RESUMO
OBJECTIVE: Diurnal salivary cortisol patterns in healthy adults are well established but have not been studied in midlife women with hot flashes. We hypothesized that frequent hot flashes are associated with aberrant cortisol patterns similar to sleep-deficient individuals. DESIGN: Cross-sectional. PARTICIPANTS: A total of 306 women, ages 40-62, randomized to a behavioural intervention for hot flashes. MEASUREMENTS: Baseline comparisons of cortisol geometric means (nmol/l) from four daily time points averaged over two consecutive days plus other calculated cortisol measures were made between groups defined by baseline: (i) mean daily hot flash frequency tertile (≤5·5, N = 103; >5·5-8·8, N = 103; >8·8, N = 100) and (ii) selected characteristics. Repeated-measures linear regression models of log-transformed cortisol evaluated group differences, adjusting for covariates. RESULTS: Women were 67% White and 24% African American, with 7·6 (SD 3·9) hot flashes per day. Salivary cortisol geometric means (nmol/l) among all women were as follows: 75·0 (SD 44·8) total, 8·6 (SD 5·6) wake, 10·0 (SD 7·5) wake +30 min, 3·7 (SD 3·3) early afternoon and 1·6 (SD 1·8) bedtime. Wake + 30-minute values showed an 18% median rise from wake values (interquartile range -24 to 96%), and means varied by hot flash frequency tertile, from lowest to highest: 11·4(SD 7·3), 10·3 (SD 6·5) and 8·6 (SD 7·8), respectively, P = 0·003. Beside the early afternoon value (P = 0·02), cortisol values did not vary by hot flash frequency. CONCLUSION: Taken together, these findings suggest that high frequency of moderate-to-severe hot flashes may be associated with subtle abnormalities in cortisol concentrations - a pattern consistent with chronic sleep disturbance.
Assuntos
Exercício Físico/fisiologia , Ácidos Graxos Ômega-3/uso terapêutico , Fogachos/prevenção & controle , Hidrocortisona/análise , Saliva/química , Adulto , Ritmo Circadiano , Estudos Transversais , Feminino , Fogachos/metabolismo , Fogachos/fisiopatologia , Humanos , Modelos Lineares , Modelos Logísticos , Menopausa/fisiologia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricosRESUMO
This study evaluated the effect of mometasone furoate (MF)/formoterol (F) versus its monocomponents, each administered via metered-dose inhaler, on asthma deteriorations and lung function. This 26-week, multicentre, double-blind, placebo-controlled study included subjects aged ≥12 yrs with not well-controlled asthma on low-dose inhaled corticosteroids. After a 2-3-week open-label run-in (MF 100 µg b.i.d.), 746 subjects were randomised to receive placebo, F 10 µg, MF 100 µg or MF/F 100/10 µg b.i.d. Co-primary end-points were time to first asthma deterioration (MF/F versus F to assess effect of MF) and change in forced expiratory volume in 1 s (FEV(1)) area under the curve of serial spirometry measurements over the 12-h period following the morning dose (AUC(0-12h)) (baseline to week 12; MF/F versus MF to assess effect of F). The therapeutic effect of MF in the combination was demonstrated by a reduction in asthma deterioration incidence with MF/F versus F and a delayed time to first asthma deterioration (p<0.001). Asthma deterioration incidence was also reduced with MF/F versus MF (p=0.006). The therapeutic effect of F in the combination was demonstrated by MF/F versus MF in FEV(1) AUC(0-12h) change (4.00 versus 2.53 L·h, respectively; p=0.001). MF/F treatment also resulted in a marked improvement in health-related quality of life. MF/F 100/10 µg b.i.d. treatment showed greater clinical efficacy than its individual components or placebo; both components contributed to the efficacy of MF/F.
