RESUMEN
INTRODUCTION: Preclinical research suggests a role of Glucagon Like Peptide-1 Receptors (GLP-1R) on the regulation of human bronchial tone. We investigated the effect of GLP-1R agonists on lung function of Type 2 Diabetes Mellitus (T2DM) population without co-existing chronic obstructive respiratory disorders. METHODS: This was a prospective cohort study that examined change in lung function measurements over two years of T2DM patients (nâ¯=â¯32) treated with metformin monotherapy (control cohort), metformin plus GLP-1R agonists (GLP-1R agonists cohort), or metformin plus insulin (insulin cohort). RESULTS: After 24 months of treatment, the forced expiratory volume in 1â¯s (FEV1) significantly (pâ¯<â¯0.05) increased from baseline in the GLP-1R agonists cohort (218â¯ml [95%CI 88-246]), but not in the control and insulin cohorts (94â¯ml [95%CI -28 - 216] and 26â¯ml [95%CI -174 - 226], respectively; pâ¯>â¯0.05 vs. baseline). The average increase in FEV1 in the GLP-1R agonists cohort was significantly greater than that in the control and insulin cohorts (delta: 110â¯ml [95%CI 18-202] and 177â¯ml [95%CI 85-270], respectively, pâ¯<â¯0.05). The forced vital capacity (FVC) also increased significantly more in the GLP-1R agonists cohort than in the control and insulin cohorts (overall delta FVC: 183â¯ml [95%CI 72-295], pâ¯<â¯0.05). The maximal expiratory flow at 50-75% significantly (pâ¯<â¯0.05) improved from baseline in the GLP-1R agonists cohort, but not in the control and insulin cohorts (pâ¯>â¯0.05). CONCLUSION: Our preliminary results suggest a potential new therapeutic perspective to treat airway disorders with GLP-1R agonists.
Asunto(s)
Bronquios/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Pulmón/fisiopatología , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/epidemiología , Quimioterapia Combinada , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Italia/epidemiología , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Metformina/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Pruebas de Función Respiratoria/métodos , Capacidad Vital/efectos de los fármacosRESUMEN
BACKGROUND: Revefenacin is a once-daily long-acting muscarinic antagonist (LAMA) in clinical development for the treatment of patients with chronic obstructive pulmonary disease (COPD). In a dose-ranging study, nebulized once-daily revefenacin had a long duration of action in patients after 7 days' administration of doses up to 700 µg. In this multiple-dose study, the bronchodilation efficacy and adverse events profile were characterized in patients administered nebulized revefenacin once daily for 28 days. METHODS: A total of 355 COPD patients (mean age 62 years, mean forced expiratory volume in 1 s [FEV1] 44% of predicted) were randomized in a double-blind, placebo-controlled parallel group study. Inhaled corticosteroids as well as short-acting bronchodilators were permitted. Once-daily treatments (44, 88, 175 or 350 µg revefenacin or matching placebo) were administered by a standard jet nebulizer, for 28 days. The primary endpoint was change from baseline in D28 trough FEV1, and secondary endpoints included weighted mean FEV1 over 0 to 24 h and rescue medication (albuterol) use. Safety evaluations included adverse events, laboratory assessments, electrocardiograms and 24-h Holter profiles. RESULTS: Revefenacin (88, 175 and 350 µg) significantly improved D28 trough FEV1 over placebo (187.4, 166.6 and 170.6 mL, respectively, all p < 0.001); 44 µg produced a sub-therapeutic response. At doses ≥88 µg, more than 80% of patients achieved at least a 100-mL increase from baseline FEV1 in the first 4 h post dose compared with 33% of placebo patients. For doses ≥88 µg, D28 24 h weighted mean differences from placebo for FEV1 were numerically similar to respective trough FEV1 values, indicating bronchodilation was sustained for 24 h post dose. Doses ≥88 µg reduced the average number of albuterol puffs/day by more than one puff/day. The 350 µg dose did not demonstrate additional efficacy over that observed with 175 µg revefenacin. Revefenacin was generally well tolerated, with minimal reports of systemic anti-cholinergic effects. CONCLUSIONS: These data suggest that 88 and 175 µg revefenacin are appropriate doses for use in longer-term safety and efficacy trials. Revefenacin offers the potential for the first once-daily LAMA for nebulization in patients with COPD who require or prefer a nebulized drug delivery option. TRIAL REGISTRATION: ClinicalTrials.gov NCT02040792 . Registered January 16, 2014.
