Nasal Eosinophil Cationic Protein Research Articles

Diagnostic value of a novel test paper detection of ECP in nasal secretion for allergic rhinitis

Objective:To explore the diagnostic value of a novel test paper, which detect eosinophil cationic protein（ECP） of nasal secretion in allergic rhinitis（AR）. Methods:Nasal secretion and serum samples from 107 patients with allergic rhinitis（AR group） and 40 healthy volunteers（control group） were selected. The nasal symptoms were also evaluated in AR group. The degree of ECP coloration was evaluated by nasal secretion eosinophil cationic protein-myeloperoxid（ECP-MPO） test paper, and the concentration of ECP in nasal secretion and the concentration of cytokines in serum were detected at the same time. The difference and correlation among these indexes were analyzed. The best cutoff value and test efficiency of ECP chromogenic grade and concentration of nasal secretion were calculated by receiver operating characteristic curve（ROC）. Results:The concentration of ECP in nasal secretion of AR patients was significantly higher than that of healthy controls（P<0.05）. The color grade of nasal secretion detected by the test paper was positively correlated with the concentration of ECP in nasal secretion（P<0.05）, and there was significant difference among different grades（P<0.05）. There was a satisfying symmetry between the ECP color grade of nasal secretion and the serum specific IgE（sIgE） level as well as a high diagnostic consistency between them（P<0.05）. The area under the curve（AUC） of ECP concentration ROC in nasal secretion was 0.807 2, corresponding to 64% sensitivity and 85% specificity when the cutoff value was set at 0.980 5; when the cutoff value was set at 1, the AUC of nasal secretion ECP color grading was 0.941 9, corresponding to 92% sensitivity and 94% specificity. No clear correlation between the concentration of ECP in nasal secretion and serum cytokines was found（P>0.05）. Conclusion:The results of this novel test paper is in good agreement with those of serological allergens. It could serve as a preliminary test to evaluate the severity of allergy with satisfactory sensitivity and specificity, and is especially suitable in clinical practice for primary hospital.

Local nasal immunotherapy for allergic rhinitis: A systematic review and meta-analysis.

Local nasal immunotherapy (LNIT), an alternative noninjection immunotherapy method, is theoretically an efficient method for inducing immunotolerance directly in the affected organ. LNIT is more convenient and less invasive than injection immunotherapy, with fewer systemic reactions. The development of adjuvants to overcome LNIT's limitations raises the possibility of it being an alternative allergen immunotherapy. To evaluate the clinical and immunological efficacy and safety of LNIT for patients with allergic rhinitis. A systematic search for randomized controlled trials comparing LNIT and placebo was performed using OVID Medline and Embase. Outcomes were total nasal symptom score (TNSS), symptom-medication score (SMS), medication score, immunological assessment, and nasal provocation threshold. Data were pooled for meta-analysis. A total of 20 studies with 698 participants were included. The LNIT group had greater posttreatment improvement in TNSS, SMS, and medication score than control (TNSS: standardized mean difference [SMD], -1.37 [95% confidence interval [CI], -2.04 to -0.69]; SMS: SMD, -1.55 [95% CI, -2.83 to -0.28]; and medication score: SMD, -1.09 [95% CI, -1.35 to -0.83]). Immunological assessments showed no significant differences in serum-specific IgE (mean difference [MD], 6.35; 95% CI, -4.62 to 17.31), nasal IgE (MD, -0.59; 95% CI, -1.99 to 0.81), or nasal eosinophil cationic protein (MD, 7.63; 95% CI, -18.65 to 33.91). Only serum IgG significantly increased with LNIT (MD, 0.45; 95% CI, 0.20, 0.70). Posttreatment, nasal provocation threshold was higher with LNIT (MD, 27.30; 95% CI, 10.13-44.46). No significant adverse events were reported. LNIT is a safe alternative allergen immunotherapy route without significant adverse events. It improves clinical symptoms, reduces medication usage, and increases the nasal provocation threshold.

Nasal ventilation is an important factor in evaluating the diagnostic value of nasal nitric oxide in allergic rhinitis.

