The management of cystic fibrosis. Observations on gentamycin when used with other antibiotics in pulmonary infections associated with cystic fibrosis.
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Anti-Bacterial Agents↗
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Results for “CYSTIC FIBROSIS”
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Maximal work capacity in relation to nutritional status in children with cystic fibrosis.
In children with cystic fibrosis, objective parameters of exercise tolerance are needed which are easy to measure in nonspecialized centres. We investigated maximal workload (W'max) in children with cystic fibrosis in relation to body weight and fat-free mass, and compared this with results for maximal oxygen consumption (V'O2,max). Fourteen patients with cystic fibrosis performed an incremental maximal exercise test on a bicycle ergometer. W'max, V'O2,max, body weight and fat-free mass were measured. W'max and V'O2,max were significantly correlated (r = 0.91; p < 0.001). Using standard deviation scores in relation to reference values, W'max and V'O2,max per kilogram body weight were significantly higher than uncorrected W'max and V'O2,max (mean difference (95% CI) 0.63 (0.24-1.01) and 0.91 (0.32-1.49) SD units, respectively). There was no such difference after correction for fat-free mass. Standardized V'O2,max was significantly higher than standardized W'max (mean difference (95% CI): 1.59 (1.14-2.04)), also after correction for body weight and fat-free mass. In children with mild-to-moderate cystic fibrosis, maximal workload per kilogram fat-free mass, but not per kilogram body weight, is a useful parameter to correct for diminished nutritional status. In these patients, maximal workload is consistently lower than maximal oxygen consumption. Taking into account this difference, maximal workload and maximal workload per kilogram fat-free mass can be used for follow-up of paediatric patients with cystic fibrosis in nonspecialized settings.
Adolescent↗
Spine deformities and cystic fibrosis.
Patients with cystic fibrosis have an increased risk for developing kyphosis and scoliosis. The risk for both kyphosis and scoliosis increases with age. The severity of kyphosis did not appear greater in the older age groups. Patients with retarded bone age may be more likely to have a significant spinal deformity. The presence of spine deformity does not correlate with the severity of pulmonary involvement, height, weight, serum protein and albumin in patients with cystic fibrosis.
Adolescent↗
Nasal potential difference: a clinical diagnostic test for cystic fibrosis.
Patients with cystic fibrosis (CF) demonstrate a markedly more negative potential difference (PD) across respiratory epithelia than normal or "diseased" controls. A technique is described for the measurement of nasal PD in both children and adults. 145 non-CF subjects showed a mean PD of -19.0 mV (range -2 to -36) in comparison to 60 patients with cystic fibrosis with mean of -46.0 mV (range -32 to -77). Amongst the latter group those with more severe disease had a more negative PD. Measurement of nasal PD is easily learnt and rapidly performed and may provide an additional means of diagnosis for CF.
Adolescent↗
[Dietetic management of cystic fibrosis: intervention strategies].
Cystic fibrosis is a systemic disease whose prognosis has improved thanks multidisciplinary researches and above all better knowledges and care of nutritional problems. It is important, for a good therapy, considering each case singularly, with a differentiated and individualized dietetic approach, which focuses on its specific needs and features. A "step by step" process could be useful to manage patient suffering from cystic fibrosis; it is based on 5 different patterns of possible nutritional dietetic methods. The development of the nutritional techniques of treatment for this kind of desease both with the individualized and differentiated approach have led to improve prognosis and especially the patient's standard of life.
Cystic Fibrosis↗
Hepatic insulin resistance and defects in substrate utilization in cystic fibrosis.
