RESUMO
Eosinophilia is an established marker of asthma-related inflammation. We assessed the effect of omalizumab on peripheral blood eosinophil counts using a pooled analysis of data from five randomized, double-blind, placebo-controlled studies in patients with moderate-to-severe persistent allergic asthma receiving moderate-to-high-dose inhaled corticosteroids (omalizumab, n=1136; placebo, n=1100). Relationships between omalizumab, peripheral blood eosinophils, serum free IgE concentrations and clinical outcomes were explored. Baseline mean eosinophil counts were similar in each treatment group. Post-treatment eosinophil counts were significantly reduced from baseline in the omalizumab group (p<0.0001) but were not significantly different in the placebo group. Greater reductions in eosinophil counts were observed in patients who had post-treatment free IgE levels <50ng/mL. Three studies included steroid-stable and steroid-reduction phases. At the end of each phase in these studies, a significantly greater reduction in eosinophil counts was achieved in the omalizumab group compared with the placebo group (p<0.0001). A consistent pattern of improved clinical outcomes/decreased eosinophils and worsened clinical outcomes/increased eosinophils was observed for both omalizumab and placebo treatment groups. The findings from our analysis of a large patient population are consistent with earlier reports of the inhibitory effect of omalizumab on eosinophils.
Assuntos
Antiasmáticos/farmacologia , Asma/complicações , Eosinofilia/tratamento farmacológico , Eosinófilos/efeitos dos fármacos , Imunoglobulina E/sangue , Adolescente , Adulto , Idoso , Anticorpos Anti-Idiotípicos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Asma/sangue , Asma/tratamento farmacológico , Criança , Relação Dose-Resposta a Droga , Eosinofilia/sangue , Eosinófilos/metabolismo , Feminino , Humanos , Imunoglobulina E/efeitos dos fármacos , Inflamação/sangue , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Omalizumab , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto JovemRESUMO
Asthma is a chronic inflammatory disease of the airways in which immunoglobulin E (IgE) plays a key role by activating a variety of inflammatory cells through interactions with FcepsilonRI and FcepsilonRII receptors. The role of IgE in allergic inflammation provided the rationale for developing omalizumab, a humanized monoclonal anti-IgE antibody, for patients with moderate-to-severe or severe allergic asthma. The reductions in circulating levels of IgE resulting from omalizumab treatment leads to reductions in FcepsilonRI expression on mast cells, basophils and dendritic cells. This combined effect results in attenuation of several markers of inflammation, including peripheral and bronchial tissue eosinophilia and levels of granulocyte macrophage colony stimulating factor, interleukin (IL)-2, IL-4, IL-5 and IL-13. By blocking IgE binding to its receptors and diminishing dendritic cell FcepsilonRI receptor expression, omalizumab may also reduce allergen presentation to T cells and the production of Th2 cytokines. The anti-inflammatory effects of omalizumab may, therefore, explain the reductions in asthma exacerbations and symptoms seen in clinical trials in patients with moderate-to-severe or severe, persistent, inadequately controlled allergic asthma.
Assuntos
Anticorpos Monoclonais/farmacologia , Asma/patologia , Inflamação/tratamento farmacológico , Antiasmáticos , Anticorpos Anti-Idiotípicos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Biomarcadores/análise , Humanos , Inflamação/diagnóstico , OmalizumabRESUMO
OBJECTIVE: This study aimed to evaluate the effectiveness of omalizumab among adolescents with moderate-severe allergic asthma inadequately controlled with inhaled corticosteroids. PATIENTS AND METHODS: Data from patients 12 to 17 years of age were pooled from 5 placebo-controlled registration trials of omalizumab. Impact on asthma control was assessed by need for rescue bursts of oral corticosteroids, lung function, symptom scores, and unscheduled office visits. RESULTS: In adolescents (n = 146), addition of omalizumab decreased mean number of rescue bursts (0.3 vs 0.9) versus placebo; relative risk 0.47 (95% confidence interval [CI], 0.22-0.99; P = .047). At study conclusion, mean forced expiratory volume in 1 second increased 268 mL (13.8%) in omalizumab-treated subjects versus 98 mL (5.5%) for placebo (least squares mean treatment difference 146 mL [95% CI, 19.4-272.6; P = .024]). Omalizumab significantly improved asthma symptom scores and reduced unscheduled office visits. CONCLUSION: Omalizumab added to baseline therapy improves measures of asthma control in adolescents with persistent moderate-severe allergic asthma.
