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CF Patients (cf + patient)
Selected AbstractsIdentification and Characterization of CFTR Gene Mutations in Indian CF PatientsANNALS OF HUMAN GENETICS, Issue 1 2009N. Sharma Summary Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study was performed on Indian CF patients (n = 50) to investigate the spectrum of mutations in the CFTR gene and their association with intragenic and extragenic marker haplotypes. We report identification of 14 previously known and eight novel mutations, namely 3986-3987delC, 876-6del4, 1792InsA, L69H, S158N, Q493L, I530L and E1329Q. The frequency of delta F508 was found to be 27%. Absolute linkage between delta F508 and the KM.19-GATT-TUB9-M470V-T854T haplotype (2-2-1-1-1) predicts a relatively recent appearance of delta F508 in Indian CF patients. Low frequency of delta F508 mutation and detection of eight novel and thirteen rare mutations reflect a heterogeneous spectrum of mutations in Indian CF patients. Failure to detect mutations in 34% of alleles indicates the possible presence of gross deletions involving one or more exons or may indicate the location of the molecular defects in either the noncoding parts of the gene or in the promoter region, which warrants analysis of those regions. [source] Plastic bronchitis as an unusual cause of mucus plugging in cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 9 2009Dimas Mateos-Corral MD Abstract Cystic fibrosis patients are known to produce abundant, purulent sputum consisting mainly of DNA and cellular debris. We present a case of a CF patient with recurrent airway obstruction caused by a rare condition known as plastic bronchitis (PB). PB is characterized by the formation of casts of the airways that cause obstruction. Multiple etiologies have been proposed, but to our knowledge, no CF patient has been reported in any PB classification. Histological analysis and in-vitro testing of the cast were important factors in choosing the adequate therapy in this patient. Pediatr Pulmonol. 2009; 44:939,940. © 2009 Wiley-Liss, Inc. [source] Treatment of allergic bronchopulmonary aspergillosis (ABPA) in CF with anti-IgE antibody (omalizumab)PEDIATRIC PULMONOLOGY, Issue 12 2008Adaobi Kanu MD Abstract Allergic bronchopulmonary aspergillosis (ABPA) results from IgE induced pulmonary response to aspergillus species. Recognition and management of ABPA is challenging in cystic fibrosis (CF) patients because changes in symptoms, lung function and chest radiograph are similar to that seen in CF related pulmonary infection. Standard therapy for ABPA includes systemic steroids and adjunctive use of antifungal agents. Little has been published regarding the use of monoclonal anti-IgE antibody in those with ABPA. We report a CF patient with her third exacerbation of ABPA who was treated with monoclonal anti-IgE (omalizumab) antibody; she had unfavorable side effects with prednisone therapy. This therapy resulted in improvement of pulmonary symptoms and lung function not achieved with antibiotics or prednisone alone. Pediatr. Pulmonol. 2008; 43:1249,1251. © 2008 Wiley-Liss, Inc. [source] Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host,pathogen interactions in cystic fibrosisAPMIS, Issue 2 2009CLAUS MOSER The dominant cause of premature death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes significant genetic changes, resulting in diversifying geno- and phenotypes. Such an adaptation may generate different host responses. To experimentally reflect the year-long chronic lung infection in CF, groups of BALB/c mice were infected with clonal isolates from different periods (1980, 1988, 1997, 1999 and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non-mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production of macrophage inflammatory protein-2 (MIP-2) and granulocyte colony-stimulating factor (G-CSF). In contrast, the mucoid clones were more virulent and virulence increased with time, resulting in impaired pulmonary clearing of the latest clone, severe inflammation and increased pulmonary MIP-2 and G-CSF production. In conclusion, adaptation of P. aeruginosa in CF is reflected by changed ability to establish lung infection and results in distinct host responses to mucoid and non-mucoid phenotypes. [source] Worldwide distribution of Pseudomonas aeruginosa clone C strains in the aquatic environment and cystic fibrosis patientsENVIRONMENTAL MICROBIOLOGY, Issue 7 2005Ute Römling Summary Highly successful bacterial clones have the ability to effectively colonize environmental niches and patients. However, the factors which determine the complex interplay between the colonization of environmental niches and patients are mainly unknown. In this study we show that Pseudomonas aeruginosa clone C strains are distributed worldwide and highly prone to infect cystic fibrosis (CF) patients in Canada, England, France and Germany. In Hanover, Germany and Vancouver, Canada, clone C strains are highly prevalent in the CF patient community, although the mechanisms of acquisition may have been different. All clone C strains showed highly related macrorestriction fragment pattern of the whole genome as visualized by pulsed-field gel electrophoresis and harboured the 102 kbp plasmid pKLC102. Comparison of three prevalent P. aeruginosa clones with different distribution between the environment and patients revealed that neither enhanced biofilm formation nor antibiotic resistance was responsible for the spread of clone C. Clone M, which was highly prevalent in the clinical environment such as sanitary facilities, lacked motility, which could explain its relatively low prevalence in CF patients. Elucidation of the mechanisms which lead to the prevalence of clone C strain in patients and the environment requires the investigation of additional phenotypes. [source] Ceramide in Pseudomonas aeruginosa infectionsEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 10 2007Joachim Riethmüller Abstract Cystic fibrosis (CF), the most common autosomal recessive disorder, at least