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Eur Respir J 2003; 22:743-747
Copyright ©ERS Journals Ltd 2003

Prostaglandin E2 in the expired breath condensate of patients with asthma

K. Kostikas, G. Papatheodorou, K. Psathakis, P. Panagou and S. Loukides

Pneumonology and Clinical Research Dept, Athens Army General Hospital, Athens, Greece

CORRESPONDENCE: S. Loukides, Smolika 2 16673, Voula Athens, Greece. Fax: 32 106914312. E-mail: ssat@hol.gr

Keywords: asthma, bronchial hyperresponsiveness, exhaled breath condensate, prostaglandin E2

Received: January 3, 2003
Accepted June 3, 2003


   Abstract
TOP
 Abstract
Methods
 Results
 Discussion
 References
 
Inhaled prostaglandin (PG)E2 has been found to cause bronchodilation in asthmatics, although it does not have bronchodilative effects in normal subjects. The aim of this study was to investigate the levels of PGE2 in the expired breath condensate of patients with asthma, the possible contribution of smoking habit to its levels and the possible relationship between PGE2 and the degree of bronchial hyperresponsiveness, as assessed by the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20).

A total of 30 mild asthmatics (15 smokers, all steroid-naive, FEV1 88±6 (%±sd)) and 20 healthy control subjects (10 smokers) were studied. Histamine challenge testing was performed in all subjects and the PD20 was determined.

The results showed that asthmatic smokers had significantly higher values of PGE2 compared to asthmatic nonsmokers and control subjects (40±21 versus 14.5±4.5 versus 11.7±3 pg·mL–1, respectively). Further analysis showed that PGE2 levels were significantly higher in asthmatic smokers compared to smoker and nonsmoker controls (40±21 versus 11.6±2 versus 11.7±4 pg·mL–1, respectively). No significant difference was observed between asthmatic nonsmokers and both control smokers and control nonsmokers. No significant correlation was found between PGE2 levels and PD20 in all groups of asthmatics, irrespective of smoking habit.

In conclusion, the elevation of prostaglandin E2 in the expired breath condensate of patients with asthma is mainly attributed to smoking habit and prostaglandin E2 levels do not predict the degree of bronchial hyperresponsiveness.

Eicosanoids are important inflammatory mediators in asthma. These lipid mediators include leukotrienes, prostaglandins and thromboxanes. Prostaglandin (PG)E2 is a dominant cyclooxygenase product of airway epithelium and smooth muscle, and is considered to be immunomodulatory and predominantly bronchoprotective 1.

PGE2 inhibits both exercise-induced bronchoconstriction 2 and allergen-induced early and late asthmatic responses 3, and also prevents aspirin-induced bronchoconstriction in aspirin-sensitive asthma 4. PGE2 has also been shown to decrease exhaled nitric oxide 5 and to prevent the induction of inducible NO synthase in certain cell lines 6. In vitro studies have shown that PGE2 inhibits many inflammatory events, including mast cell mediator release and eosinophil activation 7.

The measurement of markers in the expired breath condensate (EBC) has proven to be a useful noninvasive method for the assessment and monitoring of airway inflammation 8. EBC is a simple, noninvasive technique for monitoring airway inflammation. It reflects abnormalities in markers obtained bronchoscopically, in sputum and in exhaled air 8. Measurement of PGE2 in EBC of asthmatic patients, when compared to normal subjects, has not shown any significant differences 9, 10. However, recent evidence suggests that cigarette smoke stimulates the formation of PGE2 in airway macrophages 11.

Despite their clinical value, previous studies have not investigated the stability and repeatability of PGE2 measurements at different time intervals, the effect of smoking on PGE2 levels and the possible protective effect of high levels of PGE2 inEBC during bronchial hyperresponsiveness induced by histamine challenge testing. The primary aim of the current study was to investigate the repeatability and stability of measurements, to evaluate PGE2 concentration in the EBC of asthmatic patients, to account for the possible confounding effects of smoking habit and to see whether there is an association between PGE2 concentration in EBC and bronchial hyperresponsiveness, as assessed by the provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20).


