Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis

Abstract

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.

Keywords: Chronic rhinosinusitis; Immune response; Paranasal sinuses; Quality of life; Sinus treatments (sinus surgery, nasal irrigation); United airways; Upper airway colonisation (Pseudomonas aeruginosa, Burkholderia cepacia, Achromobacter xylosoxidans); s-IgA.