Leukotriene B 4 in Exhaled Breath Condensate and Sputum Supernatant in Patients With COPD and Asthma

Κostikas, Κonstantinos; Gaga, Mina; Papatheodorou, Georgios; Karamanis, Thomas; Orphanidou, Dora; Loukides, Stelios

doi:10.1378/chest.127.5.1553

Cited by 112 publications

(87 citation statements)

References 20 publications

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“…These studies highlight a previously unappreciated inhibitory effect of 5-LO metabolites on alveolar remodeling and MMP production. At present it is not clear whether this effect is mediated by the LTB 4 , which is produced in an exaggerated manner in our modeling system and in lung tissues from patients with COPD (59,60). This is, however, a tempting speculation because LTB 4 has known profibrotic properties, and the magnitude of alveolar destruction after injury is inversely proportional to one's ability to generate a fibrotic response and heal.…”

Section: Discussionmentioning

confidence: 83%

Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling

Shim

Zhu

Zheng

et al. 2006

The Journal of Immunology

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Exaggerated levels of IL-13 and leukotriene (LT) pathway activation frequently coexist at sites of Th2 inflammation and in tissue fibrotic responses. However, the relationship(s) between the IL-13 and LTs in these responses have not been defined. We hypothesized that the 5-lipoxygenase (5-LO) pathway of LT metabolism plays an important role in the pathogenesis of IL-13-induced chronic inflammation and remodeling. To test this hypothesis, we evaluated the effects of IL-13 on components of the 5-LO metabolic and activation pathways. We also compared the effects of transgenic IL-13 in C57BL/6 mice with wild-type and null 5-LO genetic loci. These studies demonstrate that IL-13 increases the levels of mRNA encoding cytosolic phospholipase A2, LTA4 hydrolase, and 5-LO-activating protein without altering the expression of 5-LO, LTC4 synthase, LTB4 receptors 1 and 2, and cysteinyl-LT receptors 1 and 2. They also demonstrate that this activation is associated with the enhanced accumulation of LTB4 but not of cysteinyl-LTs. Furthermore, they demonstrate that this stimulation plays a critical role in the pathogenesis of IL-13-induced inflammation, tissue fibrosis, and respiratory failure-induced death while inhibiting alveolar remodeling. Lastly, mechanistic insights are provided by demonstrating that IL-13-induced 5-LO activation is required for optimal stimulation and activation of TGF-β1 and the inhibition of matrix metalloproteinase-12. When viewed in combination, these studies demonstrate that 5-LO plays an important role in IL-13-induced inflammation and remodeling.

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Section: Discussionmentioning

confidence: 83%

Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling

Shim

Zhu

Zheng

et al. 2006

The Journal of Immunology

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“…Therefore, it was concluded that saliva is a possible source of LTB 4 in EBC. LTB 4 levels in EBC have been reported to be increased in several respiratory diseases such as asthma, COPD [17] and cystic fibrosis [9]. The levels reported are generally in the 10-130 pg?mL -1 concentration range, although, in more recent publications, the data are expressed as amounts of LTB 4 obtained during a defined time period of tidal breathing [18].…”

Section: Discussionmentioning

confidence: 99%

Saliva is one likely source of leukotriene B₄in exhaled breath condensate

Gaber¹,

Acevedo²,

Delin³

et al. 2006

Eur Respir J

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Leukotriene (LT)B 4 in exhaled breath condensate (EBC) has been reported to be elevated in airway inflammation. The origin of leukotrienes in EBC is, however, not established.The aims of this study are to measure LTB 4 levels in EBC collected in two challenges characterised by a strong neutrophilic airway inflammation and to compare LTB 4 levels in EBC with levels in sputum and saliva.LTB 4 and a-amylase were measured in EBC from 34 healthy subjects exposed in a pig confinement building or to a lipopolysaccharide provocation. These markers were also measured in induced sputum in 11 of the subjects. For comparison, LTB 4 and a-amylase were measured in saliva from healthy subjects.Only four out of 102 EBC samples had detectable LTB 4 (28-100 pg?mL -1 ). a-amylase activity was detected in the LTB 4 -positive samples. In contrast, LTB 4 was detected in all examined sputum supernatants in the same study (median 1,190 pg?mL -1 ). The median LTB 4 level in saliva was 469 pg?mL -1 .High levels of leukotriene B 4 in saliva and the presence of leukotriene B 4 in exhaled breath condensate only when a-amylase was detected, indicate that leukotriene B 4 found in exhaled breath condensate is the result of saliva contamination. As leukotriene B 4 was consistently present in sputum supernatants, exhaled breath condensate may be inappropriate for monitoring airway leukotriene B 4 .

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“…There is considerable variability in exhaled pH in COPD patients, which is greater than in normal subjects [555]. There is an increase in the concentration of leukotriene B 4 in COPD patients, which is further increased during exacerbations [551,556,557]. Increases in prostaglandin E 2 and IL-6 have also been reported in COPD patients [556,558].…”

Section: Inflammatory Mediatorsmentioning

confidence: 99%

Outcomes for COPD pharmacological trials: from lung function to biomarkers

Cazzola¹,

MacNee²,

Martínez³

et al. 2008

Eur Respir J

751

566

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The American Thoracic Society/European Respiratory Society jointly created a Task Force on “Outcomes for COPD pharmacological trials: from lung function to biomarkers” to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

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Leukotriene B 4 in Exhaled Breath Condensate and Sputum Supernatant in Patients With COPD and Asthma

Cited by 112 publications

References 20 publications

Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling

Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling

Saliva is one likely source of leukotriene B₄in exhaled breath condensate

Outcomes for COPD pharmacological trials: from lung function to biomarkers

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Leukotriene B 4 in Exhaled Breath Condensate and Sputum Supernatant in Patients With COPD and Asthma

Cited by 112 publications

References 20 publications

Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling

Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling

Saliva is one likely source of leukotriene B4in exhaled breath condensate

Outcomes for COPD pharmacological trials: from lung function to biomarkers

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Product

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Saliva is one likely source of leukotriene B₄in exhaled breath condensate