Mutations that permit residual CFTR function delay acquisition of multiple respiratory pathogens in CF patients.
Mutations that permit residual CFTR function delay acquisition of multiple respiratory pathogens in CF patients.
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DOI：
10.1186/1465-9921-11-140
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发表时间：
2010-10-08
影响因子：
5.8
通讯作者：
Cutting GR
中科院分区：
文献类型：
--
作者：
Green DM;McDougal KE;Blackman SM;Sosnay PR;Henderson LB;Naughton KM;Collaco JM;Cutting GR
肺部感染的各种生物体是囊性纤维化（CF）的一个特征。CFTR基因型对铜绿假单胞菌（Pa）的获得有影响，但对经常先于Pa的其他感染性生物的获得的影响相对未知。了解CFTR在获得首次在患者中检测到的生物体中的作用可能有助于指导CF的症状和基于分子的治疗。肺部感染被定义为单个阳性呼吸道培养，在1,381例CF患者中评估了13种生物体。受试者按预测的CFTR功能分为：“残余”：携带至少一个部分功能CFTR突变（IV类或V类）和“最小”那些不携带部分功能突变。Kaplan-Meier估计是用来评估CFTR对每种生物获得年龄的影响。采用Cox比例风险模型来控制可能的辅助因素。使用单独的Cox回归来确定使用其他标准定义Pa、黏液Pa或曲霉（Asp）感染是否会影响结果。采用分层Cox回归方法，按肺部疾病类别评估获取时肺部疾病严重程度的影响。具有“最小”CFTR功能的受试者比具有“残余”功能的患者获得所研究的13种生物体中的9种的风险更高（基于所研究的生物体，风险比从1.7到3.78不等）。在13种微生物中，有12种CFTR功能最小的受试者获得感染的年龄小于功能剩余的受试者（p值范围< 0.001至0.017）。当使用三种不同的Pa、黏液Pa或Asp感染定义时，最小CFTR功能也与较年轻的感染年龄相关。在肺功能良好的患者中，9个微生物中有8个与CFTR功能相关，而在肺功能较差的患者中，9个微生物中只有1个与CFTR功能相关（<50%）。CFTR功能的残留与CF患者体内广泛培养的微生物引起的晚发性呼吸道感染相关。在晚期肺部疾病的CF患者中，残留CFTR功能的保护作用减弱。
Lung infection by various organisms is a characteristic feature of cystic fibrosis (CF). CFTR genotype effects acquisition of Pseudomonas aeruginosa (Pa), however the effect on acquisition of other infectious organisms that frequently precede Pa is relatively unknown. Understanding the role of CFTR in the acquisition of organisms first detected in patients may help guide symptomatic and molecular-based treatment for CF. Lung infection, defined as a single positive respiratory tract culture, was assessed for 13 organisms in 1,381 individuals with CF. Subjects were divided by predicted CFTR function: 'Residual': carrying at least one partial function CFTR mutation (class IV or V) and 'Minimal' those who do not carry a partial function mutation. Kaplan-Meier estimates were created to assess CFTR effect on age of acquisition for each organism. Cox proportional hazard models were performed to control for possible cofactors. A separate Cox regression was used to determine whether defining infection with Pa, mucoid Pa or Aspergillus (Asp) using alternative criteria affected the results. The influence of severity of lung disease at the time of acquisition was evaluated using stratified Cox regression methods by lung disease categories. Subjects with 'Minimal' CFTR function had a higher hazard than patients with 'Residual' function for acquisition of 9 of 13 organisms studied (HR ranging from 1.7 to 3.78 based on the organism studied). Subjects with minimal CFTR function acquired infection at a younger age than those with residual function for 12 of 13 organisms (p-values ranging: < 0.001 to 0.017). Minimal CFTR function also associated with younger age of infection when 3 alternative definitions of infection with Pa, mucoid Pa or Asp were employed. Risk of infection is correlated with CFTR function for 8 of 9 organisms in patients with good lung function (>90%ile) but only 1 of 9 organisms in those with poorer lung function (<50%ile). Residual CFTR function correlates with later onset of respiratory tract infection by a wide spectrum of organisms frequently cultured from CF patients. The protective effect conferred by residual CFTR function is diminished in CF patients with more advanced lung disease.
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影响因子：
17.1
作者：
Stoltz DA;Meyerholz DK;Pezzulo AA;Ramachandran S;Rogan MP;Davis GJ;Hanfland RA;Wohlford-Lenane C;Dohrn CL;Bartlett JA;Nelson GA 4th;Chang EH;Taft PJ;Ludwig PS;Estin M;Hornick EE;Launspach JL;Samuel M;Rokhlina T;Karp PH;Ostedgaard LS;Uc A;Starner TD;Horswill AR;Brogden KA;Prather RS;Richter SS;Shilyansky J;McCray PB Jr;Zabner J;Welsh MJ
通讯作者：
Welsh MJ
DOI：
10.1016/j.jcf.2004.01.005
发表时间：
2004-06-01
期刊：
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
影响因子：
--
作者：
Courtney, J M;Dunbar, K E A;Elborn, J S
通讯作者：
Elborn, J S
影响因子：
24.5
作者：
Ahmed, N;Corey, M;Durie, P
通讯作者：
Durie, P
影响因子：
3.1
作者：
Kanthan, Senthooran Kathirgama;Bush, Andrew;Buchdahl, Roger
通讯作者：
Buchdahl, Roger
DOI：
10.1073/pnas.092160899
发表时间：
2002-05-14
影响因子：
11.1
作者：
Schroeder, TH;Lee, MM;Pier, GB
通讯作者：
Pier, GB