Journal of Cystic Fibrosis

An overview of international literature from cystic fibrosis registries: 2. Neonatal screening and nutrition/growth

2010-03-01

Abstract: Background: This is the second article related to a review of the literature based on data from national cystic fibrosis (CF) registries up to June 2008 and covering a total of 115 studies. It focuses on two topics: neonatal screening (NS) and nutritional status, with particular reference to growth.Methods: Ten papers meeting the inclusion criteria were found on the topic of NS and its impact on the course of the disease, and were analyzed according to a dedicated grid. The issue of nutrition was addressed by 14 studies, analyzed according to similar criteria.Results: Most of the studies report benefits of early diagnosis by NS, albeit to variable degrees. The benefits were assessed in terms of better nutritional status and growth, but also in terms of lower overall morbidity rate as compared to subjects diagnosed by symptoms. The main biases of these studies, which partly undermine the validity of their results, are also analyzed.A part of our analysis on nutrition/growth is dedicated to the identification of the most suitable parameters to define malnutrition: in children older than two years the body mass index percentile (BMIp) appears to be the most sensitive and significantly associated with respiratory function. Better nutritional status and satisfactory growth appear to be associated with better lung function and lower risk of death. The relationship between nutritional status and socio-economic status is also of interest.Conclusions: CF registry studies support the outcome of cohort observational studies i.e. that pre-symptomatic early diagnosis is beneficial, especially in terms of nutritional status and growth. Studies on nutrition indicate that good nutritional status is associated with better respiratory function and prognosis. Regarding methods, the need emerged to manage potential biases of this kind of non randomized studies, resorting to suitable statistical techniques, such as matching and stratification and, above all, to multivariate methods able to provide estimates adjusted for the main covariates tested.

Myeloperoxidase-dependent oxidative metabolism of nitric oxide in the cystic fibrosis airway

2010-03-01

Abstract: Background: Decreased expired nitric oxide (eNO) is commonly observed in cystic fibrosis (CF) patients and is usually explained by dysregulation of NO synthase (NOS) isoforms in respiratory tract epithelium. Later stages of this disease are accompanied by intense airway infiltration of phagocytes with high NOS activity, abundant levels of the hemoprotein myeloperoxidase (MPO) and significant production of significant reactive oxygen species.Methods: This study characterizes the contribution of the high airway levels of MPO to decreased eNO levels in adult CF patients. NO metabolites (NOx) and MPO levels in fresh sputum of control and adult CF patients were determined and related to measurements of eNO and to in vitro consumption of NO in CF sputum.Results: Despite essentially equal levels of NOx in sputum, eNO was 2- to 3-fold lower in CF patients compared to healthy controls. In CF patients, eNO levels were negatively associated with sputum peroxidase activity. In vivo correlations were confirmed by ex vivo studies of NO consumption by MPO in CF sputum. Immunodepletion studies confirmed MPO as the major heme peroxidase in CF sputum contributing to the hydrogen peroxide (H2O2)-dependent consumption of NO.Conclusions: In CF airways MPO acts as a phagocyte-derived NO oxidase that diminishes NO bioavailability at airway surfaces, possibly identifying this peroxidase as a potential target for therapeutic intervention.

Osteoclast function, bone turnover and inflammatory cytokines during infective exacerbations of cystic fibrosis

2010-03-01

Abstract: Background: Raised levels of pro-inflammatory, pro-resorptive cytokines during pulmonary infection may contribute to osteoporosis in cystic fibrosis (CF). We assessed osteoclast number and activity during infective exacerbations and examined their relationship to serum inflammatory cytokines and bone turnover markers.Methods: Serum samples from 24 adults with CF were obtained before, during and after treatment of infection. Osteoclastic cells were generated from peripheral blood mononuclear cells and their number and activity assessed. Serum osteocalcin, type 1 collagen cross-linked N-telopeptide (NTx), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG) were measured.Results: Osteoclast number and activity were increased at the start of exacerbation and decreased with antibiotic therapy. Significant correlations were demonstrated between osteoclast formation and serum TNFα, OPG, osteocalcin and NTx and between osteoclast activity and serum IL-6 and NTx.Conclusions: The systemic response to infection is associated with increased bone resorptive activity in patients with CF.

Genotype based evaluation of Pseudomonas aeruginosa eradication treatment success in cystic fibrosis patients

2010-03-01

Abstract: Background: Longitudinal data regarding the genotypes of Pseudomonas aeruginosa isolates after eradication treatment are limited. We followed cystic fibrosis patients after a first ever isolation of P. aeruginosa and evaluated the P. aeruginosa-free time period after eradication therapy.Methods: Between January 2003 and December 2008 respiratory samples were cultured prospectively from 41 patients with a first ever P. aeruginosa isolate. Twenty five patients had at least one subsequent isolate. Treatment efficacy was assessed based on the time to a second isolation and on comparison of the RAPD genotypes of the P. aeruginosa isolates.Results: Eleven patients became chronically colonized during the study period. For ten of these the second isolate had the same genotype as the first isolate. Moreover, these patients had a significantly shorter P. aeruginosa-free time interval between the first ever and the second isolate compared to the 14 not chronically colonized patients (median 0months versus 7.5months, p<0.05).Conclusion: Our results indicate that the presence of a genotypically identical subsequent P. aeruginosa isolate and/or a short P. aeruginosa-free time interval after treatment are ominous signs and might be useful additional tools to predict impending chronic colonization. Current routine bacteriological methods for the detection of P. aeruginosa may lack the sensitivity to discriminate between true eradication and low bacterial persistence.

