Eosinophil Cationic Protein Values Research Articles

Evaluation of Eosinophilic Cationic Protein as a Marker of Alveolar and Cystic Echinococcosis.

Echinococcosis is a neglected zoonotic disease and a worldwide public health problem caused by infection with the larval stages of taeniid cestodes of the genus Echinococcus. In vitro studies have demonstrated a protoscolecidal effect of eosinophilic cationic protein (ECP), a granule protein of eosinophilic granulocytes, against E. granulosus. Therefore, the main objective of this study was to evaluate ECP as a biomarker in the treatment of alveolar echinococcosis (AE) and cystic echinococcosis (CE). Data were collected retrospectively from the Vienna Echinococcosis Cohort over 7 years until December 2020. Altogether, 32 patients (16 AE and 16 CE) were included. In the selected patients, serum ECP values were compared before and after the beginning of an operative and/or benzimidazole (BMZ) therapy. Mean ECP serum levels before intervention were significantly (p < 0.05) elevated at 34.0 ± 22.9 μg/L in AE patients and at 38.6 ± 19.9 μg/L in CE patients compared to the control group. After the intervention, mean ECP levels decreased significantly (p < 0.05) to 20.4 ± 14.6 μg/L in AE patients and to 22.4 ± 8.3 μg/L in CE patients. Furthermore, ECP showed a significant (p < 0.05) correlation of k = 0.56 with PET–CTI. Based on the significant decrease after operative and/or BMZ treatment and the correlation with clinical markers such as PET–CTI, it is recommended to investigate ECP more intensively as a marker of AE and CE in prospective studies with larger cohorts.

Eosinophil Cationic Protein (ECP), a predictive marker of bullous pemphigoid severity and outcome

Bullous Pemphigoid (BP) is an inflammatory rare autoimmune bullous dermatosis, which outcome cannot be predicted through clinical investigations. Eosinophils are the main immune infiltrated cells in BP. However, the release of Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN), and Eosinophil Cationic Protein (ECP) upon eosinophil activation has still not been evaluated with respect to BP development. MBP, EDN and ECP were measured by ELISA in serum (n = 61) and blister fluid (n = 20) of patients with BP at baseline, and in serum after 2 months of treatment (n = 41). Eosinophil activation in BP patients was illustrated at baseline by significantly higher MBP, EDN and ECP serum concentrations as compared with control subjects (n = 20), but without distinction according to disease severity or outcome. EDN and ECP values were even higher in the blister fluids (P < 0.01 and P < 0.05, respectively), whereas MBP values were lower (P < 0.001). ECP serum concentration decreased after 60 days of treatment in BP patients with ongoing remission but not in patients who later relapsed (P < 0.05). A reduction of at least 12.8 ng/mL in ECP concentrations provided a positive predictive value for remission of 81%, showing that ECP serum variation could be a useful biomarker stratifying BP patients at risk of relapse.

The impact of passive smoking on asthma control in children

Objectives: To determine whether passive smoking affects spirometry parameters and allergy blood test results in children; to verify if there is a difference in spirometry parameters and allergy blood test results in children whose household members smoke within the household and children whose household members smoke outside the household; to verify if there is a difference in spirometry parameters and allergy blood test results in children in regard to the number of smokers in the household; to determine if there is a connection between tobacco smoke and the number of allergens in children; to determine if the number of daily smoked cigarettes inside the household correlates with the spirometry parameters and allergy blood test results in children. Design: A retrospective cohort study was conducted. Settings: The study was conducted in the allergy clinic of the Children's ward of the Clinical Medical Centre Split. Patients and methods: The study included 60 children, aged between 5 and 18 with a diagnosis of asthma, who were brought in the allergy clinic by their parents. Children were divided into two groups: a group of 36 children whose household members smoke and a group of 24 children whose household members do not smoke. We analyzed: spirometric parameters (PEF, FVC, FEV1, FEF25, FEF50, FEF75) before and after (VENT_FEF50, VENT_FEF75) we performed a bronchodilatator test with two salbutamol 100 micrograms/dose inhalations; allergy blood tests (Dunger test, relative eosinophile count, concentration of eosinophil cationic protein (ECP), total serum IgE concentration) and eosinophile count in the nasal swab. All the necessary data was gathered from the questionnaire filled out by the parents and by accessing the patients' medical history on the computer. Results: There is no statistically significant difference in spirometry parameters (PEF, FVC, FEV1, FEF25, FEF50, FEF75, VENT_FEF50, VENT_FEF75), eosinophile count in the nasal swab and allergy blood tests (Dunger test, relative eosinophile count, concentration of eosinophil cationic protein (ECP), total serum IgE concentration) between the group of children whose household members smoke and whose household members do not smoke. ECP concentration has shown a statistically significant difference between the group of children whose household members smoke within the household and the group of children whose household members smoke outside the household (P = 0,009). The number of daily smoked cigarettes inside the household statistically significantly correlates with relative eosinophile count in children (P = 0,048). There is no statistically significant difference in spirometry parameters (PEF, FVC, FEV1, FEF25, FEF50, FEF75, VENT_FEF50, VENT_FEF75), eosinophile count in the nasal swab and allergy blood tests (Dunger test, relative eosinophile count, concentration of eosinophil cationic protein (ECP), total serum IgE concentration) between the groups of children in regard to the number of smokers in the household. There is no statistically significant connection between the smoking of the household members and the number of allergens in children. Conclusion: Even though most of the published papers have proven that passive smoking has an effect on development of childhood asthma, this research did not find statistically significant difference in spirometry parameters (PEF, FVC, FEV1, FEF25, FEF50, FEF75, VENT_FEF50, VENT_FEF75), eosinophile count in the nasal swab and allergy blood tests (Dunger test, relative eosinophile count, concentration of eosinophil cationic protein (ECP), total serum IgE concentration) between the groups of children whose household members smoke and children whose household members do not smoke. The number of smokers in the household also did not show significant effect on the aforementioned values. We did not find a connection between passive smoking and the number of allergens in children. A statistically significant difference was found in the ECP value between the group of children whose household members smoke within the household and the group whose household members smoke outside the household. Also, a positive correlation was found between the number of daily smoked cigarettes and relative eosinophile count. These results suggest that passive smoking might have an effect on childhood asthma. There is an obvious difference in the sensitivity of the observed parameters, but despite the small number of patients in this research, it was still possible to find a significant difference in some of the parameters. This way we can explain why the values of ECP and relative eosinophile count showed a statistically significant difference while other observed parameters did not. It is possible that in a larger number group of patients, other parameters would also show statistically significant difference.

Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma

BackgroundLittle information is available regarding eosinophil activation and cytokine profiles in relation to age in virus-induced bronchial asthma. We therefore explored the association between age, respiratory viruses, serum eosinophil cationic protein (ECP), and cytokines/chemokines in acute exacerbations of childhood asthma. MethodsWe investigated viruses in nasal secretions from 88 patients with acute exacerbation of childhood asthma by using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, and the serum levels of ECP and 27 types of cytokines/chemokines in 71 virus-induced acute asthma cases and 13 controls. ResultsViruses were detected in 71(80.7%) of the 88 samples. The three major viruses detected were rhinoviruses, RS viruses, and enteroviruses; enteroviruses were found to be dominant in patients aged ≥3 years. There was no change in the levels of rhinoviruses and RS viruses between the two age groups, defined as children aged <3 years and children aged ≥3 years. Serum concentrations of ECP, IL-5, and IP-10 were significantly elevated in virus-induced acute asthma cases compared with controls. Serum ECP values were significantly higher in patients with virus-induced asthma at age ≥3 years compared with those aged <3 years. Among the 27 cytokines/chemokines, serum IP-10 was significantly higher in virus-induced asthma in patients <3 years than in those ≥3 years. Serum ECP and IL-5 production correlated significantly with age, whereas serum IP-10 showed an inverse correlation with age. ConclusionsAge-related differences in cytokine profiles and eosinophil activation may be related to virus-induced acute exacerbations of childhood asthma.

Nasal Allergy and Otitis Media : A Real Correlation ? = إلتهاب الأذن الوسطى و الأرجية الأنفية : علاقة حقيقية ؟

The correlation between middle ear pathology and nasal allergy has been debated for almost 30 years. This study aimed to evaluate the relationship between otitis media with effusion (OME) and persistent allergic rhinitis symptoms versus intermittent rhinitis in children. The study included 100 atopic children (52 boys, 48 girls) aged 5-9 years with otological symptoms who were patients of the University of Siena Hospital, Italy. Ear, nose and throat evaluations, tympanometry, skin prick tests (SPTs), mucociliary transport time (MCTt) and Eustachian tube function tests were performed. The SPTs revealed 50 children sensitised to Dermatophagoides pteronyssinus, 34 to grass pollen and 16 to Parietaria. Of all patients, mild symptoms were intermittent in 19 children and persistent in 18; moderate/severe symptoms were intermittent in 22 and persistent in 41. Tubal dysfunction was present in 25 children, whereas middle ear effusion was present in 45 children undergoing myringotomy. The MCTt was slower in the persistent group (21 ± 2 mins) versus the intermittent group (16 ± 2 mins) with a significant difference (P <0.01). Mean eosinophil cationic protein (ECP) values in the middle ear effusions of children who had undergone myringotomy were 251 ± 175.2 μg/L, and mean ECP blood values were 25.5 ± 16.3 μg/L, with significant differences (P < 0.001). There was a significant association between OME, delayed MCTt, ECP values in middle ear effusion and persistent symptoms of allergic rhinitis. These results suggest a direct involvement of the middle ear mucosa as a target organ in persistent forms.

