Duration of effect of intravenous antibiotics on spirometry and sputum cytokines in children with cystic fibrosis

Abstract

Intravenous (IV) antibiotics are a mainstay of therapy in children with cystic fibrosis. It is unclear, however, over what period associated improvements in pulmonary function are maintained, and to what extent the underlying inflammatory process is impeded in children admitted for a course of IV antibiotics. This was a prospective, interventional study of 14 children (median age, 14 years; interquartile range, 10-14) with cystic fibrosis who were regular sputum producers and who required admission for a 2-week course of IV antibiotics. Children performed spirometry and provided a sputum sample prior to starting IV antibiotics and then weekly for 6 weeks, the first 2 weeks of which IV antibiotics were given. Sputum IL-8, TNF-alpha, IL-6, IL-10, MIP1-alpha, and elastase were measured. Seven children were asked to repeat the protocol in a subsequent exacerbation to assess similarities in response to therapy. Significant improvements were seen in forced expired volume in 1 sec (FEV(1)) in association with IV antibiotics (27% relative improvement in predicted from baseline to end of week 1, median FEV(1) 41.3% increasing to 52.2%), but this continued only 1 week following cessation of antibiotics. Although IL-8 demonstrated a trend for reduction in association with antibiotics, no significant profile was demonstrated for any of the cytokines assessed. IL-10 was detectable in 64% of samples (all <100 pg/ml). In children with two episodes assessed, although there was a close correlation of FEV(1) and FVC between exacerbations (before antibiotics), no significant correlation was seen for IL-8, TNF-alpha, or IL-10 measured in both sets of samples at any sample point (indeed, a discordant response was seen between sample points in the two exacerbations). Although FEV(1) temporarily improves in response to admission for IV antibiotics, no such response is seen in sputum cytokine values. In addition, assessment of cytokines in subsequent exacerbations does not show a similar pattern of response to treatment.

Continuous vs thrice-daily ceftazidime for elective intravenous antipseudomonal therapy in cystic fibrosis

“…To the best of our knowledge, the intra-individual reactions of patients to repeated courses of elective antimicrobial therapy have not been described in the literature. Cunningham and coworkers [16] examined cytokines after the treatment of acute exacerbations and found no correlation between the responses to first and second treatment episodes, and some individuals even showed an opposite response in terms of individual cytokines. The mean plasma ceftazidime concentrations during continuous application in our study correspond well to the data from the literature.…”

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

“…Of note, other groups have not found significant differences in sputum inflammatory markers between periods of exacerbation and stability (114,131,134). Elevated sputum inflammatory markers have also been demonstrated in those with chronic P. aeruginosa endobronchial infection (115,132).…”

Circulating RNA Transcripts Identify Therapeutic Response in Cystic Fibrosis Lung Disease

“…Although many markers of airway inflammation can be detected in the sputum, multiple previous studies (particularly of this size) have not been able to detect changes in sputum concentrations of inflammatory markers associated with the treatment of an acute pulmonary exacerbation (33)(34)(35)(36)(37)(38). Thus, to directly compare identified changes in PBMC expression with specific inflammatory markers in the sputum, sputum markers of inflammation were not analyzed as a part of this study..…”