The role of microRNAs in chronic pseudomonas lung infection in Cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is the most common life limiting genetic disorder, characterized by chronic respiratory failure secondary to inflammation and chronic bacterial lung infection. Pseudomonas aeruginosa lung infection is associated with more severe lung disease and rapid progression of respiratory failure when compared to Staphylococcus aureus infection. We hypothesized that a specific signature of epigenetic factors targeting specific gene transcripts contributes to the increased morbidity seen in CF patients with chronic Pseudomonas infection. METHODS: We collected exhaled breath condensate (EBC) from 27 subjects and evaluated miRNA signatures in these samples using commercial PCR array. We identified predicted mRNA targets and associated signaling pathways using Ingenuity Pathway Analysis. RESULTS: We found 11 differentially expressed miRNAs in EBC of patients infected with Pseudomonas aeruginosa compared to EBC from CF patients who were not chronically infected with Pseudomonas aeruginosa (p < 0.05). Six of these miRNAs (hsa-miRNA-1247, hsa-miRNA-1276, hsa-miRNA-449c, hsa-miRNA-3170, hsa-miRNA-432-5p and hsa-miR-548) were significantly different in the CF Pseudomonas positive group when compared to both the CF Pseudomonas negative group and healthy control group. Ingenuity pathway analysis (IPA) revealed organismal injury and abnormalities, reproductive system disease and cancer as the top diseases and bio functions associated with these miRNAs. IPA also detected RELA, JUN, TNF, IL-10, CTNNB1, IL-13, SERPINB8, CALM1, STARD3NL, SFI1, CD55, RPS6KA4, TTC36 and HIST1H3D as the top target genes for these miRNAs. CONCLUSION: Our study identified 6 miRNAs as epigenetic factors specifically associated with chronic Pseudomonas infection in patients with CF.

Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial.

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence. OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence. METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial in children with CF, 6 months to 18 years of age, with early Pa. Azithromycin or placebo was given 3× weekly with standardized TIS. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the time to pulmonary exacerbation requiring antibiotics and the secondary endpoint was the time to Pa recurrence, in addition to other clinical and safety outcomes. A total of 221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the NHLBI because the trial had reached the prespecified interim boundary for efficacy. The risk of pulmonary exacerbation was reduced by 44% in the azithromycin group as compared with the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.37-0.83; P = 0.004). Weight increased by 1.27 kg in the azithromycin group compared with the placebo group (95% confidence interval, 0.01-2.52; P = 0.046). No significant differences were seen in microbiological or other clinical or safety endpoints. CONCLUSIONS: Azithromycin was associated with a significant reduction in the risk of pulmonary exacerbation and a sustained improvement in weight, but had no impact on microbiological outcomes in children with early Pa. Clinical trial registered with clinicaltrials.gov (NCT02054156).

Vitamin D deficiency is associated with pulmonary dysfunction in cystic fibrosis.

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 2 months 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±12.8 ng/ml (SD). Serum 25(OH)D levels showed a significant correlation with forced expiratory volume in 1s (FEV1) % predicted (r=0.20, p<0.0001) and forced vital capacity % predicted (r=0.13, p=0.0019). Multivariate analysis revealed that serum 25(OH)D remained an independent predictor of FEV1 % 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.

Efficacy and safety of a unique enteric-coated bicarbonate-buffered pancreatic enzyme replacement therapy in children and adults with cystic fibrosis.

BACKGROUND: Pancreatic enzyme replacement therapy (PERT) is used to treat exocrine pancreatic insufficiency in cystic fibrosis. RESULTS/METHODS: Efficacy and safety of a unique enteric-coated (EC) bicarbonate-buffered PERT product (PERTZYE®/PANCRECARB®; Digestive Care, Inc., Bethlehem, PA, USA) was studied in a randomized, double-blind, placebo-controlled cross-over design. Subjects were stabilized on EC-bicarbonate-buffered PERT and a high-fat diet. During two treatment periods, subjects were randomized to EC-bicarbonate-buffered PERT or placebo, followed by a 72-h stool collection employing an ingested stool dye marker. Mean coefficient of fat absorption with EC-bicarbonate-buffered PERT was 82.5% compared with 46.3% with the placebo (absolute difference 36.2%; p < 0.001), a 78.2% improvement for active over placebo. Similar improvements in nitrogen absorption were observed. Overall stool frequency and stool weight decreased (p < 0.001). No safety concerns were identified. SUMMARY: EC-bicarbonate-buffered PERT is effective in treating cystic fibrosis-associated exocrine pancreatic insufficiency.