Oxidative Stress and Nasal Polyposis: Does it Affect the Severity of the Disease?

Nasal polyposis (NP) is a chronic inflammatory disease and the waste products of this inflammation are reactive oxygen species composed of free radicals. Changes in oxidative status have already been revealed in NP. The aim of this study was to investigate the effect of oxidative status to the severity of the disease and the quality of life. The study group included 24 patients with NP and 20 controls. The Turkish version of the Rhinosinusitis Disability Index, visual analog scale (VAS), polyp stage, computed tomography (CT) score, and the eosinophilic cationic protein (ECP) levels in nasal lavage (NAL) fluid were used to assess the severity of the disease. Malondialdehyde, nitric oxide (NO), and the total antioxidant status (TAS) levels in NAL fluids were measured representing the oxidative stress. NO values were correlated with nasal congestion (p = 0.031). TAS values were correlated with nasal obstruction (p = 0.039). ECP values showed correlation with all the nasal obstruction (p = 0.003), congestion (p = 0.009), rhinorrhea (p = 0.009), and VAS scores (p = 0.039). In NP, ECP levels detected in NAL fluid were significantly high and were correlated with the severity of the disease. Moreover, the severity of oxidative stress, in the forms of TAS and NO, is significantly correlated with the severity of the nasal obstruction and congestion, respectively.

Efficacy and Safety of Sterols/Sterolins in Allergic Rhinitis: A Randomised Double Blind placebo-controlled Clinical Trial

Objective: Sterols/sterolins (Moducare®) have demonstrated immunomodulation and anti-inflammatory effects in preclinical studies, but no clinical trial of patients with allergic rhinitis has yet been published. Thus, our aim was to investigate the safety and efficacy of sterols/sterolins in patients with allergic rhinitis. Methods: The framework was a pilot double-blind randomized controlled clinical trial. Forty patients were randomized to receive Moducare® capsules or placebos for 12 weeks. Patients were evaluated at weeks 4, 8 and 12 with symptom severity questionnaires and immunological assays, including: serum total immunoglobulin E (IgE), eosinophil, and eosinophil cationic protein (ECP). The primary efficacy endpoint indicated the mean change of the allergic rhinitis symptoms score in the therapeutic period at week 12; the secondary efficacy endpoints represented the changes of the Mini-Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) monthly score and the immunological assays of IgE, eosinophil and ECP at week 12. Results: A total of 28 patients (70%) completed the 12-week study, with eight patients dropping out of the Moducare® group and four patients dropping out of the placebo group. The results showed no significant adverse events of sterols/sterolins in this 12-week study. The results of the allergic rhinitis symptoms score, Mini-RQLQ, total IgE, eosinophil count and ECP value had no statistically significant changes in either group. Conclusions: While sterols/sterolins were well tolerated and safe in patients with allergic rhinitis, no significant clinical and immunological benefits were demonstrated in this 12-week pilot study.

Lower airway inflammation before and after house dust mite nasal challenge: An age and allergen exposure-related phenomenon

Upper and lower airways allergic disease is currently considered unitarily. Allergic inflammation in one site can extend to other sites of the respiratory tract. To evaluate bronchial inflammation before and after allergen-specific nasal challenge (ASNC) in rhinitic and asthmatic children, considering the different levels of allergen exposure, i.e. summer (low) and winter (high). Fourteen children with rhinitis and 15 with rhinitis and asthma, all monosensitized to mites and 10 healthy controls were studied. Nasal IgE were measured before ASNC in summer and in winter season. Nasal clinical score, eosinophil cationic protein (ECP), nasal tryptase, bronchial clinical score, FEV(1), PEF, sputum ECP, sputum tryptase and exhaled nitric oxide (eNO) were evaluated before and after ASNC in summer and winter season. Nasal scores significantly increased after ASNC in rhinitic and asthmatic children in both seasons. Nasal IgE were significantly higher in summer compared to winter. Bronchial symptoms, FEV(1) and PEF showed no mean differences in rhinitic and asthmatic children after ASNC, with an increase of bronchial symptoms and a decrease of FEV(1) and PEF occurring in 3/15 asthmatic children. In both groups nasal tryptase and ECP after ASNC significantly increased in summer and winter, while sputum tryptase was undetectable before or after ASNC in both groups. Sputum ECP and eNO at baseline were significantly higher in patients than in controls (summer P=0.002, winter P=0.001). Sputum ECP significantly increased after ASNC in 3/15 asthmatics in summer and in 11/15 in winter, as well as in 3/14 rhinitics in summer and in 4/14 in winter. eNO significantly increased after ASNC in 3/15 asthmatics in summer and in 10/15 in winter, and in 1/14 rhinitics in summer and in 4/14 in winter. A significant median increase of sputum ECP (P=0.0007) and eNO (P=0.0012) after ASNC in asthmatic and of eNO (P=0.013) in rhinitic children was also found in winter. Basal sputum ECP and eNO values, significantly higher before ASNC in rhinitic patients compared to control subjects, confirm the inflammatory link of upper and lower airways. The more frequent detection of inflammatory changes induced by ASNC in winter suggests that allergen exposure favours the transfer of nasal inflammation to lower airways.