Asunto(s)
Antagonistas Muscarínicos/administración & dosificación , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Flujo Espiratorio Máximo/fisiología , Persona de Mediana Edad , Nebulizadores y Vaporizadores/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: Neuromuscular blocking drugs have been implicated in intraoperative bronchoconstrictive episodes. We examined the effects of clinically relevant doses of cisatracurium and rocuronium on the lung mechanics of pediatric subjects. We hypothesized that cisatracurium and rocuronium would have bronchoconstrictive effects. METHODS: We studied ASA physical status I and II pediatric subjects having elective dental or urological procedures, requiring general anesthesia with endotracheal intubations with either cisatracurium or rocuronium. Pulmonary function tests were performed before and after neuromuscular blocking drug dosing and again after albuterol administration. Using forced deflation and passive deflation techniques, forced vital capacity (FVC) and maximum expiratory flow rate at 10% (MEF10) of FVC were obtained. Fractional changes from the baseline were used to compare subjects. Changes in MEF10 of >30% were considered clinically significant. A Shapiro-Wilk test, paired t test, and Wilcoxon rank sum test were used to analyze the data. RESULTS: Twenty-five subjects (median age = 5.25 years; range = 9 months-9.9 years) were studied; 12 subjects received cisatracurium and 13 subjects received rocuronium. Data are shown as mean proportional change ± SD or, in the case of not normally distributed, median proportional change (first, third quartile) with P values. In the cisatracurium group, there were no differences between baseline and postneuromuscular blocker administration in the fractional change from the baselines of FVC (1.00 ± 0.04, P = 0.5), but there was a significant decrease in MEF10 (0.80 ± 0.18, P = 0.002). In the rocuronium group, there were small yet significant decreases of FVC (0.99 [first quartile 0.97, third quartile 1], P = 0.02) and significant decreases in MEF10 (0.78 ± 0.26, P = 0.008). After administration of albuterol in the cisatracurium group, FVC increased slightly but significantly from baseline values (1.02 ± 0.02, P = 0.005). MEF10 increased significantly beyond baseline values (1.24 ± 0.43, P =0.04). In the rocuronium group, there were also significant differences between baseline and postalbuterol administration from the baseline value of FVC (1.02 ± 0.02, P = 0.004) and MEF10 (1.23 ± 0.29, P = 0.01). CONCLUSIONS: At clinically relevant doses, both cisatracurium and rocuronium caused changes in lung function, indicating constriction of smaller airways. In general, these changes were mild and not clinically detectable. However, in the rocuronium group, 3 of 13 patients showed more noticeable decreases in MEF10 (≤50%), demonstrating the potential for significant broncho-bronchiolar constriction in susceptible patients.
Asunto(s)
Androstanoles/efectos adversos , Anestesia General , Atracurio/análogos & derivados , Broncoconstricción/efectos de los fármacos , Pulmón/efectos de los fármacos , Fármacos Neuromusculares no Despolarizantes/efectos adversos , Factores de Edad , Atracurio/efectos adversos , Niño , Preescolar , Femenino , Humanos , Lactante , Intubación Intratraqueal , Pulmón/fisiopatología , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Pennsylvania , Factores de Riesgo , Rocuronio , Capacidad Vital/efectos de los fármacosRESUMEN
RATIONALE: The efficacy of inhaled tobramycin on chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) has been established in clinical trials. However, little is known about its clinical effectiveness on lung function outside randomized controlled trial settings; conventional analysis of existing registry data has heretofore been confounded by treatment selection bias. OBJECTIVE: To determine effectiveness of inhaled tobramycin on FEV1 decline in patients with chronic P. aeruginosa infections using observational data from the Cystic Fibrosis Foundation Patient Registry. METHODS: Patient-level tobramycin use was measured at first chronic P. aeruginosa infection (n = 13,686 patients; age, 6-21 yr). Decline in FEV1 2 years after infection was estimated for patients treated with tobramycin and compared with untreated patients. Multiple linear regressions with confounder adjustment and propensity scores were used to estimate mean FEV1 decline for each group. Because care is organized by centers, we used center-specific prescription rates as an instrument to reduce treatment-by-condition bias. MEASUREMENTS AND MAIN RESULTS: Using center-level prescribing rates, instrumental variables analysis showed less FEV1 decline for patients who received tobramycin when first eligible compared with those who did not receive tobramycin (difference, 2.55% predicted; 95% confidence interval, 0.16-4.94; P = 0.0366). CONCLUSIONS: Inhaled tobramycin is effective in reducing lung function decline among patients 6 to 21 years of age with CF. Because CF care is organized by center, using center-specific prescription rates as an instrumental variable is a feasible approach to using the Cystic Fibrosis Foundation Patient Registry to determine treatment effectiveness. More generally, this approach can correct for treatment-by-condition bias arising from observational studies.