Assuntos
Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Etanolaminas/administração & dosagem , Pregnadienodiois/administração & dosagem , Adulto , Anti-Inflamatórios/efeitos adversos , Asma/fisiopatologia , Broncodilatadores/efeitos adversos , Progressão da Doença , Quimioterapia Combinada , Etanolaminas/efeitos adversos , Feminino , Fumarato de Formoterol , Humanos , Masculino , Pessoa de Meia-Idade , Furoato de Mometasona , Pregnadienodiois/efeitos adversos , Qualidade de Vida , Testes de Função Respiratória , Sono/efeitos dos fármacos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Indacaterol is a novel, once-daily beta(2)-agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Studies were required to determine optimal dose(s) for continuing investigation. OBJECTIVE: A dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol. METHODS: A total of 436 patients with persistent asthma receiving inhaled corticosteroids were randomized to 7 days treatment with once-daily indacaterol 50, 100, 200, or 400 microg via multi-dose dry-powder inhaler (MDDPI; Certihaler), indacaterol 400 microg via single-dose dry-powder inhaler (SDDPI), or placebo. Serial 24-h spirometry was performed on days 1 and 7. Vital signs, laboratory evaluations, and adverse events were monitored. RESULTS: All doses of indacaterol increased the mean time-standardized area under the curve of forced expiratory volume in 1 s (FEV(1)) from 22 to 24 h postdose (P Assuntos
Asma/tratamento farmacológico
, Indanos/administração & dosagem
, Inaladores Dosimetrados
, Quinolonas/administração & dosagem
, Administração por Inalação
, Adolescente
, Adulto
, Idoso
, Asma/diagnóstico
, Relação Dose-Resposta a Droga
, Método Duplo-Cego
, Esquema de Medicação
, Feminino
, Seguimentos
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Análise Multivariada
, Probabilidade
, Valores de Referência
, Testes de Função Respiratória
, Índice de Gravidade de Doença
, Espirometria
, Resultado do Tratamento
RESUMO
This open-label study was performed to characterize the acceptance, reliability, and adverse event profile of a dry powder delivery system for albuterol. A total of 1235 asthmatic outpatients, aged 11 to 84 years, were studied for 1 month. Each patient enrolled was documented as having a specific complaint concerning the use of a standard metered-dose inhaler. At the end of 4 weeks of treatment, the patients completed a questionnaire to record their opinions and preferences. The results were as follows: 93% stated that Rotacaps were easy to use; 92% that they could use Rotacaps during an asthma attack; 99% that they had no problems with breakage of the device; 94% that the drug tasted pleasant or had no taste; 70% that they could inhale a full dose with one breath; and 79% that Rotacaps were at least as effective as the metered-dose inhaler they had used previously. Drug-related adverse events were reported by 6% of the patients; no single event was reported by more than 1% of the patients. The results indicate that Rotacaps are a safe, effective, and well-accepted alternative to metered-dose inhalers in asthmatic patients.
Assuntos
Albuterol/administração & dosagem , Asma/tratamento farmacológico , Administração por Inalação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuterol/efeitos adversos , Albuterol/uso terapêutico , Asma/psicologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Cooperação do PacienteRESUMO
Two multicenter, randomized, double-masked, placebo-controlled, parallel-group studies were conducted in adult patients with mild-to-moderate persistent asthma to assess the effects of 4 weeks of treatment with inhaled corticosteroids on hypothalamic-pituitary-adrenal (HPA) axis function. The first study compared fluticasone propionate 100 and 500 microg twice daily, triamcinolone acetonide 300 and 500 microg twice daily, oral prednisone 10 mg every morning, and placebo. The second study compared fluticasone propionate 100 and 250 microg twice daily, flunisolide 500 microg twice daily, and placebo. Therapeutic doses of fluticasone propionate, triamcinolone acetonide, and flunisolide were found to be comparable to each other and to placebo in their lack of adrenal suppressive effects, based on mean plasma cortisol responses to 6-hour cosyntropin infusion. Prednisone produced significantly greater suppression of HPA-axis function than did any of the inhaled corticosteroids or placebo (P<0.001). Mean reductions from baseline in 8-hour area under the plasma concentration-time curve (AUC) and 8-hour peak plasma cortisol concentrations and the mean percentage of change from baseline in 8-hour AUC were significantly greater after treatment with triamcinolone acetonide 500 microg twice daily compared with placebo (P< or =0.042). These findings indicate that fluticasone propionate has no greater systemic effect than either triamcinolone acetonide or flunisolide at doses appropriate for patients with mild-to-moderate persistent asthma.