The role of nasal nitric oxide (NO) in the diagnosis of allergic rhinitis (AR) is controversial. The aim of this study was to identify factors that may affect levels of nasal NO in AR patients and evaluate the role of nasal NO in the diagnosis of AR. Seventy-five AR patients and 31 healthy controls were enrolled in this study. AR symptom scores were assessed using the visual analog scale. Eosinophil cationic protein (ECP) was detected by enzyme-linked immunoassay, nasal NO was measured using a chemiluminescence analyzer, and nasal airway resistance (NAR) was assessed by active anterior rhinomanometry. Nasal obstruction score, ECP, and NAR were found to be independently associated with nasal NO. Nasal NO level in patients with nasal obstruction score<7 (mild-to-moderate obstruction) was significantly increased compared with healthy subjects (282.1±122.6 vs 150.7± 48.4 ppb; p<0.001), and significantly decreased in patients with nasal obstruction score≥7 (severe obstruction) (97.2±52.2 vs 150.7±48.4 ppb; p<0.001). Nasal NO and ECP in secretion were positively correlated in patients with mild-to-moderate nasal obstruction (r=0.678), but not in patients with severe nasal obstruction (r=0.077). In patients with NAR <0.65 Pa/cm3 /s, the correlation coefficient was highest between NO and ECP (r=0.685). The areas under the receiver operating characteristic curve for nasal NO level were 0.878 and 0.939 in patients with nasal obstruction scores<7 and NAR<0.65Pa/cm3 /s, respectively. Nasal patency affects nasal NO level significantly, and may reflect the severity of nasal inflammation in AR patients with mild-to-moderate nasal obstruction, but not in patients with severe nasal obstruction.

Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis

BackgroundMinimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. MethodsWe designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outside the pollen season (UMIN000008410). Nasal provocation with paper discs containing extracts of Japanese cedar pollen was performed once a day for 3 consecutive days. Onset of nasal symptoms was monitored over 15 min after each provocation. The levels of eosinophil cationic protein (ECP) and tryptase in nasal secretions were examined. Fluticasone furoate nasal spray or placebo treatment was started one day before the first provocation. ResultsIn the placebo group, 25% of the patients showed onset of nasal symptoms following provocation on the first day. In addition, 75% and 68% of the patients showed symptom onset on the second and third day of provocation, respectively. After the first provocation, the levels of ECP and tryptase in nasal secretions were significantly increased. These increases were seen not only in symptomatic but also in asymptomatic subjects in response to provocation, and the levels were similar between these subjects. Prophylactic treatment with fluticasone significantly suppressed the increase in nasal ECP and tryptase associated with repeated provocations. ConclusionsThese results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation.

The Impact of School Environment on Children's Respiratory Health

Background/Aims: School indoor air quality is important because children spend most of their time outside home within the school environment. This study aimed to investigate the school environment and its impact on the respiratory health of the children. Methods: A total of 191 pupils in the 9- to 11-year age group were selected from 5 primary state schools. Validated school and health questionnaires, spirometry, acoustic rhinometry, nasal lavage, urine for environmental tobacco smoke biomarkers and traffic counts were used. Results: Cumulative (32.98%) and current wheezing (17.8%) were in keeping with the International Study of Asthma and Allergies in Childhood Malta data. Southern schools had the highest prevalence of current wheezers (OR 3.77; p = 0.012), rhinoconjunctivitis (OR 3.59; p = 0.003) and nasal eosinophilic cationic protein levels (p < 0.001). Small openable window areas increased rhinitic symptoms (OR 3.14; p = 0.016). Classes facing roads had increased current wheezers (OR 2.27; p = 0.03) and exhaled carbon monoxide (eCO) levels (p < 0.001). Current wheezing was significantly associated with the number of light and heavy vehicles passing near the school (p < 0.001). The presence of smokers at home was significantly associated with urinary cotinine and 3HC (p < 0.001). Proximity to power plants increased the current wheezers (OR 5.89; p = 0.001) who had impaired spirometry (p = 0.003). Asthma symptoms (OR 5.25; p = 0.001) and elevated eCO levels (p < 0.001) were associated with fuel storage facilities near schools. The accumulation of dust on flat surfaces within classrooms was related to wheezing (OR 5.23; p = 0.001). Conclusions: The school environment had a direct impact on the respiratory health of children, with several factors having a direct impact on the children's health.

