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PubMed1994

Protease-antiprotease imbalance in the lungs of children with cystic fibrosis.

Cystic fibrosis (CF) is characterized in the lung by chronic purulent bronchitis culminating in pulmonary insufficiency. There is evidence to suggest that neutrophil elastase (NE) released by neutrophils on the respiratory epithelial surface plays a major role in the pathogenesis of this lung disease. This study sought to determine the age of onset of the chronic neutrophil-dominated inflammation in CF and the consequences to the NE-anti-NE screen on the respiratory epithelial surface of the CF lung. NE and anti-NE defensive molecules were evaluated in respiratory epithelial lining fluid (ELF) in 27 children with stable CF (1 to 18 yr of age). Despite normal antigenic concentrations of alpha 1-antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI), 25 of 27 children with CF had neutrophil-dominated inflammation (> 500 neutrophils/microliters ELF). Active NE was found in ELF in 20 of 27 children, including two of four aged 1 yr. Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded. These observations demonstrate that a chronic imbalance of the NE-anti-NE protective screen develops early on the respiratory epithelial surface in persons with CF and is likely well established by 1 yr of age, with resultant potential for lung damage.

Adolescent↗

PubMed2000

Myeloperoxidase and protein oxidation in cystic fibrosis.

Cystic fibrosis (CF) is associated with chronic pulmonary inflammation and progressive lung dysfunction, possibly associated with the formation of neutrophil myeloperoxidase (MPO)-derived oxidants. Expectorated sputum specimens from adult CF patients were analyzed for MPO characteristic protein modifications and found to contain large amounts of active MPO as well as high levels of protein-associated 3-chlorotyrosine and 3,3'-dityrosine, products that result from MPO activity, compared with expectorated sputum from non-CF subjects. Sputum levels of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), indicating local production of nitric oxide (NO. ), were not elevated but in fact were slightly reduced in CF. However, there was a slight increase in protein-associated 3-nitrotyrosine in CF sputum compared with controls, reflecting the formation of reactive nitrogen intermediates, possibly through MPO-catalyzed oxidation of NO(2)(-). CF sputum MPO was found to contribute to oxidant-mediated cytotoxicity toward cultured tracheobronchial epithelial cells; however, peroxidase-dependent protein oxidation occurred primarily within sputum proteins, suggesting scavenging of MPO-derived oxidants by CF mucus and perhaps formation of secondary cytotoxic products within CF sputum. Our findings demonstrate the formation of MPO-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF, which collectively may contribute to bronchial injury and respiratory failure in CF.

Adult↗

PubMed1997

Conventional and modified nasal potential-difference measurement in cystic fibrosis.

Cystic fibrosis (CF) is associated with impaired ion transport across epithelial membranes and an increased transepithelial potential difference (PD) that can be measured in airway epithelium. The aim of this study was to investigate the diagnostic value of nasal PD in CF, and to test a modified approach to the measurement of this PD. The reproducibility and diagnostic sensitivity and specificity of nasal PD measurements were tested with the perfusion technique and with a simplified modification of the technique done with a novel, solid-state exploring electrode. With the perfusion method, basal PD values were different in CF patients (mean +/- SEM: -51.6 +/- 0.9 mV, n = 104) than in normal (-15.5 +/- 0.9 mV, n = 58, p < 0.01) subjects. CF patients with acute rhinitis or other nasal pathology had mean PD values that were intermediate between those of the patients and normal and disease-control groups (-28.3 +/- 1.2 mV, n = 40, p < 0.01, different from normal). The diagnostic sensitivity of the perfusion method for CF was 91.3%, and the specificity was 96.4%. PD measurements with the modified technique correlated highly with the results achieved with the perfusion method (r = 0.94, n +/- 158). The measurement of nasal PD effectively distinguishes CF from control subjects. Care must be taken in the interpretation of measurements made on acutely inflamed epithelium. The modified method was simpler than the conventional perfusion technique, and equally effective.

Adolescent↗

PubMed2002

Persistent infections and immunity in cystic fibrosis.