Baseline characteristics and factors associated with nutritional and pulmonary status at enrollment in the cystic fibrosis EPIC observational cohort.

SUMMARY BACKGROUND: The EPIC Observational Study is an ongoing prospective cohort study investigating risk factors for and clinical outcomes associated with early Pseudomonas aeruginosa (Pa) acquisition in young children with cystic fibrosis (CF). OBJECTIVES AND HYPOTHESIS: To describe the baseline characteristics of the cohort and evaluate associations between potential risk factors and nutritional and respiratory characteristics at enrollment. We hypothesized that distinct demographic and environmental risk factors could be identified for poorer nutritional status and lung function at enrollment. METHODS: During 2004-2006, 1,700 children with CF were enrolled at 59 US CF centers. Children

Safety and tolerability of a new formulation of pancrelipase delayed-release capsules (CREON) in children under seven years of age with exocrine pancreatic insufficiency due to cystic fibrosis: an open-label, multicentre, single-treatment-arm study.

Exocrine pancreatic insufficiency (EPI) is a deficiency of digestive enzymes caused by diseases such as cystic fibrosis (CF). Patients with EPI due to CF require pancreatic enzyme replacement therapy (PERT) in order to maintain adequate nutrition. A new formulation of pancrelipase delayed-release capsules (CREON) recently received US FDA approval and has demonstrated efficacy and safety in patients with CF aged > or =7 years. The objectives of this study were to observe the safety and tolerability of new formulation pancrelipase delayed-release capsules (study drug) versus the standard of care PERT (standard therapy) in children aged <7 years with CF and EPI. Secondary objectives were to assess the ease of accurate dosing of study drug, monitor clinical symptoms and compare the efficacy of both treatments. This was an open-label, multicentre, single-treatment-arm study in children aged <7 years with a confirmed diagnosis of CF and EPI. After the screening period (approximately 14 days), all patients entered a 3-day assessment period on their usual PERT (standard therapy), followed by the study drug treatment phase (10-14 days; target dose 8000 lipase units/kg bodyweight/day), which included a second 3-day assessment period. The safety and tolerability of both treatments were documented by recording adverse events (AEs). Clinical symptoms (mean daily stool frequency, abdominal pain, stool consistency and flatulence) were monitored and ease of accurate dosing, as judged by caregivers, was reported. Efficacy was determined by comparison of percent stool fat in spot stool samples collected during both 3-day assessment periods. Of the 19 patients who had informed consent from their parent/legally acceptable representative, one was withdrawn as a screen failure and was excluded from the safety and efficacy analyses; thus, 18 patients completed the study. The median age (range) was 23 (4-71) months and 13 (72%) were male. During study drug treatment, patients received a mean +/- SD dose in lipase units/kg bodyweight/day of 7542 +/- 1335 versus 6966 +/- 3392 on standard therapy. Overall, nine (50%) patients had at least one treatment-emergent AE (TEAE) whilst receiving either treatment. All TEAEs in this study were reported as mild and none resulted in patient discontinuation. The caregivers had a slight preference for study drug over standard therapy in terms of ease of accurate dosing: six (33.3%) caregivers thought the study drug was easier to dose while only one (5.6%) thought the study drug was harder to dose than standard therapy. Clinical symptom assessment results were similar between treatments. There was no clinically meaningful difference (significance not tested) between study drug and standard therapy in the mean +/- SD percent of stool fat: 28.1 +/- 9.9 and 27.9 +/- 8.9, respectively. In this study in children aged <7 years with EPI due to CF, the new formulation pancrelipase delayed-release capsules (CREON) were clinically comparable with standard therapy in terms of safety, tolerability and efficacy.

Efficacy and tolerability of a new formulation of pancrelipase delayed-release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency and cystic fibrosis: a multicenter, randomized, double-blind, placebo-controlled, two-period crossover, superiority study.

