Gulnur Com

Dietary essential amino acids are highly anabolic in pediatric patients with cystic fibrosis

BACKGROUND Current nutritional approaches have been partially successful in Cystic Fibrosis (CF). Essential amino acids mixtures with high Leucine levels (EAA) have anabolic properties in catabolic conditions, however data in CF are lacking. METHODS On two days according a randomized crossover design, 15 pediatric CF patients ingested 6.7 g EAA versus mixture of total amino acids as present in whey. Whole body protein and Arginine metabolism (as EAA lack Arginine) were assessed by stable isotope methodology. RESULTS Protein synthesis (P<0.05) but not protein breakdown was higher after EAA and 70% higher values for net anabolism (P<0.001)were found both in patients with and without nutritional failure. Arginine turnover was lower (P<0.001) and de novo Arginine synthesis tended lower (P=0.09) after EAA. Nitric oxide synthesis was not different. CONCLUSIONS CF patients are highly responsive to EAA intake independent of their nutritional status. Addition of Arginine to the EAA mixture may be warranted in CF.

Adenosine Receptors, Cystic Fibrosis, and Airway Hydration

Adenosine (Ado) regulates diverse cellular functions in the lung through its local production, release, metabolism, and subsequent stimulation of G-protein-coupled P1 purinergic receptors. The A(2B) adenosine receptor (A(2B)AR) is the predominant P1 purinergic receptor isoform expressed in surface airway epithelia, and Ado is an important regulator of airway surface liquid (ASL) volume through its activation of the cystic fibrosis transmembrane conductance regulator (CFTR). Through a delicate balance between sodium (Na(+)) absorption and chloride (Cl(-)) secretion, the ASL volume is optimized to promote ciliary activity and mucociliary clearance, effectively removing inhaled particulates. When CFTR is dysfunctional, the Ado/A(2B)AR regulatory system fails to optimize the ASL volume, leading to its depletion and interruption of mucociliary clearance. In cystic fibrosis (CF), loss of CFTR function and resultant mucus stasis leaves the lower airways susceptible to mucus obstruction, chronic bacterial infection, relentless inflammation, and eventually panbronchiectasis. Adenosine triphosphate (ATP) also regulates transepithelial Cl(-) conductance, but through a separate system that relies on stimulation of P2Y(2) purinergic receptors, mobilization of intracellular calcium, and activation of calcium-activated chloride channels (CaCCs). These pathways remain functional in CF, and may serve a protective role in the disease. In this chapter, we will review our current understanding of how Ado and related nucleotides regulate CFTR and Cl(-) conductance in the human airway, including the regulation of additional intracellular and extracellular signaling pathways that provide important links between ion transport and inflammation relevant to the disease.

Stimulated nitric oxide production and arginine deficiency in children with cystic fibrosis with nutritional failure.

OBJECTIVE To determine whether upregulated whole body de novo arginine synthesis and protein breakdown are present as a compensatory mechanism to meet the increased demand for arginine and nitric oxide (NO) production in pediatric patients with cystic fibrosis (CF) and nutritional failure. STUDY DESIGN In 16 children with CF, studied at the end of antibiotic treatment for a pulmonary exacerbation, and 17 healthy controls, whole body arginine, citrulline (Cit), and protein turnover were assessed by stable isotope methodology and de novo arginine synthesis, arginine clearance, NO synthesis, protein synthesis and breakdown, and net protein balance were calculated. The plasma isotopic enrichments and amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. RESULTS Increased arginine clearance was found in patients with CF (P < .001), whereas whole body NO production rate and plasma arginine levels were not different. Whole body arginine production (P < .001), de novo arginine synthesis, and protein breakdown and synthesis (P < .05) were increased in patients with CF, but net protein balance was comparable. Patients with CF with nutritional failure (n = 7) had significantly higher NO production (P < .05), de novo arginine synthesis, Cit production (P < .001), and plasma Cit concentration (P < .05) and lower plasma arginine concentration (P < .05) than those without nutritional failure (n = 9). CONCLUSIONS Nutritional failure in CF is associated with increased NO production. However, up-regulation of de novo arginine synthesis and Cit production was not sufficient to meet the increased arginine needs leading to arginine deficiency.

