dinoprost and Hyperventilation

Evaluate the effect of the marine lipid fraction of the New Zealand green-lipped mussel (Perna canaliculus) PCSO-524 (Lyprinol/Omega XL), rich in omega-3 fatty acids, on airway inflammation and the bronchoconstrictor response to eucapnic voluntary hyperpnea (EVH) in asthmatics.. Twenty asthmatic subjects, with documented HIB, participated in a placebo controlled double-blind randomized crossover trial. Subjects entered the study on their usual diet and were then placed on 3 weeks of PCSO-524 or placebo supplementation, followed by a 2 week washout period, before crossing over to the alternative diet. Pre- and post-eucapnic voluntary hyperpnea (EVH) pulmonary function, fraction of exhaled nitric oxide (FENO), asthma symptom scores, medication use, exhaled breath condensate (EBC) pH, cysteinyl leukotrienes (cyst-LT), 8-isoprostane and urinary 9α, 11β-prostaglandin (PG)F2 and Clara (CC16) protein concentrations were assessed at the beginning of the trial and at the end of each treatment period.. The PCSO-524 diet significantly reduced (p < 0.05) the maximum fall in post-EVH FEV1 (-8.4 ± 3.2%) compared to usual (-19.3 ± 5.4%) and placebo diet (-22.5 ± 13.7%). Pre- and post- EVH EBC cyst-LT and 8-isoprostane, and urinary 9α, 11β-PGF2 and CC16 concentrations were significantly reduced (p < 0.05) on the PCSO-524 diet compared to the usual and placebo diet. EBC pH and asthma symptom scores were significantly improved (p < 0.05) and rescue medication use significantly reduced (p < 0.05) on the PCSO-524 diet compared to the usual and placebo diet.. PCSO-524 (Lyprinol)/Omega XL) may have beneficial effects in HIB and asthma by serving as a pro-resolving agonist and/or inflammatory antagonist.

Topics: Adrenergic beta-Agonists; Animals; Anti-Asthmatic Agents; Asthma; Biological Products; Biomarkers; Bivalvia; Breath Tests; Bronchitis; Bronchoconstriction; Bronchodilator Agents; Constriction, Pathologic; Cross-Over Studies; Dietary Supplements; Dinoprost; Double-Blind Method; Fatty Acids, Omega-3; Female; Forced Expiratory Volume; Humans; Hyperventilation; Lipids; Male; Medication Adherence; Nitric Oxide; Uteroglobin; Young Adult

The role of mast cells in the airway response to exercise and the benefit of sodium cromoglycate (SCG) in athletes are unclear.. The purpose of this study was to clarify the role of mast cell mediators in the airway response to exercise in athletes and to investigate the effect of SCG.. Eleven athletes with exercise-induced bronchoconstriction (EIB+) and 11 without (EIB-) performed a eucapnic voluntary hyperpnea (EVH) test (a surrogate for exercise) 10 min after inhalation of a placebo or 40 mg of the mast cell stabilizing agent sodium cromoglycate. The urinary concentrations of 9a,11β-PGF2 (a metabolite of PGD2 and a marker of mast cell activation) and leukotriene E4 (LTE4) were measured by enzyme immunoassay 60 min before and for 90 min after the challenge.. In the EIB+ group, the maximum fall in forced expiratory volume in 1 s (FEV1) of 20.3% ± 3% on placebo was reduced to 11.5% ± 1.9% after SCG (P = 0.003). There was an increase in the urinary excretion of 9α,11β-PGF2 on the placebo day after EVH in both groups (P < 0.05) that was abolished by SCG. In the EIB+ group, there was also an increase of urinary LTE4 on the placebo day that was abolished by SCG, whereas the urinary excretion of LTE4 was inconsistent in the EIB- group.. The results support mast cell activation with release of bronchoconstrictive mediators after hyperpnea in athletes with and without EIB and inhibition by SCG. The degree of airway responsiveness to the specific mediator released is likely to determine whether or not bronchoconstriction will occur after EVH.