BACKGROUND: Pancreatic enzyme replacement therapy (PERT) is essential for maintaining adequate nutrition in children with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). The US Food and Drug Administration regulations now require all PERT products to undergo clinical efficacy and safety studies before they can be considered for marketing approval. OBJECTIVE: This study was conducted to compare the efficacy of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules with placebo in children with EPI due to CF. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, 2-period crossover, superiority study of the new formulation of pancrelipase delayed-release 12,000-lipase unit capsules in children aged 7 to 11 years with CF and EPI. In each period, pancrelipase or identical placebo capsules were taken for 5 days. The primary outcome measure was the coefficient of fat absorption (CFA); secondary outcome measures were the coefficient of nitrogen absorption (CNA) and clinical symptoms. The latter were assessed based on patient-reported daily stool frequency, stool consistency (hard, formed/normal, soft, or watery), flatulence (none, mild, moderate, or severe), and abdominal pain (none, mild, moderate, or severe). Safety measures included vital signs, physical examinations, standard laboratory safety tests (hematology and biochemistry), and adverse events. RESULTS: Seventeen patients were randomized to treatment and 16 completed the study; 1 patient withdrew consent during the first treatment period and was not included in the efficacy analysis. Patients' median age was 8.0 years (range, 7-11 years); 12 patients (70.6%) were male. CFA values were significantly greater for pancrelipase compared with placebo, with least squares mean (SE) values of 82.8% (2.7%) and 47.4% (2.7%), respectively (P < 0.001). The results were similar for CNA, with mean values of 80.3% (3.2%) and 45.0% (3.2%) (P < 0.001). Pancrelipase treatment had significantly greater effects on CFA and CNA in patients with a placebo CFA <50% than in those with a placebo CFA >50% (both parameters, P < 0.001 and P = 0.008, respectively). Significant improvements in stool fat, weight, and nitrogen and a significant reduction in daily stool frequency were observed with pancrelipase compared with placebo (all, P < 0.001). Symptoms of EPI were less severe and remained relatively stable during pancrelipase treatment, but worsened slightly during receipt of placebo. Treatment-emergent adverse events were reported in 5 patients (29.4%) during receipt of pancrelipase and in 9 patients (56.3%) during receipt of placebo; these were predominantly gastrointestinal events. There were no discontinuations due to treatment-emergent adverse events and no serious adverse events. CONCLUSIONS: In this study in children with EPI due to CF, the new formulation of pancrelipase delayedrelease capsules was associated with improvements in CFA, CNA, stool properties, and EPI symptoms compared with placebo. Pancrelipase delayed-release capsules appeared to be well tolerated. ClinicalTrials.gov identifier: NCT00690820. (Clin Ther.

Efficacy and Safety of a New Formulation of Pancrelipase (Ultrase MT20) in the Treatment of Malabsorption in Exocrine Pancreatic Insufficiency in Cystic Fibrosis.

Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (PI). Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in patients with CF and PI. Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs), and overall signs and symptoms. Methods. Patients (n = 31) were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared. Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp., P < .0001 for both), reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE. Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.

Efficacy and safety of Creon 24,000 in subjects with exocrine pancreatic insufficiency due to cystic fibrosis.

BACKGROUND: Pancreatic enzyme replacement therapy is critical for adequate nutrition in cystic fibrosis (CF) patients with exocrine pancreatic insufficiency (EPI). METHODS: This was a double-blind, randomised, placebo-controlled, two-period crossover study assessing efficacy and safety of Creon 24,000-unit capsules in CF subjects > or =12 years with EPI. Patients were randomised to one of two 5-day sequences, Creon/placebo or placebo/Creon (target dose, 4000 lipase units/g fat). Primary outcome was the coefficient of fat absorption (CFA); secondary outcomes were coefficient of nitrogen absorption (CNA), symptoms, and safety. RESULTS: Thirty-two subjects were randomised. Mean CFA and CNA were significantly greater with Creon than placebo (CFA, 88.6% vs. 49.6%; CNA, 85.1% vs. 49.9%; p<0.001 for both). Symptoms were improved and fewer treatment-emergent adverse events were reported with Creon than placebo. One patient discontinued for weight loss unrelated to study drug. CONCLUSIONS: This study demonstrated Creon was effective in treating EPI due to CF and was safe and well tolerated.

Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health.

