RESUMO
UNLABELLED: This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 µg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 µg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. ( CLINICAL TRIAL NUMBER: ISRCTN60408425).
Assuntos
Antiasmáticos/administração & dosagem , Asma/prevenção & controle , Administração por Inalação , Adolescente , Adulto , Idoso , Androstadienos/administração & dosagem , Androstadienos/efeitos adversos , Antiasmáticos/efeitos adversos , Asma/fisiopatologia , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Criança , Combinação de Medicamentos , Inaladores de Pó Seco , Etanolaminas/administração & dosagem , Etanolaminas/efeitos adversos , Feminino , Fluticasona , Volume Expiratório Forçado/efeitos dos fármacos , Fumarato de Formoterol , Humanos , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório/efeitos dos fármacos , Resultado do Tratamento , Adulto JovemRESUMO
Normalisation of eosinophil counts in sputum of asthmatic patients reduces eosinophilic exacerbations. However, the effect of this strategy on airway remodelling remains to be determined. We compared bronchial inflammation and collagen deposition after 2 yrs of treatment guided by either sputum eosinophils (sputum strategy, SS) or by clinical criteria (clinical strategy, CS). As a pilot study, 20 mild asthmatic patients were randomly assigned to CS or SS strategies. Bronchial biopsies were obtained when minimum treatment needed to maintain control was identified and this was continued for 2 yrs. Biopsies were immunostained for inflammatory cells, mucin 5A (MUC5A) and collagen. The mean dose of inhaled corticosteroids at the start and end of the study was similar in both SS and CS groups. Forced expiratory volume in 1 s increased in both groups at the study end. In SS, mucosal lymphocyte and eosinophil counts, but not neutrophils, were reduced at the end of the study. In CS, only activated eosinophil and neutrophil counts decreased. MUC5A staining decreased in SS but not CS. No change in collagen deposition underneath the basement membrane was observed in either strategy. Treatment strategies that normalise sputum eosinophils also reduce mucosal inflammatory cells and MUC5A expression, but do not change subepithelial collagen deposition in mild to moderate asthma.
Assuntos
Remodelação das Vias Aéreas , Asma/imunologia , Bronquite/imunologia , Eosinófilos , Escarro/citologia , Adulto , Asma/patologia , Biópsia , Bronquite/patologia , Contagem de Células , Feminino , Humanos , Masculino , Projetos PilotoRESUMO
BACKGROUND: Asthma phenotypes are well described among children. However, there are few studies comparing airway inflammation in different clinical presentations of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated with a predominant noneosinophilic inflammation in the airways, as assessed by induced sputum. The objective of this study was to evaluate the cytological characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA) and nonatopic nonasthmatic children (NANA). METHODS: Of 90 selected children, 77 met eligibility criteria for performing IS and were classified as: AA, n = 28, NAA, n = 29 and NANA, n = 19. Subjects answered to a set of ISAAC-based questions and were skin-tested for common aeroallergens. A defined series of exclusion criteria was applied. RESULTS: Induced sputum was obtained from 54 (70.1%) subjects (21 AA, 20 NAA and 13 NANA). Demographic data and mean FEV(1) were similar in the three groups. The proportion of eosinophils [median, inter quartile range (IQR)] was significantly higher in the sputum of AA [(6.0.)12)] compared with NAAs [0 (2)] and NANAs [0 (1)], P < 0.001. The proportion of children with sputum eosinophilia (eos > 3%) was also significantly higher in AA (71.4%) when compared with NAA (28.6%); none of the NANA had sputum eosinophilia. Nonatopic asthmatic children had significantly higher proportions and absolute number of neutrophils than AA and controls. CONCLUSIONS: The results suggest that nonatopic children present IS with a cell pattern that is predominantly neutrophilic while eosinophilia is the hallmark of airway inflammation in the majority of atopic wheezing children not treated with inhaled steroids.