Risk Factors for Irritable Bowel Syndrome in Turkish Population

The aim of this study was to determine the prevalence of food hypersensitivity in Turkish patients with irritable bowel syndrome (IBS). The IBS is a chronic disease of the gastrointestinal tract characterized by abdominal pain, distension, meteorism and either diarrhea or constipation. The role of diet in the pathogenesis of IBS remains controversial. Many investigators have shown that individual foods can trigger symptoms in some patients; nevertheless, the percentage of patients that benefit from dietary manipulation ranges from 15% to 67% in different reports. Skin prick test to 11 common allergens, total IgE, eosinophilic cationic protein and eosinophil counts were evaluated in 100 patients satisfying the Rome II criteria and compared with 25 healthy controls. The history and physical examination of the groups were recorded and Beck Depression and Anxiety Inventories were performed. One hundred patients were entered into the study with a mean age of 45.63+/-12.91 years. Of the patients 53 had constipation predominant, 19 had diarrhea predominant, and 28 had alternating type IBS. Skin prick tests positivity were more common among the IBS patients in comparison with controls (25% and 1%, respectively, P<0.05). Mean IgE values were higher in patients than controls (70.83+/-66.05 and 15.20+/-14.01 IU/mL, respectively, P<0.000). Eosinophilic cationic protein values were also higher in IBS patients than controls (16.75+/-11.28 and 11.56+/-4.72, respectively, P<0.05) Evaluation of Beck Depression Inventory showed that tendency to depression in patients with IBS was 38% and 4% in controls (P<0.05). According to our results, in patients complaining of IBS it is of importance to search for a food component. Clinical improvements can be observed after the introduction of an adequate exclusion diet.

The effect of montelukast on soluble interleukin-2 receptor and tumor necrosis factor α in pediatric asthma

Proinflammatory cytokines such as tumor necrosis factor (TNF) alpha and soluble interleukin 2 receptor (sIL-2R) are very important mediators in induction of inflammatory response in lung. The aim of this study was to investigate anti-inflammatory response of cysteinyl leukotriene receptor antagonist montelukast on macrophage and T-cell activation by sIL-2R and TNF-alpha in mild atopic asthmatic children. Fifteen children with mild-to-moderate atopic asthma and 15 nonatopic children as control, enrolled in the study. Asthmatic children were treated with montelukast, 5-mg tablets, for 1 month. Lung function test forced expiratory volume in 1 second (FEV1) was performed before and after treatment. Serum TNF-alpha, sIL-2R, and eosinophil cationic protein levels were determined in the control group and in asthmatic children before and after treatment. The mean eosinophil cationic protein value was significantly decreased (33.1 +/- 14.8 and 22.2 +/- 12.1; p < 0.05) and FEV1 was significantly increased (86.9 +/- 20.9 and 102.1 +/- 12.7; p < 0.05) after 1 month treatment with montelukast. The mean serum IL-2R levels were significantly higher in the before treatment group than in the after treatment group (1061.9 +/- 491 and 794 +/- 230.9; p < 0.05) or in control subjects (581.1 +/- 123; p < 0.01). The mean serum TNF-alpha level was higher in the before treatment group than in the after treatment group and control group (7.30 +/- 3.93, 5.20 +/- 1.46, and 4.95 +/- 1.27; p < 0.05). There was a significant correlation between TNF-alpha and sIL-2R in patients before montelukast treatment (r = 0.674; p < 0.01). This study indicates that montelukast improves clinical parameters and shows anti-inflammatory response by decreasing serum sIL-2R and TNF-alpha levels.

