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Previous studies have demonstrated altered immune response following exercise in healthy adults and children. As data are lacking in children with cystic fibrosis, we evaluated the immune response following acute exercise and hypothesized that acute increases in cellular changes would be seen but would be blunted in subjects with CF. Leukocytes, lymphocytes, and their subsets as well as natural killer cell number and activity were determined before, immediately after, and one hour post exhaustive exercise in 15 children with cystic fibrosis (8-21 yrs, FEV 1 69.5 ± 18.0%, colonized with P. aeruginosa) and 15 healthy controls (8 - 18 yrs, FEV 1 107.5 ± 10.7%). At baseline the cystic fibrosis group had greater leukocytes (9.25 ± 2.83 vs. 5.17 ± 0.96 × 10 9 cells/liter). Immediately post exercise, the cystic fibrosis group demonstrated increases in cell counts for leukocytes (32.4%), lymphocytes (61.8%), granulocytes (36.4%), monocytes (76.2%), and natural killer cells (315%). Similar percentage increases were seen in cell counts for the controls (leukocytes: 39.5%, lymphocytes: 78.5%, granulocytes: 32.0%, monocytes: 75.9%, and NK cells: 442%). Natural killer cell activity also increased by 57.9% in the group with cystic fibrosis and by 43.6% in the healthy controls. Except for elevated leukocyte and granulocyte counts, values returned to baseline at one hour post-exercise. In conclusion, the cellular immune response to acute exercise in children with mild to moderate cystic fibrosis appears normal.

Surfactant replacement therapy (SRT) has been in widespread clinical use for the prevention and treatment of respiratory distress syndrome (RDS) in premature infants for nearly a decade. There is no question that the use of surfactant preparations has had a significant positive impact on survival and quality of life for premature infants; however, chronic lung disease continues to develop in a significant number of premature infants. The reasons underlying this finding, an update on research regarding surfactant preparations, and a review of long-term sequelae of neonatal chronic lung disease are the subjects of this article. Surfactant therapy was last reviewed in the Pediatric Clinics of North America in October 1993. 52 The topic of surfactant's impact on chronic lung diseases in premature infants was reviewed in Clinics in Perinatology in September 1992. 36 This review is an extension of these observations,incorporating new literature and observations in practice.

a) To determine the need for intensive monitoring on the first operative night of surgery in children undergoing adenotonsillectomy for mild obstructive sleep apnea; b) to examine the effect of narcotics on postoperative obstructive sleep apnea.Randomized, prospective study.University hospital.Children, ranging in age between 1 and 18 yrs, presented to the Pediatric Otolaryngology Clinic for adenotonsillectomy for mild obstructive sleep apnea defined as from one to 15 obstructive apnea events per hour on preoperative polysomnogram.Patients were assigned to receive either a narcotic- or a halothane-based anesthetic for adenotonsillectomy. A postoperative polysomnogram was performed in the pediatric intensive care unit on the first operative night.Eighteen patients were recruited, 15 of whom met inclusion criteria: nine patients received a halothane-based anesthetic and six patients received a fentanyl-based anesthetic. When the data were analyzed by pooling both groups, the differences between pre- and postoperative sleep studies demonstrated a reduction in the number of obstructive events and less severe oxygen desaturations on the operative night. Total sleep time between the two sleep studies decreased from 371 +/- 13 to 304 +/- 14 mins. The number of obstructive apnea events/hr decreased as well. The lowest oxygen saturation measured during rapid eye movement sleep was 78 +/- 5% preoperatively and 92 +/- 1% postoperatively.Our data suggest that children without underlying medical conditions, neuromotor diseases, or carniofacial abnormalities, 1 to 18 yrs of age, who suffer from mild obstructive sleep apnea, have improvements documented by polysomnography on the night of surgery following adenotonsillectomy and do not necessarily need to be monitored intensively. These findings were not significantly affected by the choice of intraoperative anesthetic.

