Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Cyst Fibros. 2013 Sep;12 Suppl 2:S1-20. doi: 10.1016/S1569-1993(13)00150-1.
A major purpose of treating patients with cystic fibrosis (CF) is to prevent or delay chronic lung infections with CF-pathogenic Gram-negative bacteria. In the intermittent stage, bacteria can usually be eradicated from the lungs with antibiotics, but following eradication, the next lung colonisations often occur with bacteria of identical genotype. This may be due to re-colonisation from the patient's paranasal sinuses. In our study, we found that approximately two-thirds of CF patients having sinus surgery (FESS) had growth of CF-lung-pathogenic Gram-negative bacteria in their sinuses (Pseudomonas aeruginosa, Achromobacter xylosoxidans, Burkholderia cepacia complex). The environment in the sinuses is in many ways similar to that of the lower respiratory tract, e.g. low oxygen concentration in secretions. Sinus bacteria are more difficult to eradicate than in the lungs, thus, having good conditions for adapting to the environment in the lungs. In the presence of bacteria, the environment of the sinuses differs from that of the lower respiratory tract by having a higher immunoglobulin A (IgA): IgG ratio, and reduced inflammation. We found a significant correlation between the concentration of IgA against P. aeruginosa (standard antigen and alginate) in nasal secretions and saliva and CF patients' infection status (not lung colonised, intermittently colonised or chronically lung-infected with P. aeruginosa). This supports the hypothesis that infections often originate in the sinuses and can be a focus for initial lung colonisation or for maintaining lung infections in CF patients. We are confident that anti-P. aeruginosa IgA can be used as an early supplementary tool to diagnose P. aeruginosa colonisation; P. aeruginosa being the microorganism causing most morbidity and mortality in CF patients. This is important since urgent treatment reduces morbidity when CF patients are early colonised with P. aeruginosa, however, there is a lack of diagnostic tools for detecting the early colonisation in the lungs and in the sinuses. We initiated a treatment strategy for CF patients to prevent sino-nasal bacteria being seeded into the lower airways: we recommended extensive functional endoscopic FESS with creation of sufficient drainage from all involved sinuses with subsequent i.v. antibiotics and at least 6 months of twice daily nasal irrigation with saline and antibiotics. By this strategy, sinus bacteria could be eradicated in a large proportion of patients. Essentially, growth of CF-pathogenic bacteria from the lower respiratory tract was decreased following the treatment. Furthermore, a number of patients have been free from CF-pathogenic bacteria for more than one year after FESS, and thus re-classified as "not lung colonised". We also corroborated that CF patients obtain an improved quality of life and reduction in their symptoms of chronic rhinosinusitis after FESS. It is primarily intermittently lung colonised CF patients with CF-pathogenic bacteria in their sinuses that seem to benefit from the treatment strategy. This is in accordance with the fact that we did not see a significant increase in lung function and only a small decrease in specific antibodies after FESS; a high systemic immune and inflammatory response and a decreasing lung function is generally not present in patients who primarily have sinus CF-pathogenic bacteria. It is important that guidelines are created for how CF patients with CF-pathogenic bacteria in the sinuses are to be treated, including criteria for who may likely benefit from FESS, and who may be treated exclusively with conservative therapy, e.g. saline and antibiotic irrigations.
治疗囊性纤维化(CF)患者的主要目的是预防或延迟 CF 致病性革兰氏阴性菌引起的慢性肺部感染。在间歇性阶段,通常可以用抗生素从肺部清除细菌,但在清除后,下一次肺部定植通常会发生相同基因型的细菌。这可能是由于患者的鼻窦重新定植。在我们的研究中,我们发现大约三分之二接受鼻窦手术(FESS)的 CF 患者的鼻窦中生长着 CF 肺部致病性革兰氏阴性菌(铜绿假单胞菌、木糖氧化无色杆菌、洋葱伯克霍尔德菌复合体)。鼻窦的环境在许多方面与下呼吸道相似,例如分泌物中的低氧浓度。鼻窦中的细菌比肺部中的细菌更难清除,因此,它们有更好的条件来适应肺部的环境。在细菌存在的情况下,鼻窦的环境与下呼吸道不同,其免疫球蛋白 A(IgA)与 IgG 的比值更高,炎症减轻。我们发现,鼻分泌物和唾液中针对铜绿假单胞菌的 IgA(标准抗原和藻酸盐)浓度与 CF 患者的感染状态(未肺部定植、间歇性定植或慢性肺部感染铜绿假单胞菌)之间存在显著相关性。这支持了这样一种假说,即感染通常起源于鼻窦,并可能成为初始肺部定植或维持 CF 患者肺部感染的焦点。我们有信心,抗铜绿假单胞菌 IgA 可以作为一种早期补充工具来诊断铜绿假单胞菌定植;铜绿假单胞菌是 CF 患者发病和死亡的主要原因。这很重要,因为当 CF 患者早期定植铜绿假单胞菌时,及时治疗可以降低发病率,然而,目前缺乏检测肺部和鼻窦早期定植的诊断工具。我们为 CF 患者启动了一种预防鼻窦细菌播散到下呼吸道的治疗策略:我们建议进行广泛的功能性内镜鼻窦 FESS,从所有受累的鼻窦中创建足够的引流,随后静脉内使用抗生素,并至少进行 6 个月的每日两次鼻腔冲洗盐水和抗生素。通过这种策略,可以在很大一部分患者中清除鼻窦细菌。基本上,治疗后 CF 致病性细菌从下呼吸道的生长减少了。此外,许多患者在 FESS 后超过一年没有 CF 致病性细菌,因此被重新分类为“未肺部定植”。我们还证实,CF 患者在 FESS 后生活质量提高,慢性鼻窦炎症状减轻。似乎只有那些鼻窦中存在 CF 致病性细菌的间歇性肺部定植 CF 患者从治疗策略中受益。这与以下事实是一致的,即我们在 FESS 后没有看到肺功能显著改善,只有特异性抗体略有下降;在主要有鼻窦 CF 致病性细菌的患者中,通常不会出现全身性免疫和炎症反应增加和肺功能下降。为 CF 患者制定治疗方案非常重要,包括确定哪些患者可能从 FESS 中受益,以及哪些患者可能仅需要保守治疗,例如盐水和抗生素冲洗。