Cystic fibrosis: inflammatory response to infection with Burkholderia cepacia and Pseudomonas aeruginosa

Abstract

Pulmonary colonization by Burkholderia cepacia in cystic fibrosis (CF) may be associated with enhanced deterioration of pulmonary function. This may be due to a more florid host inflammatory response than in colonization by Pseudomonas aeruginosa, leading to greater lung injury.Circulating markers of inflammation were determined during infective exacerbations and periods of clinical stability in an 18 month prospective study in adults with CF colonized by P. aeruginosa (n=41). B. cepacia (n=13) and in adults who intermittently grew B. cepacia (n=6).There were no differences between the levels of the inflammation markers measured in the three groups (P. aeruginosa, B. cepacia, B. cepacia intermittent) at any of the assessment points. When clinically stable, levels of inflammatory markers in all groups were elevated compared to a matched non-CF population, indicating, continuous inflammation and the potential for lung damage between infective exacerbations.This study does not support the hypothesis that pulmonary colonization with Burkholderia cepacia is associated with a heightened inflammatory response compared with Pseudomonas aeruginosa colonization. Eur Respir J 1999; 14: 435±438. Pulmonary colonization by Burkholderia cepacia in cystic fibrosis (CF) may lead to chronic asymptomatic carriage, acceleration of a gradual deterioration in pulmonary function or, a rapid often fatal deterioration with fever, a high peripheral white cell count and progressive consolidation on the chest radiograph [1±3]. The mechanism by which B. cepacia causes pulmonary deterioration is unclear. Although virulence factors have been identified, none appears to account for its pathogenicity [4±6]. Furthermore, in animal models, B. cepacia is less virulent than Pseudomonas aeruginosa and appears to have less potential for tissue invasion [7].The pathogenicity of B. cepacia could be explained by a more vigorous host immune and inflammatory reaction than is provoked by P. aeruginosa. This prospective study, compared measurements of inflammatory markers at the onset and end of infective pulmonary exacerbations and during clinically stable periods in CF patients whose lungs were infected with B. cepacia, with those of a group of severity matched control subjects whose lungs were infected with P. aeruginosa. Patients and methodsA prospective study was conducted over an 18 month period in the Manchester Adult Cystic Fibrosis Unit. Thirteen patients with CF were chronically infected with B. cepacia (growth of the organism in three successive sputum specimens within a 6-month period). All agreed to participate in the study, forming the B. cepacia (BC) group. Patients colonized with P. aeruginosa were invited to participate in the study if their forced expiratory volume in one second (FEV1) % predicted, body mass index and Shwachman score were within the range of the B. cepacia group; 34 such patients formed the P. aeruginosa colonized (PA) group. Patients who grew B. cepacia intermittently, assessed through their sputum, but failed t...

The effect of treatment of cystic fibrosis pulmonary exacerbations on airways and systemic inflammation

“…However, in a study by Hendry et al significant reductions were observed in WCC, CRP, and pNEC following antibiotics. 18 IL-8, a powerful neutrophil chemoattractant, did not change in our study. A recent investigation did show a reduction in IL-8 following IV antibiotics.…”

Prospective evaluation of emerging bacteria in cystic fibrosis

“…cepacia complex is known to be a relevant pathogen in CF, at least in a subgroup of patients who develop a massive inflammatory response [20,21]. The prevalence of this group of pathogen was relatively low in our study making it difficult to assess the clinical relevance within this patient population.…”

Inflammatory markers in cystic fibrosis patients with transmissiblePseudomonas aeruginosa

“…Finally, measuring levels of host inflammatory markers may not provide an accurate prediction of future clinical outcome. A previous study did not find a difference in levels of blood cytokines between CF patients with P. aeruginosa and B. cepacia complex [22], despite a well-recognised increased pathogenicity of B. cepacia complex in clinical practice [28,29]. However, that study had smaller numbers of subjects and measured circulating inflammatory markers, which may not be as representative of inflammatory activity within the lung as those in bronchoalveolar lavage fluid or sputa.…”

“…The current study was designed to investigate whether adult CF patients who harbour transmissible P. aeruginosa strain MA demonstrate a more florid host inflammatory response than those who harbour sporadic strains of P. aeruginosa. Patients with chronic P. aeruginosa infection experience episodes of respiratory exacerbations that are associated with a decrease in lung function and a systemic inflammatory response, with increased levels of inflammatory markers, including TNF-a, NE/a 1 -antitrypsin complexes, IL-6, IL-8 and CRP [11,[22][23][24]. I.v.…”