Study objective To determine whether primary snoring (PS) could be distinguished from childhood obstructive sleep apnea syndrome (OSAS) by clinical history. Design Retrospective study of clinical history of 83 children with snoring and/or sleep disordered breathing who were referred for polysomnography. Setting Tertiary referral center; pediatric pulmonary sleep apnea clinic. Measurements We evaluated the ability of a clinical obstructive sleep apnea (OSA) score and other questions about sleep, breathing, and daytime symptoms to distinguish PS from OSAS in children. Parents were asked about the child's snoring, difficulty breathing, observed apnea, cyanosis, struggling to breathe, shaking the child to "make him or her breathe," watching the child sleep, afraid of apnea, the frequency and loudness of snoring, and daytime symptoms such as excessive daytime sleepiness (EDS). Results Based on polysomnography results, 48 patients were classified as PS and 35 as OSAS. Peak end-tidal CO 2 (49 ± 3.2 vs 55 ± 8.2 [SD] mm Hg); lowest arterial oxygen saturation measured by pulse oximetry (95 ± 1.9 vs 82 ± 14%); and apnea/hypopnea index (0.27 ± .3 vs 8.4 ± 6 events/h) indicated that the diagnostic criteria for PS versus OSA were reasonable. There were no differences between PS and OSA patients with respect to age, sex, race, failure to thrive, obesity, history of EDS, snoring history, history of cyanosis during sleep, or daytime symptoms except for mouth breathing. There were no significant differences in sleep variables between PS patients and those with any severity of OSAS. The OSA score misclassified about one of four patients. Comparing PS and OSA patients, significant findings were daytime mouth breathing (61 vs 85%; p=0.024); observed apnea (46 vs 74%; p=0.013); shaking the child (31 vs. 60%; p=0.01); struggling to breathe (58 vs 89%; p=0.003); and afraid of apnea (71 vs 91%; p=0.028). However, none of these were sufficiently discriminatory to predict OSAS. Conclusion We conclude that PS in children cannot be reliably distinguished from OSAS by clinical history alone.

This educational activity is adapted from a live satellite symposium held during the 29th Annual North American Cystic Fibrosis Conference in Phoenix, Arizona (online access: http://www.elseviercme.com/cysticfibrosis/598e). This educational symposium will update clinicians on the changes in disease progression that are now seen in CFTR modulator-treated patients. With the recent scientific advancements and the principles of precision medicine, disease progression and quality of life are drastically improving for patients with cystic fibrosis. Current clinical trial data shows new and emerging therapeutic options that are beneficial to specific gene mutations. Expert faculty will present comprehensive case studies and conduct interactive panel discussions to enhance your knowledge in the advanced science of cystic fibrosis and patient management strategies.

Objectives To characterize the onset of persistent signs and symptoms of cystic fibrosis (CF) lung disease and identify characteristics that predict onset. Study design Patients in the Epidemiologic Study of CF who were

Fosfomycin/tobramycin for inhalation (FTI), a unique, broad-spectrum antibiotic combination, may have therapeutic potential for patients with cystic fibrosis (CF).To evaluate safety and efficacy of FTI (160/40 mg or 80/20 mg), administered twice daily for 28 days versus placebo, in patients greater than or equal to 18 years of age, with CF, chronic Pseudomonas aeruginosa (PA) airway infection, and FEV(1) greater than or equal to 25% and less than or equal to 75% predicted.This double-blind, placebo-controlled, multicenter study assessed whether FTI/placebo maintained FEV(1) % predicted improvements achieved following a 28-day, open-label, run-in course of aztreonam for inhalation solution (AZLI).A total of 119 patients were randomized to FTI (160/40 mg: n = 41; 80/20 mg: n = 38) or placebo (n = 40). Mean age was 32 years and mean FEV(1) was 49% predicted at screening. Relative improvements in FEV(1) % predicted achieved by the AZLI run-in were maintained in FTI groups compared with placebo (160/40 mg vs. placebo: 6.2% treatment difference favoring FTI, P = 0.002 [primary endpoint]; 80/20 mg vs. placebo: 7.5% treatment difference favoring FTI, P0.001). The treatment effect on mean PA sputum density was statistically significant for the FTI 80/20 mg group versus placebo (-1.04 log(10) PA colony-forming units/g sputum difference, favoring FTI; P = 0.01). Adverse events, primarily cough, were consistent with CF disease. Respiratory events, including dyspnea and wheezing, were less common with FTI 80/20 mg than FTI 160/40 mg. No clinically significant differences between groups were reported for laboratory values.FTI maintained the substantial improvements in FEV(1) % predicted achieved during the AZLI run-in and was well tolerated. FTI is a promising antipseudomonal therapy for patients with CF.