The human surfactant protein A (SP-A) locus consists of two functional genes (SP-A1, SP-A2) with gene-specific products exhibiting qualitative and quantitative differences. The aim here was twofold: 1) generate SP-A1 gene-specific antibody, and 2) use this to assess gene-specific SP-A content in the bronchoalveolar lavage fluid (BALF). An SP-A1-specific polyclonal antibody (hSP-A1_Ab(68-88)_Col) was raised in chicken, and its specificity was determined by immunoblot and ELISA using mammalian Chinese hamster ovary (CHO) cell-expressed SP-A1 and SP-A2 variants and by immunofluorescence with stably transfected CHO cell lines expressing SP-A1 or SP-A2 variants. SP-A1 content was evaluated according to age and lung status. A gradual decrease (P < 0.05) in SP-A1/SP-A ratio was observed in healthy subjects (HS) with increased age, although no significant change was observed in total SP-A content among age groups. Total SP-A and SP-A1 content differed significantly between alveolar proteinosis (AP) patients and HS, with no significant difference observed in SP-A1/SP-A ratio between AP and HS. The cystic fibrosis (CF) ratio was significantly higher compared with AP, HS, and noncystic fibrosis (NCF), even though SP-A1 and total SP-A were decreased in CF compared with most of the other groups. The ratio was higher in culture-positive vs. culture-negative samples from CF and NCF (P = 0.031). A trend of an increased ratio was observed in culture-positive CF (0.590 +/- 0.10) compared with culture-positive NCF (0.368 +/- 0.085). In summary, we developed and characterized an SP-A1 gene-specific antibody and used it to identify gene-specific SP-A content in BALFs as a function of age and lung health.

Validation study of fractional exhaled nitric oxide measurements using a handheld monitoring device.

We tested reproducibility of exhaled nitric oxide (FE(NO)) and inter-operator handling when measured with a handheld device, NIOX MINO. We enrolled 20 volunteers using a priori goals of acceptable reproducibility to be mean within-subject standard deviation less than 3 parts per billion (ppb) for FE(NO) measurements less than 30 ppb, and mean coefficient of variation less than 10% for FE(NO) measurements more than 30 ppb. Seventeen subjects with measurements less than 30 ppb displayed a mean standard deviation of 1.15, and 3 subjects with FE(NO) more than 30 ppb had a mean coefficient of variation of 2.4%. We conclude that NIOX MINO demonstrates excellent reproducibility for all ranges of FE(NO).

Comparative sequencing of the serine-aspartate repeat-encoding region of the clumping factor B gene (clfB) for resolution within clonal groups of Staphylococcus aureus.

Molecular techniques such as spa typing and multilocus sequence typing use DNA sequence data for differentiating Staphylococcus aureus isolates. Although spa typing is capable of detecting both genetic micro- and macrovariation, it has less discriminatory power than the more labor-intensive pulsed-field gel electrophoresis (PFGE) and costly genomic DNA microarray analyses. This limitation hinders strain interrogation for newly emerging clones and outbreak investigations in hospital or community settings where robust clones are endemic. To overcome this constraint, we developed a typing system using DNA sequence analysis of the serine-aspartate (SD) repeat-encoding region within the gene encoding the keratin- and fibrinogen-binding clumping factor B (clfB typing) and tested whether it is capable of discriminating within clonal groups. We analyzed 116 S. aureus strains, and the repeat region was present in all isolates, varying in sequence and in length from 420 to 804 bp. In a sample of 36 well-characterized genetically diverse isolates, clfB typing subdivided identical spa and PFGE clusters which had been discriminated by whole-genome DNA microarray mapping. The combination of spa typing and clfB typing resulted in a discriminatory power (99.5%) substantially higher than that of spa typing alone and closely approached that of the whole-genome microarray (100.0%). clfB typing also successfully resolved genetic differences among isolates differentiated by PFGE that had been collected over short periods of time from single hospitals and that belonged to the most prevalent S. aureus clone in the United States. clfB typing demonstrated in vivo, in vitro, and interpatient transmission stability yet revealed that this locus may be recombinogenic in a primarily clonal population structure. Taken together, these data show that the SD repeat-encoding region of clfB is a highly stable marker of microvariation, that in conjunction with spa typing it may serve as a DNA sequence-based alternative to PFGE for investigating genetically similar strains, and that it is useful for analyzing collections of isolates in both long-term population-based and local epidemiologic studies.

Patterns of helium-oxygen (heliox) usage in the critical care environment.

