Cysteinyl leukotriene involvement in chronic lung disease in premature infants.
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 E4 (LTE4) 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 LTE4 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 LTE4 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 E4 was not demonstrated, pathological lung function and an enhanced urinary leukotriene E4 production in infants with chronic lung disease would tend to suggest that the cysteinyl leukotrienes were involved in the sequelae of this disease.
Cook
A J
AJ
Dept of Thoracic Medicine, King's College School of Medicine and Dentistry, London, UK.
Yuksel
B
B
Sampson
A P
AP
Greenough
A
A
Price
J F
JF
D000402:Airway Obstruction / Q000503:physiopathology; D000403:Airway Resistance / Q000502:physiology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002908:Chronic Disease; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D005500:Follow-Up Studies; D005652:Functional Residual Capacity / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000652:urine*; D007235:Infant, Premature, Diseases / Q000503:physiopathology / Q000652:urine*; D017999:Leukotriene E4 / Q000652:urine*; D008168:Lung / Q000503:physiopathology; D008171:Lung Diseases / Q000503:physiopathology / Q000652:urine*; D010102:Oxygen Inhalation Therapy; D011446:Prospective Studies; D012121:Respiration, Artificial; D013990:Tidal Volume / Q000502:physiology
D001993:Bronchodilator Agents; D017999:Leukotriene E4; D003404:Creatinine