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Flujo Espiratorio Máximo/efectos de los fármacos , Infecciones por Pseudomonas/tratamiento farmacológico , Tobramicina/administración & dosificación , Administración por Inhalación , Adolescente , Antibacterianos/administración & dosificación , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Flujo Espiratorio Máximo/fisiología , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/fisiopatología , Pseudomonas aeruginosa/aislamiento & purificación , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Nitrofurantoin is commonly used in the treatment of urinary tract infection and may cause a potential severe complication: interstitial lung diseases. CASE REPORT: A 78-year-old and an 87-year-old woman treated with nitrofurantoin since respectively 10 months and 6 years developed cough and dyspnea. Antibiotics were ineffective and interstitial lung disease was found. Nitrofurantoin's stopping allowed a clinical and radiological improvement. CONCLUSION: A good medical supervision is important when nitrofurantoin is prescribed for a long time. The treatment has to be stopped when respiratory symptoms appear to allow an improvement of the symptoms.
Asunto(s)
Antiinfecciosos Urinarios/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Nitrofurantoína/efectos adversos , Anciano , Anciano de 80 o más Años , Tos/inducido químicamente , Disnea/inducido químicamente , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/fisiopatología , Flujo Espiratorio Máximo/efectos de los fármacos , Capacidad Pulmonar Total/efectos de los fármacos , Capacidad Vital/efectos de los fármacosRESUMEN
BACKGROUND: Centralized spirometry may significantly improve quality of spirometry and reduce variability of this outcome measure in clinical trials in cystic fibrosis (CF). METHODS: Spirometry was performed during the phase 2 randomized, placebo-controlled, double-blind clinical trial of denufosol in patients with mild to moderate CF using American Thoracic Society guidelines. Uniform spirometers were used with electronic data transmission of all the data to a reading center. Spirometry was evaluated for quality by a central reader based on start of test, cough during the test, and evidence of a plateau. RESULTS: A total of 1418 spirometry values were assessed in 89 subjects during the trial. In only 5 instances did the central reading center need to give feedback to sites regarding the quality of spirometry. The study site data matched the central reading center's data for all but 78 (6%) spirometry values in 33 patients. Many of these differences were small with only 35 (3%) values differing by more than 50 mL in 26 patients. CONCLUSION: Spirometry in this clinical trial was of high quality with low rate of significant centralized over-read.
Asunto(s)
Fibrosis Quística/fisiopatología , Nucleótidos de Desoxicitosina/administración & dosificación , Espirometría/métodos , Uridina/análogos & derivados , Administración por Inhalación , Adolescente , Fibrosis Quística/diagnóstico , Fibrosis Quística/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Flujo Espiratorio Máximo/fisiología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Uridina/administración & dosificación , Capacidad Vital/efectos de los fármacos , Capacidad Vital/fisiologíaAsunto(s)
Albuterol/análogos & derivados , Androstadienos/efectos adversos , Broncodilatadores/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Albuterol/efectos adversos , Albuterol/uso terapéutico , Androstadienos/uso terapéutico , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Quimioterapia Combinada , Humanos , Flujo Espiratorio Máximo/efectos de los fármacos , Neumonía/etiologíaRESUMEN
