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To help answer the question of length of intravenous antibiotics during an acute exacerbation of cystic fibrosis (CF), we had subjects to follow daily home spirometry while on intravenous antibiotics. CF patients, 18 and older, with an acute exacerbation requiring intravenous antibiotics had a daily FEV1. The average time to a 10% increase over their initial sick FEV1 was calculated, as well as the time to a new baseline. A total of 25 subjects completed the study. Ten of the 25 subjects did not have a sustainable 10% increase in FEV1. Of the 15 subjects with a sustainable 10% increase in FEV1, it took 5.2 days (±4.5) after day 1, while a new baseline was achieved on average at 6.6 days (±4.8) after day 1. Given the wide range of time to a 10% improvement and new baseline, it is recommended there should be flexibility in length of intravenous antibiotics in CF, not by a preset number.

Monitoring and blunting are cognitive-affective informational processing styles that may predict future internalizing symptoms among youths with cystic fibrosis (CF). Forty-four youths with CF (9–23 years) and one of their parents completed measures of the youths’ monitoring, blunting, and internalizing symptoms at baseline and again two years later. Monitoring was associated with higher levels of concurrent internalizing symptoms on self- but not parent report, and did not predict changes in future symptoms. Blunting, in contrast, predicted a relative decrease in self-reported anxiety and depressive symptoms and in parent-report of youths’ depressive symptoms at Time 2. Our findings suggest that blunting may be an important protective factor in the adjustment of youths with CF.

Background Cystic fibrosis (CF) patients are often treated with aminoglycoside (AG) antibiotics during infective pulmonary exacerbations. Achieving pharmacokinetic and pharmacodynamic (PK/PD) targets to improve outcomes and counteract resistance is paramount. Purpose The primary objective was to compare the number of pediatric CF patients achieving AG PK/PD targets when a clinical pharmacist (CP) managed therapeutic drug monitoring (TDM) compared with usual care (UC). Methods A retrospective cohort study was conducted on the records of 40 CF patients that received AGs and ≥2 serum samples between 1/2007 and 5/2009. Chi-square and Student's t-test were used to analyze nominal and continuous variables, respectively. Results Twenty-nine patients with 52 courses of AGs were included the CP group, and 22 patients with 42 courses were included the UC group. Ninety-eight percent of patients in the CP group reached AG PK/PD targets compared with 71% in the UC group, P

Youths with cystic fibrosis (CF) may be at increased risk for internalizing symptoms, but factors explaining individual variation in these symptoms are not understood. Monitoring, a cognitive-affective information processing style characterized by the tendency to scan for, attend to, and magnify threatening cues when stressed, was hypothesized to be related to more internalizing symptoms. Optimism, in contrast, was hypothesized to serve as a protective factor and to be related to fewer internalizing symptoms. Eighty-seven youths with CF (ages 7–18 years) attending a clinic visit completed measures of monitoring, optimism, state anxiety, trait anxiety, and depressive symptoms. Parents also completed a measure of their child's internalizing symptoms. As hypothesized, monitoring predicted increased trait anxiety and depressive symptoms, whereas optimism predicted decreased trait anxiety, state anxiety, depressive symptoms, and parent-rated internalizing symptoms. Age, gender, respiratory function, and socioe...

Background: In 2003, the American Cystic Fibrosis (CF) Foundation published revised, evidence-based guidelines for infection control. We sought to assess potential barriers to adherence to these guidelines experienced by health care professionals (HCPs) caring for CF patients. Methods: From April 2004 to December 2005, a knowledge, attitude, and practice survey was administered to HCPs at randomly selected CF centers in the United States to explore potential barriers to adherence to selected guidelines: (1) obtaining quarterly cultures from CF patients, (2) discouraging socialization among CF patients during hospitalization, (3) educating patients and families about hand hygiene, (4) educating patients and families to clean and disinfect home nebulizers, and (5) cleaning the clinic exam rooms between CF patients. Results: The survey was completed by 528 HCPs from 25 sites (5–50 respondents per site). Only 60% of respondents were aware of the guidelines, but despite awareness, 31–47% were unfamiliar with the specific guidelines. Self-reported adherence was low; only 23–63% of respondents reported practicing the selected guidelines >75% of the time/opportunities. Lack of self-efficacy, that is, confidence in adequately performing the guidelines, was commonly experienced by respondents. Access to a copy of the guidelines was associated with increased agreement with the recommendations and increased self-efficacy. Conclusions: Strategies to reduce barriers to adherence to CF infection control guidelines are needed. Strategies could include quality improvement initiatives with enhanced education and skills workshops, sharing successful interventions among CF centers, and linking adherence to improved patient outcomes. Pediatr Pulmonol. 2008; 43:900–907. © 2008 Wiley-Liss, Inc.