in western countries, is caused by mutations of the cystic fibrosis transmembranous conductance regulator (CFTR) molecule and affects approximately 80,000 patients in Europe and the USA. Most, if not all, CF patients develop a chronic pulmonary infection with Pseudomonas aeruginosa. At present it is unknown why CF patients are highly sensitive to P.,aeruginosa infections, and most importantly, no curative treatment for CF is available. P.,aeruginosa infection results in an activation of the enzyme acid sphingomyelinase which catalyzes the release of ceramide from sphingomyelin in the cell membrane. Ceramide forms large ceramide-enriched membrane domains that are required for internalization of bacteria, induction of cell death in infected cells and a controlled release of cytokines from infected cells. Ceramide-enriched membrane platforms seem to serve the reorganization of receptors and intracellular signaling molecules involved in the infection of mammalian cells with P.,aeruginosa. The significance of the acid sphingomyelinase and ceramide for the infection of mammalian cells with P.,aeruginosa was demonstrated on mice genetically deficient for the acid sphingomyelinase. Further studies with N.,gonorrhoeae, S.,aureus and rhinoviruses indicate that ceramide-enriched membrane domains are also important for the infection of mammalian cells with other bacterial and viral pathogens, suggesting a general role of these membrane domains in infectious biology. [source] Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosisHEPATOLOGY, Issue 2 2000Nils Kinnman M.D. The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers in liver cryosections in 11 patients with CF-associated liver disease, and non-CF controls with (n = 17) and without (n = 3) liver disease. In CF patients prominent inflammatory infiltrates were not found, yet hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM-1 immunoreactivity in 3 cases, but bile ducts were otherwise negative. In 2 patients homozygous for R764X and for 1112delT no CFTR immunoreactivity was detected. Bile-duct epithelial cells in patients carrying the ,F508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the luminal surface seen in controls. No clear relationship between CFTR expression and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of ,F508 CFTR processing in intrahepatic biliary epithelium. ICAM-1 expression on bile-duct epithelial cells and inflammatory infiltrates were rare findings in CF liver tissue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF-associated liver disease. [source] Analysis of DEFB1 regulatory SNPs in cystic fibrosis patients from North-Eastern ItalyINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2010L. Segat Summary Cystic fibrosis (CF) transmembrane regulator protein (CFTR) gene is undoubtedly the main genetic factor involved in the modulation of CF phenotype. However, other factors such as human defensins and the genes encoding for these antimicrobial peptides have been hypothesized as possible modifiers influencing airways infection in CF patients, but their role in the pathogenesis of lung disease is still debated. Since DEFB1 gene encoding for human beta-defensin 1 displays features such as antimicrobial or chemotactic activity playing a role in inflammation, it has been considered as a possible candidate CF modifier gene. We analysed three single nucleotide polymorphisms (SNPs) in the 5,-untranslated region of the DEFB1 gene (namely g-52G>A, g-44C>G and g-20G>A) in a group of 62 CF patients from North Eastern Italy, and in 130 healthy controls, with the aim of verifying the possible association of these functional SNPs with the pulmonary phenotype of CF patients. DEFB1 SNPs have been genotyped by using Taqman allele-specific fluorescent probes and a real-time PCR platform. No significant differences were found for allele, genotype and haplotype frequencies of DEFB1 g-52G>A, g-44C>G and g-20G>A SNPs in CF patients stratified for Pseudomonas aeruginosa infection, as well as in patients with a severe and mild clinical phenotype or in patients stratified for CFTR genotypes. DEFB1 allele, genotype and haplotype frequencies of CF patients globally considered were similar to those of healthy controls. Our findings are discordant with respect to another recent study performed on CF patients coming from Southern Italy, probably due to different ethnicity of the patients. [source] Vitamin K prescribing patterns and bone health surveillance in UK children with cystic fibrosisJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 6 2007D. S. Urquhart Abstract Background, Bone disease has become an increasingly recognized complication of cystic fibrosis (CF). Although causes of CF bone disease are multifactorial, there has been recent interest in the role of vitamin K in CF bone disease. Aims,and,methods, A questionnaire survey of all UK paediatric CF centre dietitians and centre directors was carried out to ascertain current practice with regard to vitamin K prescribing and bone health surveillance. Results, The survey had a 97% response rate representing 3414 CF children. Twenty-three centre directors and 19 dietitians responded, and at least moderate agreement was noted with kappa scores >0.41 for all but one question assessed. Ninety-three per cent centres report that >90% pancreatic insufficient patients receive vitamins A, D and E, yet only 18% centres routinely supplement vitamin K. The majority (60%) report that <10% of their CF patients receive vitamin K, whilst vitamin K dosage varied from 0.3,0.5 to 10 mg day,1. Only one centre undertook no bone health surveillance, and vitamin D levels are measured in 89%, calcium intake assessed in 82% and dual-energy X-ray absorptiometry scans performed in 61% centres. Discussion, Heterogeneity in both vitamin K prescribing practices and bone health surveillance in CF across the UK were noted, underlining the need for a national consensus on bone health management, as well as acting as a call for longitudinal research into the clinical effectiveness of