The objective of this study was to describe the patterns of heliox use in critical care units of an academic medical center. The design was a prospective case series involving 7 critical care units of an academic medical center. All patients receiving heliox therapy over a 4-year period were studied, with prospective recording of patient demographics and the location, mode, indication for, and duration of heliox use. Use pattern comparisons based on anatomic location (upper vs lower airway) and age group (pediatric vs adult) were performed by alpha(2) analysis and unpaired Student t test. Eighty-nine patients, aged 17.4 +/- 20.9 years, received heliox for 30.5 +/- 44.6 hours on 92 occasions. Pediatric (

Use of a remifentanil-propofol mixture for pediatric flexible fiberoptic bronchoscopy sedation.

BACKGROUND: Flexible fiberoptic bronchoscopy is an important diagnostic tool for pediatric pulmonologists. Because of its favorable respiratory profile, ketamine has become a popular sedative for this procedure, but may be associated with unpleasant emergence reactions in the older child. Remifentanil is a newer, ultra-short acting opioid that has been shown to provide effective sedation and cough suppression for fiberoptic bronchoscopy when combined with intermittent propofol boluses. However, delivery of these agents as a combined, single infusion has not been described. METHODS: Children > or =2 years of age undergoing fiberoptic bronchoscopy were enrolled. Remifentanil was mixed in a single syringe with undiluted propofol giving final drug concentrations of 10 mg x ml(-1) of propofol and 15-20 microg x ml(-1) of remifentanil. Sedation was induced with a bolus of approximately 0.1 ml x kg(-1) of this mixture and maintained by titrating the drip throughout the procedure. Vital signs, sedative effectiveness, recovery patterns, and complications were prospectively recorded. RESULTS: Fifteen patients aged 9.0 +/- 5.3 years were sedated. Sedation was induced with 1.2 +/- 0.4 mg x kg(-1) propofol (2.4 +/- 0.8 microg x kg(-1) remifentanil) and maintained with 4.1 +/- 1.8 mg x kg(-1) x h(-1) propofol (0.13 +/- 0.06 microg x kg(-1) x min(-1) remifentanil). Five patients received low-dose ketamine to augment sedation. The maximal decrease in respiratory rate was 6.1 +/- 5.3 b x min(-1) (27.6 +/- 21%) and no patient became hypoxemic. All procedures were completed easily without significant complication. Patients recovered to baseline 13.3 +/- 8.5 min following infusion discontinuation. CONCLUSIONS: A remifentanil/propofol mixture provided effective sedation and rapid recovery in pediatric patients undergoing fiberoptic bronchoscopy.

Safety and efficacy of ketamine sedation for infant flexible fiberoptic bronchoscopy.

OBJECTIVE: To describe our experience with ketamine sedation during infant flexible fiberoptic bronchoscopy. DESIGN: Retrospective chart review. Infants were sedated with midazolam and ketamine with or without fentanyl. The sedation regimen, final procedure performed, procedure duration, and complications were recorded. Complication rates between infants 6 months of age and between infants with upper vs lower airway symptoms were compared by chi(2) test with a contingency table. RESULTS: Fifty-nine procedures were performed in 55 patients aged 6.1 +/- 3.1 months (mean +/- SD). Sedation was achieved with ketamine and midazolam (n = 30) or ketamine, midazolam, and fentanyl (n = 29). Bronchoscopy with BAL was performed in 44 patients and bronchoscopy alone in 3 patients. In 11 patients, severe upper airway obstruction and/or anomalies prevented subglottic passage of the bronchoscope. One patient could not be adequately sedated. There were no major complications. Minor complications occurred in 14 patients (23.7%), most commonly mild hypoxemia (n = 9). Brief central apnea developed in three patients. Complication rates were unaffected by age or indication for bronchoscopy. CONCLUSIONS: Infant flexible fiberoptic bronchoscopy can be safely and effectively performed using ketamine sedation. Complications, especially mild hypoxemia, appear more common in infants, likely due to smaller airway diameter. Regardless of the sedative(s) used, additional vigilance is required when performing bronchoscopy in this population.

Aortic hiatus gastric hernia.

Congenital diaphragmatic hernias are a relatively common anomaly that can present with significant respiratory morbidity and mortality. We report on a case of an aortic-hiatal gastric hernia that initially presented with repeated episodes of respiratory distress, which was diagnosed as asthma. The diagnosis of a diaphragmatic hernia was made at 18 months of age. In the operating room, it was noted that it was an aortic hiatal hernia, which was surgically repaired. Subsequently, there has been improvement in daily respiratory symptoms.