Patients with cystic fibrosis (CF)-related diabetes (CFRD) have clinical features of both type 1 and type 2 diabetes. Past studies have documented peripheral insulin resistance in CF, and some studies have noted high hepatic glucose production (HGP) in CF patients. We hypothesized that patients with CF, similar to patients with type 2 diabetes, have hepatic insulin resistance. Cystic fibrosis is a catabolic condition, yet the etiology of catabolism is poorly understood. De novo lipogenesis is energy wasteful and precludes ketogenesis. Patients with CFRD rarely develop ketogenesis, despite insulin deficiency. We speculated that CF patients have de novo lipogenesis, and therefore evaluated substrate utilization in CF. Using [6,6-2H2]glucose and a three-step hyperinsulinemic-euglycemic clamp, we measured HGP in 29 adult CF subjects and 18 control volunteers. Using indirect calorimetry, we measured lipid oxidation, oxidative glucose metabolism, and resting energy expenditure at baseline and at high levels of insulin. All subjects were characterized by oral glucose tolerance testing (OGTT) and National Diabetes Data Group criteria. The CF subjects had increased HGP when compared with control subjects (CF, 3.5+/-0.6; control, 2.5+/-0.5 mg x kg(-1) x h(-1); P = 0.002). Baseline HGP correlated with glucose levels obtained 2 h after a glucose load given for OGTT (r = 0.69, P = 0.001). Suppression of HGP by insulin was significantly less in all CF subgroups than in control subjects at peripheral insulin levels of 16 and 29 microU/ml. At peripheral insulin levels of 100 microU/ml and 198 microU/ml, there was no difference in insulin suppression of HGP between CF and control subjects. At baseline, there was no significant difference between control and CF subjects for glucose or lipid oxidation. During maximum insulin stimulation, there was a greater tendency for nonoxidative glucose metabolism in all CF subjects. The CF subjects with abnormal glucose tolerance also had de novo lipogenesis. Our results indicate that CF patients have several defects in substrate utilization, including de novo lipogenesis. Furthermore, these results suggest that high hepatic glucose production and hepatic insulin resistance contribute to the high incidence of abnormal glucose tolerance in CF.
Adolescent↗
Preatherosclerotic aortic lesions in cystic fibrosis.
Patients with cystic fibrosis have fat malabsorption, providing an experimental model for evaluation of the hypothesis that a low-fat intake may prevent atherosclerosis. We studied the frequency and extent of aortic precursor lesions (fatty streaks, early fibromusculoelastic lesions, late fibromusculoelastic lesions) found at autopsy in this disease as well as in other patients with debilitating disorders but with no apparent impairment of fat absorption. Fatty streaks were less common in the cystic fibrosis group, as were the late fibromusculoelastic lesions. There was no significant difference in the frequency, length, or thickness of the early fibromusculoelastic lesions. The findings suggest that fat may be responsible for progression but not initiation of the fibromusculoelastic precursor lesions, and support the concept that early restriction of dietary fat may prevent, delay, or otherwise modify atherosclerosis in the adult.
Adolescent↗
Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients.
In cystic fibrosis (CF) patients early antibiotic treatment of lung infection has been shown to lead to Pseudomonas aeruginosa eradication. The present study determined: 1) the time period from eradication to new P. aeruginosa acquisition; 2) P. aeruginosa re-growth and new acquisition; and 3) the impact of eradication therapy on lung function, antimicrobial resistance, emergence of other pathogens and treatment costs. Ciprofloxacin and colistin were used to eradicate P. aeruginosa in 47 CF patients. Bacterial pathogens, lung function decline, P. aeruginosa antimicrobial resistance and anti-pseudomonal serum antibodies were assessed quarterly and compared with an age-matched CF control group. Additionally, costs of antibiotic therapy in both groups were assessed. Early antibiotic therapy leads to a P. aeruginosa free-period of a median (range) of 18 (4-80) months. New acquisition with different P. aeruginosa genotypes occurs in 73% of episodes. It also delays the decline of lung function compared with chronically infected patients, prevents the occurrence of antibiotic resistant P. aeruginosa strains, does not lead to emergence of other pathogens, and significantly reduces treatment costs. The treatment substantially lowers P. aeruginosa prevalence in CF. In conclusion, early antibiotic therapy exerts beneficial effects on the patient's clinical status and is cost-effective compared with conventional antibiotic therapy for chronically infected cystic fibrosis patients.
Adolescent↗
Analysis of ClC-2 channels as an alternative pathway for chloride conduction in cystic fibrosis airway cells.