Assuntos
Androstadienos/uso terapêutico , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Fluocinolona Acetonida/análogos & derivados , Glucocorticoides/uso terapêutico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Prednisona/uso terapêutico , Triancinolona Acetonida/uso terapêutico , Administração por Inalação , Administração Oral , Adulto , Androstadienos/administração & dosagem , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Área Sob a Curva , Asma/fisiopatologia , Cosintropina/metabolismo , Método Duplo-Cego , Feminino , Fluocinolona Acetonida/administração & dosagem , Fluocinolona Acetonida/uso terapêutico , Fluticasona , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Triancinolona Acetonida/administração & dosagemRESUMO
Two multicenter, randomized, double-masked, placebo-controlled studies involving 451 adolescent and adult patients with mild-to-moderate asthma compared the efficacy and safety of salmeterol powder 50 micrograms twice daily with albuterol 180 micrograms four times daily or placebo (with albuterol as needed) for 12 weeks. Patients had forced expiratory volume in 1 second (FEV1) of 50% to 80%. Throughout the 12-week treatment period, the mean change from baseline in percentage of predicted FEV1 was significantly greater with salmeterol than with placebo; mean area under the curve for FEV1 was significantly greater with salmeterol than with albuterol or placebo. Significant improvements in morning and evening peak expiratory flow, percentage of nights without awakening, and asthma symptoms were observed with salmeterol. Salmeterol was well tolerated, and no clinically significant changes in electrocardiographic activity were observed.
Assuntos
Albuterol/análogos & derivados , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Adolescente , Adulto , Albuterol/administração & dosagem , Albuterol/efeitos adversos , Albuterol/uso terapêutico , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Asma/fisiopatologia , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pico do Fluxo Expiratório/efeitos dos fármacos , Testes de Função Respiratória , Xinafoato de SalmeterolRESUMO
A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.
Assuntos
Antialérgicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Adolescente , Adulto , Idoso , Antialérgicos/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Criança , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Fluxo Máximo Médio Expiratório/efeitos dos fármacos , Pessoa de Meia-Idade , Furoato de Mometasona , Pico do Fluxo Expiratório/efeitos dos fármacos , Pregnadienodiois , Resultado do Tratamento , Capacidade Vital/efeitos dos fármacosRESUMO
BACKGROUND: This double-blind, randomized, parallel-group, placebo-controlled study investigated the efficacy and tolerability of fluticasone propionate aerosol (25, 50, or 100 mg bid for 12 weeks) administered as primary maintenance therapy to patients whose mild to moderate asthma was inadequately controlled by as-needed use of an inhaled beta-agonist. RESULTS: At all clinic visits, fluticasone propionate compared with placebo was associated with significant (P<.05) improvement in pulmonary function indexed by forced expiratory volume in 1 second (FEV1) as well as fewer night awakenings and less use of rescue albuterol. Values for patient-measured morning peak expiratory flow rates (PEFR) were significantly (P<.05) higher and the use of rescue albuterol was significantly (P<.05) lower beginning 3 to 5 days after initiation of therapy in the groups treated with fluticasone propionate, compared with the placebo group. Maximal improvement in FEV1 was achieved during the second week of treatment and maintained throughout the course of therapy. Differences among the three fluticasone propionate dosing groups for these efficacy measures were not statistically significant. The incidence of adverse events was similar across groups. CONCLUSIONS: These data indicate that fluticasone propionate aerosol is an effective and well-tolerated treatment for asthma and significantly improves pulmonary function within days of initiation of treatment in patients whose asthma is inadequately controlled with as-needed beta-agonists.
Assuntos
Androstadienos/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Adolescente , Adulto , Aerossóis , Androstadienos/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/fisiopatologia , Método Duplo-Cego , Feminino , Fluticasona , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Topical corticosteroids are widely regarded as the reference standard in allergic rhinitis therapy because they are well tolerated and effective against all rhinitis symptoms. We evaluated the efficacy, onset of action, and safety of two dosing regimens of the new corticosteroid fluticasone propionate compared with that of beclomethasone dipropionate in patients with moderate to severe seasonal allergic rhinitis. METHODS: In this double-blind, randomized multicenter trial, 110 adolescents and 128 adults were treated for 4 weeks with one of the following regimens: fluticasone aqueous nasal spray 100 micrograms twice daily or 200 micrograms once daily, beclomethasone aqueous nasal spray 168 micrograms twice daily, or placebo. RESULTS: Patient-rated scores for nasal obstruction, rhinorrhea, and combined nasal symptoms indicated that the two fluticasone regimens were equally effective and that both were superior to beclomethasone during most of the study (P < or = .05) and to placebo throughout the study (P < or = .01). Both fluticasone regimens also demonstrated significant clinical efficacy by 24 hours after the first dose. Clinician-rated mean total nasal symptoms scores for all three active treatments were superior to placebo at most time points but were not significantly different from each other. All treatments were well tolerated, with similar incidence and type of adverse events in all treatment groups and no apparent effects on hypothalamic-pituitary-adrenal (HPA) axis function. CONCLUSIONS: Fluticasone aqueous nasal spray was effective in relieving nasal symptoms in adolescents and adults with seasonal allergic rhinitis. Fluticasone administered once or twice daily was superior to beclomethasone administered twice daily in relieving nasal obstruction and rhinorrhea and in reducing nasal symptoms more quickly.