Congenital anomalies of the right main bronchi have not been fully described. Bronchial anomalies are usually asymptomatic unless they coexist with other abnormalities. We describe a rare bronchial anomaly in a 2-month-old girl in which the right upper lobe, middle lobe, and lower lobe bronchi all originated at the same point as a result of a developmental teratogenic long right main bronchus and an absent bronchus intermedius. Furthermore, the left main bronchus contained a proximal segment of stenosis. This combination of anomalies, along with right upper lobe atelectasis and left-sided hyperinflation, resulted in a severe right mediastinal shift and respiratory distress. The mediastinum was returned to midline with endoscopic placement of an in-dwelling tracheobronchial stent into the left main bronchus. To the best of our knowledge, the specific developmental anomaly in our patient has not been previously described.

Objective To evaluate several alternative measures of forced expiratory volume in 1 second percent predicted (FEV 1 %pred) variability as potential predictors of future FEV 1 %pred decline in patients with cystic fibrosis. Study design We included 13 827 patients age ≥6 years from the Epidemiologic Study of Cystic Fibrosis 1994-2002 with ≥4 FEV 1 %pred measurements spanning ≥366 days in both a 2-year baseline period and a 2-year follow-up period. We predicted change from best baseline FEV 1 %pred to best follow-up FEV 1 %pred and change from baseline to best in the second follow-up year by using multivariable regression stratified by 4 lung-disease stages. We assessed 5 measures of variability (some as deviations from the best and some as deviations from the trend line) both alone and after controlling for demographic and clinical factors and for the slope and level of FEV 1 %pred. Results All 5 measures of FEV 1 %pred variability were predictive, but the strongest predictor was median deviation from the best FEV 1 %pred in the baseline period. The contribution to explanatory power (R 2 ) was substantial and exceeded the total contribution of all other factors excluding the FEV 1 %pred rate of decline. Adding the other variability measures provided minimal additional value. Conclusions Median deviation from the best FEV 1 %pred is a simple metric that markedly improves prediction of FEV 1 %pred decline even after the inclusion of demographic and clinical characteristics and the FEV 1 %pred rate of decline. The routine calculation of this variability measure could allow clinicians to better identify patients at risk and therefore in need of increased intervention.

Background Vitamin D deficiency is common in CF. Whether vitamin D affects pulmonary function in CF is unknown. Methods Data were abstracted from clinically stable CF patients who had pulmonary function studies and serum 25-hydroxyvitamin D [25(OH)D, ng/ml] levels drawn within 2months of each other. Findings were adjusted for multiple variables known to affect pulmonary function in CF. Results Enrollees totaled 597. Overall mean 25(OH)D level was 29.6±12.8ng/ml (SD). Serum 25(OH)D levels showed a significant correlation with forced expiratory volume in 1s (FEV 1 ) % predicted ( r =0.20, p r =0.13, p=0.0019). Multivariate analysis revealed that serum 25(OH)D remained an independent predictor of FEV 1 % predicted even after controlling for multiple other factors known to affect CF lung function. Conclusions Serum 25(OH)D levels are significantly associated with pulmonary function in CF. Further study is required to determine whether this association is causal.