Assuntos
Asma/imunologia , Inflamação/imunologia , Neutrófilos/imunologia , Escarro/imunologia , Adolescente , Asma/fisiopatologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/fisiopatologia , Inflamação/fisiopatologia , Masculino , Neutrófilos/citologia , Escarro/citologiaRESUMO
Asthma is a serious health problem throughout the world. During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively. However, recommendations for asthma care need to be adapted to local conditions, resources and services. Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations. A comprehensive workshop report entitled "A Global Strategy for Asthma Management and Prevention", first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines. The 2006 report contains important new themes. First, it asserts that "it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained," and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions. The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised.
Assuntos
Asma/diagnóstico , Asma/prevenção & controle , Asma/terapia , Corticosteroides/farmacologia , Antiasmáticos/uso terapêutico , Asma/epidemiologia , Diagnóstico Diferencial , Gerenciamento Clínico , Saúde Global , Guias como Assunto , Humanos , Comunicação Interdisciplinar , Saúde Pública , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Pneumologia/métodos , Fatores de RiscoRESUMO
One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils
Assuntos
Asma/diagnóstico , Asma/tratamento farmacológico , Espirometria , Escarro/citologia , Adulto , Contagem de Células , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The role of inhaled corticosteroids in the management of chronic obstructive pulmonary disease (COPD) remains controversial. The purpose of this study was to evaluate whether sputum eosinophilia (defined as eosinophils > or = 3%) predicts clinical benefit from inhaled corticosteroid treatment in patients with smoking-related clinically stable moderate-to-severe COPD. Forty consecutive patients with effort dyspnoea (mean age 67 yrs; 52 pack-yr smoking history; post-bronchodilator forced expiratory volume in one second (FEV1) <60% predicted, consistent with moderate-to-severe smoking-related chronic airflow limitation) were enrolled. Subjects were treated with inhaled placebo followed by inhaled budesonide (Pulmicort Turbuhaler 1,600 microg.day(-1)), each given for 4 weeks. While the treatment was single-blind (subject level), sputum cell counts before and after treatment interventions were double-blind, thus removing bias. Outcome variables included spirometry, quality-of-life assessment and 6-min walk test. Sputum eosinophilia was present in 38% of subjects. In these, budesonide treatment normalised the eosinophil counts and, in comparison to placebo treatment, resulted in clinically significant improvement in the dyspnoea domain of the disease-specific chronic respiratory questionnaire (0.8 versus 0.3) and a small but statistically significant improvement in post-bronchodilator spirometry (FEV1 100 mL versus 0 mL; p<0.05). In conclusion, sputum eosinophilia predicts short-term clinical benefit from high-dose inhaled corticosteroid treatment in patients with stable moderate-to-severe chronic obstructive pulmonary disease.
Assuntos
Budesonida/administração & dosagem , Eosinófilos , Glucocorticoides/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Escarro/citologia , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Eosinofilia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/complicações , Método Simples-Cego , FumarRESUMO
BACKGROUND: Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma. METHODS: A multicentre, randomised, placebo controlled, parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of > or =3.5%. RESULTS: Eighteen patients received low dose fluticasone (250 mug/day), 19 received montelukast (10 mg/day), and 13 were given placebo for 8 weeks. Fluticasone treatment resulted in a greater reduction in sputum eosinophils (geometric mean (SD) 11.9 (2.3)% to 1.7 (5.1)%) than montelukast (10.7 (2.3)% to 6.9 (3.8)%; p = 0.04) or placebo (15.4 (2.4)% to 7.8 (4.2)%; p = 0.002), and improvement in FEV(1) (mean (SD) 2.6 (0.9) l to 3.0 (0.9) l) than montelukast (2.8 (0.7) l to 2.8 (0.9) l; p = 0.02) or placebo (2.4 (0.8) l to 2.4 (0.9) l; p = 0.01). Treatment with fluticasone suppressed sputum eosinophilia within a week while montelukast only attenuated it. The effect of montelukast was maximal at 1 week and was maintained over 4 weeks. The effect of fluticasone was maintained over 8 weeks while that of montelukast was not. CONCLUSIONS: Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naive eosinophilic asthma.