Background Despite improving survival in cystic fibrosis (CF) patients, there is a mortality peak in early adulthood. Defining risk factors that predict significant worsening of lung disease in young adulthood may identify opportunities to improve outcomes in adults. Methods We identified 4,680 patients in the Epidemiologic Study of Cystic Fibrosis 1994–2005 with data in both adolescence (age 14.0–17.4 years) and young adulthood (age 18.5–22.0 years) and analyzed 2,267 who had ≥5 encounters and ≥5 measurements of forced expiratory volume in 1 second (FEV1) spanning ≥1 year during both adolescence and young adulthood, and ≥1 encounter with weight and height and ≥1 FEV1 measurement age 17.5–18.5 years. We compared the annualized rates of decline in FEV1 during adolescence and young adulthood stratified by best FEV1 around age 18. Logistic regression was used to identify risk factors associated with substantial decline (>20 points) in FEV1% predicted in young adulthood. Results Annual rate of decline was greater in young adulthood than in adolescence. Risk factors for substantial decline included slower rate of FEV1 decline, greater FEV1 variability, faster body mass index (BMI) decline, male sex, chronic inhaled antibiotics, Haemophilus influenzae detection, and absence of multidrug-resistant Pseudomonas aeruginosa in adolescence, and lower than expected FEV1 and BMI around age 18. Conclusions Decline in lung function accelerates in young adults with CF, especially in those with early stage lung disease. Adolescents at risk for substantial decline in lung function in young adulthood have higher FEV1 and worse nutritional status, among other identifiable risk factors. Pediatr Pulmonol. 2012; 47:135–143. © 2011 Wiley Periodicals, Inc.

States develop specific protocols for cystic fibrosis (CF) newborn screening to reflect the population served. We hypothesized that mutation distribution and detection rates would differ between Hispanic and non-Hispanic CF patients diagnosed by IL newborn screen with more Hispanic infants carrying mutations not detected by the state panel. Data from CF cases diagnosed via newborn screen in IL between 3/1/2008 and 10/31/2010 were reviewed. More Hispanic infants with CF had one or more undefined mutations after screening, in comparison to non-Hispanic Caucasian patients (40% vs. 9.5%; p < 0.002). The risk of having a positive diagnosis of CF with only one mutation noted by positive newborn screen increases 2-fold in Hispanic Caucasian versus non-Hispanic Caucasian infants (5% vs. 2.4%). Health care providers must be aware of the limitations of CF newborn screening to ensure appropriate counseling and prompt referral for a positive newborn screen, even when zero or one mutations are identified.

SUMMARY A select group of microorganisms inhabit the airways of individuals with cystic fibrosis. Once established within the pulmonary environment in these patients, many of these microbes adapt by altering aspects of their structure and physiology. Some of these microbes and adaptations are associated with more rapid deterioration in lung function and overall clinical status, whereas others appear to have little effect. Here we review current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis.

BACKGROUND: Newborn screening for cystic fibrosis (CF) in Illinois uses an immunoreactive trypsinogen/DNA methodology; most false-positive results identify unaffected carriers. METHODS: Parents whose child received a negative result from the sweat test after a positive newborn screening for CF were surveyed ≥6 weeks later by telephone. All parents received genetic counseling while waiting for the sweat-test results. RESULTS: A total of 90 parents participated. Overall knowledge of CF was high (78%), but the ability to understand the CF screening results was mixed. Although 94% of the parents understood that their child did not have CF, only 79% (62 of 78) of participants whose child had a mutation knew their child was definitely a carrier, and only 1 of 12 parents whose child had no mutation understood that the child may be a carrier. Respondents stated that most relatives were not interested in genetic testing. Both parents had been tested in only 13 couples. Fewer than half (36 of 77 [47%]) of the untested couples expressed interest in genetic testing. Although most participants were satisfied with the process, parents expressed frustration because of the lack of prospective newborn screening discussions by prenatal and pediatric providers and lack of knowledge and sensitivity by those who initially notified them of the abnormal newborn screening results. Speaking to a genetic counselor when scheduling the sweat test decreased anxiety for many parents (53 of 73 [73%] were “very worried” at notification versus 18 of 73 [25%] after scheduling; P < .001). CONCLUSIONS: Parental knowledge about CF is high, but confusion about the child's carrier status and the concept of residual risk persist despite genetic counseling. Relatives express low interest in carrier testing.

* Abbreviations: ABP — : American Board of Pediatrics SOC — : Scholarship Oversight Committee What is the goal of pediatric subspecialty training, how long should the training period be, and what is the value of a scholarly activity? A committee of the American Board of Pediatrics (ABP) grappled with these and other questions from 2000 to 2003. Previously the ABP supported the view of the Federation of Pediatric Organizations that “the principal goal of fellowship training should be to develop future academic pediatricians”1 and required all applicants for subspecialty certification to have evidence of “meaningful accomplishment in research,” usually a peer-reviewed publication. A number of concerns spawned the 2000 to 2003 ABP review, including subspecialty workforce shortages, decreasing numbers of pediatric physician–scientists, and trends toward nonacademic careers among subspecialty fellowship graduates, concerns that persist today. Based on the committee’s recommendations, in 2004 the ABP issued new fellowship training requirements providing greater curricular flexibility to better prepare subspecialists with varied career aspirations.2 In place of “meaningful accomplishment in research,” the ABP embraced a variety of scholarly activities that could be tailored to individual career goals. Furthermore, fellows were to be mentored by a Scholarship Oversight Committee (SOC) that approved their scholarship work product. Examples of scholarship offered by the ABP included basic, clinical, translational, and health … Address correspondence to F. Bruder Stapleton, MD, Department of Pediatrics, Seattle Children’s Hospital, 4800 Sand Point Way NE, RB2:401, Seattle, WA 98105. E-mail: bruder.stapleton{at}seattlechildrens.org