P45 Sputum And Nasal Markers Of Inflammation In Severe Asthma - A Pilot Study

Introduction and objectives The Manchester Severe Asthma Team has successfully been using sputum eosinophil monitoring for several years to help tailor steroid medication. Whilst very useful for patients able to produce a sputum sample, some patients cannot produce a sample. As a result we looked at developing an alternative method of monitoring using nasal lavage samples to study the intra-individual changes in inflammation in severe asthma. Methods Patients requiring sputum monitoring as part of their clinical management were invited to take part in this pilot and to provide an additional nasal lavage sample obtained using an olive method. Participants were clear of infection at time of sampling. Sputum was either spontaneous or induced using the traditional 3%-4%-5% nebulised sodium chloride procedure. ECP (Eosinophil Cationic Protein) was measured in sputum and nasal supernatants using a commercial ELISA kit (Mesacup, MBL). Differential cell count (DCC) was attempted for both sputum and nasal sample types. Results This abstract show the results obtained for the first 32 consecutive patients. Our patient population is described in Table 1, 69% female, 69% atopic (as defined by positive RAST of elevated total IgE), and 50% were non-smokers, 7.6 current smokers and 42.4% ex-smokers. No patient was immunosuppressed or on IM Triamcinolone. ECP levels were as follows: Sputum: median 2650 (min:20.76–28603 ng/ml), 100% of samples had detectable levels. Nasal lavage: 0(0–7.6), 20%. DCC were as follows: Sputum: 38% patients were eosinophil positive (as defined by >3%), Nasal lavage: no eosinophil was detected, 38.5% of samples had a DCC but interpretation was hindered by low cell yield. Sputum DCC/ECP did not correlate significantly with nasal ECP (Pearson R=0.168, p = 0.374 and R=-0.048, p = 0.807 respectively). Nasal DCC data could not be computed as no patient was found to be eosinophil positive. Sputum DTT and sputum ECP correlated significantly (Pearson R=0.607, p = 0.001) as reported in the literature. Conclusions At this stage of our pilot, intermediate data analysis shows that nasal sampling does not appear to be a successful alternative to sputum monitoring in severe asthma.

Exhaled nitric oxide and nasal tryptase are associated with wheeze, rhinitis and nasal allergy in primary school children

Rhinitis and asthma are the most common respiratory diseases in children. We assessed whether airway inflammation markers were associated with nasal allergies and self-reported symptoms of wheeze and rhinitis in 130 children 6–12 year old in an epidemiological context. Independent of sex and age, the fraction of exhaled nitric oxide (FeNO) and nasal mast cell (MC) activation (tryptase ≥ 5 ng/mL) were positively associated with wheeze, rhinitis and with nasal allergy. Nasal eosinophil cationic protein (ECP) and exhaled breath condensate (EBC) markers (pH, 8-isoprostane, interleukin-1β) were not associated with symptoms or with nasal allergy. In conclusion, FeNO and nasal tryptase reflect allergic inflammation in the respiratory system.

Noninvasive biological evaluation of response to pranlukast treatment in pediatric patients with Japanese cedar pollinosis

Pranlukast (PLK) is a cysteinyl leukotriene receptor 1 antagonist approved for the treatment of bronchial asthma and allergic rhinitis in Japan. We previously reported that PLK dry syrup (DS) improved the total nasal symptom score, as well as sneezing, nasal discharge, and nasal obstruction scores over placebo. We investigated the efficacy of PLK DS with a noninvasive method in 10- to 15-year-old children with Japanese cedar (JC) pollinosis challenged with pollen allergen using an artificial exposure chamber (OHIO Chamber). Levels of eosinophil cationic protein (ECP) in nasal secretions, nasal obstruction score, and the relationship with nasal obstruction scores were analyzed. The estimated difference of means in ECP levels (PLK DS--placebo) was -22.9 micrograms (95% CI, -45.2 to -0.5), suggesting PLK DS reduced ECP significantly when compared with placebo (p = 0.0454). The difference in the least square means for nasal obstruction between the PLK DS and placebo was -0.25 (95% CI, -0.36 to -0.14) with a value of p < 0.0001. In addition, a statistically significant, although weak, positive correlation between the nasal obstruction score and nasal ECP levels was observed with placebo treatment (correlation coefficient = 0.2394; p = 0.0428). Moreover, the inhibition rate of nasal ECP with PLK DS relative to placebo was statistically significant, although weak, positively correlated with the inhibition rate of nasal obstruction (correlation coefficient = 0.3373; p = 0.0219). PLK DS significantly decreases nasal ECP levels and nasal obstruction score compared with placebo in children with JC pollinosis challenged with pollen allergen. Suppression of mucosal eosinophilic inflammation is one of the pathways by which PLK DS improves pollinosis-induced nasal obstruction.