Assuntos
Acetatos/administração & dosagem , Androstadienos/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Antagonistas de Leucotrienos/administração & dosagem , Eosinofilia Pulmonar/tratamento farmacológico , Quinolinas/administração & dosagem , Acetatos/efeitos adversos , Adulto , Androstadienos/efeitos adversos , Antiasmáticos/efeitos adversos , Ciclopropanos , Método Duplo-Cego , Eosinófilos/efeitos dos fármacos , Feminino , Fluticasona , Humanos , Antagonistas de Leucotrienos/efeitos adversos , Masculino , Cooperação do Paciente , Quinolinas/efeitos adversos , Escarro/citologia , Sulfetos , Resultado do TratamentoRESUMO
Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant. A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (> or =5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol. The median (interquartile range, i.e. 75th-25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed. In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.
Assuntos
Acetatos/uso terapêutico , Asma/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Antagonistas de Leucotrienos/uso terapêutico , Prednisona/uso terapêutico , Quinolinas/uso terapêutico , Adulto , Idoso , Análise de Variância , Asma/diagnóstico , Estudos Cross-Over , Ciclopropanos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Eosinófilos/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Valores de Referência , Testes de Função Respiratória , Medição de Risco , Índice de Gravidade de Doença , Escarro/citologia , Escarro/efeitos dos fármacos , Sulfetos , Falha de TratamentoRESUMO
Asthma is a chronic inflammatory disorder of the airways that is characterized by episodic symptoms. In this regard, asthma management has classically involved periodic re-assessment by the health-care provider, during which therapy is altered mainly based on clinical and physiological parameters, such as assessment of symptoms, spirometry and peak expiratory flow monitoring. In this context, various markers of airway inflammation (e.g. eosinophils in the induced sputum, nitric oxide in the exhaled air) have been proposed to assess the severity of asthma and to adjust the therapy accordingly. The evaluation of airway hyper-responsiveness with different stimuli has also been suggested as a new tool to monitor asthma. However, the lack of definite relationships between airway inflammation and asthmatic symptoms strongly limit the use of markers of asthma severity in the clinical setting. Therefore, the need of new tools to assess the severity of asthma is raised. The ideal measurement employed to establish the proper asthmatic therapy should be safe, non-invasive, easy to perform, reproducible and accurate, and have the capability to monitor the changes induced by the therapeutic interventions. A careful review of the available techniques, and the evaluation of their sensitivity and specificity in the clinical setting is warranted.
Assuntos
Asma/tratamento farmacológico , Asma/fisiopatologia , Brônquios/fisiopatologia , Pulmão/fisiopatologia , Asma/patologia , Testes Respiratórios , Testes de Provocação Brônquica , Doença Crônica , Humanos , Pico do Fluxo Expiratório , Qualidade de Vida , Sensibilidade e Especificidade , Espirometria , Escarro , Inquéritos e Questionários , Resultado do TratamentoAssuntos
Contagem de Células/métodos , Separação Celular/métodos , Escarro/química , Escarro/citologia , Asma/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Manejo de EspécimesAssuntos
Albuterol/administração & dosagem , Asma/diagnóstico , Lavagem Broncoalveolar/efeitos adversos , Broncoconstrição/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Solução Salina Hipertônica/farmacologia , Escarro/citologia , Administração por Inalação , Testes de Provocação Brônquica/efeitos adversos , Testes de Provocação Brônquica/métodos , Lavagem Broncoalveolar/métodos , Broncodilatadores/administração & dosagem , Feminino , Humanos , Masculino , Prevenção Primária , Medição de Risco , Sensibilidade e Especificidade , Escarro/químicaRESUMO
The inflammatory component of asthma is usually assessed indirectly by symptoms and spirometry, these may be inaccurate. It can now be assessed directly and reliably by the examination of sputum cell counts. There is no information on how clinical assessment of the presence and type of airway inflammation compares with actual measurements. In this single-centre observational study, sputum was collected from 76 consecutive adults with asthma attending a tertiary chest clinic after their physicians had recorded the expected cell counts in sputum. The authors examined the extent of agreement between clinical judgement of sputum cell counts and actual counts in asthmatic patients (Cohen's Kappa) and the possible predictors of agreement (multiple logistic regression). Sixty-seven of the 76 sputum samples were suitable for analysis. Agreement between expected and actual cell counts occurred in 30/67 patients. The overall agreement for the different cell types was poor (estimated K=0.14, 95% confidence interval (CI)=0.02, 0.26). The experience of the physician in using sputum cell counts in clinical practice, steroid requirement at the time of assessment, and control of asthma as assessed by the physician or by the patient could not predict the chances of agreement or disagreement. Unaware of the sputum results, the physicians often changed treatment in a way that seemed inappropriate for the cell counts present. There is poor agreement between clinical judgement of the presence and type of airway inflammation in asthmatic patients and sputum cell counts. The impact of sputum examination on the outcomes of anti-inflammatory treatment now needs investigation.
