Asthma control in Brazil: a systematic review.

OBJECTIVES: To explore asthma control in patients undergoing pharmacotherapy on studies in the last 20 years in Brazil. Asthma is a chronic airway inflammation disease with a high prevalence worldwide. Even with a variety of drug treatment improvements, attaining asthma control is challenging, since it should have a personalized approach. In Brazil, studies on the prevalence of asthma control are scarce and usually from a small sample size. DATA SOURCES: A systematic review was performed to assess asthma control in Brazilian population. Terms related to "asthma", "asthma control" and "Brazil" were used in the search strategies in PubMed, BVSalud, Embase and Cochrane Library, including Brazilian Journal of Allergy and Immunology as data sources. A narrative synthesis was performed to report key outcome. STUDY SELECTIONS: In total, 23 studies were included. Most of them were conducted in the Southeastern and Northeast regions, in a short duration. RESULTS: Pediatric and non-pediatric population were assessed, with a higher proportion of female. In pediatric population, those with poorly controlled asthma usually had severe or persistent disease. In elderly, an increased asthma severity was found, although proper treatment might be effective. Most studies (70%) also described exacerbations, hospitalizations (48%), quality of life (39%), and emergency visits (30%). Despite heterogeneity of outcomes and population, studies show an important prevalence of uncontrolled asthma even in patients being treated, with better disease control with treatment improvements. CONCLUSIONS: Studies in Brazil have shown that asthma control remains a challenge and there is still a need for improvement on disease management.

Case series of patients under biweekly treatment with laronidase: a report of a single center experience / Série de casos de pacientes em tratamento com laronidase quinzenal: relato da experiência de um centro

ABSTRACT Objective: To report the stabilization of urinary glycosaminoglicans (GAG) excretion and clinical improvements in patients with mucopolysaccharidosis type I (MPS I) under an alternative dose regimen of laronidase of 1.2 mg/kg every other week. Methods: We participated in a dose-optimization trial for laronidase in MPS-I patients using four alternative regimens: 0.58 mg/kg every week, 1.2 mg/kg every two weeks, 1.2 mg/kg every week and 1.8 mg/kg every other week (EOW). After the trial ended, the patients resumed the recommended dose and regimen of 0.58 mg/kg every week. Under this regimen, some patients presented difficulties in venous access and were unable to commute weekly to the treatment center. Therefore, we used an alternative regimen that consisted of 1.2 mg/kg EOW in eight patients. A retrospective study of medical records of MPS-I patients who underwent both enzyme replacement therapy (ERT) regimens, of 0.58 mg/kg every week and 1.2 mg/kg EOW, was done. Results: Patients remained clinically stable under the alternative regimen, did not present elevation of urinary GAG nor any adverse event. Conclusions: The switch of dose regimen to 1.2 mg/kg EOW of laronidase was safe, and did not cause any clinical worsening in patients who had been previously under standard dose ERT.

RESUMO Objetivo: Descrever a manutenção dos níveis de glicosaminoglicano (GAG) excretados na urina e da estabilização clínica em pacientes com mucopolissacaridose do tipo I (MPS I) com o uso da laronidase num regime de dose alternativo de 1,2 mg/kg a cada duas semanas. Método: Alguns pacientes do nosso serviço participaram de um estudo de otimização de dose da laronidase para o tratamento da MPS I no qual foram comparados quatro esquemas terapêuticos: 0,58 mg/kg/semana, 1,2 mg/kg a cada duas semanas, 1,2 mg/kg/semana e 1,8 mg/kg a cada duas semanas. Após o término do estudo, todos os pacientes passaram a receber a terapia de reposição enzimática (TRE) na dose padrão de bula, que é de 0,58 mg/kg/semana, e nesse regime alguns pais se queixaram da dificuldade em comparecer ao centro todas as semanas, além da dificuldade de se obter acesso para punção venosa. Com base nessas queixas, oito pacientes passaram a receber a TRE no regime alternativo de 1,2 mg/kg a cada duas semanas. Foi feito o estudo retrospectivo de dados de prontuário de pacientes com MPS I que fizeram TRE com laronidase nas doses 0,58 mg/kg/semana e 1,2 mg/kg a cada duas semanas. Resultados: Os pacientes mantiveram-se clinicamente estáveis, não apresentaram aumento dos níveis de GAG urinários nem eventos adversos durante o regime alternativo de dose. Conclusões: A mudança para o esquema de 1,2 mg/kg de laronidase a cada duas semanas foi segura e não acarretou piora clínica nos pacientes que já estavam em TRE na dose padrão.