OBJECTIVE: To assess the effects of bisoprolol on exercise capacity and ventricular function in patients with heart failure. METHODS: Clinical and hemodynamic variables, ventricular function and remodeling, and ergospirometry of patients with heart failure of different etiologies were evaluated before and after the administration of bisoprolol. RESULTS: Twenty-two patients were analyzed; one patient did not tolerate medication and 14 patients reached the study goal. The group consisted of 9 men and 5 women, the mean age was 52 (36-64) years, and patients were followed during 551 days (238-1109). We observed an improvement in NYHA functional class, reduction in resting heart rate (78.8+/-8.7 vs 63+/-6.4 bpm, p <0.001), increase in left ventricular ejection fraction (31.3+/-8.5% vs 39+/-14.7%. p=0.043), and a tendency towards improved quality of life scores (31+/-20.6 vs 17.8+/-14.8. p=0.058). The maximum heart rate dropped during exercise (138.1+/-20.2 vs 116.7+/-27.1. p=0.01), as did peak oxygen consumption (20.9+/-6.8 vs 15.1+/-3.5. p<0.001); no change was observed on the EV/VCO2 slope. The effects were observed for all etiologies, including Chagas disease. CONCLUSION: Bisoprolol was safe and well tolerated in patients with heart failure. Bisoprolol therapy improved the symptoms, hemodynamic variables, as well as the cardiac function for all etiologies; however, it did not result in improved exercise capacity.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Bisoprolol/uso terapéutico , Ejercicio Físico , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas Adrenérgicos beta/administración & dosificación , Adulto , Bisoprolol/administración & dosificación , Ergometría , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Persona de Mediana Edad , Consumo de Oxígeno/efectos de los fármacos , Estudios Prospectivos , Calidad de Vida , Espirometría , Estadísticas no Paramétricas , Volumen Sistólico/efectos de los fármacos , Factores de TiempoRESUMEN
OBJETIVO: Avaliar o efeito do bisoprolol sobre a capacidade de exercício e a função ventricular em pacientes com insuficiência cardíaca. MÉTODOS: Foi feita a análise das variáveis clínicas e hemodinâmicas, da função e do remodelamento ventricular, e da ergoespirometria de pacientes com insuficiência cardíaca com diferentes etiologias, antes e após administração de bisoprolol. RESULTADOS: Foram analisados 22 pacientes, dos quais 1 paciente não tolerou a medicação e 14 pacientes alcançaram a meta do estudo. A média das idades foi de 52 anos (36 a 64 anos), 9 pacientes eram do sexo masculino e 5 eram do sexo feminino, com tempo médio de seguimento de 551 dias (238 a 1.109 dias). Foram observados melhora da classe funcional, redução da freqüência cardíaca de repouso (78,8 + 8,7 bpm vs. 63 + 6,4 bpm; p < 0,001), aumento da fração de ejeção do ventrículo esquerdo (31,3 + 8,5 por cento vs. 39 + 14,7 por cento; p = 0,043) e tendência a melhora do escore de qualidade de vida (31 + 20,6 vs. 17,8 + 14,8; p = 0,058). Ocorreu queda da freqüência cardíaca máxima no exercício (138,1 + 20,2 vs. 116,7 + 27,1; p = 0,01) e do consumo máximo de oxigênio (20,9 + 6,8 vs. 15,1 + 3,5; p < 0,001). Não houve modificação do slope VE/VCO2. Os efeitos ocorreram em todas as etiologias, inclusive na doença de Chagas. CONCLUSÃO: O bisoprolol produziu melhora clínica e hemodinâmica e de função cardíaca nas diferentes etiologias, sem, entretanto, apresentar efeitos de melhora na capacidade de exercício.
OBJECTIVE: To assess the effects of bisoprolol on exercise capacity and ventricular function in patients with heart failure. METHODS: Clinical and hemodynamic variables, ventricular function and remodeling, and ergospirometry of patients with heart failure of different etiologies were evaluated before and after the administration of bisoprolol. RESULTS: Twenty-two patients were analyzed; one patient did not tolerate medication and 14 patients reached the study goal. The group consisted of 9 men and 5 women, the mean age was 52 (36-64) years, and patients were followed during 551 days (238-1109). We observed an improvement in NYHA functional class, reduction in resting heart rate (78.8±8.7 vs 63±6.4 bpm, p <0.001), increase in left ventricular ejection fraction (31.3±8.5 percent vs 39±14.7 percent. p=0.043), and a tendency towards improved quality of life scores (31±20.6 vs 17.8±14.8. p=0.058). The maximum heart rate dropped during exercise (138.1±20.2 vs 116.7±27.1. p=0.01), as did peak oxygen consumption (20.9±6.8 vs 15.1±3.5. p<0.001); no change was observed on the EV/VCO2 slope. The effects were observed for all etiologies, including Chagas' disease. CONCLUSION: Bisoprolol was safe and well tolerated in patients with heart failure. Bisoprolol therapy improved the symptoms, hemodynamic variables, as well as the cardiac function for all etiologies; however, it did not result in improved exercise capacity.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Adrenérgicos beta/uso terapéutico , Bisoprolol/uso terapéutico , Ejercicio Físico , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas Adrenérgicos beta/administración & dosificación , Bisoprolol/administración & dosificación , Ergometría , Estudios de Seguimiento , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Flujo Espiratorio Máximo/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Estudios Prospectivos , Calidad de Vida , Espirometría , Estadísticas no Paramétricas , Volumen Sistólico/efectos de los fármacos , Factores de TiempoRESUMEN
