Risk stratification model to detect early pulmonary disease in infants with cystic fibrosis diagnosed by newborn screening.

OBJECTIVE: The clinical benefit of newborn screening (NBS) for cystic fibrosis (CF) has been primarily nutritional, with less overt respiratory impact. Identification of risk factors for infant CF lung disease could facilitate targeted interventions to improve pulmonary outcomes. METHODS: This retrospective study evaluated socioeconomic information, clinical data, and results from routine infant pulmonary function testing (iPFT) of infants diagnosed with CF through NBS (N = 43) at a single CF center over a 4-year period (2008-2012). A five-item composite clinical score was developed and combined with socioeconomic indicators to facilitate identification of CF infants at increased risk of early-onset respiratory impairment. RESULTS: Paternal education was positively associated with lung function (P = 0.02). Clinical score <7 (on a scale of 0-10) predicted diminished pulmonary measure (P < 0.005). Retrospective risk stratification by clinical score and paternal education identified CF infants at low, intermediate, or high risk of pulmonary disease. Forced expiratory volume (FEV0.5 %, mean ± SD) averaged 115 ± 19% in the low-risk group, 97 ± 17% in the intermediate-risk group, and 90 ± 8% in the high-risk group (P < 0.005). Results were similar for mid-expiratory flows (FEF25-75 %). Multiple regression analysis confirmed the predictive value of this risk stratification model of CF infant pulmonary health. CONCLUSION: We combined socioeconomic and clinical data to risk-stratify CF infants for early-onset lung disease as quantified by iPFT. Our model showed significant differences in infant pulmonary function across risk groups. The developed tool offers an easily available, inexpensive, and non-invasive way to assess risk of respiratory decline in CF infants and identify those meriting targeted therapeutic attention. Pediatr Pulmonol. 2016;51:1168-1176. © 2016 Wiley Periodicals, Inc.

Sustained improvement in nutritional outcomes at two paediatric cystic fibrosis centres after quality improvement collaboratives.

OBJECTIVE: To describe the characteristics of sustained improved nutritional outcomes through the use of quality improvement (QI) methodology. DESIGN: Retrospective analysis of a QI intervention in two institutions, implemented as part of larger national collaboratives. SETTING: Paediatric cystic fibrosis (CF) programmes in academic centres in Alabama and Illinois. PARTICIPANTS: All paediatric patients enrolled in the CF Foundation (CFF) Patient Data Registry were included. INTERVENTIONS: Improved and sustained nutrition outcomes occurred through implementation of the CFF practice guidelines for CF nutrition management via care delivery processes, nutritional interventions, team engagement and data display. MEASUREMENT: Mean body mass index (BMI) percentile, percentage of patients less than 50th percentile and percentage less than 10th percentile for all patients aged 2-20 years were tracked through run charts and statistical process control charts. Mann-Whitney U and χ(2) tests were used to determine significance between each centre and national outcomes. RESULTS: Each centre achieved rapid improvement in mean BMI percentile in patients, one centre rising from the 40th percentile in 2001 to the 49th percentile in 2003, the other rising from the 37th percentile in 2003 to the 45th percentile in 2004. These centres have also maintained improved nutritional outcomes, so that they were at the 60th and 55th percentiles, respectively, in 2011. Sustained improvement was accomplished through QI methodology, use of data as a driver for improvement and a change in culture. CONCLUSIONS: Participation in collaboratives led to improved nutrition outcomes while a strong culture of QI facilitated sustained improvement.

Clearance of initial mucoid Pseudomonas aeruginosa in patients with cystic fibrosis.

BACKGROUND: Accelerated lung function decline in cystic fibrosis (CF) is associated with mucoid Pseudomonas aeruginosa infection. Recent data suggest that mucoid P. aeruginosa may amenable to elimination from the airway. We aim to determine whether the initiation of an aggressive antibiotic eradication regimen upon initial discovery of mucoid P. aeruginosa in the CF airway could be successful in clearing the organism from the CF lung. METHODS: We performed a retrospective analysis of patients with CF who demonstrated new growth of mucoid P. aeruginosa in an airway culture between January 2003 and December 2008. The primary endpoint was clearance of mucoid P. aeruginosa, based upon the Leeds criteria, with no further growth of mucoid P. aeruginosa cultures within 12 months of the initial discovery and treatment. Factors associated with successful clearance were also evaluated. RESULTS: Forty-eight of 355 patients with CF had a new diagnosis of mucoid P. aeruginosa during the study period; 15 patients underwent an eradication attempt, while 33 patients received no increase in therapy. We observed clearance of mucoid P. aeruginosa in 73.3% of patients undergoing an eradication attempt, whereas 36.6% of those that did not undergo attempted eradication cleared the organism at 1 year (P < 0.05). Prolonged mucoid P. aeruginosa airway clearance (>24 months) for mucoid P. aeruginosa was seen in 60.0% in subjects undergoing eradication compared to 21.2% (P = 0.02) in control patients. At the study conclusion, lung function was greater in subjects who underwent an eradication attempt than in patients who did not undergo an eradication attempt (FEV(1) %: 91.7% vs. 75.0%, P = 0.04). CONCLUSIONS: Clearance of initial mucoid P. aeruginosa from the airways of select patients with CF is possible with current antibiotic regimens, and the attempt may be associated with improved lung function.

Rapid onset of iatrogenic adrenal insufficiency in a patient with cystic fibrosis-related liver disease treated with inhaled corticosteroids and a moderate CYP3A4 inhibitor.

OBJECTIVE: To report the rapid onset of adrenal insufficiency and subsequent development of Cushing syndrome precipitated by a CYP3A4-mediated drug-drug interaction that may have been enhanced by the presence of cystic fibrosis (CF)-related liver disease. CASE SUMMARY: A 9-year-old girl with CF and cirrhosis experienced a decline in lung function that led to a diagnosis of asthma. After initiation of asthma therapy with inhaled fluticasone 110 µg/actuation, the patient experienced improvement in lung function to baseline. Seven weeks after the initiation of inhaled fluticasone, she developed vaginal candidiasis and was prescribed fluconazole 100 mg/day, a CYP3A4 inhibitor. Three days after starting fluconazole, she developed polyuria and polydipsia and was found to have severe hyperglycemia, which led to the diagnosis of Cushing syndrome. Fluticasone was discontinued, and the patient's adrenal function normalized. DISCUSSION: Patients with CF are commonly prescribed complex medication regimens that may affect drug metabolism. CYP3A4 inhibitors may significantly decrease metabolic clearance in patients using chronic inhaled corticosteroids. Iatrogenic Cushing syndrome has been reported in patients with CF treated concomitantly, and for extended duration, with inhaled corticosteroids and CYP3A4 inhibitors. This case highlights rapid onset of adrenal insufficiency in a patient with CF-related liver disease treated briefly with a moderate CYP3A4 inhibitor. Use of the Horn drug interaction probability scale indicates that the interaction between fluticasone and fluconazole was probable. CONCLUSIONS: CYP3A4-mediated drug interactions represent a significant risk in patients treated with long-term inhaled corticosteroids. The presence of clinically significant CF-related liver disease may enhance this risk.

Creating a culture of improvement: experience of a pediatric cystic fibrosis center.

Quality improvement (QI) efforts at the University of Alabama at Birmingham/Children's Hospital Cystic Fibrosis Center began in the spring of 2004, with a collaborative sponsored by the Cystic Fibrosis Foundation. As the authors gained experience with QI processes, significant system changes ensued. In this article, we describe how the center created a culture of improvement that has resulted in significant improvements in clinical outcomes in our patient population.