Assuntos
Antiasmáticos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Asma/tratamento farmacológico , Glucocorticoides/administração & dosagem , Hipersensibilidade/tratamento farmacológico , Administração por Inalação , Administração Oral , Adolescente , Anticorpos Anti-Idiotípicos , Anticorpos Monoclonais Humanizados , Asma/diagnóstico , Asma/etiologia , Criança , Quimioterapia Combinada , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/diagnóstico , Masculino , Visita a Consultório Médico/estatística & dados numéricos , Omalizumab , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
African Americans as a group have a higher incidence of chronic hepatitis C (CHC) than Caucasians but are often under-represented in clinical trials used to define response rates to interferon therapy. The aim of this study was to compare African Americans with Caucasians with respect to end-of-treatment response to interferon. This retrospective study had 61 African Americans and 49 Caucasians with CHC. All patients were treated for at least 12 weeks with interferon-alpha2b (Intron A) thrice weekly. End-of-treatment response was defined as three consecutive nondetectable HCV RNA measurements at least 1 month apart. Sustained response was defined as a negative serum HCV RNA 6 months after end of treatment. Of the 110 patients, 19 achieved an end-of-treatment response (17%) but only four achieved a sustained response (4/110=4%). Of the patients achieving a sustained response, one was genotype 1 (male Caucasian), three were genotype 2/3 with four patients having no follow-up information. The end-of-treatment response was 7% for patients with genotype 1 and 71% for genotype non-1 (P < 0.005 for genotype non-1). The end-of-treatment response was significantly higher in Caucasians (14/49=31%) compared with African Americans (5/61=8%; P < 0.05). A lower response rate in African Americans with genotype 1 in contrast to Caucasians was the primary reason for the difference in end-of-treatment response (1/45=2% vs. 5/33=15%, P < 0.05). Hence, interferon treatment resulted in a poor sustained response rate in the group of patients representative of the urban populations with the highest prevalence of hepatitis C. A genotype other than type 1 was the strongest predictor of end-of-treatment response in patients treated but over 86% of patients in this urban clinic were genotype 1. Caucasians were more likely to respond than African Americans, especially in patients with genotype 1.
Assuntos
População Negra , Hepatite C Crônica/terapia , Interferons/uso terapêutico , População Branca , Adulto , Negro ou Afro-Americano , Doença Crônica , Feminino , Genótipo , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Viral/análise , Estudos Retrospectivos , Estados UnidosRESUMO
As our understanding of asthma has evolved, so have pharmaceutical strategies for managing this disorder. Once considered a disorder of airway smooth muscle, asthma now is regarded primarily as a chronic inflammatory disorder of the airways. Traditional therapy sought to suppress bronchoconstriction and other signs and symptoms of asthma when they occurred, but contemporary strategies center on managing the underlying inflammation through long-term medications intended to reduce the overall risk of acute attacks. Direct and indirect costs of illness for asthma were estimated at $6.2 billion in 1990. Undoubtedly the costs are considerably higher today due to the increasing prevalence of the disorder. The costs associated with the illness are not distributed evenly among the 15 million Americans with asthma. About 20% of the patients account for 80% of the expenditures. By identifying the high-cost patients and educating them regarding the proper use of medication, it may be possible to curtail costs associated with asthma. Healthcare professionals, especially in their role as educators, are critical to reducing morbidity, mortality, and costs associated with asthma patients.
Assuntos
Asma/terapia , Custos de Cuidados de Saúde , Antiasmáticos/uso terapêutico , Controle de Custos , Humanos , Cooperação do Paciente , Resultado do TratamentoRESUMO
A 7-year-old boy with asthma was receiving the leukotriene receptor antagonist pranlukast (Ultair; SmithKline Beecham; Pittsburgh) as part of an open-label clinical trial. The patient's asthma improved, and he remained asymptomatic; but routine study evaluations 9 to 12 months into therapy showed microhematuria, proteinuria, glucosuria, anemia, and renal insufficiency. Renal biopsy demonstrated changes classic for acute allergic tubulointerstitial nephritis (ATIN), with mixed interstitial inflammatory infiltrate including eosinophils. Within 6 months of pranlukast withdrawal, anemia resolved and urinary sediment and renal function normalized. The case demonstrates that hypersensitivity reaction to pranlukast and resultant ATIN is possible, and that periodic urine testing in patients receiving pranlukast should be considered.
Assuntos
Cromonas/efeitos adversos , Antagonistas de Leucotrienos/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Doença Aguda , Asma/tratamento farmacológico , Biópsia , Criança , Creatinina/sangue , Seguimentos , Glicosúria/etiologia , Glicosúria/urina , Hematúria/etiologia , Hematúria/urina , Humanos , Masculino , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Proteinúria/etiologia , Proteinúria/urinaRESUMO
All 2,617 children who received midazolam and meperidine for a variety of endoscopic procedures were monitored for the development of adverse behavioral problems. Thirty-six (1.4%) of the children (ages 1-17 years) experienced a paradoxical behavioral reaction, which consisted of inconsolable crying, combativeness, disorientation, dysphoria, tachycardia, agitation, and restlessness. The reaction occurred at a mean of 17 minutes after the administration of midazolam. Following treatment with flumazenil, the reaction dissipated within a mean of 14 minutes. Three of the 36 patients underwent additional endoscopic procedures utilizing only meperidine. No similar reaction was observed in these patients. Awareness of the reaction and prompt administration of flumazenil decreased the duration of the reaction.