OBJECTIVE: Dipyrone (Novalgin) is an effective analgesic, antipyretic agent also with spasmolytic effects on various types of smooth muscles. It has recently been reported that dipyrone relaxes tracheal smooth muscle of guinea pig. In this present study, we aimed to investigate whether this and previously reported in vitro results have any consequences on the respiratory function of normal healthy volunteers and chronic obstructive pulmonary disease (COPD) patients. METHODS: In this one-centered, non-randomized, non-comparative, open labelled study, 15 normal healthy volunteers and 15 stable COPD patients, with partially reversible bronchospasm, diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were enrolled in the study at the time they had any indication of dipyrone use. The spirometric tests were performed by a portable notebook and Medikro Spiro2000 spirometry programme-software 1.6 version, before 30, 60, 90, and 120 min after 20 mg/kg of orally dipyrone intake. Groups were compared with the General Linear Model Repeated Measures analysis of variance. RESULTS: None of the spirometric parameters evaluated showed any significant differences when compared with the baseline values in both groups. CONCLUSION: While dipyrone had no bronchodilator effects on either COPD patients or normal volunteers, it also did not impair the spirometric parameters. Since COPD is a disease characterized by a progressive and largely irreversible airflow limitation, dipyrone has no observable bronchodilator effect. However, since dipyrone does not impair the pulmonary function, it can be used safely in COPD patients when there is an indication.
Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Dipirona/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Adulto , Anciano , Analgésicos/administración & dosificación , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Capacidad Vital/efectos de los fármacosRESUMEN
INTRODUCTION: The duration of bronchodilator action of the long-acting beta-agonist formoterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of formoterol, administered from the combination budesonide/formoterol (BUD/F) Turbuhaler significantly attenuates the circadian rhythm in airway tone over 24 h. METHODS: Twenty subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, placebo-controlled, cross-over study. Subjects inhaled, in random order, placebo or BUD/F (2x100/6 microg) administered in the evening (2000 h) on two separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h. RESULTS: Compared with placebo, BUD/F significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.20L (0.04-0.35L). BUD/F attenuated the biphasic pattern of the circadian rhythm in airway tone. CONCLUSION: The single evening administration of formoterol from the combination BUD/F inhaler resulted in a duration of bronchodilation of at least 24 h.
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Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Budesonida/administración & dosificación , Etanolaminas/administración & dosificación , Administración por Inhalación , Adolescente , Adulto , Asma/fisiopatología , Cronoterapia , Ritmo Circadiano/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Combinación de Medicamentos , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Fumarato de Formoterol , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVES: To study whether Formoterol treatment affect the bronchodilator response to salbutamol after methacholine-provocation test (MPT) in asthmatic children. STUDY DESIGN: A prospective, double-blind, randomized, placebo-controlled study. Children aged 7-16 years with mild-persistent to moderate asthma treated with inhaled corticosteroids, were enrolled. After 2-weeks of run-in period, subjects were randomized to inhaled Formoterol 9 microg bid (n=19) or placebo (n=19) for 2 weeks. MPT with salbutamol-recovery curve was performed at the beginning and at the end of the trial period. Measurements of peak expiratory flow rate (PEFR), symptoms score, rescue bronchodilator usage and side effects were recorded daily. The primary end-points were the change in FEV1 0-10 min after salbutamol inhalation and the recovery time from 80 to 100% of pretest FEV1. Statistical analyses were performed by ANOVA with repeated measures. RESULTS: There was a decrease in the bronchodilator response to salbutamol and an improved PEFR in the Formoterol group. There was no difference in all other parameters. CONCLUSION: Formoterol decreases the bronchodilator response to salbutamol following MPT. Whether this phenomenon has clinical implication during acute asthma needs further studies.