Serum ECP and total IgE levels in children with acute laryngotracheobronchitis

Eosinophilic cationic protein (ECP) and immunoglobulin E (IgE) are important mediators of allergic inflammation and they are commonly used in the diagnosis and follow-up of allergic diseases. But serum levels of these molecules can also be elevated by some other diseases including viral infections. Acute laryngotracheobronchitis (ALTB) is an important viral infection of upper airway and serum levels of ECP and IgE may increase in patients with ALTB. In the present study serum ECP and IgE levels were measured before treatment and on the third day and third week after treatment in 27 patients with ALTB aged 10 months to 5 years and were compared with a age matched healthy controls. All patients were treated with nebulized budesonide. We found that pre-treatment ECP levels were significantly higher than post-treatment third days and third weeks (28.3+/-2.3 ng/ml versus 20.2+/-3.2 ng/ml and 11.4+/-1.1 ng/ml, respectively). Similarly, the mean pre-treatment serum IgE values were significantly higher than post-treatment values (131.6+/-17.5 IU/ml versus 83.6+/-12.4 IU/ml and 68.2+/-6.7 IU/ml). A positive correlation was found between serum ECP and IgE values for pre-treatment and post-treatment third week values (r=062, p=0.01 and r=0.64, p=0.01, respectively). The pre-treatment serum ECP and IgE levels were significantly higher than those of controls (10.8+/-1.5 ng/ml and 43.8+/-6.6 IU/ml, respectively p<0.05). In this study it was shown that, serum ECP and IgE levels increase in the acute phase of infection and return to normal after treatment in patients with ALTB such as in allergic patients. This effect of ALTB on serum ECP and total IgE levels should be kept in mind and these parameters should not be used in the diagnosis and follow-up of allergic diseases in children who had had ALTB in recent weeks.

Do tryptase, ECP and specific IgE measurement by nasal incubation increase the specific nasal provocation test sensitivity?

The specific Nasal Provocation Test (sNPT) is a third level diagnostic tool. Fitted to reproduce natural exposure condition to pick the responsible allergen for nasal symptoms out, it is applied when prick test and RAST responses are doubtful. SNPT results have been evaluated measuring nasal resistance (anterior rhinomanometry) and nasal symptoms (clinical score), reaching 50% of sensitivity. This study focused on the determination of allergic response markers, triggered by nasal challenge: tryptase levels in the nose, specific IgE and ECP (Eosinophil Cationic Protein). The aim was to increase sNPT sensitivity. Twenty patients suffering from allergic rhinitis and 16 age-matched-nonallergic subjects were enrolled in the study. Tryptase, specific IgE and ECP were determined in nasal mucosa applying a new method, based on in situ incubation, before and after sNPT. The latter was performed following a standardized method. Tryptase levels increased in 13 patients (65%), were unchanged in four patients (20%), and slightly decreased in three patients (15%). The increase recorded was significant in mite allergic patients (p=0.005), but not significant (p> 0.05) in pollen allergic patients. ECP values increased in 13 patients (65%), were unchanged in two patients (10%), and highly decreased in five patients (25%). ECP increase was not significant (p> 0.05). Specific IgE levels increased in seven patients (35%), were unchanged in 11 patients (55%) and decreased in two patients (10%). The IgE increase was significant in pollen-allergic patients (p<0.05), while it was not significant in mite-allergic patients (p>0.05). Tryptase, ECP, and specific IgE were not detected in the control group. The data obtained showed a positive sNPT response in 12 patients (60%). Comparing our results with those derived from classical-parameter employment, we gathered an improvement of 10%. On the basis of the usual parameters, in fact, we recorded 50% positivity, while the use of mediators provided an additional 10% improvement in sNPT sensitivity: taking together the usual parameters and nasal allergic mediators values, we reached an sNPT over-all sensitivity of 85%.

Serum Eosinophil cationic protein (ECP) elevation correlates with asthma symptoms and reduced FEV 1 in an outpatient screening population

Rationale Current research indicates that eosinophil mediators, such as the eosinophil cationic protein (ECP), are not only a common feature of the asthmatic lung, but are also increased in acute exacerbations and may be predictive of clinical course. We seek to identify if a correlation exists between serum ECP and asthma symptoms. Methods Subjects were selected from individuals who volunteered to be screened for allergies by a serum Phadiatop Test. Each participant completed an asthma symptom questionnaire, identifying if they at any time had experienced wheezing, persistent cough, chest tightness, nighttime symptoms and/or shortness of breath. Mean ECP levels were compared on 125 individuals, between the affirmative and negative symptom groups using a student t test for each individual asthma symptom. Pulmonary function tests were also performed on 43 individuals. Results Although not statistically significant (p values 0.67, 0.32. 0.28, 0.25, and 0.11 respectively for each of the above symptoms), the mean ECP values were consistently higher in those patients reporting asthma symptoms, than those who did not. Additionally, Forced Expiratory Volume in 1 second (FEV1) was compared to ECP in 43 individuals, demonstrating a mean ECP slightly higher (p=0.89) in those individuals with FEV1 <70% than those with FEV1 ≥70%. Conclusion Based on the data from this study, more research on the correlation of serum ECP and asthma symptoms and pulmonary function is needed. With a larger population sample, including controls, there may be a better basis for establishing a link between serum ECP and asthma symptoms.