Assuntos
Androstadienos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Idoso , Androstadienos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Beclometasona/administração & dosagem , Beclometasona/uso terapêutico , Criança , Método Duplo-Cego , Feminino , Fluticasona , Glucocorticoides , Humanos , Masculino , Pessoa de Meia-Idade , Rinite Alérgica Sazonal/fisiopatologiaRESUMO
BACKGROUND: Arformoterol is a single-isomer (R,R-formoterol) nebulized long-acting beta(2)-agonist approved for use in patients with chronic obstructive pulmonary disease (COPD). Exposure (plasma concentrations of (R,R)-formoterol) and forced expiratory volume in 1s (FEV(1)) were compared for 15 microg nebulized arformoterol and 12 and 24 microg racemic formoterol (containing 6 and 12 microg (R,R)-formoterol, respectively) delivered by dry powder inhaler (DPI). METHODS: An open-label, randomized, three-way crossover study in 39 subjects with COPD (FEV(1) 1.4L, 44.4% predicted). Twice-daily treatments included nebulized arformoterol (15 microg) and racemic formoterol DPI (12 and 24 microg) for 14 days. Plasma concentrations of (R,R)- and (S,S)-formoterol were determined on days 1 and 14 of each treatment period. Airway function efficacy endpoints included the percent change in trough FEV(1) from baseline on day 14 of each treatment period. RESULTS: At steady state, exposure to (R,R)-formoterol was similar following nebulized 15 microg arformoterol (C(max): 6.5 pg/mL; AUC(0-tau): 56.5 pgh/mL) and 12 microg racemic formoterol DPI (C(max): 6.2 pg/mL; AUC((0-)(tau)()): 46.3 pgh/mL). The geometric mean ratios between these two treatments (90% confidence intervals) for C(max) and AUC((0-)(tau)()) were 0.91 (0.76, 1.09) and 1.16 (1.00, 1.35), respectively. Treatment with 24 microg racemic formoterol DPI resulted in dose proportionally higher (R,R)-formoterol: C(max) (10.8 pg/mL) and AUC((0-)(tau)()) (83.6 pgh/mL). Detectable (S,S)-formoterol was consistently measured only after treatment with racemic formoterol. The mean percent increase in trough FEV(1) was 19.1% in the arformoterol group, and 16.0% and 18.2% in the 12 and 24 microg racemic formoterol groups, respectively. Changes in (R,R)-formoterol concentrations over time paralleled changes in FEV(1). CONCLUSIONS: In this study, plasma exposure to (R,R)-formoterol was similar for nebulized 15 microg arformoterol and 12 microg racemic formoterol DPI, and 40% lower than 24 microg racemic formoterol DPI. There was no evidence of chiral interconversion following treatment with arformoterol. Finally, temporal changes in airway function in all treatment groups corresponded to changes in (R,R)-formoterol plasma concentrations.