Angiogenesis is an important mechanism of airway remodeling in lung disease. We previously demonstrated that serum vascular endothelial growth factor (VEGF) is elevated in cystic fibrosis (CF) patients and declines with therapy for pulmonary exacerbation. We hypothesized that VEGF is elevated early in the course of CF and is associated with markers of tissue hypoxia. A prospective, single-visit evaluation of thirty stable infants and children with CF was performed. Serum was analyzed for VEGF and for other markers of tissue hypoxia (erythropoietin (EPO), insulin-like growth factor binding protein-1 (IGFBP-1)) and for inflammatory mediators (IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha (TNFα)) using Meso Scale multi-spot serum immunoassays. Measurements were correlated between assay groups; and with age in months and pulmonary function (FEV0.5 or FEV1). VEGF, EPO, TNFα and IL-8 were elevated compared to published normative values. VEGF levels were not significantly correlated with any inflammatory mediators. However, VEGF correlated with EPO (r=0.505; P0.05). There was no correlation between lung function and markers of inflammation or tissue hypoxia. VEGF is elevated in young, stable infants and children suggesting angiogenesis as a contributing mechanism for early lung disease in CF. VEGF elevation does not show significant correlation with inflammatory mediators known to be increased in CF, but is significantly correlated with EPO levels. We propose that VEGF elevation and angiogenesis contribute to early lung disease and may result from a direct tissue hypoxia pathway in CF.

Hispanic ethnicity is an independent risk factor for increased morbidity and mortality in cystic fibrosis (CF) patients. In order to compare the prevalence of risk factors for morbidity and mortality between the Hispanic CF population and the non-Hispanic CF population, we performed a cross-sectional study of patients in the 2004 Cystic Fibrosis Foundation Patient Registry. Among 22,714 CF patients, 1,511 were identified as ethnic Hispanic. Hispanic patients were diagnosed earlier (2.8 vs. 3.3 years, P = 0.005) and acquired Pseudomonas aeruginosa at a younger age (6.6 years vs. 10 years, P0.001). FEV(1) was lower for Hispanic patients (81.5% vs. 87% predicted for those under 18 years old [P0.001] and 2.1 L vs. 2.3 L for those 18 years and older [P = 0.01]). Hispanic patients had similar or better nutritional status. Hispanic patients were more likely to be diagnosed with liver disease (OR 1.31 [1.1, 1.56]) but less likely to be diagnosed with depression (OR 0.53 [0.39, 0.68]), bone and joint disease (OR 0.55 [0.41, 0.71]), or CF-related diabetes (OR 0.53 [0.43, 0.62]). Hispanic patients had lower median income by zip code ($41,930 vs. $47,341; P0.001), a higher rate of government insurance (55.2% vs. 32.0%; P0.001), and greater percentage of mothers with less than a high school education (26.7% vs. 6.5%; P0.001). We conclude that there is an increased prevalence of important risk factors for morbidity and mortality in the Hispanic CF population.

BackgroundEUR-1008 (Zenpep™ [pancrelipase]) is a new, enteric-coated, porcine-derived pancreatic enzyme product (PEP) developed for the treatment of cystic fibrosis (CF) patients with malabsorption associated with exocrine pancreatic insufficiency (EPI). Unlike currently marketed PEPs, EUR-1008 contains the label-claimed lipase content. Safety and efficacy were assessed in younger (

Pseudomonas aeruginosa (PA) from acute and chronic (eg, cystic fibrosis (CF)) infections differ in several respects, but they can worsen prognosis in each context. Factors that facilitate conversion from an acute to chronic phenotype are poorly understood. T3 secretion proteins are virulence factors associated with poorer outcomes in acute infections, but little is known about their role in CF. We wished to characterize T3 secretion in CF PA isolates and to examine its role in clinical outcomes. A total of 114 CF subjects were divided into 3 cohorts: 1st infected individuals, CI children, and adults. Serial respiratory cultures were analyzed for T3 secretion. Serial spirometry and exacerbation data were collected prospectively. In 1st infection, 45.2% +/- 9.1% of PA isolates secreted T3 proteins compared with 29.1% +/- 4.2% and 11.5% +/- 3.0% in CI children and CI adults, respectively (P0.001). An inverse correlation was observed between duration of PA infection and percent T3 positive isolates (r = -0.32, P0.001). Overall, no association was observed between T3 secretion and pulmonary outcomes, but in the subgroup of subjects who had at least 1 T3 positive organism, T3 secretion was inversely correlated with the forced expiratory volume in 1 s (FEV(1)) decline (r = -0.35, P = 0.02). In 1st infection, 82% of cultures grew either all or no T3-positive organisms. In these patients, T3 secretion was associated with a greater risk of subsequent PA isolation (P0.001). In CF, PA T3 secretion decreases with residence time in lung, may predict FEV(1) decline in patients who have detectable T3 organisms, and may facilitate persistence after 1st infection.