Cystic fibrosis (CF) is the most common autosomal recessive lethal disease in the Caucasian population. Chronic respiratory infections with Pseudomonas aeruginosa, neutrophil-dominated airway inflammation and progressive lung damage are the major causes of morbidity and mortality in CF. Two persistent infection phenotypes expressed by this bacterium are biofilm and mucoidy. Biofilm, also called the microcolony mode of growth is the surface-associated adherent bacterial community, while mucoidy refers to a phenotype conducive to copious amounts of mucoid exopolysaccharide (MEP)/alginate that provides a matrix for mature biofilms conferring resistance to host defenses and antibiotics. Recent completion of the whole genomic sequence of the standard reference strain P. aeruginosa PAO1 has led to discoveries that many clinical isolates of this species possess unique genomic sequences (genomic islands) due to horizontal gene transfer. We propose this type of genetic exchange may play an important role in causing intrinsic genomic diversity of this organism. Therefore, the diversity, as revealed through profiles of restriction fragment length polymorphism (RFLP), may be linked to an array of novel and unexplored pathogenic mechanisms in P. aeruginosa. CF mouse models, while displaying many clinical similarities to human CF, have yet to demonstrate a chronic pulmonary disease phenotype. This review is intended to provide an overview of P. aeruginosa persistent infection phenotypes (biofilm and mucoidy) and an aerosol infection mouse model for CF. Genomic diversity of P. aeruginosa and its implications in the pathogenesis in CF will also be discussed.

Animals↗

PubMed2004

[Oral health risks in patients with cystic fibrosis].

Cystic Fibrosis (CF) patients can hypothetically be considered as being high caries risk patients; they frequently consume sugar-rich in-between-meal snacks/drinks and they have a high intake of sugar containing syrups and aerosols (also acidic) and salivary flow reducing medication (beta-2-adrenergica). The aim of this study was to investigate the determining factors of oral health in CF homozygotes, CF heterozygotes and healthy controls. CF homozygotes had significantly the lowest caries experience, while CF heterozygotes had a borderline not significant higher caries experience than healthy controls. CF homozygotes also had significant lower Streptococcus mutans counts than both other groups. CF homozygotes also had significant less gingival bleeding, while no significant differences in plaque and calculus amount were found between the three groups. On behalf of oral hygiene habits, no significant differences were found between the three groups. CF homozygotes appeared to consume more dairy products than the others. The influence of the typical CF medication on oral health did not play a significant role. CF homozygotes had a significant higher total salivary protein concentration than the others, while SDS-PAGE analysis showed a 68 kDa protein being specific in appearance for CF heterozygotes. CF homo- and heterozygotes had significant higher salivary sodium concentrations than controls. CF homozygotes also had a significant higher salivary phosphate concentration than both other groups. The impression that CF patients seem to possess an intrinsic salivary compensatory mechanism should be further investigated.

Adolescent↗

PubMed1986

Calcium and cystic fibrosis.

Cystic fibrosis (CF) is a generally lethal, congenital, genetic disease of unknown etiology. It is likely that a defective regulation of ion and water transport in exocrine glands and possibly also in other epithelial cells has a central role in the pathogenesis of this disease. Calcium has been implicated in the basic defect underlying CF because of findings of abnormally high calcium levels in some secreted fluids and some cells of CF patients. Using X-ray microanalysis, we have demonstrated elevated calcium concentrations in cultured fibroblasts and in goblet cells of the bronchial epithelium of CF patients. A factor produced by CF fibroblasts in culture can increase the calcium concentration in healthy cells, although this may be an indirect effect. In animal models for CF, such as the chronically reserpinized rat and the chronically isoproterenol-treated rat, abnormally high calcium levels in the acinar cells of the submandibular gland could be demonstrated, similar to the situation in CF patients. In the acinar cells of the parotid gland in these animal models, the calcium levels are, however, abnormally low. This suggests that the changes in cell calcium content are secondary to other changes, possibly changes in the secretory proteins. A study of the effect of the serum calcium level and of the calciotropic hormone calcitonin suggested that neither of these factors could be directly linked with CF. It is concluded that several lines of evidence point to a secondary rather than a primary role for calcium in the pathogenesis of CF.

Animals↗

PubMed1984

Heat acclimation in cystic fibrosis.

