Pediatric Cystic Fibrosis Patients Research Articles

DNA and Inflammatory Mediators in Bronchoalveolar Lavage Fluid From Children With Acute Inhalational Injuries

The aim of this study was to assess the feasibility of using serial bronchoalveolar lavage fluids (BALFs) to characterize the course of cell damage and inflammation in the airways of pediatric patients with acute burn or inhalation injury. This was a prospective, longitudinal, descriptive pilot study conducted at the Burn and Pediatric Intensive Care Units in a tertiary care medical center. Six consecutively intubated and mechanically ventilated pediatric patients with acute inhalational injuries were studied. Serial BALF specimens from clinically indicated bronchoscopies were used to measure DNA and cytokine levels. BALF DNA levels for the six pediatric burn subjects were the highest within the first 72 hours after burn injury and declined thereafter. At the early stages after injury, BALF DNA levels (median [min, max] 3789 [1170, 11,917] ng/ml) were similar to those in adult burn patients and pediatric cystic fibrosis or bronchiectasis patients and was higher than those in pediatric recurrent pneumonia patients. BALF DNA levels in children and adults with inhalation injury correlated significantly with BALF interleukin-6, interleukin-8, and transforming growth factor-β1 levels. The patient with the most severe early visible airway mucosal damage and soot pattern at bronchoscopy, as well as the most extensive burns, also had the highest average early BALF DNA level (11,917 ng/ml) and the longest ventilator course and hospital stay. Procedures were well tolerated. In children with acute burn and inhalational injury, airway cellular damage and inflammation (reflected in high BALF DNA levels) appear to peak during the first 72 hours after burn or inhalation injury followed by a slow decline. Serial analysis of factors in airway secretions is feasible and has the potential to reveal important pathophyisiologic pathways and therapeutic targets for the treatment of acute inhalational injuries.

Clinical pharmacist impact on care, length of stay, and cost in pediatric cystic fibrosis (CF) patients

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.

Bacteriology of the paranasal sinuses in pediatric cystic fibrosis patients.

Bacteriology of the paranasal sinuses in pediatric cystic fibrosis patients.

608 Reduced Lipoxin A4/Leukotriene B4Ratio in Early Cf Bal - Impaired Airway Epithelial Lipoxin A4Synthesis Capacity

Cystic Fibrosis (CF) is characterised by impaired muco-ciliary clearance, persistent neutrophilic inflammation and bacterial infection. Normal resolution of inflammation involves an active switch in mediators that predominate in exudates. Early...

Incidence of viral respiratory pathogens causing exacerbations in adult cystic fibrosis patients

Respiratory infections caused by respiratory viruses are common in paediatric cystic fibrosis (CF) patients and are associated with increased morbidity. There is only little data on the incidence of viral respiratory pathogens causing exacerbations in the adult CF patient population. In this observational pilot study we show, by using molecular as well as conventional techniques for viral isolation, that during 1 y a viral pathogen could be isolated in 8/24 (33%) adult CF patients who presented with a pulmonary exacerbation. This result shows that there is a considerable incidence of viral pathogens in pulmonary exacerbations in adult CF patients. Newly identified viruses such as pandemic influenza A/H1N1, human metapneumovirus, human bocavirus, and human coronavirus NL63 were not detected in our population, except for 1 human coronavirus NL63.

Growth retardation and reduced growth hormone secretion in cystic fibrosis. Clinical observations from three CF centers

