RESUMO
Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in immunocompromised patients, particularly those with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplant recipients. The optimal therapy for invasive aspergillosis relies on the restoration of leukocyte counts and effective antifungal treatment initiated at the earliest stage of infection. Several alternative antifungal compounds are currently available. A rational approach should take into account not only the degree of certainty of infection (as codified by the EORTC/MSG classification), but also previous exposure to other antifungals, the pharmacokinetic and pharmacodynamic characteristics of the antifungals employed and the clinical characteristics of the patient.
Assuntos
Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Humanos , Aspergilose Pulmonar Invasiva/prevenção & controle , Contagem de Leucócitos , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/microbiologia , Fatores de TempoRESUMO
OBJECTIVE: To evaluate a high-resolution computed tomography (HRCT) scoring system, clinical parameters, and pulmonary function measurements in patients with cystic fibrosis (CF) before and after therapy for a pulmonary exacerbation. STUDY DESIGN: Patients (n = 17) were evaluated by spirometer-triggered HRCT imaging, clinical parameters, and pulmonary function tests (PFTs) before and after treatment. HRCT scans were reviewed by 3 radiologists using a modified Bhalla scoring system. RESULTS: Bronchiectasis, bronchial wall thickening, and air trapping were identified in all subjects on initial evaluation. The initial total HRCT score correlated significantly with the Brasfield score (r = -.91, P <.001) and several PFT measures. After treatment, there were improvements in the acute change clinical score (ACCS) (P <.001), most pulmonary function measurements, and total HRCT score (P <.05). Bronchiectasis, bronchial wall thickening, and air trapping did not significantly change. Mucus plugging subcomponent HRCT score, slow vital capacity (SVC), forced expiratory volume in 1 second (FEV(1)), and forced vital capacity (FVC) (percent predicted) and reversible and total HRCT scores were most sensitive to change by effect size analysis. CONCLUSIONS: Improvements occurred with treatment in total and reversible HRCT scores, PFTs, and ACCS. Total and reversible HRCT scores and percent predicted SVC, FEV1, and FVC were the most sensitive to change. The greatest change was seen in the mucus plugging subcomponent HRCT score.
Assuntos
Fibrose Cística/diagnóstico , Espirometria/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Criança , Fibrose Cística/fisiopatologia , Fibrose Cística/terapia , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Pulmão/fisiopatologia , Masculino , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVES: To determine patterns of bone mineral acquisition in children and young adults with cystic fibrosis (CF) and to identify clinical and laboratory correlates of change in bone mineral density (BMD). STUDY DESIGN: Bone mineral and clinical status were assessed in 41 patients with CF (26 female, aged 9 to 50 years) at baseline and 1.5 years later. Bone mineral content of the lumber spine, femoral neck, and whole body was determined by dual-energy x-ray absorptiometry and expressed as BMD and bone mineral apparent density (BMAD). Changes in weight, height, pubertal status, glucocorticoid use, physical activity, disease severity, and biochemical markers of bone turnover were examined for associations with changes BMD and BMAD. RESULTS: Mean BMD Z-scores (adjusted for age and sex) were reduced at the spine, hip, and whole body at baseline in both adults and youths, and decreased further at all sites among youths at follow-up (-0.4 at spine, p < 0.05; -0.3 at hip, p < 0.10; -0.5 for whole body, p < 0.0005). These data indicate failure to gain bone mineral at the expected rate. BMAD was also reduced at follow-up, suggesting that the observed osteopenia could not be explained by small bone size. Bone loss at multiple sites was observed in four youths and two adults. In general glucocorticoid use, change in body mass, physical activity, and disease severity were the most significant correlates for change in BMD and in BMD Z-score. CONCLUSIONS: Osteopenia in CF generally reflects inadequate gains in bone mineral, although bone loss may occur, particularly in patients requiring glucoc therapy. Late gains in bone mineral may accompany weight gain and pubertal development, but the catch-up appears to be incomplete.
Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/complicações , Fibrose Cística/fisiopatologia , Adolescente , Adulto , Doenças Ósseas Metabólicas/fisiopatologia , Remodelação Óssea , Criança , Fibrose Cística/complicações , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de RegressãoRESUMO
To study the relationship between serum IgG subclass deficiency and clinical host defense impairment, we reviewed the clinical and immunologic features of 123 patients with a history of recurrent infection who had been examined for immunodeficiency in our laboratory (group 1). We then compared immunoglobulin isotype levels with those in sera from 127 age-matched control subjects without recurrent infection from whom blood had been drawn for evaluation of atopy (group 2). There was a significantly higher prevalence of IgG4 deficiencies among patients with recurrent infections (17% vs 7%; p less than 0.02), solely because of a higher prevalence of isolated IgG4 deficiency (n = 9; 7.3%) than in atopic control subjects (n = 1; 0.8%; p less than 0.05); there was a comparable prevalence of multiple isotype deficiencies that included low levels of IgG4 (9.8% and 6.3%, respectively). All nine group 1 patients with isolated IgG4 deficiency had severe recurrent respiratory tract infections requiring multiple hospitalizations; in addition, five were atopic, five had asthma, and one had chronic diahrrea. Antibody responses to bacterial polysaccharide antigens were normal for age in all patients with isolated IgG4 deficiency; two had defective antibody responses to protein antigens. Isolated IgG4 deficiency appears to be associated with impaired respiratory tract defenses and may occur in the absence of an easily definable antibody deficiency state. This association suggests a physiologic defense role for mucosal IgG4.
Assuntos
Disgamaglobulinemia/complicações , Hipersensibilidade/complicações , Deficiência de IgG/complicações , Infecções Respiratórias/complicações , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Disgamaglobulinemia/imunologia , Feminino , Humanos , Hipersensibilidade/imunologia , Deficiência de IgA/complicações , Imunodifusão , Imunoglobulina A/análise , Imunoglobulina G/análise , Isotipos de Imunoglobulinas/análise , Lactente , Masculino , Otite Média/complicações , Otite Média/imunologia , Recidiva , Reprodutibilidade dos Testes , Infecções Respiratórias/imunologia , Estudos RetrospectivosRESUMO
Allergic reactions to anti-Pseudomonal penicillin derivatives are an increasing problem in therapy of cystic fibrosis lung disease. We evaluated 15 patients, ages 12 to 37 years, with documented allergic reactions to carbenicillin, ticarcillin, or piperacillin. Intradermal skin test reactions were positive for benzylpenicillin in seven patients, penicilloyl-polylysine in one, and ticarcillin or piperacillin in eight, for a total of 11 of 11 tested. Results of radioallergosorbent testing to penicilloyl conjugates were positive in eight of 14 patients and equivocal in four others. Overall, skin tests or RAST results were positive in 13 of 15 patients. All patients were desensitized with a semisynthetic penicillin by continuous serial intravenous infusion of 10-fold dose increments, beginning with 10(-6) of the therapeutic dose. Desensitization was successful in 25 of 26 instances. After intravenously administered therapy, maintenance of desensitization with dicloxacillin orally was unsuccessful in four of six patients. We conclude that (1) allergy to semisynthetic penicillins in cystic fibrosis usually is IgE mediated; (2) such allergy can be evaluated by skin testing; (3) it can be safely and in most cases successfully treated by intravenous desensitization; and (4) allergic patients should be desensitized on each subsequent admission for intravenously administered therapy.
Assuntos
Fibrose Cística/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Penicilinas/efeitos adversos , Infecções por Pseudomonas/tratamento farmacológico , Adolescente , Adulto , Benzenoacetamidas , Carbenicilina/efeitos adversos , Carbenicilina/uso terapêutico , Criança , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Testes Intradérmicos , Masculino , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/uso terapêutico , Penicilina G/efeitos adversos , Penicilina G/uso terapêutico , Penicilinas/uso terapêutico , Piperacilina/efeitos adversos , Piperacilina/uso terapêutico , Polilisina/efeitos adversos , Polilisina/análogos & derivados , Polilisina/uso terapêutico , Teste de Radioalergoadsorção , Ticarcilina/efeitos adversos , Ticarcilina/uso terapêuticoRESUMO
We studied the incidence and levels of circulating immune complexes by the 125I-Clq-binding assay in patients with cystic fibrosis in relation to clinical respiratory status and specific IgG and IgE antibodies to Pseudomonas aeruginosa. Staphylococcus aureus, Aspergillus fumigatus, and Candida albicans. Overall prevalence of CIC was 43%, but 86% of serially studied patients had evidence of CIC at some time. Patients with acute respiratory exacerbations and deteriorating pulmonary function had a higher incidence of CIC (76%) as compared to stable patients (36%, P less than 0.01), as well as significantly higher levels of CIC. Acute exacerbations were also associated with significant increases in IgG antibody to Pseudomonas (P less than 0.005) but not in other antibodies. CIC did not correlate with Pseudomonas-specific IgG nor with any other specific antibody studied. A variety of age-related differences in specific antibody levels were seen. The episodic appearance of CIC is common in CF and is usually associated with exacerbation of lung disease.