vitamin K therapy in CF. [source] Five-year prospective analysis of dietary intake and clinical status in malnourished cystic fibrosis patientsJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2003J. Walkowiak Abstract Background, Poor growth and malnutrition still pose a problem in cystic fibrosis (CF). The aim of the present study was to assess nutrition, as well as clinical status, of malnourished CF patients during a nutritional care programme. Material and methods, The study comprised 38 CF patients, aged 1,18 years old. The prospective annual assessment of dietary intake and clinical status was carried out during 1994,98. Results, The energy intake increased, in comparison with recommended daily allowances, from 83.6 ± 4.8% in 1994 to 107.9 ± 4.9% in 1998. A similar tendency was observed for the percentage of energy derived from fat (30.3 ± 0.8% versus 35.1 ± 0.8%) and protein (11.4 ± 0.4% versus 13.8 ± 0.4%). In subsequent years of the study, an improvement in the fat profile of the diet (with a higher consumption of polyunsaturated fatty acids) was observed. The observed increase of vitamin A and E consumption was related chiefly to changes in the doses of supplementation. During these 5 years, an improvement in nutritional status (Z-score: height ,1.34 ± 0.13 versus ,1.08 ± 0.14 and weight ,1.40 ± 0.09 versus ,1.12 ± 0.08) and lung function (forced expiratory volume in 1 s: 75.5 ± 2.0% versus 77.8 ± 2.2%) was observed. Conclusion, The nutritional care programme resulted in stable quantitative and qualitative changes in dietary intake. Although the diet does not reach the recommended level of high-energy intake, the positive impact of increasing nutrient intake on the nutritional and clinical status of malnourished CF patients was documented. [source] Increased soluble CD40 ligand levels in cystic fibrosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2004A. Falco Summary., Chronic inflammation represents a key pathogeneric event in the progression of lung disease in cystic fibrosis (CF). To identify novel mechanisms of the inflammatory reaction in CF and analyze its relation with coagulative activation, we carried-out a cross-sectional study to evaluate circulating levels of the inflammatory mediators soluble (s) CD40L, C-reactive protein (CRP), interleukin (IL)-1,, the coagulation markers activated factor VII (FVIIa) and prothrombin fragment (F) 1+2, as well as urinary 11-dehydro-thromboxane (TX)B2, an index of in vivo platelet activation, in 34 CF patients and 34 matched healthy subjects. We observed that CF patients displayed significantly increased circulating levels of sCD40L compared to controls [2.8 (0.4,15.6) vs 1.1 (0.2,2.7) ng mL,1 ,P = 0.0003]. sCD40L levels inversely correlated with forced expiratory volume at 1 second (FEV1) (, = ,0.788, P = 0.0001), whereas it directly correlated with CRP and IL-1, levels (, = 0.621, P = 0.0004; and , = 0.745, P = 0.0001, respectively), which were also elevated in CF patients. CF patients had also enhanced levels of FVIIa and F1+2 compared to controls [39.2 (22.6,69.8) vs 22.3 (16.2,32.4) mU mL,1, P = 0.0001; 0.60 (0.30,1.80) vs 0.17 (0.10,0.40) nmol L,1, P = 0.0001, respectively]. A direct correlation was observed between sCD40L and both plasma FVIIa (, = 0.691, P = 0.0001) and F1+2 (, = 0.545, P = 0.0017) as well as between sCD40L and urinary 11-dehydro-TXB2 (, = 0.433, P = 0.0129). Our findings suggest that in CF patients, sCD40L could represent a biochemical link between the inflammatory state, and endothelial damage and coagulative activation, leading to progressive impairment of pulmonary function. [source] One-year glargine treatment can improve the course of lung disease in children and adolescents with cystic fibrosis and early glucose derangementsPEDIATRIC DIABETES, Issue 3 2009Enza Mozzillo Background:, Diabetes increases morbidity and mortality in cystic fibrosis (CF) patients, but several studies indicate that also prediabetic status may have a potential impact on both nutrition and lung function. Objective:, To evaluate the effect of glargine on the clinical course in CF patients with early glucose derangements. Methods:, CF population was screened for glucose tolerance. CF patients with age >10 yr were screened with fasting hyperglycemia (FH). CF patients with age >10 yr without FH and those with age <10 yr with occasional FH were evaluated for glucose abnormalities on the basis of oral glucose tolerance test and/or continuous glucose monitoring system. All CF patients with glucose derangements were enrolled in an open clinical trial with glargine. Body mass index (BMI) z-score, forced expiratory volume in the first second (FEV1), number of acute pulmonary exacerbations and hemoglobin A1c, were as outcome measures at baseline and after 1 yr of treatment. Results:, After 12 months of therapy, BMI z-score improved only in patients with baseline BMI z-score less than ,1 (p = 0.017). An 8.8% increase in FEV1 (p = 0.01) and 42% decrease in the number of pulmonary exacerbations (p = 0.003) were found in the whole group compared with previous 12 months of therapy. Conclusion:, Glargine could represent an innovative strategy to prevent lung disease progression in CF patients with early glucose derangements. Larger controlled trials are needed to better clarify the effects of insulin on clinical status in CF patients with early glucose derangements. [source] Meconium ileus,it is time to act now!PEDIATRIC PULMONOLOGY, Issue 10 2010Matthias Kappler MD Meconium ileus is a life-threatening presentation of neonates with cystic fibrosis (CF). Notwithstanding, today the long-term prognosis of such patients is comparable to that of CF patients not diagnosed in screening programs and not suffering from this insult,1,3 as confirmed by the article of Johnson et al. in this issue of Pediatric Pulmonology. Good news then for CF patients and CF caretakers, working with the modern interdisciplinary setting of neonatal intensive care, including radiology, anesthesiology, and pediatric surgery experts. State of the art management of life-threatening neonatal ileus during this fragile early phase of life obviously balances all disadvantages associated with neonatal ileus and provides an outcome not different from that in CF patients without meconium ileus, but diagnosed later during early childhood. Pediatr Pulmonol. 