Urine Leukotriene E4: Implications as a Biomarker in Chronic Rhinosinusitis.

OBJECTIVE: To provide a comprehensive state-of-the-art review of the emerging role of urine leukotriene E4 (uLTE4) as a biomarker in the diagnosis of chronic rhinosinusitis (CRS), aspirin-exacerbated respiratory disease (AERD), and asthma. DATA SOURCES: Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. REVIEW METHODS: A state-of-the-art review was performed investigating the role of uLTE4 as a diagnostic biomarker, predictor of disease severity, and potential marker of selected therapeutic efficacy. CONCLUSIONS: uLTE4 has been shown to be a reliable and clinically relevant biomarker for CRS, AERD, and asthma. uLTE4 is helpful in ongoing efforts to better endotype patients with CRS and to predict disease severity. IMPLICATIONS FOR PRACTICE: Aside from being a diagnostic biomarker, uLTE4 is also able to differentiate aspirin-tolerant patients from patients with AERD and has been associated with objective disease severity in patients with CRS with nasal polyposis. uLTE4 levels have also been shown to predict response to medical therapy, particularly leukotriene-modifying agents.

Exposure to environmental phenols and parabens, and relation to body mass index, eczema and respiratory outcomes in the Norwegian RHINESSA study.

BACKGROUND: Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index. METHODS: Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10-17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry. RESULTS: Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant. CONCLUSIONS: Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.

Elevated Urine Leukotriene E4 Is Associated With Worse Objective Markers in Nasal Polyposis Patients.

OBJECTIVES: Urine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin-exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin-tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP. METHODS: A retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund-Mackay CT score, spirometry and lab values) were collected. RESULTS: Among the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P < .001), aspirin sensitivity (P < .001), worse Lund-Mackay CT scores (P = .002) and other objective markers of disease severity including serum IgE (P = .05), presenting blood eosinophil level (P < .001), and the highest recorded eosinophil level (P < .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (R range 0.31-0.52) than the aspirin tolerant CRSwNP group (R range -0.30-0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores). CONCLUSION: Elevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient-reported symptom measures. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:961-966, 2021.

Establishing Urinary Leukotriene E4 as a Diagnostic Biomarker for Chronic Rhinosinusitis with Comorbid Asthma and Atopy.

OBJECTIVE: While urinary leukotriene E4 (uLTE4) is a validated biomarker for the cysteinyl leukotriene pathway, which is central to the pathophysiology of asthma, atopy, and chronic rhinosinusitis (CRS), the contributions of comorbid asthma and atopy to uLTE4 levels in various CRS subtypes have not been previously characterized. We sought to (1) identify reference values for uLTE4 in subjects with and without CRS and (2) determine how the presence of comorbid atopy and asthma affects uLTE4 levels in CRS. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: A prospective case-control study was conducted to compare uLTE4 levels between patients with CRS and healthy controls. Urinary LTE4 levels were measured by enzyme immunoassay and were adjusted for urinary creatinine concentrations (pg/mg Cr). Patients with CRS were stratified by the clinical comorbidities to determine normative uLTE4 values for patients with CRS with and without comorbid asthma or atopy. RESULTS: A total of 153 patients (mean age, 47.3; 47.1% female) were included in the study. Patients with CRS demonstrated significantly higher concentrations of uLTE4 than healthy controls (1652 vs 1065 pg/mg Cr, P = .032). Within the group of patients with CRS, comorbid asthma also individually correlated with elevated uLTE4 levels (1597 pg/mg Cr, P = .0098). Patients with CRS who did not have comorbid allergy and asthma, in contrast, did not have statistically higher uLTE4 levels than healthy controls (1142 pg/mg Cr, P = .61). CONCLUSION: Urinary LTE4 serves as a noninvasive measure of the inflammatory state in CRS. Comorbid asthma and atopy contribute to elevated uLTE4 levels in CRS.