Assuntos
Asma/patologia , Escarro/citologia , Adulto , Contagem de Células , Estudos Transversais , Humanos , Pessoa de Meia-IdadeRESUMO
Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene1 (CysLT1) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils. Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19-64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second > or =65% of the predicted value and were being treated only with "as needed" inhaled beta2-agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed. Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6-0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5-9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1-(-1.4)) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and beta2-agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo. These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.
Assuntos
Acetatos/uso terapêutico , Asma/tratamento farmacológico , Antagonistas de Leucotrienos/uso terapêutico , Eosinofilia Pulmonar/tratamento farmacológico , Quinolinas/uso terapêutico , Doenças Respiratórias/tratamento farmacológico , Adulto , Asma/complicações , Asma/fisiopatologia , Ciclopropanos , Método Duplo-Cego , Eosinófilos/efeitos dos fármacos , Feminino , Humanos , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Eosinofilia Pulmonar/complicações , Eosinofilia Pulmonar/fisiopatologia , Testes de Função Respiratória , Doenças Respiratórias/complicações , Doenças Respiratórias/patologia , Segurança , Escarro/citologia , Escarro/efeitos dos fármacos , Sulfetos , Resultado do TratamentoRESUMO
BACKGROUND: Inhaled corticosteroids are effective in suppressing a chronic cough without asthma associated with sputum eosinophilia. OBJECTIVE: To investigate the inflammatory characteristics in the induced sputum of patients with a chronic cough without asthma or known cause and the effects of budesonide treatment on chronic cough in those patients. PATIENTS AND METHODS: Forty-four adults (mean [minimu, maximum] age of 45 years [20,75], 28 women, 17 atopic subjects and 32 nonsmokers], with a daily bothersome cough for at least one year and who had no evidence of asthma or other known cause for the cough, were consecutively enrolled. The trial was a randomized, double-blind, controlled parallel group trial of budesonide 400 mg twice daily for two weeks versus placebo. Patients then received open administration of the same dose of budesonide for a further two weeks. Sputum was induced before and at the end of each treatment period. Cough severity was documented by a visual analogue scale. RESULTS: Thirty-nine (89%) patients produced mucoid sputum after induction on at least one study visit. At baseline, the majority (59%) had a mild elevation in the median proportion of neutrophils (65%). All had elevated fluid phase levels of fibrinogen (3200 mg/L) and albumin (880 mg/L), and high levels of interleukin-8 and substance P. Interleukin-8 correlated with neutrophils (rho=0.72, P<0.001), fibrinogen (rho=0.65, P<0.001), albumin (rho=0.67, P=0. 001) and eosinophil cationic protein (rho=0.60, P=0.001). Substance P correlated with albumin (rho=0.60, P=0.006). No subject had an increase in eosinophils. Treatment with budesonide did not affect cough or sputum measurements. CONCLUSIONS: Patients with nonasthmatic chronic cough enrolled in this study had evidence of a mild neutrophilia and/or microvascular leakage. Chronic cough did not respond to treatment with budesonide, perhaps because the cause was not associated with sputum eosinophilia.