ObjectiveGrowth delay in cystic fibrosis is frequent and is usually the result of several interacting causes. It most often derives from severe respiratory impairment and severe malabsorption. There are however patients whose clinical condition is not severe enough to be held accountable for this phenomenon. We aimed at describing patients who showed growth delay, who were not affected by severe pulmonary disease or malabsorption and who, when tested, showed a reduced GH secretion after stimulation with conventional agents. We noticed a disproportionately large prevalence of growth hormone (GH) release deficit (GHRD) in pediatric cystic fibrosis (CF) patients. Patients and methodsWe examined all patients under our care in the period 2006–11, who were older than 5 and younger than 16years old. We focussed on those who fell below the 3rd height percentile, or whose growth during the previous 18months faltered by >2SD, and who did not present clinical conditions that could reasonably explain their failure to thrive. These patients were subjected to standard GH provocative tests. ResultsOut of 285 who matched the age criterion, 33 patients also matched the height percentile criterion. While 15/33 suffered clinical conditions that could reasonably explain their failure to thrive, 18/33 underwent GH release provocative tests and 12/18 showed a release deficit. ConclusionsWe conclude that impaired GH secretion is more frequent among CF patients compared to the prevalence of GH deficiency in the general population and that GH release impairment may be an independent cause of growth delay in CF. Our findings are in agreement with recent studies that have described low GH levels in CF piglets and in neonates with CF [1].

Serial Analysis of the Gut and Respiratory Microbiome in Cystic Fibrosis in Infancy: Interaction between Intestinal and Respiratory Tracts and Impact of Nutritional Exposures

ABSTRACTPulmonary damage caused by chronic colonization of the cystic fibrosis (CF) lung by microbial communities is the proximal cause of respiratory failure. While there has been an effort to document the microbiome of the CF lung in pediatric and adult patients, little is known regarding the developing microflora in infants. We examined the respiratory and intestinal microbiota development in infants with CF from birth to 21 months. Distinct genera dominated in the gut compared to those in the respiratory tract, yet some bacteria overlapped, demonstrating a core microbiota dominated by Veillonella and Streptococcus. Bacterial diversity increased significantly over time, with evidence of more rapidly acquired diversity in the respiratory tract. There was a high degree of concordance between the bacteria that were increasing or decreasing over time in both compartments; in particular, a significant proportion (14/16 genera) increasing in the gut were also increasing in the respiratory tract. For 7 genera, gut colonization presages their appearance in the respiratory tract. Clustering analysis of respiratory samples indicated profiles of bacteria associated with breast-feeding, and for gut samples, introduction of solid foods even after adjustment for the time at which the sample was collected. Furthermore, changes in diet also result in altered respiratory microflora, suggesting a link between nutrition and development of microbial communities in the respiratory tract. Our findings suggest that nutritional factors and gut colonization patterns are determinants of the microbial development of respiratory tract microbiota in infants with CF and present opportunities for early intervention in CF with altered dietary or probiotic strategies.

Pilot Trial of Spirometer Games for Airway Clearance Practice in Cystic Fibrosis

Many children with cystic fibrosis (CF) adhere poorly to airway clearance techniques (ACTs), and would rather play video games that challenge their dexterity and visual tracking skills. We developed gaming technology that encourages forced expiratory maneuvers. Following interviews regarding recreational activities and subjects' practice of ACTs, we conducted a pilot trial of spirometer games in 13 adolescents with CF, to test the hypothesis that games could increase subjects' engagement with forced expiratory breathing maneuvers and improve pulmonary function tests (PFTs). After baseline PFTs, subjects were provided with digital spirometers and computers set up as "game only" or "control" devices. After the first of 2 periods (each > 2 weeks), the computer was set-up for the alternate condition for period 2. The t test and non-parametric correlation analyses examined use, number of expiratory high flow events (HFEs), and change in PFTs, identifying trends at P ≤ .1, significance at P < .05. Interviews disclosed minimal awareness of ACTs among our pediatric CF patients. Subjects used games and control software a similar percentage of days during the game (26%) and control periods (32%). There was a trend toward more minutes with the game versus control setup (P = .07), though HFE count did not differ between the 2 conditions (P = .71). Game play showed no overall effect on FEV(1), though correlation analysis showed a modest relation between minutes of play and change in FEV(1) from baseline (r = 0.50, P = .09). The game period showed a trend to increased vital capacity (P = .05). Spirometer games elicit forced expiratory breath maneuvers in pediatric CF patients. Improvement in PFTs may be due to improved test performance technique, though improved obstructive/restrictive lung function due to game play cannot be excluded. A formal clinical trial of this approach is planned.