   Methods
TOP
 Abstract
 Methods
Results
 Discussion
 References
 
Subjects
The general characteristics of patients and controls are summarised in table 1Go. The recommendations of the Global Strategy for Asthma Management and Prevention 12 were used for the diagnosis and classification of asthma severity, in order to define the asthmatic patients. A total of 30 steroid-naive patients with mild asthma (15 current smokers (n±sd (range)) 13±5 (9–17) pack-yrs, FEV1 88±6% predicted) were studied. All patients were atopic, as judged by the positive skin-prick tests to six common aeroallergens and the elevated levels of total immunoglobulin (Ig)E (207±47 International Units (IU)·mL–1). None of the patients was on any other anti-inflammatory treatment, including leukotriene antagonists, theophylline, and inhaled or oral mucolytics. Patients were clinically stable and asymptomatic at the time of the measurement and had noevidence of acute exacerbation. All measurements were performed out of allergy season and none of the patients had allergic symptoms or upper airway disease, either infectious or atopic.


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  		Table 1— Subjects characteristics

 
A total of 20 control subjects were studied (10 current smokers with similar smoking habits as the asthmatic smokers, 14±4 (10–16) pack-yrs, FEV1 95±7% pred). All had a negative history of allergy (negative skin-prick tests to common allergens) and normal bronchial reactivity, with a PD20 of histamine >0.800 mg (1.6±0.2 (1.45–1.85)).

Medical history and smoking status were initially recorded in all study subjects. Subsequently, EBC collection wascarried out. Finally, pulmonary function tests and histamine challenge were performed. This was mainly designed in order to prevent the bronchoconstriction occurring after histamine challenge having any effect on the PGE2 values in the EBC-collected specimen.

The Ethics Committee of Athens Army General Hospital, Athens, Greece, approved the study protocol and all subjects gave informed written consent.

Lung function
FEV1 was measured with a dry spirometer (Vica-test, Mijnhardt, Holland). The best value of three manoeuvres was expressed as percentage of the predicted value. Bronchial hyperresponsiveness was measured by a rapid histamine inhalation test for the determination of PD20, as previously described 13. PD20 was determined by linear interpolation on a semi-logarithmic scale. Asthmatic subjects stopped short- or long-acting adrenergic bronchodilators for ≥12 h before the bronchial challenge. According to American Thoracic Society criteria 14, subjects were asked not to smoke 6 h before challenge.

Collection of expired breath condensate
The collection of EBC was performed as previously described 15. Briefly, a heat exchanger unit (RHES, model 6V3; Jaeger, Wuerzburg, Germany) was used to produce cold air of –15°C––18°C at an airflow of >80 L·min–1. A double-jacketed glass tube of 45-cm length (internal diameter 4 cm and external diameter 7 cm) was specifically adapted to the cold air system and a two-way unidirectional valve (Series 2-200; Hans-Rudolf, Kansas City, MO, USA) was connected to the proximal end of the tube, in order to separate inspiration from expiration. After mouth rinsing, subjects were comfortably seated in a chair, wearing nose clips, and breathed in a relaxed manner (tidal breathing) for 15 min. The breath condensate was collected at the distal end of the tube and was immediately stored at –70°C for later analysis. According to this design, salivary contamination was highly unlikely and was easily observed, as the proximal cold air connection was 25 cm away from the mouthpiece. Approximately 2 mL of breath condensate was collected in a 2-mL sterile plastic tube.

In order to assess the repeatability of PGE2 measurements and the stability of the frozen samples, 10 patients with mild asthma were evaluated before starting the whole protocol. All patients were asymptomatic and had similar characteristics as asthmatics participating in the study. Five of them were current smokers with similar smoking habits as the main study smoking population (13.5±3 (8–17) pack-yrs) and had normal lung function (FEV1 94±6% pred). All 10 patients received similar medical treatment to the main study population and were atopic, as judged by positive skin-prick tests to six common aeroallergens and elevated levels of total IgE (198±2 IU·mL–1). The collection of EBC was performed under the same conditions used for the main study population.