2010; 45:949,950. © 2010 Wiley-Liss, Inc. [source] Probiotic supplementation affects pulmonary exacerbations in patients with cystic fibrosis: A pilot studyPEDIATRIC PULMONOLOGY, Issue 6 2010Batia Weiss MD Abstract Objective Probiotics reduce intestinal inflammation in, and Lactobacillus GG (LGG) reduces pulmonary exacerbation rate cystic fibrosis (CF) patients. We intended to determine the effect of a mixed probiotic preparation on pulmonary exacerbations and inflammatory characteristics of the sputum in CF patients. Study Design A prospective pilot study of 10 CF patients with mild,moderate lung disease and Pseudomonas aeruginosa colonization, treated with probiotics for 6 months. Pulmonary function tests (PFT's), sputum cultures with semi-quantitative bacterial analysis, and sputum neutrophil count and interleukin-8 (IL-8) levels were compared to pre-treatment and post-treatment values. The rate of pulmonary exacerbations was compared to 2 years prior to the study. Results The exacerbation rate was significantly reduced in comparison to the previous 2 years and to 6 months post-treatment (P,=,0.002). PFT's have not changed at the end of treatment and during 6 months post-treatment. No change in sputum bacteria, neutrophil count, and IL-8 levels was observed. Conclusion Probiotics reduce pulmonary exacerbations rate in patients with CF. Probiotics may have a preventive potential for pulmonary deterioration in CF patients. Pediatr Pulmonol. 2010; 45:536,540. © 2010 Wiley-Liss, Inc. [source] The use of high resolution computerized tomography (HRCT) of the chest in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis lung disease,PEDIATRIC PULMONOLOGY, Issue 5 2010Samya Z. Nasr MD Abstract Objectives To compare the usefulness of HRCT of the chest versus spirometric measures (PFTs) in evaluating the effect of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF). Methods Thirty-two CF patients with mostly mild lung disease age ,6 years, were enrolled in a double-blind, placebo-controlled pilot study. Patients were chronically colonized with Pseudomonas aeruginosa for at least 6 months prior to and at enrollment. If patients were on TSI, they were taken off for at least 3 months prior to enrollment. Duration was 6 months; 31 subjects completed the study. HRCT and PFTs were evaluated at baseline, after 28 days of treatment and at the end of the study. Study medication was administered as 5,ml nebulized treatment twice a day for 28 days followed by 28 days off (one cycle). Study consisted of three cycles. Two radiologists scored all films using a validated system. A total HRCT score consists of the sum of subscores: linear opacities, hyperinflation, nodular opacities, peribronchial thickening, mucous plugging, and bronchiectasis; each subscore could range from 0 to 80, with potential total scores varying from 0 to 480. The percent of the maximum possible HRCT score was then calculated and used for all comparisons. Results Using two tailed paired t -test, the percent maximum HRCT score decreased by 1.4,±,2.6% (mean,±,SD) (P,=,0.049) and 0.3,±,2.8% (P,=,0.63) for the TSI group and decreased by 0.1,±,1.5% (P,=,0.74) and increased by 0.6,±,1.8% (P,=,0.23) for the placebo group between visits 1 and 2, and visits 1 and 3, respectively. The data were then analyzed using a mixed model utilizing changes in scores over the durations of the study for each group. The change of HRCT score for the TSI group was ,0.24/day (P,=,0.02) and ,0.03/day (P,=,0.22), and for the control group the change was ,0.01 (P,=,0.93) and 0.02 (P,=,0.29) between visits 1 and 2, and visits 1 and 3 respectively. FEF25,75% and FEV1% changes were not statistically significant using both analyses. Conclusion HRCT seems to be more sensitive in detecting treatment effect than PFT in CF patients with mild lung disease, especially following the first treatment period (visit 2). Total HRCT score showed some improvement at the end of the study, though not statistically significant. This is probably due to obtaining the HRCT an average of 30 days after completion of the TSI treatment, and selection of study population with mostly mild lung disease. This could indicate that the most significant improvement in the total HRCT score in this patient population occurs after the first treatment period with TSI. Pediatr Pulmonol. 2010; 45:440,449. © 2010 Wiley-Liss, Inc. [source] Short-term effect of physiotherapy on variability of the lung clearance index in children with cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 3 2010Susanne I. Fuchs MD Abstract Multiple breath washout (MBW) for measuring the lung clearance index (LCI) has been proposed as a non-invasive tool for detecting early cystic fibrosis (CF) lung disease. The LCI is highly repeatable and reproducible in healthy subjects. In patients with CF, within-test variability is low. However, application of physiotherapy (PT) immediately preceding MBW may affect LCI variability in CF patients and thus interpretation of repeat measurements and treatment effects. Therefore, the aim of the present study was to prospectively assess the short-term effect of PT on LCI in CF patients in order to address the question whether or not standardized timing of PT and MBW has to be considered when introducing MBW into clinical CF management. Twenty-seven out of 32 patients (5.7,15.9 years) with CF successfully performed two technically acceptable MBW tests with the EasyOne Pro, MBW Module (ndd, Switzerland) at intervals of 1½,hr. Sixteen out of 27 received 30,min PT in between, whereas 11/27 did not. Repeatability expressed as intraindividual coefficient of variation (CV) was 6.1% pre-PT and 6.5% post-PT. Mean difference (95% CI) of LCI between the two tests was ,0.20 (,0.51; 0.11). Reproducibility (SD) was 4.6% (3.1). Repeatability was 4.2% and 7.1% without intervention. Mean difference (95% CI) of LCI between 1st and 2nd test was 0.07 (,0.22; 0.35). Reproducibility (SD) was 2.6% (2.1). In conclusion, PT does not have a consistent effect on the LCI. Repeatability was slightly poorer than published for healthy subjects possibly reflecting variable mucus plugging, and, thus, variable trapped air in patients with CF. Reproducibility was good and independent on intervention. From our data, we conclude that timing of PT in relation to MBW can be ignored when designing study protocols or when interpreting longitudinal data and treatment effects. Pediatr Pulmonol. 