Trends in the use of routine therapies in cystic fibrosis: 1995–2005

Many therapies are used to treat manifestations of cystic fibrosis (CF). Trends in routine therapy use in Epidemiologic Study of Cystic Fibrosis patients were studied from 1995 to 2005. Patients (15,087) were assessed in 1995; 12,778 in 2005. Observed differences in therapy use of ≥2% were statistically significant at P < 0.001. Comparing the 1995 and 2005 populations, mean age was 13.9 versus 15.5 years; weight‐for‐age percentile was 30.3 versus 36.9; and mean forced expiratory volume in 1 sec (FEV₁) was 73.7% (n = 7065) versus 78.7% (n = 7867) predicted. Use of several therapies increased, including airway clearance (69.9–89.6%), inhaled bronchodilators (72.0–84.0%), dornase alfa (44.8–67.2%), inhaled corticosteroids (16.0–49.3%), inhaled antibiotics (6.5–43.1%), oral nutritional supplements (18.3–24.5%), and insulin/oral hypoglycemic agents (4.9–10.2%). Use of mast cell stabilizers (from 22.0% to 5.3%) and oral bronchodilators (from 10.4% to 1.5%) decreased. Less dramatic changes occurred for pancreatic enzymes (92.6–91.0%), oral nonquinolone antibiotics (44.7–39.8%), oral corticosteroids (7.8–5.2%), mucolytics (4.4–2.5%), NSAIDs/high‐dose ibuprofen (3.6–3.3%), enteral nutrition (5.2% vs. 8.2%), and oxygen (4.7–4.5%). Therapies not tracked in 1995 were evident in 2005, including oral macrolide antibiotics (33.8%), leukotriene inhibitors/antagonists (10.8%), and inhaled hypertonic saline (2.6%). Routine therapies were generally used more often by older patients and those with lower FEV₁. Notable increases in use of therapies, particularly of inhaled therapies, suggest that overall patient treatment burden must have risen correspondingly. Pediatr Pulmonol. 2010;45:1167–1172. © 2010 Wiley‐Liss, Inc.     

Changes in lung function measured by spirometry and the forced oscillation technique in cystic fibrosis patients undergoing treatment for respiratory tract exacerbation

Objective measures of lung function are critical for the treatment and study of lung diseases such as cystic fibrosis (CF). Spirometry is the most widely used and accepted method of pulmonary function testing in CF, but not all patients can perform the maneuvers required to obtain valid results from spirometry. The forced oscillation technique (FOT) requires less cooperation than spirometry. The goals of this study were to determine if FOT could detect changes in lung function in CF patients receiving inpatient treatment of respiratory tract exacerbations (RTEs), and to gather preliminary data on the magnitude of these changes and the variability of FOT data in such patients. We performed a retrospective chart review of CF patients admitted to the hospital for RTEs. We identified 14 patients who had both spirometry and FOT performed at the beginning and end of their treatment course. Their mean age was 15.9 years (range, 8-18). The mean forced expiratory volume in 1 sec (FEV1) on admission was 62.57% predicted. FEV1 increased by 27.1 +/- 33.15% (mean +/- SD, P = 0.008). The absolute value of reactance at 5 Hz (X5) decreased by 22.3 +/- 25.1% (P = 0.005), while resistance at 5 Hz decreased by 11.6 +/- 17.3% (P = 0.025). There was a significant relationship between changes in FEV1 and X5 (P = 0.003, r2 = 0.54). Our study demonstrates that FOT can detect significant changes in lung function in CF patients receiving treatment for RTEs. We speculate that FOT can serve as an alternative method to measure lung function in CF patients unable to perform spirometry, such as young children.     

Immunoglobulin and IgG subclass levels in a regional pediatric cystic fibrosis clinic

The aim of this study was to report serum immunoglobulin (Ig) and IgG subclass levels in a large pediatric population with cystic fibrosis, and relate these to measures of disease severity. Total immunoglobulin levels were measured in 154 patients, and IgG subclass levels were measured in 136 patients and compared to age-related normal population data and to levels reported in previously published studies of children with cystic fibrosis. Clinical data were also collected: genotype; height, weight, and BMI standard deviation scores; FEV(1) (as percent predicted); Shwachmann-Kulczycki (S-K) and Northern chest X-ray scores; and Pseudomonas aeruginosa infection status. The clinical well-being of patients with hypo- or hyper-gammaglobulinemia was compared with age- and sex-matched control patients who had normal levels of gammaglobulin. IgG subclass levels were measured, and the results were compared with previous studies. Eleven patients had hypergammaglobulinemia (7.8% compared with 0-69% in the published literature). Patients with hypergammaglobulinemia had lower FEV(1) percent-predicted values, and worse S-K and Northern chest X-ray scores than controls. Three patients had hypogammaglobulinemia (1.9% compared with 0-10.8% in the published literature). There was no difference in any clinical parameter between controls and those with hypogammaglobulinemia. Nineteen patients (14%) had low levels of IgG1, and 40 patients (29%) had low levels of IgG2. The low percentage of patients with abnormally high immunoglobulin levels probably reflects the improved respiratory status of today's children with CF. The low percentage of those with low IgG probably reflects better nutritional status. The finding of worse lung function and clinical scores in patients with hypergammaglobulinemia agrees with the published literature. The high percentage of patients with low IgG2 was unexpected and was not previously reported. The clinical significance of this in patients with CF is unknown.     