Assuntos
Broncodilatadores/administração & dosagem , Etanolaminas/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Área Sob a Curva , Broncodilatadores/farmacocinética , Estudos Cross-Over , Relação Dose-Resposta a Droga , Etanolaminas/farmacocinética , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Fumarato de Formoterol , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , EstereoisomerismoRESUMO
BACKGROUND: In this study, we investigated the early development of stress in mothers of children with Down syndrome, compared with mothers of children with developmental disabilities of mixed aetiologies. Growth modelling analyses were used to explore: (1) whether mothers of children with Down syndrome demonstrated distinct patterns of stress during their children's early development, compared with mothers of children with other developmental disabilities; and (2) whether there was a relation between child behavioural characteristics and the level and rate of change in stress observed in each population. METHOD: The stress trajectories of mothers of young children with Down syndrome (n = 25) and a mixed-aetiology comparison group (n = 49) were estimated, using growth modelling on data collected at ages of 15, 30 and 45 months. RESULTS: On average, stress in the mixed comparison group was higher at Time 1 and remained unchanged over time, while stress in the Down syndrome group was lower at Time 1 but increased steadily. After taking diagnostic group membership into account, more advanced cognitive-linguistic functioning and lower levels of maladaptive behaviours at all time points were associated with lower levels of maternal stress. CONCLUSIONS; These findings suggest that the cognitive-linguistic and behavioural trajectory observed in early development in Down syndrome may contribute to the changes in maternal stress levels observed throughout these early years. Implications for developing targeted and time- sensitive family interventions for families of children with Down syndrome are discussed.
Assuntos
Síndrome de Down/psicologia , Mães/psicologia , Estresse Psicológico/diagnóstico , Adulto , Transtornos do Comportamento Infantil/psicologia , Pré-Escolar , Interpretação Estatística de Dados , Deficiências do Desenvolvimento/psicologia , Feminino , Humanos , Lactente , Inteligência , Transtornos do Desenvolvimento da Linguagem/psicologia , Estudos Longitudinais , Masculino , Modelos Estatísticos , Estresse Psicológico/psicologiaRESUMO
Our objective was to compare the efficacy and safety of formoterol (Foradil) delivered via a novel multidose dry powder inhaler (Certihaler) with placebo and albuterol [pressurized metered-dose inhaler (pMDI)], in patients with persistent asthma. After a 2-week run-in phase, 265 patients (13-81 years) previously treated with regular/PRN bronchodilators for persistent asthma were randomized to 12 weeks' double-blind treatment with formoterol 10 microg BID via Certihaler (n = 86), albuterol 180 microg QID via pMDI (n = 88) or placebo (n = 91). The primary efficacy variable was 12-hour AUC of FEV1 after 12 weeks' treatment. Secondary efficacy variables included peak expiratory flow (PEF), rescue bronchodilator medication use, asthma-related quality of life (Juniper Mini Asthma Quality of Life Questionnaire), and asthma symptom scores. Formoterol via the Certihaler had an onset of action within 5 minutes and was associated with a clinically relevant and statistically significant increase in 12-hour AUC of FEV1 after 12 weeks' treatment compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Average PEF was significantly superior for formoterol compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Compared with placebo, rescue albuterol use during the study was significantly lower for formoterol (p < 0.01) and was accompanied by a trend toward an improvement in asthma-related quality of life (QoL). Asthma symptom scores improved to a similar extent for all treatment groups. Treatment with formoterol via Certihaler was well tolerated. Formoterol 10 microg BID, delivered via the novel Certihaler device, is well tolerated and provides rapid, long-lasting, and clinically superior bronchodilation to placebo and albuterol via pMDI in patients with persistent asthma.
Assuntos
Albuterol/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Etanolaminas/administração & dosagem , Nebulizadores e Vaporizadores , Administração por Inalação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Desenho de Equipamento , Feminino , Fumarato de Formoterol , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Intranasal steroids are highly effective drugs for treating patients with allergic rhinitis. First-line use of intranasal steroids is becoming increasingly common, and intranasal steroids can be used alone or in combination with other therapies to achieve optimal improvement in rhinitis symptoms. The major adverse effect of intranasal steroids is local irritation. This article reviews the mechanism of action of corticosteroids, the effects of intranasal steroids on chemical mediators of inflammation, and the risks and benefits associated with their use.
Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Intranasal , Corticosteroides/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Fifteen asthmatic children (mean age = 14.5 years) who required daily theophylline therapy were studied for effect of erythromycin ethyl-succinate on theophylline clearance. After a one week course of EES, there was 25.8 +/- 18.4% reduction in theophylline clearance rate (P less than 0.001), and a concomitant elevation in steady-state serum theophylline concentration of 40.0 +/- 35.3% (P less than 0.01). Three subjects reached serum theophylline concentrations greater than 20 micrograms/ml. Patients receiving therapeutic doses of theophylline are at considerable risk of theophylline toxicity if EES is co-administered.