The Effects of Add-on Zafirlukast Treatment to Budesonide on Bronchial Hyperresponsiveness and Serum Levels of Eosinophilic Cationic Protein and Total Antioxidant Capacity in Asthmatic Patients

Mild persistent asthma is most effectively controlled with inhaled corticosteroids. Leukotriene receptor antagonists have complementary effects to corticosteroids on inflammation control. The additional effect of a leukotriene receptor antagonist, zafirlukast, was investigated in stable asthma patients under control with inhaled budesonide. We conducted a randomised, double-blind, placebo-controlled, single center trial to investigate the effects of add-on zafirlukast treatment to budesonide, on symptom score, pulmonary function, bronchial responsiveness, and serum levels of eosinophilic cationic protein (ECP) and antioxidant capacity in stable asthmatic patients under control with inhaled budesonide. The present study included 21 mild or moderate asthmatic patients (8 males and 13 females), who were stable at least for 6 weeks with inhaled budesonide (400 microg/day). Serum total antioxidant capacity (TAC) and ECP levels were measured, and symptom scoring, spirometry, and bronchial provocation with methacholine were performed. Then, the patients were randomised to use either placebo or oral zafirlukast (40 mg/day) in addition to budesonide for 6 weeks. At the 6th week, symptom scoring, spirometry, and bronchial provocation tests were repeated and serum TAC and ECP levels were measured again. After add-on zafirlukast treatment to budesonide, forced expiratory volume in 1 second (FEV(1)), TAC and ECP values did not change significantly (p > 0.05) but bronchial hyperresponsiveness and symptom score decreased significantly (p = 0.022) compared to baseline. Thus, in stable asthmatic patients, add-on zafirlukast treatment to budesonide improves symptoms and decreases bronchial hyperresponsiveness.

The inflammatory marker serum eosinophil cationic protein (ECP) compared with PEF as a tool to decide inhaled corticosteroid dose in asthmatic patients

The objective of this study was to compare the inflammatory marker eosinophil cationic protein (ECP) with peak expiratory flow (PEF) in determining the therapeutic needs of inhaled corticosteroids in asthma patients assessed as asthma symptoms. A randomized, single-blind study over 6 months was performed at six specialist centres in Europe. In total, 164 adult patients with moderate to severe symptomatic asthma and regular use of inhaled corticosteroids were included. After a run-in period of 2 weeks patients were randomly allocated to the ECP or the PEF monitoring group. The dose of inhaled corticosteroids was adjusted every fourth week based on the current serum ECP value or pre-broncho-dilator morning PEF values as surrogate markers of therapeutic needs. At the end of the study there were no statistically significant differences in the mean daily symptom score or the percentage of symptom-free days between the two groups. The mean daily dose of inhaled corticosteroids was similar in the two groups at the start of the study but the algorithms used to adjust the dose of inhaled corticosteroids resulted in an increased use of inhaled corticosteroids in both groups. The mean daily dose of inhaled corticosteroids over the whole study period was significantly lower in the ECP group compared with the PEF group (1246 vs. 1667 μg,P =0·026). In the ECP group, forced expiratory volume in 1 sec (FEV1)% predicted was lower at the end of the study compared with the begining (92% vs. 87%, P=0·0009), although there was no significant difference between the two groups. None of the used algorithms for ECP and PEF led to improvement in symptom scores, in spite of increased doses of inhaled corticosteroids. In this respect, both methods were equivalent and insufficient. Recommendations suggesting lung function tests in current guidelines may be difficult to translate into clinical practice, however, a combination of inflammatory markers, lung function and symptoms may still improve asthma control.

Measurement of Inflammatory Mediators of Mast Cells and Eosinophils in Native Nasal Lavage Fluid in Nasal Polyposis

