Leukotrienes in the sputum and urine of cystic fibrosis children.

Sampson, A. P.; Spencer, DA; Green, CP; Piper, Priscilla J.; Price, JF

doi:10.1111/j.1365-2125.1990.tb05452.x

Cited by 63 publications

(34 citation statements)

References 26 publications

(25 reference statements)

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“…The levels of LTE 4 excreted in these premature infants are much higher than levels reported in normal children aged 1-13 yrs (88.4 (71.3-111) pmol·mmol -1 creatinine) [21]. This may be explained, in part, by the tendency for creatinine levels to be lower in the urine of infants (4.0 (1.3-10.5) mmol·L -1 ) than older children (10.5 (1.7-34) mmol·L -1 ).…”

Section: Discussioncontrasting

confidence: 57%

“…Previous studies in asthmatic and normal adults (TAYLOR et al [22], 1989), and cystic fibrosis and normal children (SAMPSON et al [21], 1990) have shown urinary LTE 4 levels to be log 10 normally distributed by normal probability score (Minitab). Therefore, an unpaired Student's t-test was used on log 10 normalized urinary LTE 4 values for each group, with the results expressed as the geometric mean (95% confidence intervals (95% CI)).…”

Section: Discussionmentioning

confidence: 97%

“…An aliquot (1 mL) was removed from each urine sample for creatinine analysis (Dept Clinical Biochemistry, King's College Hospital). The purification process was adapted from a technique previously described by our group [21]. Briefly, each sample was spiked with 3 H-LTE 4 (5 nCi) and partially purified using a Mega Bond-Elut C18 cartridge.…”

Section: Urinary Lte 4 Analysismentioning

confidence: 99%

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Cysteinyl leukotriene involvement in chronic lung disease in premature infants

Cook

Yüksel²,

Sampson³

et al. 1996

Eur Respir J

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C Cy ys st te ei in ny yl l l le eu uk ko ot tr ri ie en ne e i in nv vo ol lv ve em me en nt t i in n c ch hr ro on ni ic c l lu un ng g d di is se ea as se e i in n p pr re em ma at tu ur re e i in nf fa an nt ts s A.J. Cook*, B. Yuksel*, A.P. Sampson**, A. Greenough*, J.F. Price* Cysteinyl leukotriene involvement in chronic lung disease in premature infants. A.J. Cook, B. Yuksel, A.P. Sampson, A. Greenough, J.F. Price. ERS Journals Ltd 1996. ABSTRACT: The pathophysiology of chronic lung disease (CLD) in premature infants who require mechanical ventilation and prolonged oxygen supplementation has been well-described but the underlying mechanisms are not understood. Our aim was to test the hypothesis that excess cysteinyl leukotriene (LT) production was a contributing factor in CLD. We compared LT production and lung function, at 7 months of age, in nine premature infants with CLD and in eight control infants without CLD. None of the control infants developed any neonatal respiratory problems, but two subsequently required bronchodilator therapy. Respiratory function was assessed by the measurement of thoracic gas volume (TGV), airways resistance (Raw) and functional residual capacity (FRC). Total cysteinyl LT production was quantified by measurement of leukotriene E 4 (LTE 4 ) in a spot urine sample.Although all patients were asymptomatic at follow-up, there was evidence of significant lung function abnormalities in infants with CLD. The CLD infants had significantly elevated TGV, Raw and FRC values reflecting airway obstruction when compared to the controls. Urinary LTE 4 levels were significantly higher in the CLD infants when compared to the controls (geometric mean: 741 and 337 pmol·mmol -1 creatinine, respectively). There was no direct correlation between urinary LTE 4 levels in the CLD group and TGV, Raw or FRC values.Although this study is small and a direct correlation between lung function and urinary leukotriene E 4 was not demonstrated, pathological lung function and an enhanced urinary leukotriene E 4 production in infants with chronic lung disease would tend to suggest that the cysteinyl leukotrienes were involved in the sequelae of this disease. Eur Respir J., 1996Respir J., , 9, 1907Respir J., -1912 Many of the pathological features of neonatal chronic lung disease (CLD) have been attributed to the pulmonary effects of mechanical ventilation and prolonged supplementary oxygen [1]. Infants developing CLD subsequently have repeated respiratory infections and wheezing attacks, and an increased rate of hospital admission [2]. Impairment of lung function, as evidenced by reduced dynamic compliance, airway hyperreactivity, increased airway resistance and hyperinflation, has also been described [1,[3][4][5][6][7]. These abnormalities are evident in the first few years of life [3][4][5], and may persist throughout childhood [6,7].Several mechanisms have been implicated in the pathogenesis of CLD. These include an imbalance of protease/antiprotease production [8], increased lipid mediator (platelet-a...