Assuntos
Comportamento do Adolescente/efeitos dos fármacos , Ansiolíticos/efeitos adversos , Comportamento Infantil/efeitos dos fármacos , Endoscopia , Hipnóticos e Sedativos/efeitos adversos , Comportamento do Lactente/efeitos dos fármacos , Midazolam/efeitos adversos , Adjuvantes Anestésicos/administração & dosagem , Adolescente , Agressão/efeitos dos fármacos , Acatisia Induzida por Medicamentos/etiologia , Ansiolíticos/administração & dosagem , Ansiolíticos/antagonistas & inibidores , Antídotos/uso terapêutico , Criança , Pré-Escolar , Choro , Monitoramento de Medicamentos , Feminino , Flumazenil/uso terapêutico , Moduladores GABAérgicos/uso terapêutico , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/antagonistas & inibidores , Lactente , Masculino , Meperidina/administração & dosagem , Midazolam/administração & dosagem , Midazolam/antagonistas & inibidores , Orientação/efeitos dos fármacos , Agitação Psicomotora/etiologia , Taquicardia/induzido quimicamente , Fatores de TempoAssuntos
Infecções por HIV/complicações , Instalações de Saúde/normas , Tuberculose Pulmonar/prevenção & controle , Centers for Disease Control and Prevention, U.S. , Humanos , Dispositivos de Proteção Respiratória , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/transmissão , Estados UnidosRESUMO
The stability of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin in intravenous admixtures containing aztreonam and one of the other drugs was studied. Admixtures of aztreonam and gentamicin, aztreonam and tobramycin, and aztreonam and cefoxitin were each prepared in four different concentrations in both 0.9% sodium chloride injection and 5% dextrose injection. Admixtures of aztreonam and metronidazole were prepared in two different concentrations using a commercially available solution of metronidazole 5 mg/mL in a phosphate-citrate buffer. One of each of these admixtures was stored at 25 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times, 1-mL samples of the admixtures were tested for pH and assayed using high-performance liquid chromatography or fluorescence polarization immunoassay. The pH of all admixtures except admixtures of aztreonam and cefoxitin decreased only slightly during storage. Concentrations of aztreonam and tobramycin under both storage conditions decreased by less than 10%. Concentrations of cefoxitin and aztreonam decreased by more than 10% at 25 degrees C, and concentrations of gentamicin decreased by more than 10% under both storage conditions. Visual inspection of admixtures of aztreonam and metronidazole revealed an incompatibility between the two drugs, as evidenced by the appearance of a cherry-red color. Admixtures of aztreonam 10 and 20 mg/mL and tobramycin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 48 hours at 25 degrees C or seven days at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and gentamicin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for eight hours at 25 degrees C and 24 hours at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and cefoxitin 10 and 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 12 hours at 25 degrees C and seven days at 4 degrees C. Aztreonam and metronidazole should be administered separately.
Assuntos
Aztreonam/análise , Cefoxitina/análise , Gentamicinas/análise , Metronidazol/análise , Tobramicina/análise , Combinação de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Glucose/análise , Cloreto de Sódio/análiseRESUMO
Theophylline has emerged as a major prophylactic agent for controlling the symptoms of chronic asthma, but it provides little if any relief of pulmonary symptoms caused by irreversible chronic airways obstruction. Although in vitro it inhibits phosphodiesterase and antagonizes adenosine receptors, theophylline's mechanism of action in asthma is unknown. Often, 10 to 20 micrograms/ml is used as the range of serum concentrations where there is the greatest likelihood of obtaining maximal benefit safely. Slow-release products have the potential to provide more stable serum concentrations with longer dosing intervals. However, clinically important differences in rate and sometimes extent of absorption exist between the 15 formulations sold under 29 brand names in this country. In patients with more rapid elimination, few products have sufficiently slow absorption to allow twice-daily use. Often these formulations must be administered every eight hours to prevent breakthrough in asthmatic symptoms despite promotional claims to the contrary. In patients with slower elimination, differences among products are unlikely to be clinically important with 12-hour dosing intervals. Current products approved for "once-a-day" dosing are clinically inadequate because of erratic absorption or excessive serum concentration fluctuations. Moreover, food induces dose dumping of potentially toxic amounts of theophylline from Theo-24, greatly increases the extent of absorption of theophylline from Uniphyl, decreases extent of absorption from Theo-dur-Sprinkle capsules, but has no clinically important effect on Theo-Dur tablets, Theobid, Slo-Bid, or Somophyllin-CRT. The effects of food or other factors that alter gastrointestinal physiology on theophylline absorption are unknown for most other products.