Repeatability of PGE2 measurements and stability of the frozen samples were estimated as previously described 16, 17. Briefly, for repeatability data, EBC was collected on 2 consecutive days under the same conditions and a mean within-subject difference was measured. To assess the stability in the frozen condensate samples, 4 mL of condensate was collected using the same procedure under the same conditions but with a collection time of 20 min. The above-mentioned concentration was divided into 1 mL aliquots, which were each defrosted in the proportional time interval in which PGE2 concentrations were determined, i.e. after 2 days, 1 week, 2 weeks and 3 weeks of storage (the maximum time between collection and measurement in the frozen samples). All condensate samples were tested for salivary contamination by determination of amylase activity, as previously described 15.

Prostaglandin E2 measurement
PGE2 concentrations in EBC were measured by a specificimmunoassay kit (PGE2-high sensitivity; R&D Systems Europe, Oxford, UK). The detection limit of the assay was 8.0 pg·mL–1. Based on stability data, all condensate samples were measured within 2 weeks of the collection time.

Statistical analysis
Data concerning subject characteristics are expressed as mean±sd (range). Data concerning comparisons among the PGE2 values in the study groups are given as mean±sd. PGE2 values from the study groups were compared using the one-way analysis of variance with an appropriate post-hoc test (Bonferroni) for multiple comparisons. Similar statistical analysis was used for statistical estimation of stability measurements. Repeatability data were assessed using the Bland and Altman's test 18. For normally distributed data (smoking and nonsmoking controls), the paired t-test was used for statistical comparisons between two groups. For non-normally distributed data (asthmatics and controls), the Mann-Whitney U-test was used for statistical comparisons between two groups. Normality of distribution was tested with Shapiro-Wilk's test. Spearman's correlation coefficient was used to investigate the relationships between parameters. A p-value <0.05 was considered significant.


   Results
TOP
 Abstract
 Methods
 Results
Discussion
 References
 
Repeatability data
The repeated measurements of PGE2 in EBC on 2 consecutive days presented good repeatability. PGE2 levels in EBC on days 1 and 2 were 24.05 pg·mL–1 (11.8–57.2) and 30.2 pg·mL–1 (14.4–53.2), respectively. The mean difference with coefficient of variability was 6.2±9.3 and all differences were within ±2 sd. The correlation between PGE2 measurements on the 2 consecutive days was significant (r2=0.619, p=0.006). The intraclass correlation coefficient for PGE2 measurements was 0.79.

The stability of the PGE2 in frozen samples showed significant differences between the four measurements (after 2days: 23±11 pg·mL–1; after 1 week: 25±13 pg·mL–1; after 2weeks: 24±14 pg·mL–1; after 3 weeks: 41±14 pg·mL–1; p=0.43 higher after 3 weeks).

The concentration of PGE2 was significantly elevated in asthmatic smokers as compared to nonsmoking asthmatics and control subjects (40±21 versus 14.5±4.5 versus 11.7±3 pg·mL–1, respectively; p<0.0001; fig. 1Go). Further analysis showed that PGE2 levels were significantly higher in asthmatic smokers compared to smoking and nonsmoking controls (40±21 versus 11.6±2 versus 11.7±4 pg·mL–1, respectively; p<0.0001; fig. 1Go). No significant difference was observed between asthmatic nonsmokers and both control smokers and nonsmokers (14.5±4.5 versus 11.6±2 versus 11.7±4 pg·mL–1, respectively; p=0.66; fig. 1Go). Concentration of PGE2 was significantly elevated in patients with asthma as compared to the control group (27±20 versus 11.7±3 pg·mL–1; p<0.05). No significant difference was observed between smoking and nonsmoking controls (11.6±2 versus 11.7±4 pg·mL–1, respectively; p=0.9).



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  		Fig. 1.— Prostaglandin (PG)E2 concentration in exhaled breath condensate of control subjects (all n=20, smokers (S) n=10, nonsmokers (NS) n=10) and of patients with asthma (all n=30, smokers n=15, nonsmokers n=15). Individual and mean (––) values are shown. *: p<0.05; #: p=0.003; : p=0.0006.

