Leukotriene E4 in urine in patients with asthma and COPD—The effect of smoking habit

Abstract

Leukotriene E(4) (LTE(4)) is implicated in asthma pathophysiology and possibly in chronic obstructive pulmonary disease (COPD) as one of the causes of persistent bronchoconstriction and mucus hypersecretion. Cigarette smoking stimulates cysteinyl leukotrienes (CysLTs) production. We investigated whether LTE(4) is equally increased in asthma and COPD and whether smoking significantly affects LTE(4) levels. Secondary outcomes involved correlations with inflammatory and functional parameters. We studied 40 patients with COPD [20 smokers], 40 asthmatics [20 smokers] and 30 healthy subjects [15 smokers]. Spirometry (FEV(1)% pred., FEV(1)/FVC) was performed, urine was collected for measurement of LTE(4) and creatinine, induced sputum was collected for differential cell counts and serum for ECP. LTE(4)/creatinine levels (pg/mg) [mean (sd)] were increased in asthmatic patients compared to COPD and controls, [125.6(54.5) vs. 54.5(19) vs. 55.9(18.9)pg/mg, respectively, P<0.0001 for asthma]. Smoking significantly affects LTE(4) levels only in asthmatic patients [164 (48) vs. 87 (26.3), P<0.0001 for smokers]. The only significant correlation was between eosinophils in induced sputum and LTE(4)/creatinine levels in asthmatics. In conclusion, patients with asthma presented higher LTE(4) values compared to normals and patients with COPD. Smoking significantly affects LTE(4) values only in asthmatics indicating a different underlying CysLTs inflammatory process in this condition.

Smoking Affects Response to Inhaled Corticosteroids or Leukotriene Receptor Antagonists in Asthma

“…Urinary excretion of LTE 4 is closely correlated with the number of cigarettes smoked daily, and urinary LTE 4 levels increase significantly in nonsmokers who smoke six cigarettes in 12 hours (24). Gaki and associates have reported that smoking increases urinary LTE 4 in patients with asthma, but not in normal subjects or patients with COPD (26). Habitual smokers, such as those enrolled in our study, may therefore have chronically elevated leukotriene levels that may render them responsive to treatment with cysteinyl leukotriene receptor antagonists.…”

“…In addition, studies have shown a dose-related increase in urinary leukotriene E 4 (LTE 4 ) excretion in response to cigarettes in habitual smokers (24), an increase in 15-lipoxygenase activity in the airways of healthy smokers (25), and a smoking-induced increase in urinary LTE 4 in subjects with asthma, but not in subjects with chronic obstructive pulmonary disease (COPD) or normal subjects (26). These studies provide the rationale for studying montelukast in patients with asthma who smoke.…”

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

“…However, pulmonary inflammation in COPD is, to some extent, different from that in asthma, because other inflammatory cells (i.e., neutrophils, macrophages, and CD8 ϩ T lymphocytes) are implicated (Gan et al, 2004). In addition, the profile of exhaled eicosanoids may be different from that previ-LEUKOTRIENE RECEPTORS 571 ously reported in asthma: exhaled PGE 2 is selectively increased in COPD, whereas LTE 4 is increased in asthma (Montuschi et al, 2003), but not in COPD (Gaki et al, 2007). There are only a few studies of the clinical effects of LTRAs in COPD.…”

Levels of prostaglandin E2 and Cysteinyl‐leukotrienes in sputum supernatant of patients with asthma: the effect of smoking

“…This difference might be attributed to either differences in the underlying severity, differences in intensity of anti-inflammatory treatment and/or different methodology in measurement of those mediators [8,9]. Previous suggestions support that the systemic expression of leukotrienes in urine is significantly influenced by smoking -either active or passive -irrespective of the presence of asthma [12,14]. This study is the first to our knowledge that evaluates the airway concentrations of Cyst-LTs in relation to the smoking habit.…”

“…Data obtained from either asthmatics or normal subjects suggests that the measurement of leukotriene E 4 in urine is significantly affected by both the use and/or exposure to tobacco [11,12]. A single study on exhaled breath condensate in asthmatics suggests that smoking significantly affects PGE 2 levels [13].…”