Cystic fibrosis (CF) is a lethal inherited disease that results from abnormal chloride conduction in epithelial tissues. ClC-2 chloride channels are expressed in epithelia affected by CF and may provide a key "alternative" target for pharmacotherapy of this disease. To explore this possibility, the expression level of ClC-2 channels was genetically manipulated in airway epithelial cells derived from a cystic fibrosis patient (IB3-1). Whole-cell patch-clamp analysis of cells overexpressing ClC-2 identified hyperpolarization-activated Cl- currents (HACCs) that displayed time- and voltage-dependent activation, and an inwardly rectifying steady-state current-voltage relationship. Reduction of extracellular pH to 5.0 caused significant increases in HACCs in overexpressing cells, and the appearance of robust currents in parental IB3-1 cells. IB3-1 cells stably transfected with the antisense ClC-2 cDNA showed reduced expression of ClC-2 compared with parental cells by Western blotting, and a significant reduction in the magnitude of pH-dependent HACCs. To determine whether changes in extracellular pH alone could initiate chloride transport via ClC-2 channels, we performed 36Cl- efflux studies on overexpressing cells and cells with endogenous expression of ClC-2. Acidic extracellular pH increased 36Cl- efflux rates in both cell types, although the ClC-2 overexpressing cells had significantly greater chloride conduction and a longer duration of efflux than the parental cells. Compounds that exploit the pH mechanism of activating endogenous ClC-2 channels may provide a pharmacologic option for increasing chloride conductance in the airways of CF patients.
Cell Line↗
A phase 1 study, in cystic fibrosis patients, of the safety, toxicity, and biological efficacy of a single administration of a replication deficient, recombinant adenovirus carrying the cDNA of the normal cystic fibrosis transmembrane conductance regulator gene in the lung.
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Adenoviridae↗
Elemental and ion composition of exhaled air condensate in cystic fibrosis.
BACKGROUND: In cystic fibrosis (CF) the exact ion composition of the airway surface fluid is still debated and it is not clear if it differs from healthy subjects. The air that we exhale contains small droplets, which are generated by shear forces from the airway surface fluid and very likely mirror its ion composition. We hypothesized that differences between CF-patients and healthy controls would be reflected by differences in their exhaled air. METHODS: In nasally collected exhaled breath condensate from 20 children and young adults with cystic fibrosis and 20 healthy subjects, the elements and anions were determined by optical emission spectroscopy and ion-exchange chromatography. RESULTS: The concentrations of the major components Na and Cl- did not differ, Zn was higher and NO3- was lower in CF-patients. During a given time period, CF-patients produced a slightly larger volume of breath condensate and they exhaled more Na, K and Zn. Fluoride was detected in half of all samples, whereas copper, iron, magnesium, phosphorus and sulfur were present only sporadically, with no differences. CONCLUSIONS: These data detail the composition of exhaled breath condensate and suggest a similar Na and Cl- concentration in CF-airway surface fluid as in healthy subjects.
Adolescent↗
Immunoglobulin A and immunoglobulin G antibody responses to alginates from Pseudomonas aeruginosa in patients with cystic fibrosis.
Patients with cystic fibrosis have a high prevalence of mucoid, alginate-producing Pseudomonas aeruginosa that causes chronic infection of the mucosal surface of the lungs. We developed enzyme-linked immunosorbent assays (ELISAs) for determination in serum of immunoglobulin A (IgA) and IgG antibodies to alginate purified from P. aeruginosa and an ELISA for detection of IgA antibodies to a polyvalent P. aeruginosa standard antigen. Absorption experiments indicated that the assays were antigen and antibody specific and had analytical variations that ranged from 7 to 19%. Serum samples from 207 patients with cystic fibrosis, 100 healthy children, and 94 healthy adults were examined. The patients responded to P. aeruginosa infection with early IgA and IgG antibody responses that were significantly higher than in controls and noncolonized patients. Analysis of paired serum samples showed that infected patients had an increase in specific IgG and IgA antibodies that was significantly higher than in noncolonized patients. The serological data were analyzed for correlation with clinical condition; poor lung function was significantly associated with increased levels of IgA and IgG antibodies to P. aeruginosa alginate and to the standard antigen and with a relative excess of IgA antibodies to the standard antigen compared with IgA antibodies to P. aeruginosa alginate. The assays showed high predictive values if positive, but a negative test did not exclude infection, and the ELISAs should not be used for diagnostic purposes. Mucoid strains were present initially in the sputa of 28 of 54 infected patients with paired serum samples. These patients had a significant increase in anti-alginate antibodies, but it was not different from the increase seen in patients infected only with nonmucoid strains. Therefore, alginate may also be produced in vivo by nonmucoid P. aeruginosa. The study showed that early formation of IgA and IgG antibodies to P. aeruginosa alginate did not prevent development of chronic infection and that P. aeruginosa-specific IgA antibodies correlate with poor lung function.
