Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis.

OBJECTIVES: To characterize the rate of decline of forced expiratory volume in 1 second (FEV(1)) in children and adolescents with cystic fibrosis and to identify and compare risk factors associated with FEV(1) decline. STUDY DESIGN: The rate of decline in FEV(1)% predicted over 3 to 6 years in 3 different age groups was determined. Risk factors for decline were identified and compared among and within age groups as a function of disease severity with repeated-measures, mixed-model regression. RESULTS: Mean (+/-SD) baseline FEV(1)% predicted was 88.4% +/- 20.5% for 6- to 8-year-olds (n = 1811), 85.3% +/- 20.8% for 9- to 12-year-olds (n = 1696), and 78.4% +/- 22.0% for 13- to 17-year-olds (n = 1359). Decline in FEV(1)% predicted/year was -1.12, -2.39, and -2.34, respectively. High baseline FEV(1) and persistent crackles were significant independent risk factors for decline across all age groups. Female sex, Pseudomonas aeruginosa infection, low weight-for-age, sputum, wheezing, sinusitis, pulmonary exacerbations treated with intravenous antibiotics, elevated liver test results, and pancreatic insufficiency were also identified as independent risk factors in some age groups. CONCLUSIONS: This study identifies risk factors for FEV(1) decline in children and adolescents with cystic fibrosis. Clinicians should not be reassured by high lung function, particularly in young children, because this factor, among others, is independently associated with steeper decline in FEV(1).

Variability of markers of inflammation and infection in induced sputum in children with cystic fibrosis.

To determine reproducibility of inflammatory marker concentrations in induced sputum from subjects with cystic fibrosis (CF), 15 nonexpectorating children, 6 to 13 years of age with mild CF lung disease, underwent 3 weekly sputum inductions with 3% saline. Neutrophil elastase concentration and bacterial cultures were reproducible. This study provides useful information for investigators designing trials of anti-inflammatory therapies in CF involving sputum induction.

Pulmonary exacerbations in cystic fibrosis.

The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12-month baseline period, data from 11692 patients were compared with data collected during the subsequent 6-month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and >or=6 years of age. The outcome of interest was any antibiotic treatment in the 6-month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients >or=6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients.

Maximal expiratory flow at FRC (V'maxFRC): Methods of selection and differences in reported values.

We compared three methods of reporting maximal expiratory flow (V'maxFRC) measured in partial expiratory flow-volume curves (PEFVCs) at the point of functional residual capacity (FRC). PEFVCs were obtained with the rapid thoracoabdominal compression technique (RTC) on a total of 446 occasions in 281 HIV-negative, asymptomatic infants (4.8-28.1 months old). Three different expressions of V'maxFRC were recorded: 1) the highest measured flow (maxV'FRC), 2) the mean of the three highest flows (mean3V'FRC), and 3) the flow at FRC in a composite curve (compV'FRC) consisting of PEFVCs, obtained at different jacket pressures and superimposed at their distal limb. The numerical value of maxV'FRC was 7.4% (+/-5.6%) higher than the mean3V'FRC, and 11.9% (+/-17.7%) higher than the compV'FRC; the mean3V'FRC was 5% (+/-18.3%) higher than the compV'FRC. Bland-Altman analysis was used to evaluate the agreement between the three indices. The mean difference and 95% limits of agreement were: maxV'FRC -mean3V'FRC, 14 +/- 18 ml/sec; maxV'FRC - compV'(FRC), 23 +/- 58 ml/sec; and mean3V'(FRC) - compV'(FRC), 10 +/- 52 ml/sec. The differences between the slopes of the three indices (regressed against height) were statistically significant, although clinically unimportant. We conclude that despite their high correlation, the mean3V'FRC and maxV'FRC should not be used interchangeably, and that the composite analysis, although useful, does not improve the reproducibility of V'maxFRC, and thus it cannot be recommended for routine use in its current form.

Growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis.

OBJECTIVE: To determine the relation of growth and nutritional status to pulmonary function in young children with cystic fibrosis (CF). STUDY DESIGN: The relation of weight-for-age (WFA), height-for-age (HFA), percent ideal body weight (%IBW), and signs of lung disease at age 3 years with pulmonary function at age 6 years was assessed in 931 patients with CF. Associations of changes in WFA from age 3 to 6 on pulmonary function were also assessed. RESULTS: WFA, HFA, and %IBW were poorly associated with lung disease at age 3 years, but all were strongly associated with pulmonary function at age 6 years. Those with WFA below the 5th percentile at age 3 had lower pulmonary function at age 6 compared with those above the 75th percentile (FEV(1): 86 +/- 20 [SD] versus 102 +/- 18 % predicted, respectively). Pulmonary function was highest in those whose WFA remained >10th percentile from age 3 to 6 (FEV(1): 100 +/- 19 % predicted) and lowest in those who remained <10th percentile (84 +/- 21 % predicted). Patients with signs and symptoms of lung disease at age 3 years had lower pulmonary function at age 6 years. CONCLUSIONS: Aggressive intervention early in life aimed at growth and nutrition and/or lung disease may affect pulmonary function.

Factors influencing outcomes in cystic fibrosis: a center-based analysis.

CONTEXT: Guidelines for managing cystic fibrosis (CF) patients have been widely circulated, but little is known about the variations in practice between sites and their association with outcomes. OBJECTIVE: To determine whether differences in lung health existed between groups of patients attending different CF care sites and to determine whether these differences are associated with differences in monitoring and intervention. DESIGN: The analysis was conducted using data from the Epidemiologic Study of Cystic Fibrosis from 1995 through 1996. SETTING: This was an observational database collecting prospective information from a large number of CF patients undergoing routine care in North America. PARTICIPANTS: Participating sites that had at least 50 CF patients who had each made at least one visit to a center during the 2-year study period were ranked on the basis of median values for FEV(1) within each of three age groups (6 to 12 years, 13 to 17 years, and >or= 18 years). INTERVENTIONS: There were no prespecified interventions in this observational study. MAIN OUTCOME MEASURES: The frequency of patient monitoring and the use of therapeutic interventions were compared between sites in the upper and lower quartiles after stratification within the site for disease severity. RESULTS: Within-site rankings tended to be consistent across the three age groups. Patients who were treated at higher ranking sites had more frequent monitoring of their clinical status, measurements of lung function, and cultures for respiratory pathogens. These patients also received more interventions, particularly IV antibiotics for pulmonary exacerbations. CONCLUSION: We found substantial differences in lung health across different CF care sites. We found that frequent monitoring and increased use of appropriate medications in the management of CF are associated with improved outcomes.