Cystic fibrosis (CF) is characterized by chronic lung infection. Minimizing exposure to pathogens is important. Treating a CF pulmonary exacerbation includes nebulizer therapies, but little is known about pathogen exposure from nebulizer equipment in CF.To assess microbial growth in nebulizer equipment used by hospitalized CF patients.The small-volume nebulizer would not support the growth of the important CF pathogens: Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Burkholderia cepacia.During a 6-month period, we prospectively enrolled 30 patients who were admitted for pulmonary exacerbation of CF and were prescribed an aerosolized bronchodilator 4 times daily. Bronchodilator was administered via disposable small-volume nebulizer, prior to airway clearance. The nebulizer was not cleaned or disinfected between treatments, but instead was replaced after 24 hours. Sputum or throat cultures were obtained prior to admission or on the day of admission, and standard culture techniques were used for CF microbes. After the first bronchodilator treatment, a sample was taken from the residual fluid inside the nebulizer cup. The second, third, and fourth samples were taken from the nebulizer cup after it was filled with a unit dose of the bronchodilator but prior to administering the bronchodilator. At the 24th hour, the nebulizer was filled with 3 mL of sterile water, from which the fifth sample was obtained, then the nebulizer was disposed of.On respiratory culture, ten patients had Pseudomonas aeruginosa, 5 had both P. aeruginosa and S. aureus, 6 had only S. aureus, and 1 had both S. aureus and H. influenzae. Three had other organisms, 4 had normal flora, and 1 had no culture data. Of the 150 nebulizer sample cultures, only 3 showed bacterial growth. Bacillus species, Corynebacterium, coagulase-negative Staphylococcus, and Candida albicans were isolated at low colony counts.We suspect that the organisms identified were caused by skin contamination of the samples rather than contamination of the nebulizer cup. We conclude that there is a low risk of microbial contamination with CF pathogens from the interior of a disposable nebulizer over a 24 hour period.

Pseudomonas aeruginosa is a frequent cause of respiratory exacerbations in individuals with cystic fibrosis. An important virulence determinant of this pathogen is its type III protein secretion system. In this study, the type III secretion properties of 435 P. aeruginosa respiratory isolates from 56 chronically infected individuals with cystic fibrosis were investigated. Although it had been previously reported that 75 to 90% of P. aeruginosa isolates from patients with hospital-acquired pneumonia secreted type III proteins, only 12% of isolates from cystic fibrosis patients did so, with nearly all of these isolates secreting ExoS and ExoT but not ExoU. Despite the low overall prevalence of type III protein-secreting isolates, at least one secreting isolate was cultured from one-third of cystic fibrosis patients. Interestingly, the fraction of cystic fibrosis patient isolates capable of secreting type III proteins decreased with duration of infection. Although 90% of isolates from the environment, the presumed reservoir for the majority of P. aeruginosa strains that infect patients with cystic fibrosis, secreted type III proteins, only 49% of isolates from newly infected children, 18% of isolates from chronically infected children, and 4% of isolates from chronically infected adults with cystic fibrosis secreted these proteins. Within individual patients, isolates of clonal origin differed in their secretion phenotypes, indicating that as strains persisted in cystic fibrosis patient airways, their type III protein secretion properties changed. Together, these findings indicate that following infection of cystic fibrosis patient airways, P. aeruginosa strains gradually change from a type III protein secretion-positive phenotype to a secretion-negative phenotype.

Although immunization with influenza vaccine is recommended for children with chronic renal disease and after organ transplantation, the antibody response in these children has not been well described. We studied the response to the 1993-1994 trivalent influenza vaccine in children, aged 1-21 years, with chronic renal failure (n = 15), end-stage renal disease requiring dialysis (n = 10), and post renal transplantation (n = 17). Each group's antibody response was compared with that of a control group (n = 7). No significant differences were found in seroconversion rates, percentage of patients achieving protective hemagglutination-inhibition titers post vaccination or change in geometric mean titers from pre to post vaccination between study groups and controls. These results suggest that pediatric patients with renal disease will respond and therefore will benefit from currently recommended influenza immunization.