Oxidative stress in stable cystic fibrosis patients: Do we need higher antioxidant plasma levels?

Oxidative stress plays an important role in cystic fibrosis (CF). However, there is a lack of validated biomarkers of oxidative damage that correlate with the antioxidant needs of patients with CF. ObjectiveTo investigate oxidative stress in stable pediatric CF patients and evaluate if vitamin supplementation may be tailored to individual needs and oxidative status. ResultsLipid-adducts 4-hydroxynonenal (HNE-L) and malonaldehyde (MDA-L) (chromolipids) were elevated in the majority of patients despite normal plasma vitamin E, A and C. HNE-L and MDA-L increased with age, while plasma vitamins decreased. The most relevant correlation was identified between vitamin C and chromolipids. Patients with pancreatic insufficiency (PI) showed significantly higher plasma chromolipids despite no differences in plasma vitamins. ConclusionsThe majority of patients showed elevated plasma chromolipids that increased with age. Antioxidant vitamin reference ranges provide incomplete information on the redox status. CF patients with PI showed excessive oxidative stress damage.

Decreased Right Ventricular Function in Healthy Pediatric Cystic Fibrosis Patients Versus Non-Cystic Fibrosis Patients

Right ventricular (RV) dysfunction may occur in patients with cystic fibrosis (CF). Tissue Doppler imaging (TDI) and strain and strain rate analysis are new echocardiographic tools that can quantitate RV function. This study aimed to compare the RV function between healthy CF patients and non-CF patients to determine whether differences exist. Healthy CF children and age-matched non-CF children were enrolled in the study. In this study, TDI analysis of the RV free wall was performed at the level of the tricuspid valve annulus. Two-dimensional speckle echocardiography was used to measure global strain and strain rates in a six-segment model of the RV. Independent t tests were used to compare the groups. The study enrolled 18 CF patients (age, 7.7 ± 2.0 years) and 15 non-CF patients (age, 6.4 ± 2.5 years). The age difference was not significant. The forced expiratory volume in the first second (FEV(1)) for the CF patients was 91 ± 15 %. The systolic annular velocity by TDI was significantly lower in the CF group. The RV strain values in the CF group were significantly lower in four of the six segments (RV free-wall base, RV free-wall mid, RV septal apex, and RV septal mid). The global strain value, the systolic strain rate, and the early diastolic strain rate were significantly lower in the CF group. Decreased systolic and diastolic RV properties were present in young healthy CF patients. Further studies with longitudinal follow-up evaluation are needed to determine the significance of these findings for the pediatric CF population.

203 A review of the use of hypertonic saline 7% during inpatient treatment in paediatric cystic fibrosis patients

203 A review of the use of hypertonic saline 7% during inpatient treatment in paediatric cystic fibrosis patients

193 Habitual physical activity evaluation in CF children: accelerometry feasibility and comparison with questionnaires

Introduction: Physical activity is beneficial for cystic fibrosis (CF) patients. This induces to stimulate their habitual physical activity (HAP) from childhood. Thus, for HAP evaluation, we need methods that are simple, reliable, objective and well accepted by the patients. Accelerometry is one of the possibilities for evaluating HAP. We studied its feasibility, acceptability and correlation with other HAP evaluation methods in a population of paediatric CF patients. Methods: 34 CF patients, aged between 9 and 18 years, were proposed to wear accelerometers. The reasons for not wearing the accelerometer were evaluated. A correlation was measured between the data produced by accelerometry, the answers to HAES and Veerschuur questionnaires, and evaluations by medical staff. Results: – 14 children out of 34 (41%) did not wear the accelerometer, 5 of them simply refused it; 6 children (17%) have worn the accelerometer less than 5 days. Finally, 14 recordings were interpretable, i.e. 41% of the 34 children to whom the measurement was proposed. – The answers to the questionnaires appeared not to be correlated to the accelerometry data. But there was a good correlation of 62.1% (p = 0.017) between the data obtained by accelerometry and the medical evaluation. Conclusion: The feasibility of the HAP evaluation by accelerometry in a pediatric CF population is only around 40%. Therefore it cannot be used in every-day clinical practice. However, in clinical trials, the objective evaluation by accelerometry should be preferred because of the discrepancies observed with answers to standardized questionnaires on physical activity.