Assuntos
Asma/tratamento farmacológico , Eritromicina/farmacologia , Teofilina/metabolismo , Adolescente , Eritromicina/metabolismo , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Teofilina/sangue , Teofilina/uso terapêuticoRESUMO
A 14-year-old male adolescent is described with a 6-year history of active lymphadenopathy, skin rash, peripheral blood eosinophilia, and markedly elevated serum-IgE level. Complete histopathologic and immunologic evaluations established the diagnosis of Kimura's disease as first described in Japan. Because of its relative infrequency and varied features, this disorder can be difficult to diagnose when it is encountered in the United States.
Assuntos
Doenças Linfáticas/diagnóstico , Adolescente , Quimiotaxia de Leucócito , Dermatite/complicações , Eosinofilia/complicações , Humanos , Imunoglobulina E/análise , Linfonodos/imunologia , Linfonodos/patologia , Doenças Linfáticas/complicações , Masculino , Neutrófilos/imunologia , Teste de Radioalergoadsorção , Linfócitos T/classificaçãoRESUMO
The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 microg and 24 microg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 microg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12-75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 microg, formoterol 24 microg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV1), both formoterol 12 microg and 24 microg were statistically superior to placebo at all time points on all test days (p < or = 0.017) and to albuterol at most time points on all test days (p < or = 0.001). The onset of improvement in FEV1 was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 microg, formoterol 24 microg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV1 area under the curve, percentage of predicted FEV1, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.
Assuntos
Albuterol/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Etanolaminas/administração & dosagem , Administração por Inalação , Adolescente , Adulto , Idoso , Criança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Volume Expiratório Forçado , Fumarato de Formoterol , Humanos , Inaladores Dosimetrados , Pessoa de Meia-Idade , Pós/administração & dosagem , Resultado do TratamentoRESUMO
Methylprednisolone elimination is reduced in the presence of treatment with troleandomycin (TAO), a macrolide antibiotic. To assess whether a similar interaction occurs with a more commonly used and less hepatotoxic macrolide antibiotic, erythromycin, we evaluated methylprednisolone pharmacokinetics before and after a 1 wk course of erythromycin base in nine adolescent patients with chronic asthma. These data were compared to results of studies of the troleandomycin methylprednisolone interaction evaluated in 10 adolescent asthmatic patients. Methylprednisolone clearance and apparent volume of distribution were significantly decreased and mean residence time and half-life significantly increased in the presence of both erythromycin and troleandomycin. The latter caused greater inhibition of methylprednisolone elimination. A nonlinear pattern of methylprednisolone disposition was observed in the presence of concomitant macrolide antibiotic administration. Addition of erythromycin base to methylprednisolone therapy results in inhibition of methylprednisolone elimination and may potentially increase the beneficial and adverse effects of this corticosteroid.
Assuntos
Eritromicina/uso terapêutico , Metilprednisolona/sangue , Adolescente , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Asma/tratamento farmacológico , Criança , Feminino , Humanos , Masculino , Estatística como Assunto , Troleandomicina/uso terapêuticoRESUMO
This parallel-group study compared the safety and efficacy of controlled-release albuterol versus sustained-release theophylline, both administered every 12 hours. One hundred twenty-four adolescent and adult patients with asthma and with chronic reversible obstructive airway disease were studied. All patients qualified with an FEV1 less than or equal to 80% of predicted (not receiving treatment) and greater than or equal to 15% reversibility in FEV1 or greater than or equal to 25% reversibility in FEF25-75% after inhaled isoproterenol. All patients were known to be able to take theophylline without unacceptable adverse effects. Theophylline was titrated for patients to receive, unblinded, theophylline serum concentrations of 10 to 20 micrograms/ml. With subsequent randomization, 62 patients continued to receive theophylline and 62 patients started taking albuterol in the 12-week, double-blind, double-dummy portion of the study. Pulmonary function was measured during a pretreatment visit (unmedicated) and serial assessment was made starting just before the morning dose and continuing for 12 hours after the dose at the end of 1, 6, and 12 weeks of treatment. Both treatment groups exhibited statistically significant increases in FEV1 from the pretreatment visit to all times of observation at weeks 1, 6, and 12. The increases in FEV1 were not significantly different between albuterol and theophylline