Rosenfeld M, Gibson R L, McNamara S, Emerson J, Burns J L, Castile R, Hiatt P, McCoy K, Wilson C B, Inglis A, Smith A, Martin T R, Ramsey B W
Cystic Fibrosis Research Center, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA.
Pediatr Pulmonol. 2001 Nov;32(5):356-66. doi: 10.1002/ppul.1144.
A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.
深入了解囊性纤维化（CF）肺部疾病的早期自然史对于为最年幼患者制定有效干预措施至关重要。我们通过每年进行支气管肺泡灌洗（BAL）以进行培养和测量促炎和抗炎细胞因子、每半年进行婴儿肺功能测试以及每季度进行临床评估，对40名婴儿在两年期间的肺部感染、炎症和临床病程演变进行了评估。CF病原体在BAL液中的患病率及其密度均随年龄增加。无论是否检测到CF病原体，婴儿均存在嗜中性粒细胞性下呼吸道炎症且白细胞介素-8（IL-8）浓度升高。无论分离出的病原体是铜绿假单胞菌还是其他病原体，总白细胞和中性粒细胞密度以及IL-8浓度均随BAL液中CF病原体密度的增加而升高。CF患者和非CF历史对照的IL-10浓度相似。婴儿通常生长发育欠佳（体重和身高百分位数较低）且患有阻塞性肺病（呼气流量降低和气体潴留）。在BAL液中分离出CF病原体且浓度>10⁵ cfu/mL的患者气体潴留最严重，Brasfield胸部X线评分最低。我们的研究结果为未来CF肺部疾病早期干预研究（包括抗菌和抗炎治疗）奠定了基础。