Adolescent↗
Cystic fibrosis since 1938.
Cystic fibrosis (CF) was distinguished from celiac disease in 1938. Then, it was a pathologic diagnosis, life expectancy was approximately 6 months, and the autosomal recessive disease was believed to arise from abnormal mucus plugging exocrine ducts. Death often occurred from lung infection. Discovery of the sweat electrolyte defect in 1953 and standardization of the sweat test in 1959 allowed identification of milder cases, and CF was no longer considered only a disorder of mucus. In 1955, establishment of centers with programs of aggressive, comprehensive care initiated striking improvement in longevity. The pillars of care established then (attention to nutrition, airway clearance, treatment of lung infection) remain today. In 1983, chloride transport was identified as the basic physiologic CF defect, accompanied by increased sodium reabsorption. In 1980, we learned that inflammation contributes independently to lung disease and constitutes an independent therapeutic target. In 1989, the discovery of the CF gene demonstrated the basic defect to be in a cAMP-regulated chloride channel. This afforded new diagnostic tests, opportunities for research, and prospects for using the gene as therapy. Since then, substantial advances in basic and clinical research catalyzed therapeutic improvements: median survival age now exceeds 30 years. The Cystic Fibrosis Foundation center network provides not only opportunity to conduct clinical trials but also means to disseminate new therapies. In the future, treatments directed at the basic defect can be expected, with concomitant improvements in morbidity and mortality.
Cystic Fibrosis↗
The relationship between insulin, IGF-I and weight gain in cystic fibrosis.
OBJECTIVE: In cystic fibrosis, reduced body mass is related to low levels of IGF-I and changes in the IGF binding proteins. Our aim was to determine whether these abnormalities are linked to pancreatic endocrine dysfunction. PATIENTS AND DESIGN: We measured serum levels of insulin, IGF-I, IGFBP-I, IGFBP-3 and IGF bioactivity in 77 fasting subjects (43 male) mean age 9.6 years (range 2.99-17.98 years). Data were analysed with respect of body mass, puberty and stature and compared with control data established in the same laboratory. RESULTS: The mean height standard deviation score (SDS (SD)) was -0.54 (0.97) and the body mass index SDS -0.24 (1.09). Both body mass index SDS (r = -0.40, P = 0.0003) and IGF-I SDS (r = - 0.32, P = 0.009) declined with age. Insulin levels were also low and correlated with IGF-I and IGFBP-3 (r = 0.42, P = 0.0004, and r = 0.45, P = 0.0002, respectively) whereas levels of IGFBP-I were inversely related to those of IGF-I and insulin (r = - 0.43, P = 0. 0004, r = - 0.52, P < 0.0001). IGF bioactivity was reduced and inversely related to IGFBP-I (r = - 0.31, P = 0.009). In multiple regression analysis, body mass index SDS was negatively related to age (P < 0.0001) and positively related to insulin and IGF-I (P = 0. 04, P = 0.03, respectively). Height SDS was correlated with IGF bioactivity (P = 0.003) and negatively with IGFBP-I (P = 0.01). CONCLUSIONS: We conclude that progressive insulin deficiency may result in reduced IGF-I levels and IGF-bioactivity and may determine weight gain and statural growth in cystic fibrosis.
Adolescent↗
Glucocorticoid treatment reduces exhaled nitric oxide in cystic fibrosis patients.
In cystic fibrosis (CF), low concentrations of exhaled nitric oxide (NO) and reduced expression of inducible nitric oxide synthase (iNOS) in airway epithelium have been reported. However, abundant iNOS expression has been found in the subepithelial tissues and elevated concentrations of NO metabolites in breath condensate and sputum. These conflicting results may be explained by increased scavenging of NO by superoxide radicals, resulting in rapid conversion to peroxynitrite, so that only a small proportion of the NO produced in the lung tissue reaches the airway lumen. If iNOS were active in the CF lung, exhaled NO would be further reduced by glucocorticoid treatment. CF patients (n = 13) were recruited to a double-blind, placebo-controlled study with crossover. Treatment comprised prednisolone or placebo for 5 days with a 9 day washout. After each treatment, exhaled NO was measured, spirometry performed and blood collected for measurement of serum nitrogen dioxide/nitrous oxide (NO2/NO3). Ten patients (8 male) completed the study. Following prednisolone treatment (mean +/- SD) exhaled NO concentration (3.1 +/- 1.6 parts per billion (ppb)) was significantly reduced versus placebo treatment (4.9 +/- 4.2 ppb; p<0.05, Wilcoxon signed-rank test). Spirometric indices and serum NO2/NO3 concentration were unchanged. These findings support the hypothesis that glucocorticoids suppress nitric oxide production in cystic fibrosis airways by reducing inducible nitric oxide synthase expression or by inhibiting recruitment of neutrophils, cells which express inducible nitric oxide synthase.