Background: Nasal polyposis (NP) often coexists with asthma, rhinitis and sinusitis. Polyp histology typically shows chronic, eosinophilic inflammation. The inflammatory cell infiltrate generally includes eosinophils, lymphocytes, plasma cells and mast cells. Objective: To gain insight into the natural history of NP, we analysed mediator levels and leukocyte values in nasal fluids and eosinophil cationic protein (ECP), total IgE levels and eosinophils in the blood in several groups of both allergic and non-allergic patients with nasal polyps and in patients with allergic rhinitis (AR). Methods: Thirty-two patients with nasal polyps entered the study. As a control group, we studied 55 patients with AR, i.e. 20 patients with seasonal AR to grass pollen, 24 with AR sensitive to Parietaria and 11 with AR sensitive to house dust mite (HDM). Eighteen patients with nasal polyps were also allergic patients (8 were sensitive to Parietaria and 10 were sensitive to HDM), whereas 14 were non-allergic patients. Tryptase and histamine values were assayed in nasal fluids, whereas total IgE was determined in serum. ECP values were assayed both in nasal fluids and serum. Eosinophils were quantified both in the blood and nasal fluids. Results: Tryptase levels were significantly higher in the nasal lavages from patients with NP than in those from patients without NP (4.7 vs. 3.5 U/l, p < 0.001) and correlated with symptom scores (r_s = 0.42, p < 0.0001). The median levels of histamine in nasal fluids from patients with NP were also significantly higher than those observed in patients without NP (50.0 vs. 21.3 ng/ml, p < 0.001), but did not correlate with symptom scores. Finally, the median levels of ECP in nasal fluids from patients with NP were significantly higher than those observed in patients without NP (38.1 vs. 16.1 ng/ml, p < 0.001) and correlated with symptom scores (r_s = 0.38, p < 0.001). Analysis of variance showed that, among the variables studied, the presence of nasal polyps was the factor responsible for the higher levels of tryptase, histamine and ECP in nasal fluids. With regard to leukocyte counts in nasal fluids, no significant differences were observed between rhinitis patients with NP and those without NP. With regard to serum ECP and serum total IgE, no significant differences were detected between the two groups under study. Blood eosinophil levels in patients with NP were significantly higher than those observed in patients without NP (5.8 vs. 5.6, p = 0.002). Analysis of variance showed that both the presence of nasal polyps and the type of sensitisation were important. Considering the total symptom scores, no significant differences were observed between rhinitis patients with NP and those without NP. Conclusions: The present findings are consistent with the view that chronic eosinophil mucosal inflammatory disease in NP involves a self-sustaining mechanism, i.e. local release of inflammatory mediators, independent of allergen stimulation of nasal mucosa. Increased release of inflammatory mediators contributes to the development of nasal polyps, determining oedema and an increased recruitment of inflammatory cells. Besides eosinophils, mast cells also play a key role in this process.

Characteristics of the Inflammatory Response in Bronchial Lavage Fluids from Patients with Status asthmaticus

Status asthmaticus (SA) is a sudden respiratory failure characterized by an acute bronchospasm with a severe inflammation, requiring in some cases mechanical ventilation (MV). Initial postmortem studies emphasized the presence of eosinophils in the bronchial wall and of mucus plugs filling the bronchi. More recently a prominent neutrophil influx was observed in patients with fatal or near fatal asthma. The aim of our study was to evaluate characteristics of bronchial inflammation in terms of cellular influx, mediators, cytokines and chemokines. Ten patients with SA were compared with 11 patients with chronic asthma, 4 without preexisting pulmonary disease requiring MV and 8 healthy subjects. Bronchial lavages in SA were indicated to remove bronchial plugs in case of atelectasia and/or refractory SA. The main findings in patients with SA were a massive influx of neutrophils (81.5 ± 4.5%) with a dramatic increase of neutrophil elastase. Although more limited than the neutrophil influx, eosinophils were present and associated with high levels of eosinophil cationic protein (ECP), which suggested that a part of the eosinophils were activated and degranulated. In parallel to the neutrophil and eosinophil influx, we observed elevated amounts of proinflammatory (IL-1β, IL-5, IL-6, TNFα) and anti-inflammatory (IL-10, IL-1 receptor antagonist, soluble TNF receptors) cytokines with a balance in favor of a net proinflammatory activity. Chemokines were also present in large quantities with a predominance of MCP-1, MIP-α and RANTES with a significant correlation between MCP-1, RANTES, IL-5 and both eosinophil and ECP values. In addition an acute 10- to 160-fold increase of 92-kD gelatinase (MMP9) was detected in bronchial lavage fluid from patients with SA associated with a free metallogelatinolytic activity, suggesting an imbalance in the local production of proteases and antiproteases. Therefore, our results indicate that the bronchi in SA are the site of an intense production of pro- and anti-inflammatory cytokines and chemokines that are implicated in the influx of eosinophils and neutrophils. The inflammatory pattern in SA clearly differs from the usual profile observed in chronic asthma.

Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 μ g day−1) versus HFA-fluticasone propionate (1000 μ g day−1) in patients with asthma

Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extra-fine aerosol and HFA-fluticasone propionate (HFA-FP) are chlorofluorocarbon-free inhalers.We conducted an 8-week, open study to demonstrate the equivalence of HFA-BDP (800 μ g day−1) and HFA-FP (1000 μ g day−1) in moderate to severe asthma. Symptomatic patients on 500–1000 μ g day−1CFC-BDP (or equivalent) and short-acting β -agonist, were randomized to HFA-BDP (n=101) or HFA-FP (n=97) after 7–14 (±2) day run-in.In the intent-to-treat (ITT) population (n=198), both treatments provided clinically and statistically significant improvements in asthma control, with increases in peak expiratory flow in the morning (AM PEF) and asthma symptoms (within treatment analysis P<0·05). Mean (SE) change in AM PEF from baseline at week 8 was equivalent (defined as 90% CI for the mean difference between treatments within ±25 l min−1) in the two groups: 29·59 (5·19) 1 min−1for HFA-BDP vs. 17·3 (5·45) 1 min−1for HFA-FP (90% CI−0·02, 24·91). For the per-protocol population (n=121), the mean (SE) change in AM PEF from baseline was not equivalent; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [34·84 (7·08) vs. 20·63 (7·32) 1 min−1P<0·01; 90% CI; 2·66, 31·10]. At week 8 in the ITT population, there were no statistically significant differences in FEV1, β -agonist use, asthma symptom/sleep disturbance scores, or percentage of days without asthma symptoms/sleep disturbance. There was a significantly greater reduction from baseline in mean eosinophil count for HFA-BDP compared with HFA-FP at weeks 3 and 8 (P<0·01), and eosinophil cationic protein value at week 8 (P<0·01). Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters.In conclusion, this study showed that, in patients with moderate-to-severe symptomatic asthma, HFA-BDP extra-fine aerosol 800 μ g−1was at least as effective and equally well tolerated as 1000 μ g day−1HFA-FP.

Eosinophil cationic protein and specific IgE in serum and nasal mucosa of patients with grass-pollen-allergic rhinitis and asthma.

After allergen exposure, IgE-bearing mast cells surface in respiratory mucosa. Eosinophils are also recruited locally by chemotactic mediators; they are the main cell directly involved in the late phase of allergic inflammation. IgE antibody and eosinophil cationic protein (ECP) are routinely determined mainly in serum although they exert their pathogenetic role more directly on mucosal surfaces. We performed a comparative study of IgE antibody to grass and ECP on nasal mucosa and blood samples in order to evaluate the relevance of monitoring allergic inflammation in the target organ. Thirty-one patients and 10 nonatopic controls were enrolled in the protocol. Twenty-six subjects allergic to grass, 11 with rhinitis (group 1) and 15 with asthma and rhinitis (group 2), completed the study. Five patients dropped out. Specific IgE to grass and ECP was determined in nasal mucosa by our method based on in situ incubation. Serum IgE to grass did not increase during the pollen peak, as did nasal IgE, in group 1 from before the pollen peak, from 2.3 to 3.2 kU/l (P=0.02), and in group 2 at the pollen peak, from 4.8 to 12.2 kU/l (P=0.01). Serum ECP did not show any significant variation in group 1, but it increased at pollen peak from 6 to 11.2 microg/l (P=0.01) in group 2. Nasal ECP increased significantly in both groups even before the pollen peak. In group 1, ECP values rose from 15 to 39.9 microg/l (P=0.01). In group 2, ECP increase was much higher than in group 1, from 9 to 213 microg/l (P=0.001). Serum eosinophils, like nasal ECP, showed a significant increase of values from before the pollen peak in both groups, without correlation with serum ECP in rhinitic patients. Both specific IgE and ECP in the nasal mucosa showed a better correlation with allergen exposure than serum evaluations. With an appropriate method, allergic inflammation may be best monitored in the nasal mucosa.

The risks versus the benefits

The objective of this study was to compare the inflammatory marker eosinophil cationic protein (ECP) with peak expiratory flow (PEF) in determining the therapeutic needs of inhaled corticosteroids in asthma patients assessed as asthma symptoms. A randomized, single-blind study over 6 months was performed at six specialist centres in Europe. In total, 164 adult patients with moderate to severe symptomatic asthma and regular use of inhaled corticosteroids were included. After a run-in period of 2 weeks patients were randomly allocated to the ECP or the PEF monitoring group. The dose of inhaled corticosteroids was adjusted every fourth week based on the current serum ECP value or pre-broncho-dilator morning PEF values as surrogate markers of therapeutic needs. At the end of the study there were no statistically significant differences in the mean daily symptom score or the percentage of symptom-free days between the two groups. The mean daily dose of inhaled corticosteroids was similar in the two groups at the start of the study but the algorithms used to adjust the dose of inhaled corticosteroids resulted in an increased use of inhaled corticosteroids in both groups. The mean daily dose of inhaled corticosteroids over the whole study period was significantly lower in the ECP group compared with the PEF group (1246 vs. 1667 μg,P =0·026). In the ECP group, forced expiratory volume in 1 sec (FEV1)% predicted was lower at the end of the study compared with the begining (92% vs. 87%, P=0·0009), although there was no significant difference between the two groups. None of the used algorithms for ECP and PEF led to improvement in symptom scores, in spite of increased doses of inhaled corticosteroids. In this respect, both methods were equivalent and insufficient. Recommendations suggesting lung function tests in current guidelines may be difficult to translate into clinical practice, however, a combination of inflammatory markers, lung function and symptoms may still improve asthma control.