Predictors and Outcome of Low Initial Forced Expiratory Volume in 1 Second Measurement in Children with Cystic Fibrosis

OBJECTIVE To identify the characteristics of children with cystic fibrosis with low initial forced expiratory volume in 1 second (FEV1) % predicted and to investigate their outcome. STUDY DESIGN Patients were categorized into low or high initial FEV1 groups using cluster analysis. Comparisons of the demographic and clinical data were performed between the 2 groups. RESULTS From 122 children, 21 clustered into the low and 101 into the high FEV1 group. The mean FEV1 was 69% ± 12% predicted for the low and 95% ± 12% predicted for the high FEV1 group (P < .001). The low FEV1 group had lower body mass index percentiles (P = .003), were hospitalized more frequently (P = .001), and had been on dornase alfa longer (P = .006). Low FEV1 group had more patients with positive cultures for Pseudomonas aeruginosa (P = .002) and Stenotrophomonas maltophilia (P < .001) and had more total number of cultures positive for mucoid P. aeruginosa (P = .009) and methicillin resistant Staphylococcus aureus + P. aeruginosa (P = .005). The low FEV1 group continued to have low FEV1 measurements, their FEV1 declined slower, required more hospitalizations per year (P = .01), and had more cultures for mucoid (P = .003) and nonmucoid P. aeruginosa (P = .02) ± methicillin resistant S. aureus (P = .002) in comparison with the high FEV1 group. Poor adherence was associated with lower initial FEV1 values in females, and early, rapid decline of FEV1 in males. CONCLUSIONS Some children with cystic fibrosis may present with poor lung function early in life and continue to have subnormal lung function associated with reduced body mass index, more frequent hospitalization, and higher rates of infection. Such children may benefit from careful evaluation and close follow-up.

Protein is an important but undervalued macronutrient in the nutritional care of patients with cystic fibrosis.

Purpose of reviewAchieving an optimal nutritional status in patients with cystic fibrosis (CF) is important to maintain better pulmonary function, physical performance, and to prolong survival. So far, nutrition care in CF has mainly focused on fat intake and achieving energy balance, but there is increasing information on the clinical importance of muscle maintenance and protein intake in CF. Recent findingsLow muscle mass is consistently associated with pulmonary decline, bone mineral loss, and poor survival in CF. High energy and fat intake contributes to an increased prevalence of overweight and obesity in CF. Obesity per se is not related to better lung function in CF and has negative metabolic and clinical consequences, particularly when muscle wasting is present. Protein digestion capacity is severely impaired in CF, but high protein intake is needed and essential amino acid mixtures appear highly anabolic even in those with severe muscle loss. SummaryBody composition assessment and achieving protein balance in the routine care in CF is important to prevent muscle loss and further improve the clinical and overall outcome of these patients. New approaches are needed to optimize the interaction between high essential amino-acid-rich protein intake and pancreatic enzyme regimen in CF. The optimal level of protein intake needs to be assessed in clinically stable CF patients as well as in those recovering from an acute exacerbation.

Antibiotic hypersensitivity in CF: Drug-induced life-threatening hemolytic anemia in a pediatric patient

Adverse reactions to antibiotics in patients with cystic fibrosis (CF) are a growing concern. We report the case of a pediatric patient with CF with multiple comorbidities and a history of drug reactions, who developed life-threatening piperacillin-induced immune hemolytic anemia. We review drug-induced hemolytic anemia (DIIHA) in particular, and antibiotic hypersensitivity in CF in general, including the frequency, pathogenesis, and risk factors. Finally, we discuss the treatment options and propose an algorithm for the management of drug-induced hypersensitivity reactions in patients with CF.