2010; 45:301,306. © 2010 Wiley-Liss, Inc. [source] Transforming growth factor-,1 in bronchoalveolar lavage fluid from children with cystic fibrosis,PEDIATRIC PULMONOLOGY, Issue 11 2009William T. Harris MD Abstract Rationale Transforming factor ,1 (TGF-,1) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF-,1 protein levels and clinical markers of CF lung disease severity. Objectives To determine the association between protein levels of TGF-,1 in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity. Methods Total TGF-,1 was measured in BALF from 30 pediatric CF patients and 12 non-CF disease controls undergoing clinically indicated flexible bronchoscopy, and compared to four indicators of clinical disease: infection, inflammation, pulmonary function, and recent/recurrent hospitalization. Results TGF-,1 was elevated in CF BALF compared to non-CF controls (135,±,15,pg/ml vs. 57,±,10,pg/ml, P,<,0.01). In CF BALF, increased TGF-,1 was associated with elevated BALF PMN % (r,=,0.67, P,<,0.01). BALF TGF-,1 was increased in CF subjects whose FEV1 after the completion of antibiotic therapy remained below CF age-normative median values (205.9,±,20.5,pg/ml vs. 106.4,±,24.0, P,=,0.01). BALF TGF-,1 was increased in CF children hospitalized in the previous year compared to those not recently hospitalized (169.9,±,21.6,pg/ml vs. 107.5,±,17.5,pg/ml, P,=,0.04). Neither the presence of a bacterial pathogen nor bacterial quantity was associated with BALF TGF-,1. Conclusions In CF, BALF TGF-,1 is elevated compared to non-CF controls. Increased BALF TGF-,1 is associated with neutrophilic inflammation, diminished lung function and recent hospitalization. Further investigation is needed to address mechanisms behind these associations. Pediatr Pulmonol. 2009; 44:1057,1064. ©2009 Wiley-Liss, Inc. [source] Relation of bone mineral density with clinical and laboratory parameters in pre-pubertal children with cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 7 2009Nazan Cobanoglu MD Abstract To study bone mineral density (BMD) of pre-pubertal cystic fibrosis (CF) children, and its relation with clinical and laboratory parameters, we enrolled 16 CF (8 girls) (4,8 years), and 16 control children (8 girls) (4,8 years). After anthropometric measurements, BMD, serum calcium, phosphorus, total alkaline phosphatase (ALP), 25-hydroxy vitamin D (25-OHD), parathyroid hormone, osteocalcin, tumor necrosis factor (TNF)-,, soluble TNF-, receptor 2 (sTNFR2), and soluble IL-2 receptor (sIL-2R) levels, and urinary calcium and hydroxyproline excretions were assessed. Disease severity of CF patients was determined with Shwachman,Kulczycki clinical and Brasfield radiological scoring systems. The mean Shwachman,Kulczycki and Brasfield scores of CF patients were indicating well-controlled disease. The anthropometric measurements, mean BMD values, and serum calcium, phosphorus and parathyroid hormone levels were within normal range and similar in both groups. Serum osteocalcin levels were lower, and ALP and 25-OHD levels were higher in CF. Although 24-hr urinary calcium excretions was higher in CF patients, hydroxyproline excretions were similar in both groups. There was no difference between two groups for the serum levels of sIL-2R, TNF-, and sTNFR2. Children with low vertebral z -scores had higher serum sIL-2R levels in both groups, but the same relation could not be shown for TNF-, and sTNFR2. We may speculate that younger, healthier and well-nourished patients with CF may have normal BMD, but the bone disease develop as patients get older because of the other contributing factors. Future well-designed longitudinal studies with large cohorts might show a relation with BMD and cytokines in CF. Pediatr Pulmonol. 2009; 44:706,712. © 2009 Wiley-Liss, Inc. [source] Antibody response to Pseudomonas aeruginosa in children with cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 4 2009Lucimar G. Milagres PhD Abstract Cystic fibrosis (CF) is the most frequent life threatening autosomal recessive disease in white subjects. The primary cause of morbidity and mortality in children with CF is chronic pulmonary infection, mainly caused by Pseudomonas aeruginosa. The purpose of this study was to assess the value of the measurement of antibodies to P. aeruginosa in diagnosing lung infection by the bacteria in CF patients. We assessed P. aeruginosa antibody titers in CF patients from Rio de Janeiro, Brazil, using cell lysate antigens as well as recombinant PcrV, a Type III Secretion System protein. Sputum (more than 70% of the specimens) or oropharyngeal swabs were obtained whenever patients were regularly followed for their pulmonary disease. Blood samples were obtained with an average interval of 6 months for a period of 2 years. The ELISA cut-offs were assigned as the positive 95% confidence interval of the mean antibody levels from non-fibrocystic controls. Our data showed that most CF patients (81%) of whom were not chronically infected by P. aeruginosa (Groups I and II), had their first serology positive for rPcrV. Cell-lysate ELISA was able to detect P. aeruginosa antibodies before positive culture in the first serum sample of 44% of the patients from Groups I and II. When serum reactivity to rPcrV and cell lysate were combined, 94% of CF patients from Groups I and II (n,=,16) had the first serology positive for P. aeruginosa over a mean time of 20 months before the first isolation of P. aeruginosa. In conclusion, longitudinal P. aeruginosa serology should become part of respiratory care follow-up, in conjunction with other lung parameter functions. Pediatr Pulmonol. 