Urinary phthalate metabolites in relation to childhood asthmatic and allergic symptoms in Shanghai.

BACKGROUND: Few studies can be found on phthalate exposure in relation to childhood asthma and allergic symptoms from Mainland China, where a persistent increase in prevalence of childhood asthma and allergic disease has been observed. OBJECTIVES: This study aimed to assess the exposure levels to phthalates and its relationship with asthmatic and allergic symptoms among children in Shanghai, which has the highest prevalence of childhood asthma in Mainland China. METHODS: A follow-up study (2013-2014) of 434 children aged 5-10 years was conducted, based on the China, Children, Homes, Health (CCHH) study (2011-2012) in Shanghai, China. Information on asthmatic and allergic symptoms (wheeze, rhinitis, and eczema) were collected using validated questionnaires. Ten phthalate metabolites in morning urine samples were analyzed by high-performance liquid chromatography with triple quadrupole tandem mass spectrometry (HPLC-MS/MS). Multivariable logistic regression was used to estimate the associations between symptoms and urinary phthalate metabolites controlling for demographics, family history of allergic diseases and other covariates. RESULTS: Nine out of 10 phthalate metabolites were detected in all subjects (average detection rate of 93.2%). By multivariable logistic regression analyses, the 4th quartile of Mono­n­butyl phthalate (MnBP) (reference: 1st quartile) had adjusted prevalence odds ratios (aPORS) and 95% confidence intervals (95%CIs) of 2.27(1.06-4.88), 2.14(1.02-4.46) and 2.98(1.19-7.50) for wheeze, rhinitis and eczema, respectively, while those of Mono­isobutyl phthalate (MiBP) were 2.23(1.08-4.62) and 2.96(1.02-8.60) for rhinitis and eczema, respectively. The highest quartile of mono­2­ethyl­5­hydroxyhexyl phthalate(MEHHP) and mono­2­ethyl­5­oxohexyl phthalate(MEOHP) had aPORS and 95%CIs of 3.10(1.10-8.74) and 2.63(1.02-6.80) for eczema, respectively. By summing up the 4 low molecular weight metabolites (∑4LMWP) and all 9 metabolites (∑9Total), the highest quartiles of ∑4LMWP and∑9Total were significantly associated with all symptoms. In most of the above associations, a significantly increasing trend from the 1st to the 4th quartile was observed. Subjects with 2 or 3 concomitant symptoms (reference: no symptoms) had significant positive associations with a higher level (the 4th quartile) of phthalate metabolites. CONCLUSIONS: Low MW metabolites such as MnBP and MiBP, high MW DEHP and the total amount of phthalate metabolites might have adverse health effects on asthma and allergic symptoms in Chinese children.

The effects of nasal lavage with betamethasone cream post-endoscopic sinus surgery: clinical trial.

BACKGROUND: Steroid nasal irrigation for chronic rhinosinusitis patients following endoscopic sinus surgery reduces symptom recurrence. There are minimal safety data to recommend this treatment. This study evaluated the safety of betamethasone nasal irrigation by measuring its impact on endogenous cortisol levels. METHODS: Participants performed daily betamethasone nasal irrigation for six weeks. The impact on pre- and post-intervention serum and 24-hour urinary free cortisol was assessed. Efficacy was evaluated using the 22-item Sino-Nasal Outcome Test. RESULTS: Thirty participants completed the study (16 females and 14 males; mean age = 53.9 ± 15.6 years). Serum cortisol levels were unchanged (p = 0.28). However, 24-hour urinary free cortisol levels decreased (47.5 vs 41.5 nmol per 24 hours; p = 0.025). Sino-Nasal Outcome Test scores improved (41.13 ± 21.94 vs 23.4 ± 18.17; p < 0.001). The minimal clinical important difference was reached in 63 per cent of participants. CONCLUSION: Daily betamethasone nasal irrigation is an efficacious treatment modality not associated with changes in morning serum cortisol levels. The changes in 24-hour urinary free cortisol levels are considered clinically negligible. Hence, continued use of betamethasone nasal irrigation remains a viable and safe treatment option for chronic rhinosinusitis patients following functional endoscopic sinus surgery.