 
Correlations
No significant correlation was observed between PGE2 values and PD20 to histamine in asthmatic patients (rs=0.025, p=0.7). Accordingly, no significant correlation data were observed in the study subgroups (rs=0.021, p=0.9 in asthmatic nonsmokers, rs=0.11, p=0.12 in asthmatic smokers). No significant correlation was observed between smoking history (pack-yrs) and PGE2 values (rs=0.07, p=0.78).


   Discussion
TOP
 Abstract
 Methods
 Results
 Discussion
References
 
In this prospective, cross-sectional study, significant elevation of PGE2 in the EBC of asthmatic smokers was found, as compared to nonsmoking asthmatics. Additionally, PGE2 values did not predict the degree of bronchial hyperresponsiveness. The measurement seems to be repeatable but not stable after a period of 2 weeks.

Concerning the stability data presented in this study, it must be mentioned that no data are available in the literature regarding the storage of frozen PGE2 samples in EBC. The current data suggest that there are significant alterations in the rate of PGE2 concentrations over time, with a cut-off point at 2 weeks. This finding is hard to explain, but it might be partially supported by the in vitro formation of PGE2 in the frozen samples that affect the stability of PGE2 in the EBC samples over time. Such in vitro formation of PGE2 has been described previously 19. A plausible source of PGE2 might be PGH2, which is transformed to PGE2 and PGD2 through the action of prostaglandin isomerases 20.

As PGE2 has a bronchodilatory and inhibitory effect on theinflammatory process at concentrations known to be present in the airways, impaired production of PGE2 has been proposed to contribute to the pathogenesis of asthma. It would be expected that the measurement of PGE2 in biological specimens might provide decreased levels compared to normal subjects. However, the present data and previous reports regarding nonsmoking asthmatics do not confirm the above hypothesis 9, 10, 21. One explanation for the above findings is that only mild stable asthmatics were included in these studies. However, in one of the above studies 20, decreased concentrations of PGE2 in sputum supernatant were found in acute severe asthma. One reasonable hypothesis is that, as the severity of the disease progresses and more severe patients are included, the values of PGE2 might tend to decrease. Conversely, it could be argued that in more severe patients the levels of PGE2 might have a tendency to increase in an attempt to control the increased inflammatory process.

One of the findings of the current study, which has not been investigated previously, is the effect of smoking. The results presented here show that smoking significantly increased thelevels of PGE2 in asthmatic subjects, even compared to normal smoking subjects. This might be explained by previous observations that cigarette smoke stimulates the formation of PGs in alveolar macrophages, that long-term nicotine substitution diminishes the beneficial effects of smoking cessation due to the possible stimulatory effects of nicotine and cotinine on eicosanoid synthesis even in vivo 22, and, finally, that accumulation of cotinine, the major metabolite of nicotine, in foetal circulation contributes to production of PGE2 23.

The interesting finding was the significant difference in PGE2 levels between asthmatic smokers and smoking controls, and the absence of a significant difference between smokers and nonsmoking controls. PGE2 is largely produced by epithelial and airway smooth muscle cells, but all cells in the airways have the capacity to release prostanoids, and in particular macrophages 24. Since cigarette smoke stimulates the formation of PGs from macrophages and considering allthe above points together, the current authors believe that the significant difference in PGE2 levels between asthmatic smokers and smoking controls may be attributed to the different activation state of macrophages in the two groups, indicating that the higher values of PGE2 in asthmatics are mainly due to the activation of more macrophages and the greater release of PGE2 from the macrophages. The nonsignificant difference between smoking and nonsmoking controls might be based on the inactivated state of airway cells, particularly macrophages, which possibly leads to minimal release of PGE2. Although no specific correlation data are available in this study, the elevated levels of PGE2 in asthmatic smokers might serve as an index of activation of inflammatory airway cells, particularly macrophages.