Analysis of the level and significance of immunoglobulin free light chain in nasal secretion and in serum of patients with allergic rhinitis and non-allergic rhinitis

To test the immunoglobulin free light chain (FLC) from nasal secretion(s) and serum of patients with allergic rhinitis and non-allergic rhinitis for the purpose of exploring the possible immunological mechanism. Sixty consecutive patients were selected between September and December in 2009, involving 30 patients with allergic rhinitis and 30 patients with non-allergic rhinitis, diagnosed by symptoms, signs, SPT and sIgE. Thirty volunteers was chosen as health control (HC). ELISA was used to detect the total IgE, eosinophil cationic protein (ECP), mast cell tryptase (MCT), κFLC, λFLC in nasal secretion and serum. The data was statistically analyzed by SPSS 17.0 software. According to the VAS scores, the nasal symptoms of AR and NAR, including sneeze, nasal discharge, nasal obstruction and nasal itching were compared. There was no statistical difference (t value was 1.189, 0.741, 0.758, 0.797, respectively, P < 0.5); In serum, κFLC, λFLC, IgE, ECP & MCT were increased in NAR compared to HC (P < 0.05); λFLC was increased in NAR compared to AR group (P < 0.05), κFLC and ECP were increased in AR. There was no significant difference between AR and NAR (P < 0.05); In nasal secretion, κFLC, λFLC, IgE, ECP and MCT were increased in AR and NAR compared to HC, and the ECP and IgE were significantly increased in AR compared to NAR (P < 0.05). ; In nasal secretion, the FLCs revealed a significantly higher correlation with MCT (r value was 0.518 and 0.484, P < 0.01), and in serum revealed a significant correlation with ECP (r value was 0.343 and 0.342, P < 0.01). Immunoglobulin free light chain takes part in the path of physiological process of allergic rhinitis and non-allergic rhinitis with the immunological mechanism.

Early interventional treatment with intranasal corticosteroids compared with postonset treatment in pollinosis

BackgroundThe usefulness of early interventional treatment (EIT) with intranasal corticosteroids (INSs) compared with postonset treatment (POT) has not been clarified. ObjectivesTo study the efficacy and safety of EIT with INSs compared with POT and placebo in Japanese cedar/cypress pollinosis. MethodsWe designed a 3-armed, double-blinded, randomized, placebo-controlled trial. Patients received mometasone furoate nasal spray (EIT group: n = 25), placebo (n = 25), or 4 weeks of placebo followed by 8 weeks of mometasone (POT group: n = 25) for a 12-week period starting on February 1, 2011. The primary end point was the comparison of the total nasal symptom score (TNSS) among the 3 groups. Total ocular symptom score (TOSS), total naso-ocular symptom score (TSS), Allergic Rhinitis and Its Impact (ARIA) on Asthma classification, and safety were the main secondary end points. ResultsThe placebo and POT groups, but not the EIT group, had a significant exacerbation of TNSS and TOSS soon after the start of pollen counts being high on consecutive days. The 12-week mean TSS in the EIT group (score, 2.3) was significantly lower than in the placebo (5.0; P < .01) and POT (3.9; P = .03) groups. All patients in the placebo and POT groups were classified as having persistent rhinitis, whereas 80% of the EIT group met the ARIA classification criteria (P = .03). The quality-of-life score and nasal eosinophil cationic protein levels were lower in the EIT and POT groups compared with the placebo group. Daytime sleepiness, smell disturbance, and the mean dose of loratadine taken as the rescue medication were similar. Treatment with mometasone was well tolerated. ConclusionEIT with INSs is superior to POT in controlling pollinosis.

Different cytokine profile and eosinophil activation are involved in rhinovirus‐ and RS virus‐induced acute exacerbation of childhood wheezing

Because little information is available on eosinophil activation and cytokine response in virus-induced wheezing, we attempted to detect respiratory viruses and measure eosinophil cationic protein (ECP), and 27 types of cytokines/chemokines in both serum and nasal secretions from children with wheezing. This study was an observational, case-control investigation of 267 subjects, who were visited and/or hospitalized with acute respiratory symptoms (with wheezing: men, 115; women, 59; mean/median age, 3.6/3.0 years) or who were visited for regular physical examination and treatment (non-symptomatic wheezing: men, 48; women, 31; mean/median, 5.0/4.7 years), and 14 control subjects (controls: men, 9; women, 5; mean/median, 3.6/3.7 years). We detected viruses in nasal secretions from 174 patients with acute exacerbations of wheezing using antigen detection kits or reverse transcription-polymerase chain reaction, followed by direct DNA sequencing analysis. We measured peripheral eosinophil counts, and serum concentrations of ECP and 27 cytokines/chemokines using a multiplex bead-based assay in patients with wheezing or non-symptomatic wheezing. We also examined nasal ECP and 27 cytokines/chemokines in patients with wheezing. Of 174 samples from wheezing exacerbations, rhinovirus was detected in 59; respiratory syncytial (RS) virus in 44; enterovirus in 17; other viruses in 19; and no viruses in 35. Serum concentrations of ECP, IL-5, IL-6, IL-1ra, and IP-10 were significantly elevated in rhinovirus-induced wheezing compared with non-symptomatic wheezing. Similarly, serum ECP, IL-5, and IP-10 were significantly higher in rhinovirus-induced wheezing than in controls. On the other hand, IL-1ra and IP-10, but not ECP and IL-5 were significantly higher in RS virus-induced wheezing than in controls. Furthermore, only IL-5 was significantly elevated in the rhinovirus group compared with the RS virus group in both serum and nasal secretions. Different cytokine profile and eosinophil activation might be involved in rhinovirus- and RS virus-induced acute exacerbation of childhood wheezing.