2009; 44:392,401. © 2009 Wiley-Liss, Inc. [source] Reproducibility of spirometry during cystic fibrosis pulmonary exacerbations,,PEDIATRIC PULMONOLOGY, Issue 11 2008Don B. Sanders MD Abstract Objectives: To compare the within day variation of spirometry between hospital admission, discharge, and outpatient follow up among children with cystic fibrosis (CF) hospitalized for a pulmonary exacerbation. Hypothesis: Within day variation of spirometry will be greater at hospital admission than at hospital discharge or outpatient follow up. Methods: We performed a retrospective review of spirometry data for all patients with CF ,6 years old admitted to our pediatric CF center for a pulmonary exacerbation in 2004 or 2005. For patients who had previously performed spirometry successfully, measurements were used from one admission only during 2004,2005 if the spirometry occurred within 3 days of hospital admission, 3 days of discharge, or at a follow up clinic visit when well. We compared the within day coefficients of variation (CV) for FVC, FEV1, and FEF25,75 between time points using the Wilcoxon signed rank-test. We also determined the change in spirometry that is likely to be beyond measurement variability during inpatient treatment of a pulmonary exacerbation. Results: Spirometry data were available from 40 subjects at admission and follow up and 35 at hospital discharge. There was no significant difference in CV at admission, discharge, and follow up for FVC, FEV1, or FEF25,75. The mean (SD) CV was 3.1% (2.7) for FVC, 3.2% (2.1) for FEV1, and 9.7% (7.0) for FEF25,75 at admission, 2.8% (2.2) for FVC, 3.1% (2.1) for FEV1, and 8.1% (6.7) for FEF25,75 at discharge, and 2.7% (1.7) for FVC, 2.8% (2.0) for FEV1, and 8.4% (7.8) for FEF25,75 at follow up. These are similar to previous reports of outpatients with CF. The improvement in spirometry that exceeded measurement variability for our cohort was 80 ml for FVC, 70 ml for FEV1, and 220 ml/sec for FEF25,75. Conclusions: The presence of an acute pulmonary exacerbation in children and adolescents with CF does not substantially contribute to the within day variation in spirometry. Within day variation of spirometry for children with CF during pulmonary exacerbations is similar to previously reported values from clinically stable CF patients. Pediatr. Pulmonol. 2008; 43:1142,1146. © 2008 Wiley-Liss, Inc. [source] Assessment of body composition in pediatric patients with cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 10 2008Greg D. Wells PhD Abstract Rationale Cystic fibrosis (CF) leads to pathological changes in organs that express the cystic fibrosis transmembrane conductance regulator (CFTR), including secretory cells of the digestive tract and the pancreas. Maintaining nutritional sufficiency is challenging for CF patients and therefore accurate monitoring is important for their clinical management. Purpose The objectives of this study were to evaluate the effectiveness of skinfold measurements as an accurate method for determining body composition (fat mass (FM) and lean body mass (LBM)) of this population, using dual-energy X-ray absorptiometry (DEXA) as a gold standard comparison and to determine the most accurate equation for this calculation in children with CF. Methods Fifty-five pediatric patients with CF participated in the study. FM and LBM calculated via four methods: Slaughter, Durnin, Durenberg (2-site and 4-site). The relationship between the methods and DEXA results were estimated by intraclass-correlation coefficient (ICC) and Bland and Altman analyses. Results The Slaughter method was the most accurate (ICC of 0.92 for FM and 0.99 for LBM) and displayed the least bias over the range of FM and LBM in CF patients. In addition, the results of Bland Altman analyses comparing each skinfold method to DEXA, revealed that the results were evenly distributed along the range of values for the Slaughter calculation, whereas the other three methods under and over estimated % fat results at the upper and lower ends of the range respectively. Conclusion We therefore conclude that the Slaughter method may be used for body composition assessment of pediatric CF patients. This provides clinical teams with a simple, accurate and non-invasive method that can be used to monitor nutritional status in pediatric patients with CF. Pediatr Pulmonol. 2008; 43:1025,1032. © 2008 Wiley-Liss, Inc. [source] Aerosol therapy in cystic fibrosis: Weighing the evidencePEDIATRIC PULMONOLOGY, Issue S9 2008Felix Ratjen MD Abstract Aggressive treatment of CF lung disease has markedly increased survival of CF patients and intense research efforts over the last decades have led to new treatment strategies, many of which target the lower airways directly via aerosol. The addition of any new therapy not only needs to be assessed in view of its individual efficacy, but also in context with other established therapies. This review will summarize the current evidence on aerosol therapy in CF focussing on therapies that hydrate airways, mucolytic therapy with dornase alfa and inhaled antibiotics. The different therapeutic regimens will be critically assessed in context to address the question of whether these different drugs can be used interchangeably or should be used in combination in CF lung disease. Pediatr Pulmonol. 