Dynamics of soluble and cellular inflammatory markers in nasal lavage obtained from Cystic Fibrosis patients during intravenous antibiotic treatment

Abstract

BackgroundIn cystic fibrosis (CF) patients, the upper airways display the same ion channel defect as evident in the lungs, resulting in chronic inflammation and infection. Recognition of the sinonasal area as a site of first and persistent infection with pathogens, such as Pseudomonas aeruginosa, reinforces the “one-airway” hypothesis. Therefore, we assessed the effect of systemic antibiotics against pulmonary pathogens on sinonasal inflammation.MethodsNasal lavage fluid (NLF) from 17 CF patients was longitudinally collected prior to and during elective intravenous (i.v.) antibiotic treatment to reduce pathogen burden and resulting inflammation (median treatment time at time of analysis: 6 days). Samples were assessed microbiologically and cytologically. Cytokine and chemokine expression was measured by Cytometric Bead Array and ELISA (interleukin (IL)-1β, IL-6, IL-8, MPO, MMP9, RANTES and NE). Findings were compared with inflammatory markers from NLF obtained from 52 healthy controls.ResultsInitially, the total cell count of the NLF was significantly higher in CF patients than in controls. However after i.v. antibiotic treatment it decreased to a normal level. Compared with controls, detection frequencies and absolute concentrations of MPO, IL-8, IL-6 and IL-1β were also significantly higher in CF patients. The detection frequency of TNF was also higher. Furthermore, during i.v. therapy sinonasal concentrations of IL-6 decreased significantly (P = 0.0059), while RANTES and MMP9 levels decreased 10-fold and two-fold, respectively. PMN-Elastase, assessed for the first time in NFL, did not change during therapy.ConclusionsAnalysis of NLF inflammatory markers revealed considerable differences between controls and CF patients, with significant changes during systemic i.v. AB treatment within just 6 days. Thus, our data support further investigation into the collection of samples from the epithelial surface of the upper airways by nasal lavage as a potential diagnostic and research tool.

Clinical implications ofPseudomonas aeruginosalocation in the lungs of patients with cystic fibrosis

“…Comparative studies of cultures isolated from both the upper and lower airways of patients with CF have shown genotypic and phenotypic similarity between P. aeruginosa grown from sinus, sputum or endotracheal cultures, particularly in terms of bacterial type, strain and antibiotic resistance patterns in patients >8 years of age . In agreement with the descending infection hypothesis, the use of nasal lavage as a potential diagnostic tool to monitor the airways in patients with CF has been suggested by several studies …”

Increased cytokines in cystic fibrosis patients’ upper airways during a new P. aeruginosa colonization

“…Non‐invasively collected nasal lavages (NL) from the patient's UAW bear the potential not only to monitor airway colonization but also to assess host defense and inflammation. In this regard, we showed that concentrations of soluble inflammation markers in UAW sampled by NL are linked to disease severity and to the colonization status . For instance, we demonstrated that a range of soluble pro‐inflammatory and neutrophil‐related mediators, among them IL‐1β, IL‐6, and IL‐8, are more frequently detected in NL of CF patients than in NL of healthy controls .…”

Airway hydration and COPD

“…Inflammation in CF is characterized by high intraluminal IL 8 levels and high concentrations of polymorphonuclear cells [240]. The inflammatory response of the airway in COPD patients is likely more complex [241].…”