Regarding the relationship between PGE2 concentration and its effect on bronchial hyperresponsiveness, as assessed by histamine challenge, no significant correlation was observed in asthmatic patients irrespective of their smoking habit. The absence of significant correlation might be based on the fact that PGE2 inhibits challenges that work indirectly via neural pathways or mediator release but not those that act predominantly via a direct action on airway smooth muscle, such as histamine and metacholine 2, 3. The above theory is partially supported by previous observations that PGE2 inhibits acetylcholine release from cholinergic nerves 25, represents the ultimate mediator of airway smooth muscle relaxation produced by activation of sensory nerve inhibitory system 26, but fails to protect against bronchoconstriction induced by methacholine 27. Another plausible explanation might be based on the theory that the inhibitory effect ofPGE2 in histamine-induced contraction appears to be concentration-dependent 28. This means that the concentration of PGE2 released from the airways in mild stable asthma is probably too low or inadequate in order to exert a significant effect on histamine-induced contractions.

PGE2 has been shown to affect airway physiology by inhibiting both the early and late asthmatic response 3, 29, and the activation of mast cells, without resulting in significant bronchodilation. This means that it seems more plausible that the mechanisms of action of PGE2 are anti-inflammatory rather than bronchodilatory. This is partially supported by previous observations that showed that PGE2 inhibits many inflammatory events, including mast cell degranulation 9 and the expression of the cyclo-oxygenase pathway in the airways 30. Conversely, its bronchodilatory effect seems to be limited 2, 3, 5. All the above points together lead to the conclusion that exogenous administration or an increase in the endogenous production of PGE2 might have a protective anti-inflammatory effect, but that it probably has a little, nonsignificant effect on the acute bronchoconstriction process.

In conclusion, the higher prostaglandin E2 values in patients with mild asthma, as compared to normal controls, are mainly attributed to smoking habit, probably via increased production by activated inflammatory cells, particularly macrophages. The higher levels of endogenous prostaglandin E2 do not have a protective role on the bronchospasm that is induced by histamine challenge testing.


   References
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 Abstract
 Methods
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 Discussion
 References
 