Diagnostic Utility of Urinary LTE4 in Asthma, Allergic Rhinitis, Chronic Rhinosinusitis, Nasal Polyps, and Aspirin Sensitivity.

BACKGROUND: Urinary leukotriene E4 (LTE4) is a well-validated marker of the cysteinyl leukotriene pathway, and LTE4 elevation has been described in conditions such as asthma, aspirin sensitivity, and chronic rhinosinusitis (CRS). There have been a number of reports investigating the role of spot urine LTE4 to predict aspirin sensitivity; however, variability in urinary LTE4 may affect the accuracy of this approach. OBJECTIVE: Here, we explored the utility of 24-hour urinary LTE4 in 5 clinical diagnoses of allergic rhinitis, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), CRS without nasal polyps, and aspirin sensitivity. METHODS: This was a retrospective review of patients who had 24-hour quantification of urinary LTE4 by a clinically validated liquid chromatography tandem mass spectrometry method and their assigned diagnoses after assessment and clinical care. RESULTS: Twenty-four-hour urinary LTE4 elevations were seen in those with asthma and those with CRSwNP but influenced by underlying aspirin sensitivity. Elevation in LTE4 was significant in those with CRSwNP after adjusting for aspirin sensitivity. Allergic rhinitis was not associated with elevated LTE4 excretion. Receiver operator characteristic analysis of 24-hour urinary LTE4 showed that a cutoff value of 166 pg/mg Cr suggested the presence of history of aspirin sensitivity with 89% specificity, whereas a cutoff value of 241 pg/mg Cr discriminated "challenge-confirmed" aspirin-sensitive subjects with 92% specificity. CONCLUSIONS: Elevated 24-hour excretion of urinary LTE4 is a reliable and simple test to identify aspirin sensitivity in patients with respiratory diagnoses.

Thymic stromal lymphopoietin controls prostaglandin D2 generation in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Prostaglandin (PG) D2 is the dominant COX product of mast cells and is an effector of aspirin-induced respiratory reactions in patients with aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: We evaluated the role of the innate cytokine thymic stromal lymphopoietin (TSLP) acting on mast cells to generate PGD2 and facilitate tissue eosinophilia and nasal polyposis in patients with AERD. METHODS: Urinary eicosanoid levels were measured in aspirin-tolerant control subjects and patients with AERD. Nasal polyp specimens from patients with AERD and chronic rhinosinusitis were analyzed by using quantitative PCR, Western blotting, and immunohistochemistry. Human cord blood-and peripheral blood-derived mast cells were stimulated with TSLP in vitro to assess PGD2 generation. RESULTS: Urinary levels of a stable PGD2 metabolite (uPGD-M) were 2-fold higher in patients with AERD relative to those in control subjects and increased further during aspirin-induced reactions. Peak uPGD-M levels during aspirin reactions correlated with reductions in blood eosinophil counts and lung function and increases in nasal congestion. Mast cells sorted from nasal polyps expressed PGD2 synthase (hematopoietic PGD2 synthase) mRNA at higher levels than did eosinophils from the same tissue. Whole nasal polyp TSLP mRNA expression correlated strongly with mRNA encoding hematopoietic PGD2 synthase (r = .75), the mast cell-specific marker carboxypeptidase A3 (r = .74), and uPGD-M (r = 0.74). Levels of the cleaved active form of TSLP were increased in nasal polyps from patients with AERD relative to those in aspirin-tolerant control subjects. Recombinant TSLP induced PGD2 generation by cultured human mast cells. CONCLUSIONS: Our study demonstrates that mast cell-derived PGD2 is a major effector of type 2 immune responses driven by TSLP and suggests that dysregulation of this innate system contributes significantly to the pathophysiology of AERD.