Cystic fibrosis (CF) patients may be at risk for heat illness because of their high sweat chloride and sodium concentrations ([Cl-], [Na+]), but it is not known if they can heat acclimate. We studied 10 CF patients and 10 normal controls on 8 consecutive days of cycle exercise in the heat (37 degrees C dry bulb, 24-29 degrees C wet bulb). Both groups acclimated. CF peak rectal temperature (Tre) was 38.2 +/- 0.3 degrees C on day 1 and 37.8 +/- 0.4 degrees C on day 8 (P less than .005), and peak heart rates (HR) were 151 +/- 24 beats/min on day 1 and 136 +/- 22 beats/min on day 8 (P less than 0.025). Control temperature (T) and HR were similar. Controls decreased sweat [Cl-] from 37.2 +/- 14.6 meq/l on day 1 and to 24.9 +/- 10.6 meq/l on day 8 (P less than 0.005). CF sweat [Cl-] was significantly higher and did not change with acclimation (day 1, 71.1 +/- 20.9 meq/l; day 8, 72.6 +/- 21.6 meq/l, NS). Before and after acclimation, exercise-heat sessions resulted in significant decreases in serum [Cl-] in CF patients (104.5 +/- 4.6 to 101.3 +/- 4.4 meq/l on day 1, P less than 0.05; 103.5 +/- 5.1 to 99.7 +/- 4.2 meq/l on day 8, P less than 0.025) but not in controls. Serum [Cl-] was significantly lower in CF than control subjects at every measurement. Both groups had significant renal Na+ conservation after exercise on both days.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed2001

Outcomes of intensive care unit care in adults with cystic fibrosis.

Cystic fibrosis (CF) causes progressive respiratory failure and death in more than 90% of patients. Mechanical ventilation has been discouraged in CF because of poor outcomes, but improved survival and the availability of lung transplantation have increased the indications for care of CF patients in the intensive care unit (ICU). We studied the outcomes of all CF patients admitted to the University of North Carolina Hospitals Medical ICU from January 1990 through December 1998. Seventy-six patients, ranging in ages from 17 to 45 yr (mean: 27 yr), and of whom 53% were female, had 136 admissions for exacerbations of CF with respiratory failure (RF, n = 65), hemoptysis (n = 33), antibiotic desensitization (n = 30), pneumothorax (n = 3), or other reasons (n = 5). Eighty-six percent of the patients with hemoptysis and all of those with desensitization and pneumothorax were alive 1 yr after ICU discharge. Of the 42 patients with RF, 37 (88%) required assisted ventilation. Twenty-three (55%) of the patients with RF survived to ICU discharge and 19 (45%) died. Seventeen (40%) of the patients with RF received lung transplants and 14 were alive 1 yr later. Without transplantation, three (7%) of the patients with RF were alive and three (7%) were dead 1 yr later. Sex, body mass index, and respiratory bacteria did not correlate with survival. We conclude that ICU care for adults with CF who have reversible complications is appropriate and effective. Ventilatory support is appropriate for some transplant candidates.

Adolescent↗

PubMed1984

Oxygen saturation during exercise in cystic fibrosis.

Cystic fibrosis (CF) is often associated with low hemoglobin oxygen saturation and with limited exercise tolerance, yet published reports do not agree on the effect of exercise on oxygenation in CF. We studied oxygen saturation (SaO2) by ear oximetry in 91 patients with CF during progressive exercise to exhaustion. Only 13 of 91 patients changed SaO2 by 5% or more; of these, 4 patients increased SaO2 by 5% or more, whereas 9 decreased by 5% or more. Small changes in SaO2 did not relate to resting pulmonary function, but large decreases in SaO2 were much more likely to be found in patients with forced expiratory volume in one second (FEV1) less than 50% of VC than in those with better pulmonary function (desaturation of 5% or greater was found in only 1 of 62 patients with FEV1 greater than 50% of VC, but in 8 of 29 patients with FEV1 less than or equal to 50% VC). However, even in severely affected patients, modest increases or no change in saturation were more common than large decreases, and 17 of 29 patients with FEV1 less than 50% VC ended exercise with SaO2 greater than 90%, including 3 patients with initial SaO2 below 90%. No single resting pulmonary function test or combination of tests could predict oxygen changes with exercise. Most patients with CF tolerate even maximal exercise without significant desaturation, but patients with FEV1 less than 50% of VC should have supervised exercise testing with ear oximetry before undertaking an exercise program.

Adolescent↗

PubMed2006

Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis.