2008; 43:S3,S4. © 2008 Wiley-Liss, Inc. [source] The science of aerosol delivery in cystic fibrosisPEDIATRIC PULMONOLOGY, Issue S9 2008David E. Geller MD Abstract Aerosolized drugs are universally used for treatment of cystic fibrosis airway disease. Inhalation can increase topical efficacy and reduce systemic exposure and toxicity of many drugs. A wide variety of inhaled drugs already exist with many more in the therapeutic pipeline. Understanding the principles of aerosol delivery and how aerosol devices function is important in designing the best therapeutic regimens for CF patients. The variables that determine where an aerosol deposits are numerous and complex. Important aerosol-related variables include particle-size distribution, hygroscopic properties, viscosity and surface tension of the drug. Patient-related variables include inspired flow rate, tidal volume, respiratory rate, breath-holding, upper airway anatomy, lower airways obstruction, and the cognitive and physical ability to use the device. These factors vary widely between patients of different age groups and disease severities, and cause the high variability in drug delivery seen with aerosol drugs. Classic aerosol delivery devices like metered dose inhalers and dry-powder inhalers are small, portable, and have short treatment times. However, they are limited by small drug payloads and user technique problems. Jet nebulizers are commonly used for CF drugs, are easy to operate, require no special breathing pattern, and can deliver very large quantities of drug. However, they require a power or air source, cleaning and sanitizing, and are relatively time consuming. Recently, novel aerosol delivery systems and formulations have been developed to improve delivery efficiency and reduce variability and delivery time. These new systems can ease the treatment burden and improve adherence and outcomes in cystic fibrosis. Pediatr Pulmonol. 2008; 43:S5,S17. © 2008 Wiley-Liss, Inc. [source] Doll-like face: Is it an underestimated clinical presentation of cystic fibrosis?PEDIATRIC PULMONOLOGY, Issue 7 2008Mehmet Kose MD Abstract Cystic fibrosis (CF) is the most prevalant inheritable chronic disease in caucasian children. The clinical syndrome of kwashiorkor is well-recognized complication of CF. The edema of the face can be seen in kwashiorkor. As doll-like face is very rare and underestimated clinical presentation of CF patients complicated with hypoproteinemia we evaluated demographic features and laboratory characteristics of 5 patients diagnosed as CF with doll-like face. Methods: Between June 2005 and January 2008, 115 children were diagnosed as having CF enrolled in our center. Five infants were diagnosed as CF with doll-like face before the age of 6 months participitated in study. Results: The incidence of doll-like face younger than the 6 months of age were 9.4% in our center. 48 infants diagnosed as CF without doll-like face before the age of 6 months participitated in the study as controls (group2). Physical examination revealed doll-like face and pitting edema of lower extremities in group 1. Their weight and length were under the third centile. Laboratory findings of group 1 include: mean hemoglobin 7.6g/dl; mean total protein 4.4 g/dl; albumin 2.3 g/dl. When compared control group in order to; 11.4 g/dl (range 7.6,17.9); 6.2 g/dl (range 4.0,8.8); 4.7 g/dl (range 2.1,5.8). mean hemoglobin, total protein and albumin values were lower in group 1. Conclusion: In a subgroup of patients, doll-like face may be the presenting manifestation of CF. Especially in developing countries clinicians should be aware of in patients with malnutrition and doll-like face and CF should be considered in differential diagnosis. Pediatr Pulmonol. 2008; 43:634,637. © 2008 Wiley-Liss, Inc. [source] Compliance in cystic fibrosis: An examination of infection control guidelinesPEDIATRIC PULMONOLOGY, Issue 5 2008Tracy Masterson PhD Abstract The goal of this research was to begin the process of evaluating acceptability of infection control (IC) recommendations to CF patients and their families, determine whether compliance with IC guidelines differs from compliance with traditional CF medical treatment with respect to the variables predictive of compliance, and assess which patients are most likely to comply with IC recommendations. Participants were recruited during routine outpatient visits at a regional CF center located in a pediatric hospital. The sample included 44 child and adolescent patients, aged 9,18 years and their guardian, and 27 adult patients. All patients completed questionnaires and interviews. Results of this preliminary study suggest that many individuals with CF are unaware of or unconcerned with the risks involved in infection transmission via social contact with other CF patients. Further, most participants reported that they could benefit from friendships with other CF patients. Health belief variables were found to be predictive of compliance with both IC guidelines and traditional medical treatments in the adult and parent sample, but not in the child sample. Possible explanations for study findings are discussed and recommendations for future research on IC compliance are highlighted. Pediatr Pulmonol. 2008; 43:435,442. © 2008 Wiley-Liss, Inc. [source] Novel approach to the eradication of Pseudomonas aeruginosa in an infant with CF after outpatient treatment failure,PEDIATRIC PULMONOLOGY, Issue 5 2008Don Hayes Jr. MD Abstract Intravenous continuous infusion of betalactam (CIBL) antibiotic and high dose extended interval (HDEI) aminoglycoside therapy theoretically maximize bacterial killing in treatment of Pseudomonas aeruginosa (PsA) in pulmonary exacerbations of cystic fibrosis (CF). We present the case of a 3-month-old female infant with CF who failed outpatient eradication of PsA with subsequent eradication using intravenous CIBL antibiotic and HDEI aminoglycoside therapy. This antibiotic combination should be considered in order to optimize pharmacodynamics for PsA eradication in CF patients before development of chronic colonization. Pediatr Pulmonol. 