Differences in urinary leukotriene E4 levels and distribution of eosinophils between chronic rhinosinusitis patients with aspirin-intolerant and -tolerant asthma.

OBJECTIVE: Urinary leukotriene E4 (U-LTE4) concentrations are significantly elevated in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic features of eosinophilic rhinosinusitis and U-LTE4 concentration remains unknown. Here we examined the relationship between U-LTE4 level and eosinophil in chronic rhinosinusitis. METHODS: We measured the U-LTE4 concentrations and eosinophil counts in ethmoidal and maxillary sinuses and peripheral blood in 30 asthmatic patients (including 15 AIA patients). RESULTS: Eosinophil counts in ethmoidal sinuses and peripheral blood were markedly higher in asthmatic patients than in controls. Although there were no significant differences between eosinophil counts in maxillary and ethmoidal sinuses for ATA group, eosinophil counts were higher in ethmoidal sinus compared to that in maxillary sinus in the AIA group (P<.05). Eosinophil counts were higher in the maxillary than in ethmoidal sinuses for control patients (P<.05). Despite low correlation between eosinophil counts in peripheral blood and eosinophil counts in maxillary sinus (rs=0.4323, P<.001), moderate correlation was observed between eosinophil counts in peripheral blood and eosinophil counts in ethmoidal sinus (rs=0.5249, P<.0001). Basal U-LTE4 concentrations were higher in AIA patients than in those with aspirin-tolerant asthma. Despite low correlation between eosinophil counts and U-LTE4 concentration in maxillary sinus (rs=0.3849, P<.01), moderate correlation was observed between eosinophil counts and U-LTE4 concentrations in ethmoidal sinus (rs=0.4736, P<.001). CONCLUSION: We describe the differences in U-LTE4 and other parameters in AIA compared to ATA, and correlation among parameters. We demonstrate that eosinophil-dominant inflammation starts in ethmoidal sinus clinicopathogenetically in CRS with asthma. U-LTE4 concentration was not exclusively associated with eosinophil counts in ethmoidal sinus. Eosinophils in ethmoidal sinus may be a major production site for CysLTs, particularly in AIA. CRS with AIA is assumed to be characterized by leukotriene-eosinophil cross-interaction in ethmoidal sinus.

Phthalate metabolites in urine and asthma, allergic rhinoconjunctivitis and atopic dermatitis in preschool children.

Phthalate esters are among the most ubiquitous of indoor pollutants and have been associated with various adverse health effects. In the present study we assessed the cross-sectional association between eight different phthalate metabolites in urine and allergic disease in young children. As part of the Danish Indoor Environment and Children's Health study, urine samples were collected from 440 children aged 3-5 years, of whom 222 were healthy controls, 68 were clinically diagnosed with asthma, 76 with rhinoconjunctivitis and 81 with atopic dermatitis (disease subgroups are not mutually exclusive; some children had more than one disease). There were no statistically significant differences in the urine concentrations of phthalate metabolites between cases and healthy controls with the exception of MnBP and MECPP, which were higher in healthy controls compared with the asthma case group. In the crude analysis MnBP and MiBP were negatively associated with asthma. In the analysis adjusted for multiple factors, only a weak positive association between MEP in urine and atopic dermatitis was found; there were no positive associations between any phthalate metabolites in urine and either asthma or rhinoconjunctivitis. These findings appear to contradict earlier studies. Differences may be due to higher exposures to certain phthalates (e.g., BBzP) via non-dietary pathways in earlier studies, phthalates serving as surrogates for an agent associated with asthma (e.g., PVC flooring) in previous studies but not the present study or altered cleaning habits and the use of "allergy friendly" products by parents of children with allergic disease in the current study in contrast to studies conducted earlier.

Incidence of aspirin hypersensitivity in patients with chronic rhinosinusitis and diagnostic value of urinary leukotriene E4.