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or

The number of patients with cystic fibrosis (CF) whose sputum culture has yielded Stenotrophomonas maltophilia has increased in the last 5 years at St. Christopher's Hospital for Children. We conducted a case-control study to determine risk factors for recovery of S. maltophilia in respiratory secretions from patients with CF. We reviewed the outpatient and inpatient records of patients colonized with S. maltophilia between 1993 and 1997, and of age-matched (at time of initial recovery of S. maltophilia) control patients with CF who had never had a positive sputum culture for S. maltophilia. Variables included age at time of CF diagnosis, gender, severity of CF (based on Shwachman-Kulczycki (S-K) scores and spirometry), frequency of hospitalizations, use of oral, intravenous, or inhaled antibiotics, and use of oral or inhaled corticosteroids in the 2 years prior to the first isolation of S. maltophilia from respiratory secretions. Statistical methods included stepwise logistic regression to determine risk factors for acquisition of S. maltophilia. During the study period, 58 patients with CF had a positive sputum or deep throat culture for S. maltophilia. The distribution of S. maltophilia acquisition by year increased from 7 patients in 1993 (incidence, 2.8%) to 16 in 1997 (incidence, 6.2%). Patients positive for S. maltophilia were found to have significantly worse growth parameters, S-K score, and spirometric values than S. maltophilia-negative CF controls (P < 0.05). Stepwise logistic regression demonstrated that treatment with long-term antibiotics (P = 0.0016) and number of days of intravenous antibiotic therapy (P = 0.035) were significant risk factors for S. maltophilia colonization in our group of CF patients. We conclude that patients with CF whose respiratory secretions yield S. maltophilia have an overall worse clinical status at the time of initial S. maltophilia isolation than noncolonized patients, and that preceding treatment with antibiotics may have predisposed them to the acquisition of this bacterium in their respiratory secretions.

Pulse oximetry is a noninvasive method of measuring oxyhemoglobin saturation. The validity of pulse oximetry in sickle cell disease (SCD) has been questioned. We evaluated pulse oximetry, arterial blood gas analysis, and co-oximetry in patients with SCD, and we assessed the effect of dyshemoglobin and altered blood-oxygen affinity on their accuracy. Sixteen patients with SCD aged 7-21 years had arterial and venous blood drawn and transcutaneous pulse oximetry performed. Oxyhemoglobin dissociation curves were plotted from the venous blood of 15 patients. Oxyhemoglobin saturation estimated by arterial blood gas analysis (SaO(2)) and measured by pulse oximetry (SpO(2)) were both higher than the saturation by co-oximetry (FO(2)Hb) (mean +/- SD = 96.3 +/- 1.6%, 94 +/- 3.1%, and 89.1 +/- 3.8%, respectively). There was a significant, positive correlation between SpO(2) and FO(2)Hb (r = 0.7, P = 0.002). The patients had elevated levels of methemoglobin (MetHb) and carboxyhemoglobin (COHb) (2.3 +/- 1.4% and 4.7 +/- 1.3%, respectively). The oxyhemoglobin dissociation curves were frequently shifted to the right with oxygen tensions elevated when hemoglobin was 50% saturated with oxygen (P(50)) (32.5 +/- 4.5 mm Hg). There was a strong correlation between the amounts of dyshemoglobin (MetHb + COHb) and the difference between SaO(2) and FO(2)Hb (r = 0.7, P = 0.002). There was no correlation between the difference between SaO(2) and FO(2)Hb and the P(50) (r = 0.27, P = 0.33) There was also a strong positive correlation between SaO(2)-SpO(2) and dyshemoglobin fraction (r = 0.77, P = 0.001). We conclude that pulse oximetry and arterial blood gas analysis overestimate oxygen saturation when compared to co-oximetry, but that SpO(2) is consistently closer than SaO(2) to FO(2)Hb. SpO(2) is partially affected by MetHb and COHb. The discrepancy between SaO(2) and FO(2)Hb is due to the presence of dyshemoglobin and a shifted oxyhemoglobin dissociation curve, but the effect from dyshemoglobin predominates.

Oxyhemoglobin desaturation in patients with sickle cell disease has been proposed as a possible mechanism in the initiaton of vasco-occlusive pain crises. Nocturnal oxyhemoglobin desaturation (NOD) has been described with a prevalence of up to 40% in children and adolescents with sickle cell disease. The objective of this study was to evaluate the mechanisms of nocturnal oxyhemoglobin desaturation in sickle cell disease and determine the role of obstructive sleep apnea. We performed 16-channel polysomnograms and pulmonary function testing in 20 patients with sickle cell disease (ages 7-21 years) who had documented desaturation on home oximetry studies. The median saturation awake was 94% (quartile range, 88-95). Median saturation during REM sleep was 93.5% (88-95) and during non-REM sleep 93.5% (87.5-95). The median respiratory disturbance index was low (1.35 quartile range, 0.25-2.85). Twelve patients had no obstructive apnea recorded, while 3 patients had a total of 9 or 10 episodes during the entire study. The median snoring time was 5. 65% of total sleep time (quartile range, 1.35-22.65). There was no correlation between number of obstructive apneas and mean sleeping saturation (r = 0.012, p = 0.95). There was no correlation between pulmonary function data and prevalence of NOD. There was a strong, positive correlation between sleeping and awake saturation (r = 0.96, p < 0.001). We conclude that while nocturnal oxyhemoglobin desaturation may be common in children and adolescents with sickle cell disease, upper airway obstruction does not appear to play an important role in its genesis.