Patient segregation and aggressive antibiotic eradication therapy can control methicillin-resistant Staphylococcus aureus at large cystic fibrosis centres

2010-03-01

Abstract: Background: The prevalence of MRSA in patients with CF has risen in recent years. We adhere to a policy of segregation and barrier nursing to manage patients with MRSA, and we actively pursue eradication of MRSA. We have evaluated our experiences of MRSA infection in our large adult CF centre.Method: A retrospective review of all MRSA-positive patients from 1998 to 2008 was undertaken. Isolates were subjected to molecular identification to elucidate possible patient-to-patient transmission events. Eradication attempts were scrutinised.Results: We have maintained a low incidence and prevalence (below 3%) of MRSA within this large cohort. A total of 15 pulsotypes of MRSA were identified among the 24 isolates examined, epidemiological data suggested no patient–patient transmission. Based on 6month follow-up data, successful eradication was achieved in 81% patients. This includes those who had harboured infection for some time. Twenty-one (80.8%) required only one course of treatment, 3 (11.6%) patients required two different regimes and 2 (7.5%) required three courses to fully eradicate the organism.Conclusion: Strict infection control procedures can control MRSA infection and keep the prevalence low in CF clinics. Eradication is achievable in the majority of patients even when significant time has lapsed from initial isolation. In some instances, up to 3 courses of antibiotics were required to achieve eradication.

Prevalence and risk factors for recovery of filamentous fungi in individuals with cystic fibrosis

2010-03-01

Abstract: Background: Filamentous fungi are frequently recovered from respiratory cultures of individuals with CF.Methods: A CF cohort database was utilized to determine filamentous fungal prevalence and risk factors.Results: The prevalence of filamentous fungal isolation increased from 2.0% in 1997 to 28.7% in 2007. The odds of isolating filamentous fungi during a quarter was greater in CF adults [p<0.001], during chronic oral antibiotic use [p=0.002] and increased with each 10% drop in FEV1 percent predicted [p=0.005], while inhaled corticosteroids surprisingly decreased the likelihood [p=0.012]. The direction of these effects persisted after excluding individuals with ABPA. A sub-analysis determined older age [p=0.019] and use of inhaled antibiotics [p=0.011] were independent risk factors for onset of fungal colonization.Conclusions: This study suggests that isolation of filamentous fungi in CF at JHH has increased and risk factors include older age, decreased lung function, and chronic oral antibiotics.

Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis

2010-03-01

Abstract: Background: Although nontuberculous mycobacteria (NTM) are recognized pathogens in cystic fibrosis (CF), associations with clinical outcomes remain unclear.Methods: Microbiological data was obtained from 1216 CF patients over 8years (481±55patients/year). Relationships to clinical outcomes were examined in the subset (n=271, 203±23 patients/year) with longitudinal data.Results: Five hundred thirty-six of 4862 (11%) acid-fast bacilli (AFB) cultures grew NTM, with Mycobacterium abscessus (n=298, 55.6%) and Mycobacterium avium complex (n=190, 35.4%) most common. Associated bacterial cultures grew Stenotrophomonas or Aspergillus species more often when NTM were isolated (18.2% vs. 8.4% and 13.9% vs. 7.2%, respectively, p<0.01). After controlling for confounders, patients with chronic M. abscessus infection had greater rates of lung function decline than those with no NTM infection (−2.52 vs. −1.64% predicted FEV1/year, p<0.05).Conclusions: NTM infection is common in CF and associated with particular pathogens. Chronic M. abscessus infection is associated with increased lung function decline.

What is the best method for measuring renal function in adults and children with cystic fibrosis?

Natalie Soulsby, Hugh Greville, Kingsley Coulthard, Chris Doecke — 2010-03-01

Abstract: AIMS: To measure the glomerular filtration rate (GFR) in adults and children with cystic fibrosis (CF) using a radio-isotope technique as the gold standard and to compare this to serum creatinine based equations, serum cystatin C levels and tobramycin clearance, and to determine which method correlates most closely with measured GFR in this population.