administration. There was no evidence of tolerance to the bronchodilatory effect during 12 weeks in either treatment group. Only one patient in the study stopped treatment because of an adverse effect. This patient had tremor during albuterol administration. All other adverse events were tolerated or resolved during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Albuterol/administração & dosagem , Asma/tratamento farmacológico , Teofilina/administração & dosagem , Adolescente , Adulto , Albuterol/efeitos adversos , Albuterol/sangue , Asma/sangue , Asma/fisiopatologia , Cápsulas , Preparações de Ação Retardada , Método Duplo-Cego , Humanos , Pico do Fluxo Expiratório/efeitos dos fármacos , Pico do Fluxo Expiratório/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Comprimidos , Teofilina/efeitos adversos , Teofilina/sangue , Fatores de TempoRESUMO
BACKGROUND: Recent emphasis on the control of airway inflammation in asthma highlights the need for safe and effective antiinflammatory agents. Fluticasone propionate is one of the most potent antiinflammatory corticosteroids developed to date. OBJECTIVE: This study assessed the safety and efficacy of fluticasone propionate aerosol in the treatment of mild to moderate asthma. METHODS: Fluticasone propionate aerosol (25, 100, or 500 micrograms twice daily) or placebo was given for as long as 8 weeks to adults with mild to moderate asthma in a randomized, double-blind, parallel-group study. Patients were removed from the study if they showed predefined signs of worsening asthma. RESULTS: Sixty-three percent of placebo-treated patients and 23%, 13%, and 4% of patients treated with fluticasone propionate 25, 100, and 500 micrograms twice daily, respectively, were removed from the study. Mean forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow at midexpiratory phase at weekly visits throughout the study demonstrated that fluticasone propionate was more efficacious than placebo in maintaining asthma control. Measurements of peak expiratory flow and symptom scores significantly improved and nighttime awakenings and albuterol use to treat symptoms significantly declined in fluticasone propionate-treated groups relative to the placebo-treated group. Differences among fluticasone propionate groups for these variables were not statistically significant. Incidence and severity of adverse events were similar across groups. Fluticasone propionate did not affect morning or stimulated plasma cortisol concentrations, although slight, transient reductions in urinary free cortisol and urinary 17-hydroxy steroids occurred in the group receiving 500 micrograms fluticasone propionate twice daily. CONCLUSION: These data indicate that fluticasone propionate provides safe and effective treatment for mild to moderate asthma.
Assuntos
Androstadienos/administração & dosagem , Asma/tratamento farmacológico , Administração Tópica , Adulto , Aerossóis , Androstadienos/efeitos adversos , Androstadienos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/fisiopatologia , Método Duplo-Cego , Feminino , Fluticasona , Glucocorticoides , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Pacientes , Médicos , Sistema Hipófise-Suprarrenal/fisiopatologia , Espirometria , Resultado do TratamentoRESUMO
BACKGROUND: In order to accommodate increasing patient preferences a new aqueous formulation of triamcinolone acetonide nasal spray was developed for the relief of symptoms associated with seasonal and perennial allergic rhinitis. OBJECTIVE: This multicenter, randomized, double-blind study was designed to compare the efficacy and safety of once-daily triamcinolone acetonide aqueous nasal spray (220 micrograms/day) with placebo in relieving the symptoms of seasonal allergic rhinitis due to ragweed. METHODS: One hundred forty patients received either a once daily 220-microgram dose of triamcinolone acetonide aqueous nasal spray or placebo for 2 weeks. Patients evaluated the severity of seasonal allergic rhinitis symptoms daily for 2 weeks according to a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Physician and patient global evaluations of overall treatment effectiveness were assessed at the end of the treatment period. RESULTS: Patients receiving triamcinolone acetonide aqueous nasal spray, 220 micrograms/day, had significantly (P < .05) greater improvements in all rhinitis symptoms at weeks 1 and 2 and overall for the 2-week treatment period compared with the placebo group. A significant (P = .006) improvement in the nasal index occurred as early as 12 hours after the first dose of triamcinolone acetonide aqueous nasal spray. Both patients and physicians reported a greater overall improvement in symptoms for the triamcinolone acetonide aqueous nasal spray group. There were no differences between the two treatment groups in the incidence of adverse events. CONCLUSIONS: This study confirmed that a 220-microgram dose of triamcinolone acetonide aqueous nasal spray, administered once daily for 2 weeks, is well tolerated and reduces effectively the severity of symptoms of seasonal allergic rhinitis due to ragweed.