INTRODUCTION: Chronic rhinosinusitis (CRS) with nasal polyposis (NP) may be associated with hypersensitivity to nonsteroidal anti-inflammatory drugs, representing a syndrome of aspirin-exacerbated respiratory disease (AERD). OBJECTIVES: The aim of the study was to validate a simple measurement of urinary leukotriene E4 (uLTE4) excretion for the diagnosis of AERD in patients with CRS and indication for surgery. PATIENTS AND METHODS: Subjects requiring functional endoscopic sinus surgery (FESS) were recruited from the Department of Otolaryngology (n = 24). Before surgery, a standard oral placebo-controlled aspirin challenge was performed to diagnose aspirin hypersensitivity. Urine samples were collected on the placebo day and both before and within 2 to 4 hours after aspirin challenge for uLTE4 measurement. RESULTS: All patients with CRS had sinusitis confirmed by computed tomography. Previous ear, nose, and throat surgery was performed in 70% of the patients, NP was present in 86%, and asthma was diagnosed in 62.5%. AERD was diagnosed in 8 subjects (7 women and 1 man). Five of those patients had bronchoconstriction. At baseline, median uLTE4 was 7.5-times higher in AERD subjects than in the remaining patients. It increased almost 6-fold following the challenge, while remained unchanged in patients without aspirin hypersensitivity. Pretest uLTE4 had a sensitivity of 87.5% and specificity of 93.75% to diagnose aspirin hypersensitivity in patients with CRS. After the challenge, the values improved to 100% sensitivity and 93% specificity. CONCLUSIONS: Among CRS subjects requiring FESS, as many as 33.3% may have AERD and respond to a small provocative dose of aspirin with bronchoconstriction and/or mucosal and skin edema. A simple and inexpensive measurement of uLTE4 can help diagnose AERD in patients with CRS with sensitivity of 87.5%, but its specificity is limited and depends on the arbitrary threshold of uLTE4.

The effects of serum and urinary cortisol levels of topical intranasal irrigations with budesonide added to saline in patients with recurrent polyposis after endoscopic sinus surgery.

BACKGROUND: The delivery of topical intranasal corticosteroid sprays has traditionally been the primary method of treating recurrent nasal polyposis. An emerging treatment for polyposis is budesonide nasal irrigations. Delivered at concentrations nearly 100 times greater than found in prescription nasal sprays, there have been little studies on the effects of budesonide irrigation on the adrenal axis. Therefore, we investigated whether irrigation with budesonide solution was associated with any increase in serum cortisol and 24-hour urinary cortisol levels. METHODS: Patients who previously had undergone endoscopic sinus surgery and were not taking prednisone for 3 months were prospectively enrolled in this study. Patients irrigated twice daily with 0.5 mg/2 mL of budesonide mixed with 240 mL of saline solution. Serum cortisol and 24-hour urinary cortisol were collected before drug administration and 6 weeks after continuous use. RESULTS: Ten patients completed this study. The average serum cortisol and 24-hour urinary cortisol before drug administration were 9.8 +/- 5.4 microg/dL and 28.1 +/- 15.1 microg/24 hours, respectively. After 6-week follow-up, the average serum cortisol and 24-hour urinary cortisol were 12.8 +/- 3.5 microg/dL and 16.5 +/- 5.6 microg/24 hours, respectively. Normal ranges for serum cortisol and 24-hour urinary cortisol are 5-25 microg/dL and 4-50 microg/24 hours, respectively. CONCLUSIONS: Irrigation with budesonide, 0.5 mg/2 mL, in 250 mL of saline solution does not result in decreases of serum cortisol and 24-hour urinary cortisol levels. Based on this, we feel irrigation with budesonide solution is safe to perform in patients as an alternative to traditional aerosolized steroid sprays or systemic corticosteroids.

Aspirin induced asthma (AIA) with nasal polyps has the highest basal LTE4 excretion: a study vs AIA without polyps, mild topic asthma, and normal controls.