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Albuterol/farmacología , Asma/tratamiento farmacológico , Pruebas de Provocación Bronquial , Etanolaminas/uso terapéutico , Cloruro de Metacolina , Adolescente , Recuento de Células Sanguíneas , Broncodilatadores/efectos adversos , Broncodilatadores/farmacología , Broncodilatadores/uso terapéutico , Niño , Método Doble Ciego , Interacciones Farmacológicas , Tolerancia a Medicamentos , Eosinófilos/citología , Etanolaminas/efectos adversos , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Fumarato de Formoterol , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Estudios ProspectivosRESUMEN
Apart from symptomology, there are very few reports on lung function following exposure to low levels of organophosphate (OP) pesticides in man. Twenty-five occupationally exposed farmers and 22 environmentally exposed freshwater fishermen were evaluated between and during OP spray seasons. Forty marine fishermen living away from agricultural areas were recruited as a control group. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV(1)) were measured by spirometry. Haemoglobin corrected erythrocyte acetylcholinesterase (AChE) levels were measured during and between (baseline estimation) spray seasons using a portable WHO-approved Test-mate system (EQM Research, Ohio). FVC ratio was lower in the farmers as compared to the controls (P<0.001) between exposure seasons. In the farmers, FVC ratio decreased further during the exposure season (P=0.023). FEV(1) was lower in the farmers as compared to the controls in both periods (P<0.05). In the fishermen, the decrease in ratios of FVC and FEV(1) following exposure to pesticides was not significant. FEV(1)/FVC ratios were similar in the three groups between (P=0.988) and during (P=0.159) exposure periods. Following exposure to OPs, AChE levels dropped 12.75% in the farmers (P<0.001) and 5.62% in the freshwater fishermen (P=0.001). Occupational exposure to OP results in restrictive lung dysfunction, a phenomenon not observed following environmental exposure.
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Acetilcolinesterasa/sangre , Agricultura , Explotaciones Pesqueras , Insecticidas/toxicidad , Exposición Profesional/efectos adversos , Compuestos Organofosforados/toxicidad , Adulto , Biomarcadores/sangre , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Sri Lanka , Capacidad Vital/efectos de los fármacosRESUMEN
The use of metered-dose inhalers for the delivery of albuterol, a beta2-selective adrenergic agonist, is associated with drawbacks, especially in children and the elderly. This investigation was designed to assess the effectiveness of albuterol delivered intranasally and to compare this delivery route with intratracheal and intravenous delivery. Three parameters of pulmonary function (peak maximal expiratory flow, maximal expiratory flow at 50% vital capacity, and total lung capacity) in anaesthetized, artificially ventilated guinea pigs were used to determine the degree of protection produced by albuterol against bronchoconstrictor responses provoked by acetylcholine. The heart rate was also measured. Although intranasal albuterol induced a slower protective action during the very initial phase of absorption, the drug was shown to be equally effective when administered either intranasally or intratracheally. In contrast, despite a significant effect initially in the case of intravenous albuterol, its ability to influence pulmonary function faded rather rapidly. No statistically significant differences in heart rate could be detected among the different treatment groups. In conclusion, intranasal albuterol may offer an alternative to metered-dose inhalers for the treatment of acute bronchospasm and for prevention of exercise-induced asthma, especially for children and the elderly.
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Agonistas Adrenérgicos beta/administración & dosificación , Albuterol/administración & dosificación , Broncodilatadores/administración & dosificación , Acetilcolina , Administración Intranasal , Animales , Broncoconstricción/efectos de los fármacos , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intravenosas , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Ápice del Flujo Espiratorio/efectos de los fármacos , Capacidad Pulmonar Total/efectos de los fármacos , Tráquea , VasodilatadoresRESUMEN
The aim of this double-blind, double-dummy, cross-over, randomized, pilot study was to compare the acute bronchodilator efficacy of a single dose of formoterol with that of tiotropium in patients with stable chronic obstructive pulmonary disease (COPD). Because the potential of tiotropium for additive effects is yet unknown, the acute effects of adding this anticholinergic agent to formoterol were also explored. A total of 20 outpatients with stable COPD were enrolled. Single doses of 12 microg formoterol, 18 microg tiotropium, and 12 microg formoterol+18 microg tiotropium were given. Serial measurements of FEV1 were performed over 24 h. Formoterol, either alone or in combination with tiotropium, elicited a significantly faster onset of action and showed a trend for a greater maximum bronchodilation than tiotropium alone. At 24 h, mean FEV1 continued to be significantly higher than pre-dosing value following tiotropium and formoterol+tiotropium. These findings indicate that formoterol and tiotropium have different profiles that make both agents attractive alternatives in the treatment of stable COPD. Since tiotropium ensures prolonged bronchodilation, whereas formoterol adds fast onset and a greater peak effect, the two drugs appear complementary.