Cystic fibrosis (CF) is associated with many clinical complications including steatosis for which the relation to defective CF transmembrane conductance regulator protein is unclear. Choline deficiency results in hepatic steatosis. Choline is the precursor of betaine, which donates methyl groups for remethylation of homocysteine to methionine and dimethylglycine. Previously, we have shown phospholipid malabsorption and increased plasma homocysteine in children with CF. In these studies we used normal phase HPLC with tandem mass spectrometry to determine plasma choline, betaine, and dimethylglycine in children with CF (n = 34) and healthy control children without CF (n = 15). Plasma choline, betaine, and dimethylglycine were significantly lower in children with CF (means +/- SEM, 6.48 +/- 0.35, 23.8 +/- 1.49, 1.49 +/- 0.13 mumol/L, respectively) than in children without CF (8.98 +/- 0.46, 37.3 +/- 1.84, 3.01 +/- 0.17 mumol/L, respectively). Plasma choline (r = 0.373, P = 0.007) and betaine (r = 0.399, P = 0.005) were positively related to methionine, and choline was inversely related to homocysteine (r = -0.316, P = 0.03). Choline, betaine, and dimethylglycine were all significantly and positively related to the plasma S-adenosylmethionine:S-adenosylhomocysteine (SAM:SAH) ratio (r = 0.294, r = 0.377, r = 0.442, respectively; P < 0.05). The plasma choline:betaine and betaine:dimethylglycine ratios did not differ between the children with CF and the control children, suggesting no increase in betaine synthesis, or betaine-dependent remethylation of homocysteine. These studies suggest that choline depletion may contribute to increased homocysteine in children with CF. Choline depletion and altered thiol metabolism may contribute to the clinical complications associated with CF.

Adolescent↗

PubMed1996

Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis.

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG, and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability-increasing protein (BPI), a recently-characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI & FEV1: r = -0.508, p < 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (n = 6) than in those without (p < 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.

Adolescent↗

PubMed1989

Ultrastructural morphology of the lung in cystic fibrosis.

Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasians, with much of the morbidity and most of the mortality related to pulmonary complications. The underlying defect in this disease has yet to be precisely defined, so it is somewhat surprising that a comprehensive study of the ultrastructural morphology of the lung in CF has not heretofore been reported. We used transmission electron microscopy to examine the small airways in 15 patients who had died of CF, and compared the findings with 15 disease controls with non-CF chronic airways disease and 15 patients with normal lung morphology. The lung parenchyma was also examined ultrastructurally in 7 patients with CF, 4 disease controls, and 4 normal lung cases. In addition, the literature regarding the ultrastructural morphology of the large airways in CF was reviewed. Patients with CF showed non-specific ciliary abnormalities, hyperplasia of mucous cells, increased numbers of pulmonary neuroendocrine and indeterminate cells, degeneration and sloughing of epithelial cells, and colonization of bacteria of the mucous layer of the small airways when compared with normal controls. Alveoli showed non-specific injury and regeneration of type II pneumocytes. However, these changes were all similar to those observed in the disease controls. Specifically, no cellular or subcellular ultrastructural abnormality unique to CF was observed. It is probable that the most useful ultrastructural approach to the lung in CF in future studies will involve X-ray microanalytical studies of ionic composition using cryotechniques.

Adolescent↗

PubMed2003

Can nutrition counselling be more behavioural? Lessons learned from dietary management of cystic fibrosis.

Cystic fibrosis (CF) is a genetically-inherited disorder that results in energy imbalance. Undernutrition is common in children with CF and associated with poor health outcomes. To ensure optimal growth and nutrition, children with CF are recommended to consume 120-150% of the recommended daily allowance (RDA) for energy, but most studies show they typically are only able to achieve 100% of the RDA. While biological factors clearly contribute to poor dietary adherence, recent studies have documented behavioural and environmental barriers to adherence that includes parent-child interaction at mealtimes. While not 'abnormal', parent behaviours such as paying increased attention to the child in the form of coaxing, commanding and feeding when the child is engaged in behaviours incompatible with eating (food refusal, talking, leaving the meal) may serve to reinforce these child non-eating behaviours. Thus, dietary counselling alone, albeit necessary, is typically insufficient because of failure to specifically address these behavioural and environmental barriers to dietary treatment. Behavioural intervention that targets both nutrition education and behavioural management has been found to be effective in achieving an average increased energy intake of 4200 kJ (1000 kcal)/d and weight gain of 1.48 kg over 9 weeks in children with CF. This intervention utilizes self-monitoring, goal setting and shaping to structure the delivery of treatment. It also teaches parents to utilize child behaviour-management techniques to motivate children to increase their energy intake. These behavioural strategies include differential attention (praising and ignoring), contingency management and behavioural contracting. The potential application of these techniques to dietary counselling is suggested.

