Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA; The Ohio State University College of Medicine, Columbus, OH, USA.
The Ohio State University College of Medicine, Columbus, OH, USA; Department of Pediatrics, The Ohio State University, Columbus, OH, USA; Section. of Pulmonary Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
J Cyst Fibros. 2019 Nov;18(6):796-803. doi: 10.1016/j.jcf.2019.04.009. Epub 2019 Apr 26.
Pseudomonas aeruginosa is the prominent bacterial pathogen in the cystic fibrosis (CF) lung and contributes to significant morbidity and mortality. Though P. aeruginosa strains initially colonizing the CF lung have a nonmucoid colony morphology, they often mutate into mucoid variants that are associated with clinical deterioration. Both nonmucoid and mucoid P. aeruginosa variants are often co-isolated on microbiological cultures of sputum collected from CF patients. With regional variation in bronchiectasis, tissue damage, inflammation, and microbial colonization, lobar distribution of nonmucoid and mucoid P. aeruginosa variants may impact local microenvironments in the CF lung, but this has not been well-studied.
We prospectively collected lobe-specific bronchoalveolar lavage (BAL) fluid from a CF patient cohort (n = 14) using a standardized bronchoscopic protocol where collection was performed in 6 lobar regions. The lobar BAL specimens were plated on P. aeruginosa-selective media and proinflammatory cytokines (IL-1, TNF, IL-6 and IL-8) were measured via cytokine array. Correlations between infecting P. aeruginosa variants (nonmucoid, mucoid, or mixed-variant populations), the lobar regions in which these variants were found, and regional proinflammatory cytokine concentrations were measured.
P. aeruginosa mucoid and nonmucoid variants were homogenously distributed throughout the CF lung. However, infection with mucoid variants (found within single- or mixed-variant populations) was associated with significantly greater regional inflammation. The upper and lower lobes of the CF lung did not exhibit differences in inflammatory cytokine concentrations.
Mucoid P. aeruginosa infection is a microbial determinant of regional inflammation within the CF lung.
铜绿假单胞菌是囊性纤维化（CF）肺部的主要细菌病原体，导致发病率和死亡率显著增加。尽管最初定植于 CF 肺部的铜绿假单胞菌菌株具有非粘液型菌落形态，但它们经常突变为与临床恶化相关的粘液型变体。非粘液型和粘液型铜绿假单胞菌变体通常在 CF 患者的痰微生物培养物中同时分离出来。由于支气管扩张、组织损伤、炎症和微生物定植的区域差异，非粘液型和粘液型铜绿假单胞菌变体在 CF 肺部的叶分布可能会影响局部微环境，但这尚未得到充分研究。
我们使用标准化支气管镜检查方案，前瞻性地从 CF 患者队列（n=14）中收集叶特异性支气管肺泡灌洗液（BAL）。在 6 个肺叶区域进行采集。将肺叶 BAL 标本接种于铜绿假单胞菌选择性培养基上，并通过细胞因子阵列测量促炎细胞因子（IL-1、TNF、IL-6 和 IL-8）。测量感染的铜绿假单胞菌变体（非粘液型、粘液型或混合变体群体）、在这些变体中发现的肺叶区域以及区域促炎细胞因子浓度之间的相关性。
铜绿假单胞菌粘液型和非粘液型变体在 CF 肺部均匀分布。然而，粘液型变体（在单一或混合变体群体中发现）的感染与区域炎症显著增加相关。CF 肺部的上叶和下叶在炎症细胞因子浓度方面没有差异。
粘液型铜绿假单胞菌感染是 CF 肺部区域炎症的微生物决定因素。