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Broncodilatadores/uso terapéutico , Etanolaminas/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Derivados de Escopolamina/uso terapéutico , Administración por Inhalación , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Broncodilatadores/farmacocinética , Broncodilatadores/farmacología , Estudios Cruzados , Método Doble Ciego , Quimioterapia Combinada , Etanolaminas/farmacocinética , Etanolaminas/farmacología , Femenino , Fumarato de Formoterol , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Persona de Mediana Edad , Derivados de Escopolamina/farmacocinética , Derivados de Escopolamina/farmacología , Bromuro de Tiotropio , Resultado del TratamientoRESUMEN
UNLABELLED: Bronchodilator agents are central to the symptomatic management of Chronic Obstructive Pulmonary Disease (COPD), and long-acting inhaled bronchodilators are regarded as more convenient. The role of inhaled corticosteroids still remains controversial, but there is increasing evidence that they may improve FEV(1) and symptoms in the long-term. AIM: of the present small pilot study was to compare Salmeterol & Fluticasone (SM&FP) 50/250 microg bid via a single Diskus inhaler with SM 50 microg bid alone, and with placebo (P) in the treatment of moderate COPD. METHODS: Eighteen moderate COPD patients (53-77 yr, mean basal FEV(1)=49.1% pred.+/-5.0 s.d.; mean FEV(1) reversibility=3.6% bsln+/-3.8 s.d.) treated with theophylline 400 mg/day and beta(2) short acting prn, were divided into three matched groups of six subjects according to a double-blind design, and treated with SM&FP 50/250 microcg, or SM 50 microcg alone, or P via Diskus inhaler bid for 52 weeks. In bsln, after 4, 12, 24, 36 and 52 weeks, FEV(1) (% pred), morning PEF (l/s), the daily symptom score, and the number of exacerbations (compared with the previous year) were considered. Statistics. t-test, anova in each treatment group, and anova among basal values and among the 52 week values were used, being p<0.05 accepted. Also changes (DeltaFEV(1)) from baseline were compared at different control times. RESULTS: The mean number of exacerbations/yr decreased from 3.5+/-0.8 to 1.16+/-0.75 s.d. exacerbation/yr in the SM&FP group (t-test p<0.001); from 3.0+/-0.89 to 2.3+/-0.81 s.d. in the SM group (t-test p=ns); and from 3.16+/-1.16 to 4.16+/-0.75 s.d. in the P group (t-test p=ns). Patients receiving SM&FP showed the highest mean improvement in FEV(1) (+7.3%+/-3.3 s.d.) over the baseline pre-treatment value after 36 weeks of treatment (anova p<0.001), being FEV(1) unchanged after 52 weeks of treatment in SM group (+0.33%+/-2.4 s.d.) and with a substantial decrease following P (-2.6%+/-1.2 s.d.) (anova p<0.001). Morning PEF (l/min) increased in subjects treated with SM&FP (anova p<0.001), while it remained unchanged in SM and P group (in both, anova p=ns). After 52 weeks of treatment, only subjects treated with SM&FP showed a reduction of the daily symptoms score from 3.6+/-0.7 to 2.0+/-0.2 s.d. (anova p=0.008). Daily beta(2) short acting prn consumption was reduced only in SM&FP group from 4.2+/-0.81 to 2.2+/-1.2 s.d. after 52 weeks (anova p<0.001). CONCLUSIONS: SM&FP 50/250 microcg regularly assumed in combination via a single Diskus inhaler for a 52 week period improves respiratory function (such as FEV(1), morning PEF), and and symptom score significantly in moderate COPD previously treated with theophylline, and at an higher extent than SM alone or P. The use of beta(2) short acting prn is also reduced, together with the number of exacerbations.