Evaluation of Beta 2-Microglobulin, Cystatin C, and Lipocalin-2 as Renal Biomarkers for Patients with Fabry Disease.

BACKGROUND: Since renal failure is one of the main causes of death in patients with Fabry disease (FD), renal follow-up is an important part of clinical monitoring in these patients. Despite its known limitations, serum creatinine is still the most widely used biomarker. While new renal biomarkers are described, their effectiveness has not yet been fully evaluated in relation to FD. OBJECTIVES: This study aimed to compare renal biomarkers commonly and rarely used in the evaluation of FD patients. METHOD: The usual biomarkers for renal monitoring (microalbuminuria, proteinuria, and creatinine) and some more rarely used (cystatin C, beta 2-microglobulin [ß2M], neutrophil gelatinase-associated lipocalin/lipocalin-2) were quantified in the blood and/or urine samples of 40 FD patients, 39 controls without chronic kidney disease (CKD) paired by age and sex and 38 controls with CKD undergoing hemodialysis. RESULTS: Significant statistical differences (p < 0.05) were observed for cystatin C and lipocalin-2 in plasma levels, for ß2M and serum creatinine levels and by estimated glomerular filtration rate when compared FD patients and control group with CKD and for proteinuria and microalbuminuria in urine samples and for lipocalin-2 in plasma levels when compared FD patients and control group without CKD. Urine creatinine (UCreat), pH, and urine specific gravity did not present a significant statistical difference between groups. CONCLUSION: Considering serum creatinine as gold standard, all renal parameters evaluated, including receiver operating characteristic curve, indicated ß2M as the best biomarker, followed by cystatin C, proteinuria and microalbuminuria, while the results for lipocalin-2 and UCreat do not indicate good predictors of renal impairment. It suggests that at least 2 altered biomarkers should be considered to characterize a renal alteration, thereby establishing a better therapeutic course for FD patients. If possible, along with serum creatinine, measurement of ß2M or cystatin C for renal evaluation of Fabry's patients should be considered.

CASE SERIES OF PATIENTS UNDER BIWEEKLY TREATMENT WITH LARONIDASE: A REPORT OF A SINGLE CENTER EXPERIENCE.

OBJECTIVE: To report the stabilization of urinary glycosaminoglicans (GAG) excretion and clinical improvements in patients with mucopolysaccharidosis type I (MPS I) under an alternative dose regimen of laronidase of 1.2 mg/kg every other week. METHODS: We participated in a dose-optimization trial for laronidase in MPS-I patients using four alternative regimens: 0.58 mg/kg every week, 1.2 mg/kg every two weeks, 1.2 mg/kg every week and 1.8 mg/kg every other week (EOW). After the trial ended, the patients resumed the recommended dose and regimen of 0.58 mg/kg every week. Under this regimen, some patients presented difficulties in venous access and were unable to commute weekly to the treatment center. Therefore, we used an alternative regimen that consisted of 1.2 mg/kg EOW in eight patients. A retrospective study of medical records of MPS-I patients who underwent both enzyme replacement therapy (ERT) regimens, of 0.58 mg/kg every week and 1.2 mg/kg EOW, was done. RESULTS: Patients remained clinically stable under the alternative regimen, did not present elevation of urinary GAG nor any adverse event.Conclusions: The switch of dose regimen to 1.2 mg/kg EOW of laronidase was safe, and did not cause any clinical worsening in patients who had been previously under standard dose ERT.