Role of a Respiratory Therapist in Improving Adherence to Positive Airway Pressure Treatment in a Pediatric Sleep Apnea Clinic

BACKGROUND: Many pediatric patients need positive airway pressure (PAP) for treatment of obstructive sleep-disordered breathing. Adherence to PAP (defined as percent of nights with PAP use of > 4 h) is often poor and not sustained long-term. With any chronic disease, education has been shown to help with patient outcomes. Education of patients and parents regarding PAP can be provided by different healthcare professionals. There is no published literature assessing the role of respiratory therapists (RTs) in improving adherence to PAP in children. We hypothesized that the addition of RT visits to a PAP clinic would improve PAP adherence. METHODS: RT services for PAP patients were introduced in a multidisciplinary pediatric sleep clinic in May 2006. We identified children who had been followed in clinic, and had adherence download information before and after introduction of RT services. We collected demographic, polysomnography, and CPAP adherence data at clinic visits. RESULTS: Forty-six subjects met criteria for inclusion. The mean ± SD age was 14.9 ± 6 y. The mean ± SD apnea-hypopnea index was 26.7 ± 30 events/h. Other than the addition of the RT intervention, all subjects continued to receive the same clinical services as before. Subjects were divided into 3 groups, based on baseline adherence: 0% use, use for 1–50% of nights, and use for > 50% of nights. There was a statistically significant improvement in PAP adherence in the subjects with baseline use of 0% and 1–50%, but no improvement in those with > 50% use at baseline. There was no significant change in PAP use at subsequent RT visits. CONCLUSIONS: Utilization at clinic visits of an RT trained in the use of PAP improved adherence in pediatric subjects with obstructive sleep-disordered breathing when their baseline PAP adherence was < 50%.

Redesigning care to meet national recommendation of four or more yearly clinic visits in patients with cystic fibrosis

Cystic fibrosis (CF) is a chronic disease requiring patients to have frequent specialty healthcare visits to delay progression of lung disease, prevent and treat failure to thrive and initiate early interventions to prevent acute illness and complications. The CF Foundation recommends that patients have visits with the CF care team at least every 3 months. During participation in the CF Foundation Learning and Leadership Collaborative IV, the CF team at Arkansas Childrens Hospital initiated quality improvement work with the aim to increase the percentage of patients attending clinic four or more times a year from 35% in 2004 and 56% in 2005 (CF Foundation Registry data) to 90% or greater. We redesigned our scheduling system, rescheduled missed patient appointments in a timely fashion and created a process to monitor attendance. This quality improvement work led to a sustained increase in the percentage of patients attending clinic visits four or more times a year reaching our goal of 90% in 2012. Improvements were also noted in the number of patients with body mass index/weight-for-length centile of 25 or greater, which could be related to more frequent clinic attendance.

Assessment and Treatment of Obstructive Sleep-Disordered Breathing

Obstructive sleep-disordered breathing (OSDB) is a condition that affects 1% to 3% of the pediatric population. These disorders are difficult to diagnosis and left untreated may be serious, including not only medical comorbidities but also cognitive, academic, behavioral, and emotional sequelae. This article is designed to bring awareness of the severity and prevalence to family physicians and pediatricians. It reviews detailed information concerning OSDB, including the predisposing factors, assessment of presenting features, and treatment.

Complicated Clostridium difficile colitis in children with cystic fibrosis: Association with gastric acid suppression?

Patients with cystic fibrosis (CF) have several risk factors for Clostridium difficile colonization such as frequent hospitalization and exposure to a broad array of antibiotics utilized for the control, eradication, and prophylaxis of respiratory pathogens. However, despite this high rate of colonization, the occurrence of C. difficile infection (CDI) in CF is rare. We report three children with CF who presented with severe community-associated CDI. All three children had complicated courses and one died. These children were in good health without significant morbidities, and were not frequently hospitalized nor did they receive frequent antibiotic courses. The occurrence of 3 severe cases within a 15-month period prompted us to report these cases and review the literature in regard to CDI. We reviewed the CF GI tract as possible risk factors for a high rate of C. difficile colonization in individuals with CF. Since a high percentage of individuals with CF are on gastric acid blocking agents, we also focused on gastric acid suppression as a potential risk factor for CDI.