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Albuterol/análogos & derivados , Albuterol/uso terapéutico , Androstadienos/uso terapéutico , Broncodilatadores/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Anciano , Albuterol/administración & dosificación , Análisis de Varianza , Androstadienos/administración & dosificación , Método Doble Ciego , Quimioterapia Combinada , Femenino , Fluticasona , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Persona de Mediana Edad , Proyectos Piloto , Xinafoato de Salmeterol , Teofilina/uso terapéuticoRESUMEN
Our purpose was to develop a method of using a maximal forced expiratory maneuver (MFEM) for the study of bronchoconstriction and bronchial hyperreactivity (BHR) induced in mice by ovalbumin (OA) inhalation challenge. Eight mice (group I) were sensitized and then provocated with OA. Pulmonary function testing (PFT) at baseline and after varying doses of acetylcholine challenge was performed. Eight weight-matched normal mice served as controls (group II). Pulmonary functions include MFEM, dynamic respiratory system compliance (Crs) and respiratory system resistance (Rrs). The results showed that mice treated with OA had worse PFTs than normal controls, characterized by lower MFEF 50%, FEV0.1 and Crs but higher Rrs. The OA-sensitized mice also had more severe bronchoconstriction in response to acetylcholine, characterized by greater decreases in MFEF 50%, FEV0.1 and Crs but a higher Rrs than the controls. There was a good correlation between PD20MFEF50%Ach and PD20FEV0.1Ach with PD20CrsAch and PD20RrsAch. In conclusion, the MFEM can be used to evaluate airway obstruction and BHR induced in mice by allergen challenge.
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Obstrucción de las Vías Aéreas/fisiopatología , Alérgenos/administración & dosificación , Broncoconstricción/fisiología , Obstrucción de las Vías Aéreas/inducido químicamente , Obstrucción de las Vías Aéreas/patología , Animales , Líquido del Lavado Bronquioalveolar/citología , Broncoconstricción/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inyecciones Intraperitoneales , Pulmón/patología , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Flujo Espiratorio Máximo/fisiología , Ratones , Ratones Endogámicos BALB C , Pruebas de Función Respiratoria/métodosRESUMEN
UNLABELLED: In the present study, the effect of 200 microg salbutamol compared to placebo was evaluated on lung function parameters of 37 healthy children aged 7-14 years. Salbutamol or placebo were administered, using a single blind study design, and spirometry was performed before and after 10 min of inhalation. At the time of the study, all children were symptom-free and had not suffered from any respiratory infection during the previous 4 weeks. The administration of salbutamol resulted in a significant increase of mean forced expiratory volume in 1 s (111%-115%, P<0.05), maximal expiratory flow at 50% of forced vital capacity (101%-110%, P<0.05) and maximal expiratory flow at 25 % of forced vital capacity (96%-115%, P<0.05). The administration of placebo resulted in no significant change in lung function parameters. CONCLUSION: The administration of 200 microg salbutamol results in the occurrence of a small but significant bronchodilation in healthy, non-asthmatic children.
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Albuterol/farmacología , Broncodilatadores/farmacología , Pulmón/efectos de los fármacos , Adolescente , Niño , Femenino , Flujo Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Flujo Espiratorio Máximo/efectos de los fármacos , Valores de Referencia , Método Simple Ciego , EspirometríaRESUMEN
BACKGROUND AND PURPOSE: Leukotrienes are important inflammatory mediators of bronchial asthma that cause bronchoconstriction, mucous secretion, and increased vascular permeability. Current guidelines recommend anti-leukotriene agents as alternative treatments for asthma; however, data on their anti-inflammatory effect is lacking. METHODS: The purpose of this study was to determine the anti-inflammatory effect of zafirlukast, a leukotriene antagonist, in patients with bronchial asthma. A total of 30 adult patients with mild persistent asthma received 6 weeks of zafirlukast treatment. Peak expiratory flow rate (PEFR) was determined before and after therapy to assess clinical efficacy. Both serum and sputum samples were collected before and after therapy and concentrations of eosinophil cationic protein (ECP), prostaglandin E2 (PGE2), and leukotriene E4 (LTE4) were measured. RESULTS: A significant improvement in PEFR was found after zafirlukast therapy (p = 0.017). There was also a significant reduction in serum ECP concentration (13.6 +/- 2.4 micrograms/L vs 10.3 +/- 2.1 micrograms/L, p < 0.025) and a significant increase in sputum PGE2 concentration (112.7 +/- 14.0 pg/mL vs 176.8 +/- 32.1 pg/mL, p < 0.01). The percentage eosinophil count and the concentrations of ECP and LTE4 in the sputum were not significantly different after therapy. CONCLUSION: This study found a significant reduction in serum ECP and a significant increase in sputum PGE2 concentrations in asthmatic patients after zafirlukast treatment, both of which were significantly associated with improvement in PEFR. The modulation of PGE2 and ECP production might occur through the anti-inflammatory effect of zafirlukast.