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.

Plastic bronchitis is a condition in which large, bronchial casts with rubber-like consistency develop in the tracheobronchial tree and cause airway obstruction. We describe a 4-year-old girl who had Fontan physiology and who developed plastic bronchitis and report for the first time the use of aerosolized tissue plasminogen activator for treatment of this condition. The literature is reviewed with emphasis placed on the occurrence of this disorder in patients with single ventricle physiology.

Objectives To utilize the Cystic Fibrosis Foundation Patient Registry to evaluate whether pancreatic enzyme dose is associated with better nutritional status as measured by average body mass index (BMI) percentile. Study design A retrospective analysis of the Cystic Fibrosis Foundation Patient Registry from 2005-2008 was performed. The final analysis included 42 561 patient visits from 14 482 patients 2-20 years of age taking pancreatic enzyme replacement therapy from 179 programs. Cystic fibrosis care programs were assigned to quartiles based on adjusted mean patient BMI percentiles. Differences in median lipase dose between programs in the highest and lowest BMI quartiles were examined using a mixed effects model that adjusted for individual patient BMI, age, race, ethnicity, forced expiratory volume in 1 second percent, acid-blocker use, presence of Pseudomonas aeruginosa , nutritional supplement use, growth hormone use, and diagnosis of cystic fibrosis-related diabetes. Results A significant difference in median enzyme dose existed between the highest and lowest BMI quartiles. Multivariable analysis demonstrated the effect persisted after adjustment for covariates. Highest quartile programs had a median enzyme dose of 1755 lipase units/kg/meal compared with 1628 lipase units/kg/meal for lowest quartile programs. Conclusion Patients attending US cystic fibrosis programs achieving highest nutritional outcomes, measured by mean BMI percentile, have higher enzyme dosing than those attending programs at lower performance levels. Further randomized clinical trials are necessary to determine the role of enzyme dose in improving nutritional outcomes.

Introduction: Previous studies have shown that children with cystic fibrosis (CF) are capable of mounting a normal immune response after the stress of exercise. However, few data are available regarding the underlying mechanisms by which this immune modulation occurs. Methods: In this study, lymphocyte and leukocyte cell counts were measured before and immediately after a single bout of exhaustive exercise in 25 children (ages 8-17 yr; 12 with CF and 13 healthy controls). Catecholamine, cortisol, and insulin levels, age, nutritional parameters, and static and dynamic lung function were measured as potential correlates for immune modulation. We hypothesized that catecholamine levels would be associated with the immune changes seen after exercise in children with CF. Results: Our results demonstrated positive correlations between age and the change in cell counts after exercise for white blood cells (r = 0.44, P < 0.03), lymphocytes (r = 0.60, P < 0.002), monocytes (r = 0.43, P < 0,03), and CD3-CD16+CD56+ cells (r = 0.61, P < 0.002), Lower increases in the lymphocyte and CD3-CD16+CD56+ cells were observed in the CF group. Changes in pre- and post-exercise norepinephrine levels were weakly correlated with the changes in granulocyte, lymphocyte, and monocyte cell counts. Changes in cortisol levels correlated with lymphocyte and CD19+ cell count changes for the CF group but not for the healthy controls. Within the CF group, the severity of lung disease (as indicated by a FEV 1 ) was negatively correlated with changes in lymphocyte (r = -0.66, P < 0.02) and CD3-CD16+CD56+ cell counts (r = -0.67, P < 0.02), Conclusion: The results suggest that postexercise changes in cell counts occur in an age dependent, norepinephrine associated manner. Disease severity for children with CF also appears to enhance the postexercise leukocytosis with pronounced increases seen in natural killer cells.

The nature of a child's daily physical activity requires both aerobic and anaerobic energy metabolism. Aerobic exercise becomes compromised with advancing airway obstruction in children with cystic fibrosis (CF) and asthma (AS). Whether children with CF will have altered metabolic responses to supramaximal exercise when compared with asthmatics or healthy controls is still undetermined.Twenty-five children with CF, 22 with AS, and 23 healthy controls (CN) performed an incremental graded aerobic and Wingate anaerobic test (WAnT) on a cycle ergometer. Analysis of gas exchange and ventilatory data was collected and averaged every 5 s to estimate ventilatory kinetics and energy system contributions during both tests.The CF and AS groups had mild lower airway obstruction (FEF25-75%80%) as compared with the CN. All three groups demonstrated similar anaerobic (mean and peak power during the WAnT) and aerobic exercise performance (peak oxygen consumption). In contrast to the AS or CN groups, children with CF used a lower percentage of their peak VO2 and V(E) during each phase of the WAnT, suggesting a preferential use of ATP/phosphocreatine and glycolytic energy stores compared with aerobic pathways. Greater reliance on anaerobic pathways during the WAnT in children with CF could be due to the physiologic sequelae underlying chronic obstructive lung disease.Oxygen uptake kinetics appeared similar for all three groups. Although the energy needed to perform the WAnT can be met by subjects with CF, abnormalities in energy metabolism may exist for this group during exercise.