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 97%

Section: Urinary Lte 4 Analysismentioning

confidence: 99%

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Cysteinyl leukotriene involvement in chronic lung disease in premature infants

Cook

Yüksel²,

Sampson³

et al. 1996

Eur Respir J

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“…AA is a precursor of bioactive oxygenated metabolites known as eicosanoids, which include prostaglandins and leukotrienes. Production of these metabolites is known to be increased in CF, and several studies have drawn a connection between eicosanoid alterations and disease pathogenesis (54)(55)(56)(57)(58)(59). It is plausible that the observed benefi t of n-3 fatty acid therapy in the CF mouse model ( 6 ) and in a small subset of human trials ( 29,30 ) is due to its ability to normalize AA levels and, consequently, reduce excessive production of eicosanoids.…”

Section: Discussionmentioning

confidence: 99%

DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity

Njoroge

Laposata²,

Katrangi³

et al. 2012

Journal of Lipid Research

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in the United States to 37 years ( 2 ). Among the phenotypic manifestations of CF patients are abnormalities in blood and tissue polyunsaturated fatty acid (PUFA) levels that are independent of absorption and nutritional status (reviewed in Refs. [3][4][5]. The most consistent of these abnormalities are decreased linoleate (LA; 18:2n-6) and docosahexaenate (DHA; 22:6n-3). In addition, some studies have shown increased arachidonate (AA; 20:4n-6), palmitoleate (16:1n-7), oleate (18:1n-9), and Mead acid (20:3n-9). Similar fi ndings are seen in animal ( 6-9 ) and cell culture ( 10, 11 ) models of CF. The magnitude of fatty acid alterations in CF patients correlates with disease severity, suggesting a role for fatty acid metabolism in CF pathophysiology ( 12-17 ).There is increasing evidence that these abnormalities are due to differences in fatty acid metabolism in CF. PUFAs of the n-3 and n-6 series are metabolized in a stepwise fashion along parallel pathways (reviewed in Ref. 18 ). A common set of desaturase and elongase enzymes catalyzes the conversion of LA through multiple steps to AA and ultimately to docosapentaenoate (DPA; 22:5n-6). The same enzymes convert linolenate (LNA; 18:3n-3) to eicosapentaenoate (EPA; 20:5n-3) and subsequently to DHA. Multiple studies have demonstrated increased conversion of AA to eicosanoids (19)(20)(21)(22), stimulating increased metabolism of LA to maintain AA ( 7, 10, 11 ) and accounting for the decreased LA and increased AA levels seen in CF.Recent studies in our laboratory have uncovered a potential mechanism accounting for these metabolic changes ( 23 ). In cell culture models of CF, decreased LA and increased AA and EPA levels in CF cells correlated with increased expression and activity of the ⌬ 5-and ⌬ 6-desaturase enzymes that catalyze conversion of LA to AA and LNA to EPA. Similar increases in ⌬ 9-desaturase and elongase-6Abstract Patients and models of cystic fi brosis (CF) exhibit consistent abnormalities of polyunsaturated fatty acid composition, including decreased linoleate (LA) and docosahexaenoate (DHA) and variably increased arachidonate (AA), related in part to increased expression and activity of fatty acid desaturases. These abnormalities and the consequent CF-related pathologic manifestations can be reversed in CF mouse models by dietary supplementation with DHA. However, the mechanism is unknown. This study investigates this mechanism by measuring the effect of exogenous DHA and eicosapentaenoate (EPA) supplementation on fatty acid composition and metabolism, as well as on metabolic enzyme expression, in a cell culture model of CF. We found that both DHA and EPA suppress the expression and activity of ⌬ 5-and ⌬ 6-desaturases, leading to decreased fl ux through the n-3 and n-6 PUFA metabolic pathways and decreased production of AA. The fi ndings also uncover other metabolic abnormalities, including increased fatty acid uptake and markedly increased retroconversion of DHA to EPA, in CF cells. These results indicate that the fatty acid abnormalities of CF are ...

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“…For example, cysteinyl LTs have been found in the sputum and urine of patients with cystic fibrosis (CF) (Sampson et al, 1990;Spencer et al, 1992), a disease in which the inflammatory process contributes to progressive lung tissue damage, and their concentrations increase during disease exacerbations together with oxidative stress (Reid et al, 2007). Few studies have been conducted to test the hypothesis that LTRAs have the potential to ameliorate CF lung disease.…”

Section: Cyslt In Other Diseasesmentioning

confidence: 99%