Assuntos
Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Tosse/tratamento farmacológico , Escarro/citologia , Adulto , Idoso , Doença Crônica , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Eosinofilia PulmonarRESUMO
The kinetics of changes in inflammatory indices in induced sputum from eight prednisone dependent asthmatics whose minimum clinical maintenance and exacerbation doses were known were investigated. The study began on the last day of a course of 30 mg prednisone daily for one week. Thereafter, the daily prednisone was reduced in a structured way to below the maintenance dose. This treatment was continued until a clinical exacerbation occurred. Prednisone 30 mg daily was then given again for one week. The mean duration of prednisone reduction was 7.4 weeks and the median dose was 7.5 mg x day(-1). Increases in sputum eosinophils preceded increases in blood eosinophils by 4 weeks and worsening of symptoms and forced expiratory volume in one second by 6 weeks. The clinical exacerbation was also accompanied by sputum neutrophilia and increases in sputum eosinophil cationic protein (ECP), fibrinogen and interleukin (IL)-5. Treatment with prednisone suppressed median sputum eosinophilia (from 16.3 to 0%, p<0.001), decreased sputum ECP (from 7,480 to 700 microg x L(-1), p = 0.01), but did not improve neutrophil numbers, fibrinogen or IL-5. The results show that the reduction of prednisone treatment in prednisone-dependent asthmatics evokes a severe airway eosinophilic inflammatory response. Clinical and blood indices deteriorate later than those in sputum suggesting that sputum examination may be useful to identify the minimum regular dose of prednisone required in these patients.
Assuntos
Asma/complicações , Asma/tratamento farmacológico , Bronquite/etiologia , Eosinofilia/etiologia , Prednisona/administração & dosagem , Escarro , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed. In a single-blind, sequential crossover trial of placebo and prednisone (30 mg/day) treatment, with each given for 2 wk, we investigated whether an increased proportion of sputum eosinophils (>= 3%) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis. Patients were seen before and after each treatment. Clinical measurements were made blind to the laboratory findings and vice-versa. Eighteen of 20 patients completed the study. Eight had sputum eosinophilia and similar clinical and physiologic characteristics to those of 10 patients without a finding of sputum eosinophilia. Only in patients with sputum eosinophilia did prednisone, as compared with placebo, produce a statistically significant and clinically important mean effect on effort dyspnea of 0.8 (95% confidence interval [CI]: 0.3 to 1.2), p = 0.008, and in quality of life of 1.96 (95% CI: 0.5 to 3.3), p = 0.01, associated with a small improvement in FEV1 of 0.11 L (95% CI: - 0.04 to 0.23 L), p = 0.05. In these patients, prednisone also produced a significant decline in the median sputum eosinophil percentage, from 9.7% to 0.5% (p = 0.002), eosinophil cationic protein (ECP), from 6, 000 microgram/L to 1,140 microgram/L (p < 0.001), and fibrinogen, from 25. 3 mg/L to 5.4 mg/L (p < 0.001). These findings indicate that in smokers with severe airflow limitation, sputum eosinophilia predicts a beneficial effect of prednisone treatment. Improvement in FEV1, after prednisone treatment in this population, is small, and may not be appreciated in clinical practice.
