Hill A T, Campbell E J, Hill S L, Bayley D L, Stockley R A
Department of Medicine, Queen Elizabeth Hospital, Birmingham, UK.
Am J Med. 2000 Sep;109(4):288-95. doi: 10.1016/s0002-9343(00)00507-6.
Viable bacteria are often isolated from airway secretions in clinically stable patients with chronic bronchitis. We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation.
We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antitrypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The results were related to several indicators of the mechanisms and severity of airway inflammation.
Airway bacterial load correlated with sputum myeloperoxidase level, an indirect measure of neutrophil activation and number (r = 0.50, P<0. 001); sputum neutrophil chemoattractants [interleukin-8 level (r = 0. 68, P<0.001) and leukotriene B4 level (r = 0.53, P<0.001)]; sputum leukocyte elastase activity (r = 0.55, P<0.001); and albumin leakage from serum to sputum (r = 0.26, P<0.01). Markers of inflammation increased at bacterial loads of 10(6) to 10(7) colony-forming units per milliliter, and increased progressively with increasing bacterial load. For example, the median (interquartile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) for patients who were not colonized or who had mixed normal oropharyngeal flora alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 10(6) to 10(7) colony-forming units per milliliter (P<0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 10(7) to 10(8) colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 10(8) or greater colony-forming units per milliliter (P<0.0001). The bacterial species influenced airway inflammation; for example, sputum myeloperoxidase activity was greater (P<0.005) in patients colonized with Pseudomonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] than those colonized with nontypeable Hemophilus influenzae [4 U/mL (2 to 31 U/mL)], which in turn was greater (P = 0.01) than among those colonized with Moraxella catarrhalis [1.1 U/mL (0.6 to 1.8 U/mL)]. We did not find a relation between bacterial load and lung function.
The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function.
在临床病情稳定的慢性支气管炎患者的气道分泌物中，常可分离出活细菌。我们推测细菌数量和种类可能是气道炎症的重要调节因素。
我们对160例病情稳定的患者进行了痰液定量培养[55例慢性阻塞性肺疾病（COPD）且血清α1抗胰蛋白酶水平正常，62例COPD且严重α1抗胰蛋白酶缺乏（PiZ），43例特发性支气管扩张]。研究结果与气道炎症机制和严重程度的多项指标相关。
气道细菌负荷与痰液髓过氧化物酶水平相关，后者是中性粒细胞活化及数量的一项间接指标（r = 0.50，P < 0.001）；与痰液中性粒细胞趋化因子[白细胞介素-8水平（r = 0.68，P < 0.001）和白三烯B4水平（r = 0.53，P < 0.001）]相关；与痰液白细胞弹性蛋白酶活性（r = 0.55，P < 0.001）相关；与血清白蛋白漏入痰液（r = 0.26，P < 0.01）相关。炎症指标在细菌负荷为每毫升10⁶至10⁷菌落形成单位时升高，并随细菌负荷增加而逐渐升高。例如，未发生细菌定植或仅存在混合性正常口咽菌群的患者，痰液髓过氧化物酶水平中位数（四分位间距）为0.3 U/mL（0.1至0.5 U/mL）；每毫升有10⁵至10⁶菌落形成单位的患者为0.5 U/mL（0.2至0.7 U/mL）（P = 0.07）；每毫升有10⁶至10⁷菌落形成单位的患者为0.5 U/mL（0.3至1.2 U/mL）（P < 0.01）；每毫升有10⁷至10⁸菌落形成单位的患者为0.7 U/mL（0.3至1.2 U/mL）（P < 0.005）；每毫升有10⁸或更多菌落形成单位的患者为2.4 U/mL（0.7至4.8 U/mL）（P < 0.0001）。细菌种类影响气道炎症；例如，感染铜绿假单胞菌的患者[中位数32 U/mL（四分位间距，20至65 U/mL）]痰液髓过氧化物酶活性高于感染不可分型流感嗜血杆菌的患者[4 U/mL（2至31 U/mL）]（P < 0.005），而后者又高于感染卡他莫拉菌的患者[1.1 U/mL（0.6至1.8 U/mL）]（P = 0.01）。我们未发现细菌负荷与肺功能之间存在关联。
细菌负荷和种类在病情稳定的慢性支气管炎患者气道炎症中起作用。需要进一步研究以确定细菌定植对患者发病率和肺功能下降的影响。
