Elsevier

The Journal of Pediatrics

Volume 154, Issue 2, February 2009, Pages 183-188.e3
The Journal of Pediatrics

Original article
Impact of Pseudomonas and Staphylococcus Infection on Inflammation and Clinical Status in Young Children with Cystic Fibrosis

https://doi.org/10.1016/j.jpeds.2008.08.001Get rights and content

Objective

To assess the effects of Pseudomonas aeruginosa and Staphylococcus aureus infection on lower airway inflammation and clinical status in young children with cystic fibrosis (CF).

Study design

We studied 111 children age < 6 years who had 2 P aeruginosa–positive oropharyngeal cultures within 12 months. We examined bronchoalveolar lavage fluid (BALF) inflammatory markers (ie, cell count, differential, interleukin [IL]-8, IL-6, neutrophil elastase), CF-related bacterial pathogens, exotoxin A serology, and clinical indicators of disease severity.

Results

Young children with CF with both upper and lower airway P aeruginosa infection had higher neutrophil counts, higher IL-8 and free neutrophil elastase levels, increased likelihood of positive exotoxin A titers, and lower Shwachman scores compared with those with positive upper airway cultures only. S aureus was associated with increased lower airway inflammation, and the presence of both P aeruginosa and S aureus had an additive effect on concentrations of lower airway inflammatory markers. BALF markers of inflammation were increased with the number of different bacterial pathogens detected.

Conclusions

Young children with CF who have upper and lower airway P aeruginosa infection have increased endobronchial inflammation and poorer clinical status compared with those with only upper airway P aeruginosa infection. The independent and additive effects of S aureus on inflammation support the significance of polymicrobial infection in early CF lung disease.

Section snippets

Study Design

This cross-sectional study examined data from all subjects who had baseline BAL performed as part of 2 sequential multicenter clinical trials conducted by the CFF-TDN.23, 24 These studies were conducted with institutional review board approval at 12 centers between 2000 and 2005. Written informed consent was obtained for all enrolled subjects.

Inclusion criteria for both studies were the same, including age ≥ 6 months and < 6 years, diagnosis of CF, and at least 1 historical OP culture positive

Subject Characteristics

A total of 111 infants and young children with CF underwent baseline bronchoscopy. The subjects were categorized into 3 groups based on BALF culture results: BALF-positive for P aeruginosa (and possibly other CF bacterial pathogens), BALF-negative for P aeruginosa but positive for other CF bacterial pathogens, and BALF-negative for all CF bacterial pathogens. The clinical characteristics of each group at the time of BAL are summarized in Tables I (available at www.jpeds.com) and Table II.

Discussion

In this large multicenter study, we have demonstrated that young children with CF with lower airway P aeruginosa infection (ie, BALF-positive for P aeruginosa) had a greater degree of endobronchial inflammation (as marked by higher neutrophil counts, IL-8 levels, and free neutrophil elastase activity) and poorer clinical status (as marked by lower modified Shwachman scores) compared with those with only upper airway P aeruginosa–positive cultures. Lower airway S aureus infection also was found

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    Supported by grants from the National Institutes of Health (1 RO1 DK 57755-01, -02, K23 RR018611-05, and U01 HL081335-01), US Food and Drug Administration (FD-R-001695-01), Cystic Fibrosis Foundation Therapeutics Development Center Network, Novartis Corporation, and General Clinical Research Centers Program, National Center for Research Resources (MO1-RR00037, RR00046, RR00052, RR00064, RR00069, RR00070, RR00080, RR00188, RR02172, and RR08084). The authors declare no conflicts of interest.

    A list of additional members of the Inhaled Tobramycin in Young Children Study Group is available in the appendix (available at www.jpeds.com).

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