Progressive restrictive defect with increasing age, obstructive lung disease, and bronchodilator responsiveness have been reported in sickle cell disease (SCD). Because airway hyperreactivity (AHR) can be underestimated when assessed by bronchodilator responsiveness in patients with normal baseline lung function, the aim of this study was to investigate the prevalence of AHR in SCD by cold-air bronchial provocation testing, and to assess whether AHR can be present in symptom-free patients with SCD. Forty patients aged 6 to 19 years (mean, 10.7 years ± 3.5 SD) performed pulmonary function tests. Eighteen were known to have a history of reactive airway disease (RAD group), and 22 had no known history of RAD (non-RAD group). A control group, aged 6 to 17 years (mean, 10.5 ± 3.1 years), consisted of 10 siblings of the non-RAD SCD group. There were no significant differences in age and height among the groups. If the forced expiratory volume in 1 second (FEV 1 ) was greater than 70%, cold air challenge (CACh) was performed; if the FEV 1 was less than 70%, aerosolized bronchodilator therapy was given. A decrease in FEV 1 of more than 10% after CACh or an increase in FEV 1 of 12% or greater after bronchodilator inhalation was considered evidence of AHR. In the RAD group, the total lung capacity was 88.9% ± 14.0% of race-corrected predicted values, the forced vital capacity was 91.2% ± 12.6%, and FEV 1 was 85.3% ± 16.2%. The mean maximal percent fall in FEV 1 after CACh ( n = 13) was 18.5% ± 9.6% and was greater than 10% in 11 of 13 patients. The mean increase in FEV 1 after bronchodilator therapy ( n = 5) was 11.5% ± 8.3%, and it was greater than 12% in 4 of 5 patients. In the non-RAD group the baseline total lung capacity was 101.6% ± 11.7%, forced vital capacity was 95.5% ± 10.2%, and FEV 1 was 93.3% ± 13.2%. The mean maximal percent fall in FEV 1 after CACh ( n = 19) was 14.1% ± 8.8% and was greater than 10% in 13 of 19 patients. The mean increase in FEV 1 after bronchodilator therapy ( n = 3) was 14.7% ± 11.3%, and was 12% or greater in 1 of 3 patients. In the control group the baseline total lung capacity was 105.7% ± 12.1%, forced vital capacity was 96.2% ± 11.1%, and FEV 1 was 92.9% ± 10.3%. The mean maximal percent fall in FEV 1 was 5.0% ± 2.5%, and was greater than 10% in none of 10 patients. The prevalence of AHR in the control group, the RAD group, and the non-RAD group was zero, 83%, and 64%, respectively ( p

Cystic fibrosis (CF) patients are often treated with aminoglycoside (AG) antibiotics during infective pulmonary exacerbations. Achieving pharmacokinetic and pharmacodynamic (PK/PD) targets to improve outcomes and counteract resistance is paramount.The primary objective was to compare the number of pediatric CF patients achieving AG PK/PD targets when a clinical pharmacist (CP) managed therapeutic drug monitoring (TDM) compared with usual care (UC).A retrospective cohort study was conducted on the records of 40 CF patients that received AGs and ≥2 serum samples between 1/2007 and 5/2009. Chi-square and Student's t-test were used to analyze nominal and continuous variables, respectively.Twenty-nine patients with 52 courses of AGs were included the CP group, and 22 patients with 42 courses were included the UC group. Ninety-eight percent of patients in the CP group reached AG PK/PD targets compared with 71% in the UC group, P 0.001. Patients in the CP group reached the AG PK/PD target in a mean of 1.9 ± 0.8 days compared with 4.8 ± 3.4 days in the UC group, P 0.0001. The average LOS in the CP group was 9 ± 5 days compared with 12 ± 7.5 days in the UC group, P = 0.033. The mean number of levels per patient was 2.7 in the CP group compared with 5.2 (range of 2-20) in the UC group, P 0.001. Resource utilization associated with drug levels, dosing adjustments and LOS were $26,549, $14,069, and $1,680,000 in the CP group as compared with $40,683, $27,812, and $1,940,000, respectively, in the UC group.CP managed TDM resulted in a significantly higher percentage of pediatric CF patients achieving AG PK/PD targets 3 days sooner with an average LOS that was 3 days shorter. CP managed TDM resulted in significantly fewer dosage adjustments, drug levels, and cost associated with serum sampling, drug wastage, and LOS.

