Airway inflammation in children younger than 5 yr of age is difficult to assess, particularly in patients with cystic fibrosis (CF). Furthermore, determining responses to therapies is often subjective in infants, especially those with CF. To determine whether airway DNA levels could be used as an index of airway inflammation, we measured DNA levels in bronchoalveolar lavage fluid (BALF), using a Hoechst dye-binding assay. BALF DNA levels and neutrophils from 16 infants with CF were compared with levels obtained from seven older CF patients and nine control children who underwent bronchoalveolar lavage for evaluation of other pulmonary diseases. BALF DNA was increased in both infants (3.2 +/- 0.7 microg/ml) and older patients with CF (5.4 +/- 0.9 microg/ml) compared with the controls (0.7 +/- 0.2 microg/ml) (mean +/- SEM). BALF DNA levels were not significantly different between infants and older patients with CF. BALF neutrophil counts in CF patients were significantly higher than in controls. Furthermore, BALF DNA levels and total neutrophil counts in infants with CF correlated positively with one another. We conclude that: (1) DNA levels were easily quantifiable in BALF of young children; (2) DNA levels in BALF from CF patients were greater than in a group of children with other pulmonary diseases, and that in some infants with CF, BALF DNA levels were equivalent to those of much older patients with CF; (3) DNA levels in BALF correlate with BALF neutrophil number, an index of inflammation; and (4) some infants with CF have increased levels of DNA in BALF, which may justify a clinical trial of aerosolized rhDNase in this population.

The objective of this study was to identify risk factors for initial detection of Pseudomonas aeruginosa (P. aeruginosa) in children with cystic fibrosis (CF) identified by newborn screening. Life history data on 180 patients, collected prospectively in a follow-up study of infants and children diagnosed with CF, were examined for factors associated with the initial detection of P. aeruginosa ascertained by oropharyngeal cultures. Univariate and multivariate Cox proportional hazards regression analyses were used to assess the effect of baseline and time-varying covariates on age at first positive culture for P. aeruginosa. Seventy-nine patients (44%) had at least one culture positive for P. aeruginosa during the study. The median age of detection was 8.1 years (95% CI, 7.0, 10.0). Median length of follow-up was 4.1 years, ranging from 0.2-15.5 years. Multivariate Cox regression analysis identified female gender (RR, 1.85; 95% CI, 1.14, 3.01), the DeltaF508 homozygous genotype (RR, 2.23; 95% CI, 1.30, 3.80), and S. aureus isolations (RR, 1.30; 95% CI, 1.11, 1.52) to be independently associated with acquisition of P. aeruginosa. Other marginally independent associations were found with days hospitalized and increased height. We conclude that female gender, homozygous DeltaF508 mutation, and S. aureus isolations are important risk factors for early P. aeruginosa detection in children with CF identified through newborn screening.

Enteric-coated, delayed-release (Minimicrospheres) pancrelipase capsules are an effective treatment for steatorrhea associated with pancreatic insufficiency in patients with cystic fibrosis.

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Rationale The Early Pseudomonal Infection Control (EPIC) randomized trial rigorously evaluated the efficacy of different antibiotic regimens for eradication of newly identified Pseudomonas (Pa) in children with cystic fibrosis (CF). Protocol based therapy in the trial was provided based on culture positivity independent of symptoms. It is unclear whether outcomes observed in the clinical trial were different than those that would have been observed with historical standard of care driven more heavily by respiratory symptoms than culture positivity alone. We hypothesized that the incidence of Pa recurrence and hospitalizations would be significantly reduced among trial participants as compared to historical controls whose standard of care preceded the widespread adoption of tobramycin inhalation solution (TIS) as initial eradication therapy at the time of new isolation of Pa. Methods Eligibility criteria from the trial were used to derive historical controls from the Epidemiologic Study of CF (ESCF) who received standard of care treatment from 1995 to 1998, before widespread availability of TIS. Pa recurrence and hospitalization outcomes were assessed over a 15-month time period. Results As compared to 100% of the 304 trial participants, only 296/608 (49%) historical controls received antibiotics within an average of 20 weeks after new onset Pa. Pa recurrence occurred among 104/298 (35%) of the trial participants as compared to 295/549 (54%) of historical controls (19% difference, 95% CI: 12%, 26%, p<0.001). No significant differences in the incidence of hospitalization were observed between cohorts. Conclusions Protocol-based antimicrobial therapy for newly acquired Pa resulted in a lower rate of Pa recurrence but comparable hospitalization rates as compared to a historical control cohort less aggressively treated with antibiotics for new onset Pa.