Assuntos
Anti-Inflamatórios/uso terapêutico , Bronquite/tratamento farmacológico , Eosinofilia/patologia , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Ribonucleases , Escarro/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/análise , Bronquite/patologia , Doença Crônica , Estudos Cross-Over , Dispneia/tratamento farmacológico , Proteínas Granulares de Eosinófilos , Feminino , Fibrinogênio/análise , Seguimentos , Volume Expiratório Forçado/efeitos dos fármacos , Previsões , Humanos , Mediadores da Inflamação/análise , Masculino , Pessoa de Meia-Idade , Placebos , Qualidade de Vida , Reprodutibilidade dos Testes , Método Simples-Cego , Fumar/efeitos adversosRESUMO
BACKGROUND: Salmeterol is a potent long acting beta-agonist that is effective in relieving the symptoms and airflow limitation of asthma. OBJECTIVE: To determine whether the effect of salmeterol on clinical parameters in a mild eosinophilic exacerbation of asthma was similar to that of beclomethasone dipropionate (BDP) and, thus, is due to an anti-inflammatory property. PATIENTS AND METHODS: Thirty-four asthmatics with a persistent increase in symptoms for at least two weeks and an increase of sputum eosinophils of 4% or more were randomized in a double-blind fashion to one of three groups that received daily treatment with 100 mg salmeterol, 1 mg BDP or placebo in divided doses using identical pressurized inhalers. Patients were treated with study medications for three weeks, followed by one week of open label BDP (500 mg bid). Patients were seen at weekly intervals, and sputum and blood were obtained on each visit. The primary outcome measure was a change in sputum eosinophils, and secondary outcomes were changes in blood eosinophils, eosinophilic cationic protein (ECP) and clinical parameters. Three patients (one in each group) could not produce any sputum after randomization and were excluded from the analysis. RESULTS: Twelve patients received salmeterol, 10 received BDP and nine received placebo. Salmeterol treatment had no effect on sputum eosinophils geometric mean, (from 35.5 [24.9] to 26.9% [25.8]), blood eosinophils (from 7.6 [4.8] to 7.2% [3.9]) or ECP (from 33.1 [18.1] to 27.8 [16.3] mg/L) but improved morning peak expiratory flow (PEF) and diurnal variation of PEF, and decreased the use of rescue medication more than placebo (P<0.05 for all comparisons). In contrast, BDP improved both inflammatory indexes (sputum eosinophils from 22.5 [17.9] to 5.7% [6.8], blood eosinophils from 9.0 [5.5] to 2.1% 1.0, and serum ECP from 36.5 [22.0] to 16.1 [10.1] mg/L) as well as clinical parameters. CONCLUSIONS: These results show that salmeterol improves the symptoms and airway function of patients with asthma, but has no effect on eosinophilic airway infiltration. These findings support current asthma guidelines, which recommend the initial use of inhaled steroid to maximize clinical improvement. While salmeterol also produces clinical improvement, it does not suppress sputum eosinophilia. The analysis of induced or spontaneous sputum for inflammatory indexes may be a valuable clinical test to guide the use of inhaled steroid and/or a long acting beta-agonist.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/análogos & derivados , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Beclometasona/uso terapêutico , Eosinofilia/tratamento farmacológico , Administração por Inalação , Agonistas Adrenérgicos beta/administração & dosagem , Adulto , Albuterol/administração & dosagem , Albuterol/uso terapêutico , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Beclometasona/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Xinafoato de Salmeterol , Escarro/citologiaRESUMO
We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus). In the subjects with confirmed virus infection, five of the asthmatics had an objective exacerbation of asthma during the cold. Their sputum on Day 4 showed a high median total cell count of 19.7 x 10(6) cells/ml with a modest neutrophilia (58. 5%) and high levels of interleukin-8 (IL-8) (16,000 pg/ml), eosinophilic cationic protein (ECP) (1,880 microgram/L) and very high levels of fibrinogen (250 mg/L). In contrast, the proportion (1.3%) and absolute number of eosinophils was low. IL-2 levels were within the normal range, whereas IL-5 and interferon gamma were under the limit of detection of the assays. In the healthy subjects with a confirmed virus infection the sputum findings were qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was strongly correlated with neutrophils (rs = 0.8, p < 0.001). This correlation was also significant when each group was analyzed separately. On Day 21 there was a fall in the absolute number of neutrophils and in ECP and fibrinogen levels in both groups. Similar results were found in the two asthmatic and three healthy subjects with a cold of comparable severity but in whom viral infection was not confirmed. We conclude that induced sputum examination can be used to study the effects of natural colds and influenza on the airways of the lungs. The results also suggest that natural colds, on Day 4, cause neutrophilic lower airway inflammation that is greater in asthmatics than in healthy subjects. The greater inflammatory response in asthmatics may be due to the changes associated with trivial eosinophilia or to the different viruses involved.