Administration of the first dose of palivizumab immunoprophylaxis against respiratory syncytial virus in infants before hospital discharge: what is the evidence for its benefit?

BACKGROUND: Palivizumab is 1 of 2 agents used to prevent severe lower respiratory tract disease due to respiratory syncytial virus (RSV) infection. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend administering the first dose of RSV immunoprophylaxis to eligible infants before hospital discharge. Unfortunately, third-party payers frequently do not separately reimburse administration of this therapy to hospitalized infants. OBJECTIVE: Because palivizumab is commonly used to provide RSV immunoprophylaxis, we systematically reviewed all published data on this drug to determine whether the evidence supports the recommendation of administering the first dose before hospital discharge. METHODS: MEDLINE was searched for all articles published in English from January 1, 1996, to October 31, 2003, using the search terms palivizumab and Synagis, and the following data were extracted onto a standardized form: author(s), year of publication, study design, patient population, sample size, criteria used for administration of RSV prophylaxis, location of palivizumab prophylaxis (inpatient or outpatient), parental satisfaction with administration of prophylaxis, incidence of RSV infection, and hospitalization rates for RSV. All selected publications were reviewed to determine whether they reported differences in the incidence of RSV infection or hospitalization in patients who received palivizumab before discharge compared with those who received it after discharge. Only those publications that specifically documented administration of the first dose of palivizumab before hospital discharge were included in the final analysis. RESULTS: Six of the 166 studies reviewed met the selection criteria. Although all 6 studies reported reduced RSV hospitalization rates with palivizumab prophylaxis, no study directly compared inpatient and outpatient administration with regard to parental satisfaction or rates of RSV infection or hospitalization. Furthermore, based on the data in these studies, it was not possible to detect any differences in parental satisfaction or rates of RSV infection or hospitalization between the 2 locations of administration. CONCLUSIONS: Based on our literature review, there is no evidence to support the recommendation that palivizumab be administered before hospital discharge in every infant who meets the criteria for RSV immunoprophylaxis. Eligible infants may be given the initial dose of RSV prophylaxis as outpatients, reducing the cost to institutions that currently provide palivizumab before hospital discharge.

Nebulized fentanyl for palliation of dyspnea in a cystic fibrosis patient.

Dyspnea, the subjective symptom feeling of breathlessness, is a common symptom in terminally ill patients with cystic fibrosis (CF). The palliation of the dyspnea is a reasonable goal to improve patient comfort as the progression of the disease worsens. We report the successful use of inhaled fentanyl for 3 days in a 17-year-old female with terminal CF lung disease, as measured by improved oxygenation and a reduction in the modified Borg score, and the subjective feeling of less air hunger reported by parents and patient.

Internet-enabled interactive multimedia asthma education program: a randomized trial.

OBJECTIVE: To determine whether health outcomes of children who have asthma can be improved through the use of an Internet-enabled interactive multimedia asthma education program. METHODS: Two hundred twenty-eight children with asthma visiting a pediatric pulmonary clinic were randomly assigned to control and intervention groups. Children and caregivers in both groups received traditional patient education based on the National Asthma Education and Prevention Program. Intervention group participants received additional self-management education through the Interactive Multimedia Program for Asthma Control and Tracking. Pediatric Asthma Care Knowledge Survey, Pediatric Asthma Caregiver's Quality of Life Questionnaire, asthma symptom history, spirometry, and health services utilization data were collected at the initial visit and at 3 and 12 months. RESULTS: Interactive Multimedia Program for Asthma Control and Tracking significantly increased asthma knowledge of children and caregivers, decreased asthma symptom days (81 vs 51 per year), and decreased number of emergency department visits (1.93 vs 0.62 per year) among the intervention group participants. The intervention group children were also using a significantly lower average daily dose of inhaled corticosteroids (434 vs 754 micro g [beclomethasone equivalents]) at visit 3. Asthma knowledge of all 7- to 17-year-old children correlated with fewer urgent physician visits (r = 0.37) and less frequent use of quick-relief medicines (r = 0.30). CONCLUSIONS: Supplementing conventional asthma care with interactive multimedia education can significantly improve asthma knowledge and reduce the burden of childhood asthma.