Despite the well-recognized benefits of exercise on general health and pulmonary function, lack of participation in regular exercise remains a concern with respect to children with cystic fibrosis (CF). Data are lacking regarding parental perceptions about exercise in children and adolescents with CF. Sixty-nine parents of children with CF and 70 parents of healthy children completed the "Exercise Benefits/Barrier Scale” self administered inventory. Fifteen additional items addressing exercise issues for people with CF were also included. Data were reported as total score, and subdivided into barriers and benefits scales for analysis. Data on the CF specific questions were also reported. Parents of children with CF scored lower on both the total score and benefits portion of the inventory and scored slightly greater on the barriers portion (p < 05) representing less favorable perception of the benefits of exercise along with increased barriers. The presence of a healthy child in addition to a child with CF appeared to increase both the total score and benefits score as well as resulting in a more positive outlook on exercise related uses in CF. It appears that significant differences in parental perceptions regarding exercise indeed exist not only when compared to healthy children but within varying intra-structures of families with a child who has (CF).

To determine whether socioeconomic status (SES) influences the likelihood of antibiotic treatment of pulmonary exacerbations in patients with cystic fibrosis (CF).We used data on 9895 patients ≤ 18 years old from the Epidemiologic Study of CF. After establishing an individual baseline of clinical signs and symptoms, we ascertained whether antibiotics were prescribed when new signs/symptoms suggested a pulmonary exacerbation, adjusting for sex, presence of Pseudomonas aeruginosa, the number of new signs/symptoms, and baseline disease severity.In a 12-month period, 20.0% of patients6 years of age, 33.8% of patients 6 to 12 years of age, and 41.4% of patients 13 to 18 years of age were treated with any (oral, intravenous (IV), or inhaled) antibiotics; the percentage receiving IV antibiotics was 7.3%, 15.2%, and 20.9%, respectively. SES had little effect on treatment for pulmonary exacerbation with any antibiotics, but IV antibiotics were prescribed more frequently for patients with lower SES.SES-related disparities in CF health outcomes do not appear to be explained by differential treatment of pulmonary exacerbations.

• A retrospective study of pediatric patients with obstructive sleep apnea who underwent adenotonsillectomy between 1987 and 1990 was undertaken to determine the frequency of postoperative respiratory compromise and to determine if risk factors for its development could be identified. Sixty-nine patients less than 18 years old had polysomnographically documented obstructive sleep apnea and were observed postoperatively in the pediatric intensive care unit. Of these, 16 (23%) had severe respiratory compromise, defined as intermittent or continuous oxygen saturation of 70% or less, and/or hypercapnia, requiring intervention. Compared with patients without respiratory compromise, these patients were younger (3.4±4 vs 6.1 ±4 years) and had more obstructive events per hour of sleep on the polysomnogram (49±41 vs 19±30). They were more likely to weigh less than the fifth percentile for age (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.4 to 18.7), to have an abnormal electrocardiogram and/or echocardiogram (OR, 4.5; 95% CI, 1.3 to 15.1), and to have a craniofacial abnormality (OR, 6.2; 95% CI, 1.5 to 26). Multiple logistic regression analysis revealed the most significant risk factors were age below 3 years and an obstructive event index greater than 10. Children with obstructive sleep apnea are at risk for respiratory compromise following adenotonsillectomy; young age and severe sleep-related upper airway obstruction significantly increase this risk. We recommend in-hospital postoperative monitoring for children undergoing adenotonsillectomy for obstructive sleep apnea. ( Arch Otolaryngol Head Neck Surg. 1992;118:940-943)

To determine whether previously reported socioeconomic status (SES)-related disparities in cystic fibrosis (CF) health outcomes vary by the indicator used (median household income by zip code [MIZ], maternal educational attainment [MEA], and state insurance coverage [MA]), and whether these disparities can be explained by differences in medical treatment.A cross-sectional analysis of data on patients age18 years from the Epidemiologic Study of Cystic Fibrosis (ESCF).Disease severity showed a similar inverse correlation with all 3 SES measures. The number of stable clinic visits was unrelated to SES. Patients with MA had more sick outpatient visits and more courses of intravenous (IV) antibiotics for pulmonary exacerbations, and were more likely to be prescribed all chronic therapies. Low-MIZ patients had slightly fewer sick visits and more courses of IV antibiotics, and were more likely to receive oral nutrition supplements but less likely to receive macrolide prescriptions. Low-MEA patients were less likely to receive IV antibiotics at home, more likely to receive oral nutrition supplements, but less likely to receive macrolide prescriptions.CF health outcomes are correlated with the SES spectrum, but these disparities are not explained by differential use of health services or prescription of chronic therapy. Future investigations should focus on the possible impact of environmental exposures and differences in disease self-management.