194 The influence of nutritional status on muscle strength and physical performance in CF patients listed for lung transplantation

Introduction: Physical activity is beneficial for cystic fibrosis (CF) patients. This induces to stimulate their habitual physical activity (HAP) from childhood. Thus, for HAP evaluation, we need methods that are simple, reliable, objective and well accepted by the patients. Accelerometry is one of the possibilities for evaluating HAP. We studied its feasibility, acceptability and correlation with other HAP evaluation methods in a population of paediatric CF patients. Methods: 34 CF patients, aged between 9 and 18 years, were proposed to wear accelerometers. The reasons for not wearing the accelerometer were evaluated. A correlation was measured between the data produced by accelerometry, the answers to HAES and Veerschuur questionnaires, and evaluations by medical staff. Results: – 14 children out of 34 (41%) did not wear the accelerometer, 5 of them simply refused it; 6 children (17%) have worn the accelerometer less than 5 days. Finally, 14 recordings were interpretable, i.e. 41% of the 34 children to whom the measurement was proposed. – The answers to the questionnaires appeared not to be correlated to the accelerometry data. But there was a good correlation of 62.1% (p = 0.017) between the data obtained by accelerometry and the medical evaluation. Conclusion: The feasibility of the HAP evaluation by accelerometry in a pediatric CF population is only around 40%. Therefore it cannot be used in every-day clinical practice. However, in clinical trials, the objective evaluation by accelerometry should be preferred because of the discrepancies observed with answers to standardized questionnaires on physical activity.

257 Improving nutrition for pediatric cystic fibrosis patients

Objectives: Evaluation of tolerance and clinical efficacy of nutritional support with high energy milk formula in Russian young children with CF. Methods: During the planned hospitalization (average 12.6 days) 30 children aged 1.5−10 years old with CF and pancreatic insufficiency were given milk formula (protein 4.2 g, fat 7.7 g, carbohydrates 16.39 g, energy 150 kcal/100ml, enriched with fiber and prebiotic, vanilla taste) up to 200ml/day (1−3 years), 300ml (4−6 years), 400ml (>6 years) between meals, with addition of 2500 IE (lipase) of Creon to each 100ml of formula. Results: Four (13.3%) children rejected. 26 (86.7%) of children accepted the formula well, no allergic reactions, intolerance or stool worsening. 23 (88.5%) patients gained weight by av. 415 g, with maximum gain of 2.3 kg in a boy who received formula the longest (24 days). Skin fold thickness increased in 23 (88.5%) children by average +0.364mm over triceps, in 17 (65.4%) by av. +0.372mm over biceps, and upper arm muscle circumference increased in (84.6%) by av. +0.332 cm. The daily Creon dose per 1 kg of body weight decreased in 11 (42.3%) cases because of patient’s weight gain, and increased insignificantly in the rest. Conclusions: The formula was well-tolerated and had an overall positive influence on the nutritive status indices, despite of the short terms of application and fact that Creon daily dose wasn’t significantly increased. Thus, it can be used as the additional feeding source in the most of young children with CF. However, taking into account the cases of refusal and peculiarities of taste preferences, children with CF require wider taste spectrum of products for additional feeding.

Review of tobramycin levels in paediatric cystic fibrosis patients at Birmingham Children's Hospital

ObjectiveCystic fibrosis (CF) is a common recessive disorder with the lungs one of the primary organs affected. Many patients experience chronic pulmonary infection by Pseudomonas aeruginosa. Tobramycin, an aminoglycoside is...

