Cysteinyl leukotriene involvement in chronic lung disease in premature infants

Abstract

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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“…A single study has shown increased urinary leukotriene (LT) E4 in babies with chronic lung disease, compared with controls [15]. There was no correlation with indices of airflow obstruction.…”

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“…El factor de necrosis tumoral y la IL-6 inducen la producción de fibroblastos y colágeno que están presentes en los niños con DBP 26,30 . También se han encontrado niveles elevados de leucotrienos en pulmón de niños que desarrollan esta patología y que permanecen elevados hasta los 6 meses de edad 31 . Los leucotrienos causan una serie de alteraciones pulmonares como edema intersticial, producción de mucus y especialmente broncoconstricción y vasoconstricción 31 .…”

“…También se han encontrado niveles elevados de leucotrienos en pulmón de niños que desarrollan esta patología y que permanecen elevados hasta los 6 meses de edad 31 . Los leucotrienos causan una serie de alteraciones pulmonares como edema intersticial, producción de mucus y especialmente broncoconstricción y vasoconstricción 31 . Sin embargo, aún se desconoce cual es el factor que inicia y mantiene la respuesta inflamatoria que termina dañando el pulmón.…”

LEUKOTRIENE METABOLISM BY INTRAPULMONARY VESSELS OF NEWBORN LAMBS: Effect of Platelet-Activating Factor

“…In vivo, LTE 4 production is often used as an indication of peptide LT turnover [ 28,29] . We have used the production of LTE 4 and LTB 4 by the vessels to assess 5-lipoxygenase activity in these vessels.…”