Adult↗
Anaesthesia for liver transplantation in cystic fibrosis patients.
INTRODUCTION: Cystic fibrosis (CF) is a disease caused by an inherited genetic defect. While pulmonary and pancreatic abnormalities predominate the clinical spectrum, other organ involvement is common, including liver. The severity of liver disease does not appear to be related to the severity of exocrine pancreatic or lung function. We discuss anaesthesia in four CF patients undergoing liver transplantation. METHODS: We studied haemodynamic and oxygenation modifications during anaesthesia in four patients affected by CF with end-stage liver disease and mild to moderate pulmonary abnormalities. The patients received pancreatic enzyme prior to transplantation and two had insulin-dependent diabetes mellitus. All patients were treated with broad-spectrum antibiotic therapy. After a waiting time ranging one week to three months, all patients were successfully transplanted. General anaesthesia was induced with fentanyl, thiopental and pancuronium, and maintained with isoflurane supplemented by fentanyl in O2:air. Haemodynamic and oxygenation evaluations were made during the main phases of the transplant. After the intubation and at the end of the procedure all patients received a broncho-alveolar toilet through fiberoptic bronchoscopy. RESULTS: During anaesthesia for liver transplantation, PaO2 increased proportionally to the decreasing of Qs/Qt. In postoperative follow-up, Fev1 and FVC improved from preoperative time in all patients. In conclusion, even if cystic fibrosis is a multisystem disease, liver transplantation can be offered to CF patients with endstage liver disease and mild to moderate pulmonary function abnormalities. The four patients are still alive, enjoying good health. The improved respiratory function and quality of life of these children is remarkable.
Adolescent↗
Cystic fibrosis: current concepts.
Cystic fibrosis (CF), a common fatal genetic disease, is a multisystem disorder whose pathogenesis has recently been linked to defects in CFTR, a newly discovered protein. CFTR is a molecular channel which controls chloride concentration in secretions of the sweat glands and the respiratory, GI, and reproductive tracts. Defective forms of CFTR, arising from various mutations in its gene, are responsible for the inadequate hydration of mucus, pancreatic juice, and other exocrine secretions. The result is dysfunction of the lungs, pancreas, and other involved organs. This article describes the diagnosis, clinical features, and approach to management of CF.
Cystic Fibrosis↗
Nasal potential difference measurements in patients with atypical cystic fibrosis.
The diagnosis of cystic fibrosis (CF) is based on characteristic clinical and laboratory findings. However, a subgroup of patients present with an atypical phenotype that comprises partial CF phenotype, borderline sweat tests and one or even no common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The aim of this study was to evaluate the role of nasal potential difference (PD) measurements in the diagnosis of CF patients with an atypical presentation and in a population of patients suspected to have CF. Nasal PD was measured in 162 patients from four different groups: patients with classical CF (n = 31), atypical phenotype (n = 11), controls (n = 50), and patients with questionable CF (n = 70). The parameter, or combination of nasal PD parameters was calculated in order to best discriminate all CF patients (including atypical CF) from the non-CF group. The patients with atypical CF disease had intermediate values of PD measurements between the CF and non-CF groups. The best discriminate model that assigned all atypical CF patients as CF used: e(response to chloride-free and isoproterenol/response to amiloride) with a cut-off >0.70 to predict a CF diagnosis. When this model was applied to the group of 70 patients with questionable CF, 24 patients had abnormal PD similar to the atypical CF group. These patients had higher levels of sweat chloride concentration and increased rate of CFTR mutations. Nasal potential difference is useful in diagnosis of patients with atypical cystic fibrosis. Taking into account both the sodium and chloride transport elements of the potential difference allows for better differentiation between atypical cystic fibrosis and noncystic fibrosis patients. This calculation may assist in the diagnostic work-up of patients whose diagnosis is questionable.
Adolescent↗