Serum galactomannan in cystic fibrosis patients colonized withAspergillusspecies

Cystic fibrosis patients are often colonized by Aspergillus species. Sera from 138 pediatric and adult cystic fibrosis patients were tested for the presence of galactomannan. All serum samples were negative for galactomannan and there was no difference among patients who were chronically, intermittently, and never colonized with Aspergillus.

Bacteriology of the paranasal sinuses in pediatric cystic fibrosis patients

ObjectivesTo review the characteristic microbiology of the paranasal sinuses in patients with cystic fibrosis who undergo endoscopic sinus surgery. To examine the subtypes of organisms cultured from the maxillary sinuses and determine their sensitivity to antibiotic therapy. Study designRetrospective chart review. SettingTertiary care children's hospital. MethodsSinus cultures were obtained from 51 patients with cystic fibrosis during endoscopic sinus procedures between 2000 and 2004 at a tertiary care children's hospital. A retrospective chart review was undertaken to obtain culture and sensitivity data of the sinus contents. ResultsThe most common bacteria isolated was Staphylococcus aureus (71%), followed by Pseudomonas aeruginosa (PSA) (27%), Haemophilus influenzae (21%), Staphylococcus non-aureus (16%) and Streptococcus viridans (12%). Streptococcus pneumoniae and Moraxella catarrhalis were rarely isolated (2% and 0% respectively). Twenty-nine percent of the patients with cultures positive for PSA were of the mucoid variant. Only one patient had culture positive Escherichia coli. Antibiotic resistance among the more common organisms cultured from the sinus samples is also listed. ConclusionStaph. aureus is the most common isolate in the sinuses of this pediatric CF population followed by P. aeruginosa and H. influenzae. Although many isolates are pansensitive, some isolates are panresistant.

MRI‐based screening for metabolic insufficiency of leg muscle during aerobic exercise in Cystic Fibrosis

There is evidence for mitochondrial dysfunction in various tissues in Cystic Fibrosis (CF) including muscle. Among others, a slow rate of high‐energy phosphate resynthesis following exercise involving single limb muscle activity was found in human CF using in vivo 31P magnetic resonance spectroscopy (MRS). This raises the question whether this outcome would be ameliorated versus exacerbated if instead an exercise regime is used that puts a significant cardiopulmonary load on the body as in running or bicycling. This is of interest because exercise therapy is commonly prescribed in CF. To investigate this matter, ten pediatric CF patients (age 12–16 years) and healthy peers performed two ramp exercise tests to volitional exhaustion using a bicycle ergometer fit for use inside a MR scanner. Endurance, VO2max and heart rate were determined in the exercise laboratory. Quadriceps muscle energy‐and acid/base balance during exercise and recovery were measured on a separate day using MR imaging‐based 31P MRS. This study brings together for the first time this powerful biomedical imaging platform and whole body exercise testing in the clinical setting of human CF.

Molecular Fingerprinting of Mycobacterium abscessus Strains in a Cohort of Pediatric Cystic Fibrosis Patients

Forty-one Mycobacterium abscessus complex isolates from 17 pediatric cystic fibrosis (CF) patients were typed using a novel variable-number tandem repeat (VNTR) scheme and an automated repetitive-PCR (rep-PCR) system. Both VNTR and rep-PCR typing methods differentiate between members of the M. abscessus complex. The isolates from individual patients are indistinguishable, and the data strongly suggest that individual CF patients are persistently infected with one strain and also suggests that different CF patients can harbor the same strain.

Bordetella bronchiseptica in a Paediatric Cystic Fibrosis Patient: Possible Transmission from a Household Cat

Bordetella bronchiseptica is a zoonotic respiratory pathogen commonly found in domesticated farm and companion animals, including dogs and cats. Here, we report isolation of B.bronchiseptica from a sputum sample of a cystic fibrosis patient recently exposed to a kitten with an acute respiratory illness. Genetic characterization of the isolate and comparison with other isolates of human or feline origin strongly suggest that the kitten was the source of infection.