Upper and lower airway cultures in children with cystic fibrosis: Do not neglect the upper airways

2010-03-01

Abstract: Background: Airways of cystic fibrosis (CF) patients are colonised with bacteria early in life. We aimed to analyse differences between results of simultaneously taken upper airway (UAW) and lower airway (LAW) cultures, to describe clinical characteristics of patients with positive versus negative cultures and to follow up the patients with P. aeruginosa positive UAW cultures.Methods: Bacteriological and clinical data from 157 children were collected during annual check up. The number of positive UAW and LAW cultures and correspondence between these results and clinical characteristics were analysed.Results: Positive LAW and UAW cultures were found in 79.6% and 43.9% of patients respectively (p<0.001). Patients with positive LAW cultures were significantly older (11.9 vs. 9.8years, p<0.05) and had more LAW symptoms (73.6% vs. 46.7%, p<0.05), especially when P. aeruginosa was found. Patients with positive UAW cultures (especially S. aureus) had more nasal discharge (50.7% vs. 25.0%, p<0.001). In 65% of patients with positive UAW and negative LAW culture for P. aeruginosa the next LAW became P. aeruginosa positive.Conclusion: UAW cultures and LAW cultures differ in children with CF and there are differences in clinical characteristics between patients with positive versus negative culture results. P. aeruginosa positive UAW cultures appeared to precede positive LAW cultures in a substantial part of patients, suggesting some kind of cross-infection between the UAW and LAW.

Incorporating genetic potential when evaluating stature in children with cystic fibrosis

Zhumin Zhang, Suzanne M. Shoff, HuiChuan J. Lai — 2010-03-01

Abstract: Objective: The 2002 Cystic Fibrosis Foundation (CFF) practice guidelines recommend adjusting for genetic potential when evaluating height status in children with CF. However, there is paucity of data to support this recommendation. We compared three methods of classifying short stature: unadjusted height percentile <10th, Himes adjusted height percentile <10th, and unadjusted height below the CFF target height lower bound.Patients and methods: Data from 3306 children with parental heights documented in the 1986–2005 CFF Patient Registry were analyzed.Results: Mean height percentile of CF children (33rd) was lower than their parents' (mothers' 53rd, fathers' 57th), and 80% of CF children were below the average of their parental height percentiles. In children with short parents, Himes adjusted height percentile was significantly higher than unadjusted height percentile (27th vs. 8th), whereas the opposite was found in children with tall parents (Himes adjusted at 18th vs. unadjusted at 49th). Consequently, the prevalence of short stature decreased from 52% to 22% in children with short parents and increased from 8% to 34% in children with tall parents after Himes adjustment. In children with discrepant classification on short stature before and after Himes adjustment, percent predicted forced expiratory volume in one second was negatively associated with unadjusted height percentile but positively associated with Himes adjusted height percentile. In children with short parents, the CFF method underestimated the prevalence of short stature (9%) compared to the Himes method (22%).Conclusion: Without adjustment of genetic potential, the prevalence of short stature is underestimated and the association between height and lung function is biased.

Transient effectiveness of vitamin D2 therapy in pediatric cystic fibrosis patients

2010-03-01

Abstract: Background: The effectiveness of current treatment recommendations for vitamin D insufficiency in children with CF is unknown. Therefore, we assessed the effectiveness of vitamin D2 50,000IU once daily for 28days for vitamin D insufficiency.Methods: Retrospective chart review of pediatric CF patients from 2006–2008. Vitamin D2 50,000IU daily for 28days was given to patients with 25-OHD <30ng/mL and repeat 25-OHD levels were obtained after completion of therapy.Results: One hundred forty-seven levels from 97 individuals were assessed. Success of treatment was 54% (n=80/147). Seventeen of 39 patients (43%) followed for an additional 6–18months were able to maintain levels of ≥30ng/mL.Conclusions: Vitamin D2 50,000IU daily for 28days was effective in correcting vitamin D insufficiency in approximately 50% of subjects. However, almost half of successfully treated patients were unable to maintain normal 25-OHD levels >6months after completion of therapy, implying that this effect is transient.

Using behavioral interventions to assist with routine procedures in children with cystic fibrosis

Cynthia M. Ward, Tara Brinkman, Keith J. Slifer, Shruti M. Paranjape — 2010-03-01

Abstract: Routine cystic fibrosis (CF) medical care includes invasive procedures that may be difficult for young children and adolescents to tolerate because of anxiety, concern with health status, or unfamiliarity with the performed tasks. A growing body of pediatric psychology literature suggests that behavior therapy can effectively increase patient cooperation with stressful medical procedures such as tracheostomy care and needle sticks. Throat cultures are obtained at least quarterly in the outpatient setting or more frequently if a CF patient develops respiratory symptoms. Obtaining a throat culture from an anxious and uncooperative child poses a significant challenge for physicians, since the child may demonstrate emotional distress and avoidant behavior that disrupts efficient specimen collection during a routine clinic visit. The use of behavioral interventions, such as relaxation exercises, diaphragmatic breathing, differential reinforcement, gradual exposure, and systematic desensitization, is beneficial in addressing this commonly encountered problem in CF care.This case series describes the implementation of a behavioral therapy protocol utilizing two interventions, gradual exposure and systematic desensitization, in two young CF patients for the treatment of behavioral distress with routine throat cultures. The behavioral interventions were simple and transferred easily from mock procedures to actual specimen collection. Moreover, these cases highlight the important roles of the pediatric psychology staff on a comprehensive multidisciplinary CF care team to improve patient cooperation with routine clinic procedures and the medical treatment regimen overall.