Assessing correlations between spirometry and Shwachman-Kulczycki score in children and adolescents

A retrospective observational study was carried out to analyze the correlations between formal pulmonary function tests and the Shwachman-Kulczycki (SK) score. Forty-six Brazilian cystic fibrosis (CF) patients, clinically stable, aged 7-19 years, were included. Clinical and radiological findings of the SK score system and spirometry variables were assessed by independent observers in a blinded manner. The strongest correlation (r = 0.75; 95% CI, 0.59-0.85; P < 0.001) was found for forced expiratory volume in 1 sec (FEV1). Despite some peculiarities of our patients, the results are in agreement with studies undertaken in industrialized countries, showing good correlation between FEV1 and SK score and its usefulness in managing CF. Accordingly, in countries where pulmonary function testing is not available, the SK score remains a valuable parameter on which to base treatment results.     

Effect of Burkholderia cepacia infection in the clinical course of patients with cystic fibrosis: a pilot study in a Sydney clinic

BACKGROUND: Colonisation with Burkholderia cepacia complex in patients with cystic fibrosis (CF) has been associated with adverse outcomes. The aim of the present study was to determine the actuarial survival of CF patients colonized with B. cepacia and to evaluate the efficacy of the Royal Prince Alfred Hospital segregation policy. A secondary aim was to characterize the specific genomovars and strains of B. cepacia isolated in an Australian clinic. METHODS: Retrospective review of spirometric and microbiological data on all patients colonized with B. cepacia. Each B. cepacia-colonized subject was matched with three case-control subjects. Phenotype and genomovar typing, random amplified polymorphic DNA strain type and B. cepacia epidemic strain marker analyses were performed. The effect of B. cepacia colonization on transplant-free survival was estimated by Cox's proportional hazards regression using the entire clinic population. RESULTS: Fifteen patients were colonized with B. cepacia, of whom six (40%) had died from CF-related disease by August 1998, compared with 30 of 173 (17.3%) of the entire clinic population. Cepacia status had a significant adverse effect on survival, with a hazard ratio of 2.16 (95% confidence interval 1.0-4.69; P = 0.05). The outcome was variable in subgroups of B. cepacia. DISCUSSION: Colonization with B. cepacia had a significant adverse effect on survival within the study population. Genomovar and strain typing contributed usefully in accessing the effectiveness of the hospital's segregation policy in preventing cross-colonization.     

Lung function in 3-5-year-old children with cystic fibrosis

It is well established that the lung disease of CF can occur early in life and may progress through the preschool years when accurate lung function assessment has been challenging to perform. We hypothesized that respiratory inductive plethysmography (RIP) and spirometry could be effectively performed in 3-6-year-old children and could be used to assess both longitudinal changes in lung function and the acute changes that occur during exacerbation of pulmonary disease. Both RIP and spirometry were equally feasible; however, the success rate for spirometry gradually increased with age to become higher than that for RIP in the 6-year-old subjects. Forty-four subjects were studied longitudinally and demonstrated significant increases in FVC, FEV(1), and FEV(0.5), but not in FEF(25-75) or RIP variables. There were significant differences in FVC, FEV(1), and phase angle (a measure of thoracoabdominal asynchrony) during exacerbations of lung disease. Although both RIP and spirometry were able to show differences in lung function in subjects with acute clinical worsening, spirometry was more robust in demonstrating change in lung function longitudinally and in children who had an exacerbation of lung disease.     

Nontuberculous mycobacterial infection in young children with cystic fibrosis

Although nontuberculous mycobacteria (NTM) are recognized pathogens in adolescent and adult patients with cystic fibrosis (CF), the role of NTM in younger CF patients is not well-defined. To explore NTM infection in CF patients less than 12 years old, a retrospective review was performed. Prevalence was estimated from routine mycobacterial cultures of bronchoalveolar lavage (BAL) specimens collected over a 3-year period. NTM-positive cultures were obtained from 9 of 258 BALs collected from 7 of 114 different patients (5 months to 11 years of age). Further data were acquired from microbiological and clinical records of all pediatric patients with CF over a 10-year period. A total of 17 patients had at least one positive mycobacterial culture at less than 12 years of age, 5 of whom had positive cultures before age 5. The most commonly identified organisms were Mycobacterium avium-complex and Mycobacterium abscessus. Of the 17 patients, 10 met American Thoracic Society (ATS) microbiological criteria for mycobacterial disease, and 7 did not. The two groups did not differ with respect to age, gender, or presence of other respiratory pathogens. Patients who met ATS microbiological criteria for disease were more likely to have positive smears for acid-fast bacilli and grow Mycobacterium abscessus from culture. These patients also had a greater decline in lung function over time than patients who did not meet the microbiologic criteria. These data suggest that NTM represent a clinically significant pathogen, even in young patients with cystic fibrosis.