Congenital anomalies of the right main bronchi have not been fully described. Bronchial anomalies are usually asymptomatic unless they coexist with other abnormalities. We describe a rare bronchial anomaly in a 2-month-old girl in which the right upper lobe, middle lobe, and lower lobe bronchi all originated at the same point as a result of a developmental teratogenic long right main bronchus and an absent bronchus intermedius. Furthermore, the left main bronchus contained a proximal segment of stenosis. This combination of anomalies, along with right upper lobe atelectasis and left-sided hyperinflation, resulted in a severe right mediastinal shift and respiratory distress. The mediastinum was returned to midline with endoscopic placement of an in-dwelling tracheobronchial stent into the left main bronchus. To the best of our knowledge, the specific developmental anomaly in our patient has not been previously described.

We describe the development and psychometric properties of a survey tool designed to evaluate children's level of independence in their cystic fibrosis (CF) treatment. Children's self-care autonomy is important to measure and may have a direct effect on children's active involvement in their treatment and their adherence. Existing instruments that evaluate children's independence in their CF treatment fail to yield practical information that can help research and patient management. The Self-Care Independence Scale (SCIS) is a 44-item questionnaire that is completed by parents. The SCIS was completed by the parents of 76 patients with CF (ages 4-17 years). Youths completed two structured interviews, which screened patients for average or higher cognitive functioning (an inclusion criterion) and measured their CF treatment knowledge. Parents completed two other self-report questionnaires. Results indicated that the SCIS has acceptable internal consistency and good test-retest reliability. The construct validity of the SCIS was supported by positive correlations between patient age, number of years since diagnosis, and SCIS total scores. The concurrent validity of the SCIS was supported by correlations between a measure of nonillness-specific dependence and a measure of patient self-care knowledge. Children's SCIS total scores per age group are presented. This study supports the SCIS as a psychometrically sound measure of self-care independence in CF. This measure has several uses. For example, the SCIS may be a screening tool for adolescents who are preparing to transition to adult CF centers and who will need to assume more independence in their self-care. The SCIS may also be used to evaluate educational programs that promote self-care knowledge and skill in children with CF.

A third generation, purified fusion protein (PFP-3) vaccine was developed to prevent severe respiratory syncytial virus (RSV) disease in high-risk groups. A phase II, multi-center, adjuvant-controlled trial was performed in RSV seropositive children with cystic fibrosis (CF); 151 received the adjuvant-control and 143 received the vaccine. Details of the vaccine-induced immune response are presented. At enrollment, RSV-specific, serum antibodies were comparable between both groups. A highly sensitive and specific serum antibody vaccine profile was established for the PFP-3 vaccine. At post-vaccination and end-of-study, RSV-specific, neutralizing antibody (Nt Ab) and binding antibody (Bd Ab) to the fusion (F) protein were significantly higher in PFP-3 vaccinees. After 28 days post-vaccination, Nt Ab and Bd Ab to F protein titers declined slowly at rates of 0.23 and 0.37 log2 per month, respectively. The PFP-3 vaccine-induced a robust immune response that lasted throughout the RSV season.

Cystic fibrosis is the most common autosomal recessive fatal disease among whites. Life expectancy is now at 31 years of age. The major cause of morbidity and mortality is chronic progressive lung disease. Lung disease occurs early in cystic fibrosis, suggesting the need for early and aggressive treatment of any pulmonary symptoms and malnutrition. This treatment is ideally performed within a cystic fibrosis center, and new therapies are being sought for management of the early stages of disease.