Behavior Therapy↗

PubMed2007

Human airway surface epithelial regeneration is delayed and abnormal in cystic fibrosis.

Cystic fibrosis (CF) at an advanced stage of the disease is characterized by airway epithelial injury and remodelling. Whether CF remodelling is related to infection and inflammation or due to an abnormal regenerative process is still undecided. We have recently established the expression and secretion profiles of interleukin (IL)-8, matrix metalloproteinase (MMP)-7, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 during non-CF airway epithelial regeneration in a humanized nude mouse xenograft model. To enhance our understanding of CF remodelling, we compared the regeneration process of non-infected human CF and non-CF nasal epithelia. In both CF and non-CF situations, epithelial regeneration was characterized by successive steps of cell adhesion and migration, proliferation, pseudostratification, and terminal differentiation. However, histological examination of the grafts showed a delay in differentiation of the CF airway epithelium. Cell proliferation was higher in the regenerating CF epithelium, and the differentiated CF epithelium exhibited a pronounced height increase and basal cell hyperplasia in comparison with non-CF epithelium. In addition, while the number of goblet cells expressing MUC5AC was similar in CF and non-CF regenerated epithelia, the number of MUC5B-immunopositive goblet cells was lower in CF grafts. The expression of human IL-8, MMP-7, MMP-9, and TIMP-1 was enhanced in CF epithelium, especially early in the regenerative process. Together, our data strongly suggest that the regeneration of human CF airway surface epithelium is characterized by remodelling, delayed differentiation, and altered pro-inflammatory and MMP responses.

Adolescent↗

PubMed2000

Altered intracellular pH regulation in neutrophils from patients with cystic fibrosis.

Cystic fibrosis (CF) is a condition characterized by neutrophil-mediated lung damage and bacterial colonization. The physiological basis for reported functional alterations in CF neutrophils, including increased release of neutrophil elastase, myeloperoxidase, and oxidants, is unknown. These processes are, however, regulated by intracellular pH (pH(i)). We demonstrate here that pH(i) regulation is altered in neutrophils from CF patients. Although resting pH(i) is similar, pH(i) after acid loading and activation (N-formyl-methionyl-leucyl-phenylalanine and phorbol 12-myristate 13-acetate) is more acidic in CF cells than in normal cells. Furthermore, patients with non-CF-related bronchiectasis handle acid loading and activation in a fashion similar to subjects with normal neutrophils, suggesting that chronic pulmonary inflammation alone does not explain the difference in pH(i). This is further supported by data showing that normal neutrophils exposed to the CF pulmonary milieu respond by increasing pH(i) as opposed to decreasing pH(i) as seen in activated CF neutrophils. These pH(i) differences in activated or acid-loaded CF neutrophils are abrogated by ZnCl(2) but not by amiloride and bafilomycin A(1), suggesting that passive proton conductance is abnormal in CF. In addition, DIDS, which inhibits HCO(3)(-)/Cl(-) exchange, causes alkalinization of control but not of CF neutrophils, suggesting that anion transport is also abnormal in CF neutrophils. In summary, we have shown that pH(i) regulation in CF neutrophils is intrinsically abnormal, potentially contributing to the pulmonary manifestations of the condition.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2005

Reduced iC3b-mediated phagocytotic capacity of pulmonary neutrophils in cystic fibrosis.

