophils by using depolarized light scatter. Disease activity was assessed by baseline FEV1 and airway responsiveness to histamine (PC20). RESULTS: Sputum eosinophils showed higher expression of CD11b (P<0.001) and lower expression of L-selectin (P<0.001) compared with peripheral blood eosinophils. CD11b and L-selectin expression on eosinophils from blood or sputum did not differ between the three groups. Similar results were obtained for neutrophils. The PC20 in the patients with moderate-to-severe asthma was related to CD11b expression on blood (R=-0.92, P=0.001) and sputum eosinophils (R=0.75, P=0.02). CONCLUSIONS: Flow cytometry of induced sputum granulocytes from asthmatic as well as normal subjects is feasible. We conclude that the modulated expression of CD11b and L-selectin on airway granulocytes is not specific for asthmatic airway inflammation, but is probably the result of tissue migration per sé. This implies that CD11b and L-selectin expression on granulocytes in induced sputum cannot be used as marker of disease activity.
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Asma/inmunología , Eosinófilos/inmunología , Selectina L/análisis , Antígeno de Macrófago-1/análisis , Neutrófilos/inmunología , Esputo/citología , Esputo/inmunología , Adulto , Asma/sangre , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Volumen Espiratorio Forzado , Histamina/administración & dosificación , Humanos , Selectina L/sangre , Antígeno de Macrófago-1/sangre , Masculino , Persona de Mediana EdadAsunto(s)
Asma/diagnóstico , Inflamación/diagnóstico , Esputo/citología , Asma/fisiopatología , Pruebas de Provocación Bronquial , Humanos , Inflamación/fisiopatología , Reproducibilidad de los Resultados , Pruebas de Función Respiratoria , Sistema Respiratorio/fisiopatología , Sensibilidad y EspecificidadRESUMEN
Sputum induced by inhalation of nebulized hypertonic saline is increasingly used to monitor airways inflammation in asthma. The aim of this study was to assess the repeatability of measuring cellular and soluble markers of inflammation in whole sputum samples as obtained by sputum induction in patients both with mild and moderate-to-severe asthma. Twelve patients with mild, atopic asthma without inhaled steroid treatment and nine patients with moderate-to-severe, atopic asthma treated with inhaled steroids were studied on two separate days at least 2 days apart. Whole sputum samples, induced by inhalation of hypertonic (4.5%) saline, were homogenized, and analysed for differential cell counts and for concentrations of albumin, fibrinogen, interleukin-8 (IL-8), and eosinophil cationic protein (ECP). Repeatability was expressed as intraclass correlation coefficient (Ri), and as coefficient of repeatability (CR) in percentage cells or in doubling concentration. Samples from two patients with mild asthma contained more than 80% squamous cells and were excluded from analysis. The repeatability for cell differential counts in both groups combined was: for neutrophils, Ri = 0.57 and CR = 31.0; for eosinophils, Ri = 0.85 and CR = 12.4; and for lymphocytes, Ri = 0.76 and CR = 6.9. The repeatability of the fluid phase measurements was: for albumin, Ri = 0.71 and CR = 3.2; for fibrinogen, Ri = 0.88 and CR = 2.8; for IL-8, Ri = 0.66 and CR = 2.2; and for ECP, Ri = 0.82 and CR = 1.1. We conclude that the repeatability of cellular and soluble markers of inflammation in induced sputum from patients with mild and moderate-to-severe asthma is satisfactory. Hence, induced sputum, processed by using the whole expectorated sample, seems to be a valuable method to monitor airway inflammation in asthma.