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Published on: August 7, 2017
Exhaled eicosanoid profiles in children with atopic asthma and healthy controls
Edyta Glowacka1, Urszula Jedynak-Wasowicz, Marek Sanak
1University Children Hospital, Kraków, ul. Wielicka, Poland.
Insights
This study found specific eicosanoid profiles in exhaled breath condensate (EBC) of children with asthma. These profiles, particularly the eicosanoids asthma classification ratio (EACR), show promise for diagnosing and monitoring childhood asthma non-invasively.
Area of Science:
- Biochemistry
- Pediatric Pulmonology
- Biomarker Discovery
Background:
- Chronic endobronchial inflammation in pediatric asthma involves the arachidonic acid pathway.
- Non-volatile metabolites of this pathway can be measured in exhaled breath condensate (EBC).
- Previous studies explored single substances as biomarkers for childhood asthma.
Purpose of the Study:
- To compare a wider range of eicosanoids in EBC between children with asthma and healthy controls.
- To evaluate the diagnostic potential of these eicosanoids and derived ratios.
Main Methods:
- EBC samples were collected from 33 children with stable atopic asthma and 25 healthy controls.
- High-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS2) was used to quantify 13 eicosanoids.
- Exhaled nitric oxide (FeNO) and bronchial hyperresponsiveness (BHR) were also assessed.
Main Results:
- Significantly higher levels of PGEM, PGD2, 6keto-PGF1α, LTC4, trans-LTC4, and 5HETE were found in asthmatic children.
- 11-dehydro TXB2 levels were significantly lower in asthmatics.
- An eicosanoids asthma classification ratio (EACR), using PGEM, PGD2, LTC4, and 5HETE, effectively discriminated asthmatic from healthy children.
Conclusions:
- Feasible measurement of specific eicosanoids (PGEM, PGD2, LTC4, 5HETE) in small EBC volumes using HPLC-MS2.
- The EACR demonstrated superior discrimination compared to FEV1, FeNO, or BHR.
- Further evaluation of EACR is warranted for diagnosing and monitoring childhood asthma.
Rationale:
Chronic endobronchial inflammation is a hallmark of pediatric asthma and involves the arachidonic acid pathway. Its non-volatile metabolites can be quantified in the exhaled breath condensate (EBC), and single substances have been studied as non-invasive biomarkers for the diagnosis and monitoring of children with asthma. The aim of this study was to compare the content and profile of a wider range of eicosanoids in the EBC between patients and a control group.
Materials And Methods:
EBC was sampled from 33 children (aged 12.4 ± 3.1 years) with stable atopic asthma (26 on inhaled steroid treatment) and 25 healthy controls (11.8 ± 3.2 years). Validated high performance liquid chromatography coupled with a tandem mass spectrometry platform (HPLC-MS2 ) was used to measure 13 different compounds. In addition, exhaled nitric oxide levels (FeNO) were measured and bronchial hyperresponsiveness (BHR) was assessed by an exercise challenge test in all subjects. An analytical approach was used for multivariate regression modeling of disease status using the most relevant variables.
Results:
The levels of PGEM (P < 0.001), PGD2 (P < 0.001), 6keto-PGF1α (P = 0.03), LTC4 (P < 0.001), trans-LTC4 (P = 0.04), and 5HETE (P = 0.02) were significantly higher in asthmatics compared to healthy children, while 11-dehydro TXB2 was significantly less abundant (P = 0.02). The eicosanoids asthma classification ratio (EACR) was computed as the logistic regression function using four variables: PGEM, PGD2, LTC4, and 5HETE. This composite parameter discriminated asthmatic from healthy children better than FEV1, FeNO, or BHR.
Conclusion:
Complementary measurements of PGEM, PGD2, LTC4, and 5HETE in small-volume EBC samples are feasible by HPLC-MS2 and showed a specific profile in our study population. EACR should be evaluated further in the context of diagnosing and monitoring childhood asthma.
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