  1. Philipps RP, Stein SH, Roper LR. A new view of prostaglandin E2 regulation of the immune response. Immunol Today 1991;12:349–352.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  2. Pavord DI, Tattersfield AE. Bronchoprotective role for endogenous prostaglandin E2. Lancet 1994;344:436–438.
  3. Pavord DI, Wong CS, Williams J, Tattersfield AE. Effect ofinhaled prostaglandin E2 on allergen-induced asthma. Am Rev Respir Dis 1993;148:87–90.[ISI][Medline] [Order article via Infotrieve]
  4. Pasargiklian M, Bianco C, Allegra L, et al. Aspects of bronchial reactivity to prostaglandins and aspirin in asthmatic patients. Respiration 1977;34:79–91.[ISI]
  5. Kharitonov SA, Sapienza MA, Barnes PJ, Chung KF. Prostaglandins E2 and F2a reduce exhaled nitric oxide in normal and asthmatic subjects irrespective of airway caliber changes. Am J Respir Crit Care Med 1998;158:1374–1378.[Abstract/Free Full Text]
  6. Tetsuka T, Morrison AR. Tyrosine kinase activation is necessary for inducible nitric oxide synthase expression by interleukin-1ß. Am J Physiol 1995;269:55–59.
  7. Peters SP, Schulman ES, MacGlashan DW, Schleimer RP, Newball HH, Lichtenstein LM. Pharmacological and biochemical studies of human lung mast cells. J Allergy Clin Immunol 1982;69:150–158.
  8. Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001;163:1693–1622.[Free Full Text]
  9. Montuschi P, Barnes PJ. Exhaled leukotrienes and prostaglandins in asthma. J Allergy Clin Immunol 2002;109:615–620.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  10. Antczak A, Montuschi P, Kharitonov S, Gorski P, Barnes PJ. Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma. Am J Respir Crit Care Med 2002;166:301–306.[Abstract/Free Full Text]
  11. Hwang D, Chanmugam P, Boudreau M, Sohn KH, Stone K, Pryor WA. Activation and inactivation of cyclo-oxygenase in rat alveolar macrophages by aqueous cigarette tar extracts. Free Radic Biol Med 1999;27:673–682.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  12. Global strategy for asthma management prevention. NIH Publication No. 02-3659. Bethesda, MD, National Institutes of Health, National Heart, Lung and Blood Institute, 2002.
  13. Sovijarvi AR, Malberg LP, Reinikminen K, Ryhila Poggins H. A rapid dosimetric method with controlled tidal breathing for histamine challenge. Chest 1993;104:164–170.[Abstract/Free Full Text]
  14. American Thoracic Society official statement. Guidelines for Methacholine and Exercise Challenge Testing - 1999. Am J Respir Crit Care Med 2000;161:309–329.[Free Full Text]
  15. Ganas K, Loukides S, Papatheodorou G, Panagou P, Kalogeropoulos N. Total nitrite/nitrate in expired breath condensate of patients with asthma. Respir Med 2001;95:649–654.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  16. Huszar E, Vass G, Vizi E, et al. Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma. Eur Respir J 2002;20:1393–1398.[Abstract/Free Full Text]
  17. Jobsis Q, Raatgeep HC, Schelleke SL, Hop WCJ, Hermans PW, de Jongste JC. Hydrogen peroxide in exhaled air of healthy children: reference values. Eur Respir J 1998;12:483–485.[Abstract]
  18. Bland JM, Altman DG. Statistical method for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–310.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  19. Finley RR, Bogert CL, Alberts DS, et al. Measurement of prostaglandin E2 in rectal mucosa in human subjects: a method study. Cancer Epidemiol Biomarkers Prev 1995;4:239–244.[Abstract]
  20. O'Byrne P.. Prostanoids In: Barnes PJ, Drazen JM, Rennard S, Thompson NC, editors. Asthma and COPD. San Diego, Academic Press, 2002; pp. 221–226.
  21. Pavord ID, Ward R, Woltmann G, Wardlaw AJ, Sheller JR, Dworski R. Induced sputum eicosanoid concentrations in asthma. Am J Respir Crit Care Med 1999;160:1905–1909.[Abstract/Free Full Text]
  22. Riutta A, Saareks V, Mucha I, Alanko J, Parviainen M, Vapaatalo H. Smoking cessation and nicotine substitution modulate eicosanoid synthesis ex vivo in man. Naunyn Schmiedebergs Arch Pharmacol 1995;352:102–107.[ISI][Medline] [Order article via Infotrieve]
  23. Rama Sastry BV, Hemontolor ME, Olenick M. Prostaglandin E2 in human placenta: its vascular effects and activation of prostaglandin E2 formation by nicotine and cotinine. Pharmacology 1999;58:70–86.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  24. Barnes PJ, Chung KP, Page PC. Inflammatory mediators of asthma. An update. Pharmacol Rev 1998;50:515–596.[Abstract/Free Full Text]
  25. Zhao WW, Robinson NE, Yu MF. PGE2 inhibits acetylcholine release from cholinergic nerves in canine airways. Prostaglandins Leukot Essent Fatty Acids 1994;51:347–355.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  26. Szarek JL, Spurlock B, Gruetter CA, Lemke S. Substance P and capsaicin release prostaglandin E2 from rat intrapulmonary bronchi. Am J Physiol 1998;275:1006–1012.
  27. Pavord ID, Wisniewski A, Mathur R, Wahedna I, Knox A, Tattersfield AE. Effects of inhaled prostaglandin E2 on bronchial reactivity to sodium metabisulphite and metacholine in subjects with asthma. Thorax 1991;46:633–637.[Abstract]
  28. Knight DA, Stewart GA, Thompson PJ. Prostaglandin E2 but not prostacyclin inhibits histamine-induced contraction of human bronchial smooth muscle. Eur J Pharmacol 1995;272:13–19.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  29. Hartert TV, Dworski RT, Mellen BG, Oates JA, Murray JJ, Sheller JR. Prostaglandin E(2) decreases allergen-stimulated release of prostaglandin D(2) in airways of subjects with asthma. Am J Respir Crit Care Med 2000;162:637–640.[Abstract/Free Full Text]
  30. Bonazzi A, Bolla M, Buccellati C, et al. Effect of endogenous and exogenous prostaglandin E(2) on interleukin-1 beta-induced cyclooxygenase-2 expression in human airway smooth-muscle cells. Am J Respir Crit Care Med 2000;162:2272–2277.[Abstract/Free Full Text]



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