UNLABELLED: Cysteinil Leukotrienes (LTs) are products of the arachidonic acid cascade which are synthetised by 5-lipoxigenase in inflammatory cells, particularly in eosinophils. Urinary leukotriene E4 concentration (LTE4), that reflects the whole body production of cysteinil-leukotrienes, is particularly increased in patients with aspirin-intolerant asthma (AIA). Aim of the present study was to assess basal urinary LTE4 levels from AIA patients with nasal polyps to those from AIA patients with only rhinitis (without polyps), and those from mild atopic asthmatics and normal controls. SUBJECTS & METHODS: 34 normal subjects (N; 19 - 57y, FEV1 = 102.1% pred. +/- 8.2 sd; negative MCh challenge; negative prick test); 39 mild-persistent atopic asthmatics (A; 18-66y, FEV1 = 92.1 %pred. +/- 14.6 sd; PD20 FEV1 = 380.7mcg +/- 481.2 sd); 24 subjects with AIA with rhinitis (AIA/R; 18 - 56y, FEV1 = 71.6%pred +/- 15.5 sd; reversibility = 15.1% bsln +/- 2.1 sd after salbutamol 200mg), and 10 subjects with AIA and nasal polyposis (AIA/NP; 22-49 y; FEV1 = 70.6%pred. +/- 7.1 sd; reversibility = 13.2% bsln +/- 1.6 sd after salbutamol 200 microg) were studied. After their informed consent, urine were collected in the morning for the LTE4 quantitative immunoenzimatic assay (pg/mg creatinine; Cayman Chemical, Ann Arbour, Mi, USA). STATISTICS: Wilcoxon signed rank test was used, and p<0.05 accepted as the lowest level of statistical significance. RESULTS: AIA/NP subjects had the highest levels of urinary LTE4 (432.3 pg/mg +/- 88.1 sd) compared to AIA/R (330.7 pg/mg +/- 72.3s, p < 0.01), to A (129.1 pg/mg +/- 74.8sd, p < 0.001), and to N controls (66.5 pg/mg +/- 20.6 sd, p < 0.001). Moreover, urinary LTE4 levels measured in AIA/R subjects proved significantly higher than those measured in A (p < 0.001) and in N controls (p<0.001), while LTE4 levels in A proved significantly higher than those in N controls (p<0.001). Furthermore, basal LTE4 levels seem inversely related to those of basal FEV1 (102.1 % pred. +/- 8.2sd in N, 92.1 % pred +/- 14.6 sd in A, 71.6 % pred. +/- 15.5 sd in AIA/R, 70.6 % pred +/- 7.1 sd in AIA/P, respectively). Respiratory function in the two sub-groups of AIA patients proved reduced than in atopic asthmatics (p<0.001) and in normal controls (p < 0.001), even though the difference between these two subgroups of subjects did not reach the statistical significance. CONCLUSIONS: Cys-LTs confirm their relevant pathogenetic role in AIA, but also in early stages of atopic asthma. Urinary LTE4 exexcretion proves directly proportional to the extent of nasal structural changes occurring in ASA-intolerant asthmatics, being subjects with nasal polyps those with the highest LTE4 values, immediately followed by those with hypertrophic rhinitis. Routinary measurements of urinary LTE4 should be regarded as a sensitive indicator in monitoring the clinical evolution of nasal involvement in AIA.

The role of catecholamines in specific hyposensitization.

With the use of modern techniques for the evaluation of catecholamines, this work studies the behavior of catecholamines in the urine of a group of 33 allergic patients before and after injection of allergens as part of immunotherapy. In 24 of these patients the amount of adrenalin and norepinephrine had increased 24 hours after the injection of the allergens (p less than 0.001). This confirms the noradrenergic role of the allergen, apart from the release of histamine as a result of the immunologic mechanism. Histamine is released as a result of the increase of the norepinephrine and is evidence of a homeostatic mechanism, as had been established in a previous investigation by the authors.