Topics: Adrenergic Agonists; Adult; Androstadienes; Asthma, Exercise-Induced; Athletes; Bronchodilator Agents; Cromolyn Sodium; Dinoprost; Exercise Test; Female; Fluticasone; Forced Expiratory Volume; Humans; Hyperventilation; Inflammation Mediators; Leukotriene E4; Male; Mast Cells; Young Adult

The mechanisms of cough in asthma are unclear. Asthma is associated with an oxidative stress. Many reactive oxygen species sensitize or activate sensory C-fibers which are capable to induce cough. It was hypothesized that oxidative stress in the airways might contribute to the cough severity in asthma. Exhaled breath condensate samples were collected in ten healthy and 26 asthmatic subjects. The concentration of 8-isoprostane was measured. In addition, the subjects filled in Leicester Cough Questionnaire and underwent cough provocation tests with dry air hyperpnoea and hypertonic saline, among other measurements. Among the asthmatic subjects, high 8-isoprostane was associated with severe cough response to hyperpnoea (p=0.001), low Leicester Cough Questionnaire values (indicating severe subjective cough, p=0.02), and usage of combination asthma drugs (p=0.03-0.04). However, the 8-isoprostane concentrations did not differ significantly between the healthy and the asthmatic subjects. Airway oxidative stress may be associated with experienced cough severity and measured cough sensitivity in asthma.

Topics: Adult; Asthma; Breath Tests; Bronchial Provocation Tests; Case-Control Studies; Chronic Disease; Cohort Studies; Cough; Dinoprost; Exhalation; Female; Humans; Hyperventilation; Male; Middle Aged; Oxidative Stress; Reference Values; Severity of Illness Index; Spirometry; Statistics, Nonparametric

This study was designed to test the hypothesis that hyperventilation-induced bronchoconstriction (HIB) results from the combined effects of prostanoid and leukotriene metabolism. A bronchoscope was used in anesthetized dogs to record peripheral airway resistance and HIB before and after combined treatment with inhibitors of cyclooxygenase (indomethacin) and 5-lipoxygenase (MK-0591). Bronchoalveolar lavage fluid (BALF) cells and mediators from hyperventilated and control airways were also measured. Pretreatment with MK-0591 and indomethacin significantly attenuated, but did not abolish, HIB. However, addition of atropine nearly eliminated the residual response. Blockade of eicosanoid metabolism markedly reduced the concentrations of eicosanoids recovered in BALF after hyperventilation. Positive correlations between posthyperventilation BALF prostanoid and epithelial cell concentrations are suggestive of mucosal injury-induced mediator production and release. We conclude that HIB is prevented in the presence of eicosanoid and muscarinic-receptor blockade and that both classes of eicosanoids contribute similarly to the development of HIB.

Topics: Animals; Arachidonate 5-Lipoxygenase; Asthma; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Cyclooxygenase Inhibitors; Dinoprost; Dogs; Eicosanoids; Epithelial Cells; Hyperventilation; Indomethacin; Leukotrienes; Male; Muscarinic Antagonists; Receptors, Muscarinic; Thromboxane A2

While studying the significance of the short chain fatty acids (SCFAs) in the pathogenesis of hyperventilation, we have found that experimental rabbits injected with SCFA sodium salt (4 mmol/kg b.wt) develop hyperventilation 20 min later. This hyperventilation results in a decrease of PCO2 in the arterial blood from 32.05 +/- 1.18 to 24.55 +/- 0.83 (p < 0.001). The SCFAs also bring about pronounced mixed alkalosis. The prostaglandin F2-alpha (PGF2-alpha) in both the arterial and venous blood of rabbits increased significantly after treatment with SCFAs salts. If the rabbits are pretreated with indomethacin (10 mg/kg), the SCFAs do not cause hyperventilation. Therefore we can conclude, that the SCFAs bring about hyperventilation through an increase in the PGF2-alpha synthesis.

Topics: Alkalosis; Animals; Carbon Dioxide; Dinoprost; Fatty Acids; Hyperventilation; Hypocapnia; Indomethacin; Male; Oxygen; Partial Pressure; Rabbits