2008; 43:511,513. © 2008 Wiley-Liss, Inc. [source] Partial splenectomy for portal hypertension in cystic fibrosis related liver diseasePEDIATRIC PULMONOLOGY, Issue 12 2007Dominique Louis MD Abstract Aims To review the middle- and long-term effects of partial splenectomy (PS) on portal hypertension (PHT) and its complications in patients with cystic fibrosis (CF) related liver disease risky PHT. Method Over a 20 years period, 19 patients aged 7,23 years underwent partial PS for massive splenomegaly, hypersplenism, and / or severe PHT. Results In all but three cases, PHT and hypersplenism have improved for long periods. Noticeable improvement of hepatic tests occurred simultaneously. In all patients PS resolved abdominal discomfort. Fifteen patients are alive and a stabilization of the liver disease occurred with a follow-up of 1,20 years (mean 7.9). One patient died following respiratory insufficiency 10 years after PS although PHT was stable. Manifestations recurred in 2 patients 5 and 6 years after PS. In two patients, the course of the disease evolved to hepatic insufficiency without recurrence of PHT 3 and 8 years after PS. PS did not give the expected results in three cases only, in which PHT was not modified or reoccurred during the following year. No severe complication was observed. Early (three patients) or late (one patient) eventration required surgical procedure. Conclusions Our results show that PS is a reliable and well-tolerated technique. Therefore, it is a therapeutic option for the management of PHT in CF patients with a preserved liver function. It can prevent and significantly delay a liver transplantation and its constraints. Pediatr Pulmonol. 2007; 42:1173,1180. © 2007 Wiley-Liss, Inc. [source] Sputum antibiotic concentrations: Implications for treatment of cystic fibrosis lung infection,PEDIATRIC PULMONOLOGY, Issue 11 2007T.F. Moriarty PhD Abstract Background The success of antibiotic therapy may be predicted based on the achievement of pharmacodynamic indices (PDIs), which are determined by the susceptibility of the infecting bacteria and the concentrations of antibiotics achieved at the site of infection. The aim of this study was to determine whether PDIs associated with clinical effectiveness for ceftazidime and tobramycin were achieved at the site of infection in the lungs of cystic fibrosis (CF) patients following intravenous administration during treatment of an acute exacerbation. Methods Serum and sputum samples were collected from 14 CF patients and the concentration of both antibiotics in the samples determined. The susceptibility of bacteria cultured from sputum samples to both antibiotics alone and in combination was also determined. Results A total of 22 Pseudomonas aeruginosa isolates and 4 Burkholderia cepacia complex isolates were cultured from sputum samples with 55% and 4% of isolates susceptible to ceftazidime and tobramycin, respectively. Target PDIs for ceftazidime and tobramycin, an AUC/MIC ratio of 100 and a Cmax/MIC ratio of 10, respectively, were not achieved in serum or sputum simultaneously or even individually for any patient. Although the combination of ceftazidime and tobramycin was synergistic against 20 of the 26 isolates cultured, the concentrations of both antibiotics required for synergy were achieved simultaneously in only 38% of serum and 14% of sputum samples. Conclusion Key PDIs associated with clinical effectiveness for ceftazidime and tobramycin were not achieved at the site of infection in the lungs of CF patients. 2007;42:1008,1017. © 2007 Wiley-Liss, Inc. [source] Superior vena cava syndrome related to indwelling intravenous catheters in patients with cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 7 2006Susan Garwood MD Abstract Patients with cystic fibrosis (CF) often need long-term implanted vascular-access devices for intravenous antibiotics for chronic lower respiratory tract infections. These devices are not without complications, including infection, occlusion, and vascular thrombosis. Such thrombosis can result in superior vena cava (SVC) syndrome due to the position of the catheter proximal to the right atrium. SVC syndrome in CF patients, however, is rarely reported in the literature, suggesting that its incidence is uncommon. We describe three patients with SVC syndrome as a consequence of implanted vascular-access devices. Pediatr Pulmonol. 2006; 41: 683,687. © 2006 Wiley-Liss, Inc. [source] Usefulness of a program of hospital-supervised physical training in patients with cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 2 2004Attilio Turchetta MD Abstract Exercise is an important part of normal childhood, but the ability to exercise may be impaired in chronic lung diseases such as cystic fibrosis (CF). Improving exercise performance by training is very attractive. The aim of the present study was the evaluation of the effects of a physical aerobic training program, performed in the Children's Hospital and Research Institute "Bambino Gesù" (Rome, Italy) in outpatient CF children, supervised by a physician. Twelve patients (mean forced expiratory flow in 1 sec (FEV1), 71%), age range 12,24 years (16.7 ± 4.4 years), were enrolled. They performed a maximal exercise stress test on the treadmill (modified Bruce protocol) with breath-by-breath determination of oxygen consumption (VO2) to maximum at end-exercise; we measured time of exercise (TE), maximal heart rate (Hrmax) in beats per minute (bpm), and maximal systolic blood pressure (SBPm) in mmHg. The program consisted of 12 weeks of training twice a week. Each training session consisted of walking or running on the treadmill for 30 min at the speed that allowed the child to attain 60% of the maximal heart rate obtained during a baseline stress test for 4 weeks, 70% in the following 4 weeks, and 80% in the last 4 weeks, under strict medical supervision. HR was continously monitored. There was no change in FEV1 and forced vital capacity after the treatment period. Hrmax and SBPm also remained the same (P,=,0.37 and P,=,0.25, respectively). There was a significant increase in TE (P,<,0.002), VO2, VO2/kg, and pulmonary ventilation (VE) (P,<,0.0001, P,<,0.001, and P,<,0.001, respectively). This pilot study showed that a simple training program improves short-term cardiopulmonary fitness in children with CF. Further studies with a larger sample and for a more prolonged time are necessary to assess if sport can have a long-term effect on lung function or survival in CF patients. Pediatr Pulmonol. 2004; 38:115,118. © 2004 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||