A multi-centre, randomised, controlled trial of BAL directed therapy in young children with cystic fibrosis.

囊性纤维化（CF）儿童的管理旨在延迟慢性下呼吸道感染（LRTI）和炎症导致的肺部疾病的不可避免的进展。柔性支气管镜检查（FB）和支气管肺泡灌洗（BAL）越来越多地用作CF婴儿LRTI管理的研究和临床工具，并且是未来药物试验和基因治疗监测的组成部分。早期LRTI，特别是CF中的铜绿假单胞菌（Pa）与肺功能下降以及发病率和死亡率增加相关。国际上许多CF中心现在使用积极的抗生素方案治疗患有CF的幼儿，以试图根除感染。大多数中心使用口咽标本诊断LRTI，灵敏度约为45%，特异性约为90%。因此，许多儿童错过了治疗或不必要地接触抗生素。使用抗生素本身可能会增加耐药微生物感染的风险，从而使幼儿药物试验的设计复杂化，因为监测耐药新微生物的出现需要BAL。因此，检查FB和BAL的安全性和价值并获得长期结局至关重要。在澳大利亚，管理CF患者的财务成本估计每年超过8500万美元。早期干预战略可能会降低医疗费用，因为发病率的改善，或可能会增加成本，由于干预。这将是第一次对CF儿童的早期管理和干预的成本效益进行经济评估，这将使这一重要患者群体能够制定负责任的医疗保健计划。这项试验提供了一个独特的机会来研究LRTI和炎症之间的关系以及长期结果，如肺功能和放射学评分，并将为设计未来的试验提供关键证据。

The management of children with cystic fibrosis (CF) aims to delay the inevitable progression of lung disease that results from chronic lower respiratory tract infection (LRTI) and inflammation. Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) are increasingly used as research and clinical tools in the management of LRTI in CF infants and are integral to the monitoring of future drug trials and gene therapy. Early LRTI particularly with Pseudomonas aeruginosa (Pa) in CF is associated with a decline in pulmonary function and an increase in morbidity and mortality. Many CF centres internationally now treat young children with CF using aggressive antibiotic protocols in an attempt to eradicate infection. Most centres use oropharyngeal specimens to diagnose LRTI with a sensitivity of around 45% and specificity of around 90%. Thus many children miss out on treatment or are exposed unnecessarily to antibiotics. The use of antibiotics themselves may increase the risk of infection with resistant organisms thus complicating the design of drug trials in young children as monitoring for the emergence of resistant new organisms requires BAL. It is thus of key importance that the safety and value of FB and BAL is examined and long term outcomes are obtained. The financial costs of managing patients with CF in Australia may be estimated at more than $85 million-annum. Early intervention strategies may reduce health costs because of improved morbidity or may increase costs due to the intervention. This will be the first time an economic evaluation of early management and the cost effectiveness of an intervention in children with CF has been undertaken which will enable responsible health care planning for this important group of patients. This trial provides a unique opportunity to study the relationship between LRTI and inflammation and long term outcomes such as lung function and radiological scores and will provide key evidence for designing future trials.