Leukotriene D4

Cysteinyl-leukotrienes (Cys-LTs), including leukotriene C4 (LTC4), leukotriene D4 (LTD4), and leukotriene E4 (LTE4), are generated from arachidonic acid (AA) via 5-lipoxygenase (5-LOX) pathway (Samitas, Chorianopoulos et al. 2009). Cys-LTs are well-recognized inflammatory mediators (Zagorska, Grzela et al. 2013). The concentration of the exhaled compounds could reflect the phenomena of inflammation and oxidative stress in patients. The measurement of mediators in exhaled breath condensate (EBC) helps to monitor the status and severity of pulmonary inflammation and oxidative stress (Ciebiada, Gorski et al. 2012). Higher level of Cys-LTs was detected in several inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Since Cys-LTs have been mostly analyzed by enzyme immunoassay (EIA) which detects the complex of LTC4, LTD4, and LTE4, it is difficult to obtain each individual level (Pelclova, Fenclova et al. 2012). Although LC-ESI-MS/MS might be a platform to analyze and detect individual Cys-LT in EBC, urine, and plasma, most of studies still measured Cys-LTs as a whole composition by EIA. Description of disease(s) related to Leukotriene D4 (LTD4):

Asthma

Asthma is an inflammatory respiratory disease. Cys-LTs have been detected in EBC of patients with asthma. EBC Cys-LTs concentration was significantly higher in patients with asthma than in healthy subjects. The level of Cys-LTs would gradually increase according to the severity of asthma. Cys-LTs were involved in the pathogenesis of asthma. Cys-LTs may be a potential biomarker of bronchial asthma.

Sleep Apnea Syndromes

In adenotonsillar tissue and EBC of children with sleep apnea, the concentration of Cys-LTs was elevated. In urine, Cys-LTs concentration was significantly related to the severity of sleep-disordered breathing (SDB). Cys-LTs might be the cause of pathogenesis of obstructive sleep apnea (OSA), or the consequence of upper airway obstruction during sleep. Detection of Cys-LTs concentration in EBC or urine could be a non-invasive method to estimate the status of SDB.

Rhinitis, Allergic, Perennial

Basal level of Cys-LTs in EBC of allergic rhinitis (AR) patients was significantly higher than that in healthy subjects. Therefore, the measurement of Cys-LTs in EBC could be a fast and effective screening method to early detect the possibility of suffering AR. After the treatment of intranasal corticosteroid fluticasone propionate (FP), basal Cys-LTs level was significantly reduced in AR patients with and without asthma.

Sarcoidosis

The mean concentration of Cys-LTs was higher in EBC in sarcoidosis subjects as compared to healthy subjects.

Asthma, Aspirin-Induced

Subjects with asthma had significant increased level of LTD4 in EBC as compared to healthy control subjects. Following aspirin challenge, Cys-LTs level was lower in subjects with aspirin-induced asthma/aspirin-intolerant asthma (AIA) as compared to subjects with aspirin-tolerant asthma (ATA).

Asthma, Occupational

Total Cys-LTs in EBC were higher in patients with occupational asthma (OA). The level of Cys-LTs in EBC could be used to estimate the status of inflammation and oxidative stress, and reflect the severity of OA.

Bronchoconstriction

Asthmatic children with exercise-induced bronchoconstriction (EIB) had higher concentration of Cys-LTs than subjects without exercise-induced bronchoconstriction (non-EIB) and control subjects. The effect of inhaled LTD4 on bronchoconstriction is similar to bronchoconstriction induced by exercise challenge.

Carcinoma, Non-Small-Cell Lung

Cys-LTs were found in exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALf) of studied patients with diagnosed non-small cell lung cancer (NSCLC). Compared with healthy controls, patients had significantly higher concentration of Cys-LTs in EBC. In patients, although Cys-LTs concentration in BALf was significantly higher than in EBC, there was a significant and positive correlation between Cys-LTs concentration in EBC and in BALf, which makes the non-invasive, breath-based detection method become feasible to monitor and diagnose lung cancer disease.

Lung Neoplasms

It had been demonstrated that lung carcinogenesis could induce local inflammation and enhance oxidative stress. Cys-LTs were increased in lung cancer microenvironment. Since factors unrelated to lung neoplasms, such as age and smoking status, were excluded, the difference of Cys-LTs concentration between patients and healthy control groups was mainly related to the studied neoplasmatic disease.

Pneumoconiosis

Patients with pneumoconiosis were divided into asbestos exposure and silica exposure groups. Cys-LTs were elevated in EBC of asbestos exposure subjects. Besides, LTD4 was elevated in EBC of both asbestos exposure and silica exposure subjects, compared to control subjects. The level of LTD4 in EBC was correlated with the level in urine and plasma.

Pulmonary Disease, Chronic Obstructive

The level of Cys-LTs in EBC of patients with exacerbated chronic obstructive pulmonary disease (COPD) was different at different therapeutic stages (including outpatient clinic or hospital visit (visit 1), antibiotic therapy visit (visit 2), post-therapy visit (visit 3), and follow-up visit). Cys-LTs level at visit 1 stage was significantly greater than other stages, and the level had a decreasing trend during treatment. High Cys-LTs level might be derived from the increased 5-lipoxygenase enzyme activity in COPD patients.

Silicotics

The level of LTD4 was higher in subjects with silicosis as compared to control subjects. LTD4 had a positive correlation with the silica exposure level and the severity of silicosis.

Summary of extracted biomedical information