We investigated the effect of different levels of O2 tension (hypoxia, normoxia, and hyperoxia) on the breath-by-breath onset and peak electromyographic (EMG) activity of the genioglossus (GG) muscle during a five-breath end-expiratory tracheal occlusion of 20- to 30-s duration. GG and diaphragmatic (DIA) EMG activity were measured with needle electrodes in eight anesthetized tracheotomized adult cats. In response to occlusion, the increase in the number of animals with GG EMG activity was different during hypoxia, normoxia, and hyperoxia (P = 0.003, Friedman). During hypoxia, eight of eight of the animals had GG EMG activity by the third occluded effort. In contrast, during normoxia, only four of eight and, during hyperoxia, only three of eight animals had GG EMG activity throughout the entire five-breath occlusion. Similarly, at release of the occlusion, more animals had persistent GG EMG activity on the postocclusion breaths during hypoxia than during normoxia or hyperoxia. Breath-by-breath augmentation of peak amplitude of the GG and DIA EMGs on each occluded effort was accentuated during hypoxia (P less than 0.01) and abolished during hyperoxia (P = 0.10). These results suggest that hypoxemia is a major determinant of the rapidity of onset, magnitude, and sustained activity of upper airway muscles during airway occlusion.

• The recent identification of the cystic fibrosis (CF) gene confirms that genetic heterogeneity occurs in CF. A three—basepair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product, termed the CF conductance regulator protein , accounts for 70% of cases of CF in white subjects. However, this gene defect occurs in only 37% of affected blacks. Analysis of CF genes from American blacks has revealed a number of mutations, most of which are unique to that population. We therefore searched for potential differences in expression of CF between 24 black and 48 white patients with CF matched for birth date and gender. Black patients more frequently presented with only respiratory symptoms (38% vs 10%). Black patients had fewer hospitalizations for pulmonary exacerbations (2 vs 6.9), a better mean forced vital capacity (77% vs 62% of predicted), and higher chest roentgenogram scores (18.2 vs 14.4) than white patients. Complication rates were similar except for a higher incidence of hyponatremic dehydration (21% vs 2%) and peptic ulcer disease (13% vs 0%) in blacks. Survival time appeared to be longer in blacks, but the difference was not statistically significant. We conclude that phenotypic differences exist between black and white patients with CF, which may be due to the genetic heterogeneity between these two populations. ( AJDC . 1991;145:94-97)

In adults, the critical nasal pressure (Pcrit) at which the upper airway collapses is higher in patients with the obstructive sleep apnea syndrome (OSAS) than in those with primary snoring. Pediatric OSAS differs clinically from adult OSAS. We therefore compared Pcrit between prepubertal children with OSAS and primary snoring. Pcrit was determined by correlating the maximal inspiratory airflow with the level of positive or negative nasal pressure applied via a nasal mask. As in adults, we found that the maximal inspiratory airflow varied in proportion to the upstream (nasal) rather than the downstream (esophageal) pressure changes. Pcrit was 1 +/- 3 cmH2O in OSAS compared with -20 +/- 9 cmH2O in primary snorers (P < 0.002). In three OSAS patients reevaluated after tonsillectomy and adenoidectomy, Pcrit declined to -7.2 +/- 4.0 cmH2O. We conclude that the pediatric airway behaved as predicted by the Starling resistor model and that Pcrit, a measure of airway collapsibility, correlated with the degree of upper airway obstruction and was reduced postoperatively, consistent with increased upper airway stability.

Objective: To determine whether polysomnography is useful in the evaluation of readiness for decannulation in children with long-term tracheotomy. Design: Descriptive, retrospective case series. Setting: Tertiary care pediatric center, pediatric sleep disorders laboratory, and pediatric otolaryngology referral center. Patients: Children (younger than 18 years) with tracheotomy undergoing polysomnography to assess their dependence on tracheotomy. Intervention: Polysomnography in all patients; endoscopy and decannulation in those judged clinically ready. Main Outcome Measures: Success of decannulation. Results: Thirteen of 16 patients with favorable polysomnographic data were successfully decannulated. Conclusion: Polysomnography is a useful supplement to airway endoscopy in the evaluation of readiness for decannulation in children with long-term tracheotomy and dynamic airway issues. Arch Otolaryngol Head Neck Surg. 1996;122:721-724