Cystic fibrosis (CF) is characterized by a neutrophil-dominated chronic inflammation of the airways with persistent infections. In order to investigate whether neutrophils contribute to an inadequacy in the pulmonary defence mechanism, the phagocytic activity of pulmonary and peripheral blood neutrophils from CF and non-CF respiratory patients were compared. Neutrophils were isolated from both the blood and bronchoalveolar lavage fluid of 21 patients with CF (12 male, 9 female; mean age 7.5 years, range 0.25-16.4 years) and 17 non-CF subjects (9 male, 8 female; mean age 5.4 years, range 0.2-13.1 years). The ex vivo phagocytic rate of normal pulmonary neutrophils to internalize zymosan particles opsonized with iC3b was faster than that of circulating neutrophils (P < 0.05), but the maximum capacity (9 particles/cell) was similar. In contrast, pulmonary neutrophils from patients with CF had a lower phagocytic capacity than circulating neutrophils either from the same patients or from normal subjects. This deficiency could not be attributed to (i) the cell surface density of CR3 (CD18/CD11b) receptors, which were not significantly different between the other groups (ii) the signalling ability of the CR3 receptors, using cytosolic free Ca(2+) signalling as the receptor activity read-out or (iii) a decrease in cellular ATP concentration. As CFTR was not detectable on neutrophils from any source by either histochemistry or Western blotting, it was concluded that the reduced phagocytic capacity was not the direct result of a CFTR mutation, but was attributed to a failure of neutrophil phagocytic priming during translocation into the CF lung.

Adenosine Triphosphate↗

PubMed1994

Insulin sensitivity in cystic fibrosis.

Cystic fibrosis (CF) patients demonstrate a spectrum of pancreatic beta-cell abnormalities. Those with no exocrine insufficiency (NEXO) have normal insulin secretion. Exocrine-insufficient CF patients with overt diabetes (EXO-IT) have impaired insulin secretion and fasting hyperglycemia. Exocrine-insufficient patients without diabetes (EXO) have impaired insulin secretion but maintain normoglycemia. We postulated that EXO individuals compensate for insulin deficiency by increasing insulin sensitivity and investigated glucose utilization in CF. To examine hepatic and peripheral insulin sensitivity, euglycemic-hyperinsulinemic clamp studies were performed by using the hot GINF isotope dilution technique. Insulin was sequentially infused at 0.25, 1.0, and 10.0 mU.kg-1.min-1. Glucose-mediated glucose uptake (GMGU) was assessed on another day with hyperglycemic clamp studies, during which insulin and somatostatin were infused to hold insulin-mediated glucose uptake constant between the two clamp studies. Skeletal muscle GLUT4 levels were assessed in EXO and control patients with Western blotting. Three patterns of peripheral and hepatic insulin sensitivity were seen that were related to the degree of pancreatic beta-cell dysfunction. NEXO individuals had normal peripheral and hepatic insulin sensitivity. EXO individuals had enhanced peripheral insulin sensitivity that was not associated with a change in skeletal muscle glucose transporter abundance compared with control patients; paradoxically, EXO subjects demonstrated hepatic insulin resistance. EXO-IT had peripheral and hepatic insulin resistance. GMGU was diminished in both EXO and EXO-IT subjects. The unique combination of increased hepatic glucose production and increased peripheral glucose utilization seen in EXO may be a metabolic adaptation to increased peripheral energy needs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1998

Pleural disease in patients undergoing lung transplantation for cystic fibrosis.

Cystic fibrosis (CF) is associated with varying degrees of pleural inflammatory reaction that occurs as a result of chronic pulmonary infections and intervention to pleural space. The amount of pleural reaction is associated with the difficulty involved when performing the pneumonectomy at the time of lung replacement. The aim of this study is to identify possible pre-transplantation parameters that may predict the extent of pleural adhesion density. The charts of the 32 CF patients who underwent lung transplantation were reviewed. The degree of pleural adhesions was graded as none, minimal, moderate or severe, by extensive retrospective chart review of the operative and pathology reports. Available Brasfield radiographic scores, chest computerized tomographic (CT) scan scores, and pulmonary function test results were correlated to the pleural density grades. CT scans were scored by one radiologist as none, mild focal, moderate focal, diffuse mild or severe pleural disease. The presence of severe adhesions was associated with lower diffusion capacity corrected for volume (DL(CO)/VA) (p=0.0022) and older age (p<0.05) at the time of transplant. The typical radiographic and pulmonary function findings of airway obstruction, parenchymal nodularity and air trapping did not correlate with pleural adhesion density. The eleven patients with severe pleural adhesions had a longer ICU course and remained intubated longer than the thirteen patients with none or minimal adhesions. The extent of severe adhesions associated with CF cannot be predicted by preoperative Brasfield radiographic scores of parenchymal disease or spirometry data. However, chest CT imaging and DL(CO)/VA measurements may be useful in predicting the extent of pleural adhesions and the degree of dissection difficulty associated with the pneumonectomies for lung transplantation in the CF recipients.

Adolescent↗