Increased Eosinophilic Cationic Protein in Nasal Fluid in Hospitalized Wheezy Infants with RSV Infection

Respiratory syncytial virus (RSV) is a major respiratory pathogen which causes bronchiolitis with dyspnea and wheezing in children less than 2 years old. RSV bronchiolitis in infancy severe enough to cause hospitalization might be a risk factor for allergic sensitization and bronchial asthma in future. However, the pathophysiology behind this development has not been clearly characterized. To evaluate the existence of airway inflammation and characteristic of RSV bronchiolitis, we analyzed and compared the concentrations of eosinophilic cationic protein (ECP) in nasal fluid and plasma. From 69 infants (aged <2 years) hospitalized for possible lower respiratory tract infections including RSV infection, we collected nasal fluid and plasma and determined the ECP concentrations. ECP concentrations in nasal fluid were significantly higher in patients with wheezing and/or bronchial rales than in patients without them (1733 ± 660 ng/mL vs 680 ± 450 ng/mL, p = 0.018), and those of the respiratory syncitial virus-infected group were significantly higher than those of the uninfected group (p = 0.04). Meanwhile, there was no significant difference in plasma ECP levels between patients with wheezing and patients without wheezing, and no significant difference between RSV-infected and other pathogen-infected patients. There were significant correlations between nasal fluid ECP concentrations and both neutrophil and eosinophil counts in the peripheral blood. Nasal fluid ECP concentrations are increased in infants with lower respiratory infections including RSV infection accompanied with wheezing. ECP probably originates from neutrophils as well as eosinophils migrated into airways. The monitoring of ECP concentration in nasal fluid may be useful for evaluating leukocyte (including eosinophils and neutrophils)-mediated airway inflammation during infancy and its severity.

Serum eosinophil granule proteins predict asthma risk in allergic rhinitis

Allergic rhinitis is a common disease, in which some patients will deteriorate or develop asthma. It is important to characterize these patients, thereby offering the possibility for prevention. This study evaluated eosinophil parameters as potential indicators of deteriorating allergic airway disease. The subjects of the study included all patients who suffered seasonal allergic rhinitis and had participated in a study 6 years earlier, in which blood eosinophils, serum eosinophil cationic protein (ECP) serum eosinophil peroxidase (EPO), nasal lavage ECP and nasal lavage EPO levels were measured. Patients in the present study were interviewed on occurrence of rhinitis symptoms during the last season, rhinitis outside season, asthma-like symptoms and asthma diagnosis, and were skin-prick tested for common aeroallergens. Eosinophil parameters from the study 6 years earlier were then tested for the ability to predict occurrence of new allergies, worsening of rhinitis and occurrence of asthma. Forty-four patients participated in the study. In four patients seasonal rhinitis symptoms had deteriorated, 10 had experienced perennial rhinitis symptoms, 14 reported asthma-like symptoms and seven had been diagnosed with asthma. Thirteen had developed additional sensitization. Patients developing asthma-like symptoms compared with patients with no such symptoms had significantly higher serum ECP (16.7 microg/l vs 8.2 microg/l; P < or = 0.01) and serum EPO (17.9 microg/l vs 8.8 microg/l; P < or = 0.05). Results were similar, considering patients diagnosed with asthma. Blood eosinophils and nasal lavage parameters were not related to development of asthma and asthma-like symptoms. No eosinophil parameter was related to deterioration of rhinitis or additional sensitization. Serum ECP and EPO in patients with seasonal rhinitis demonstrated a high predictive ability for later development of asthma.

Acute Upper and Lower Respiratory Effects in Wildland Firefighters

To assess acute respiratory effects experienced by wildland firefighters. We studied two Interagency Hotshot Crews with questionnaires, spirometry, and measurement of albumin, eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as indicators of inflammation in sputum and nasal lavage fluid. Assessments were made preseason, postfire, and postseason. Fifty-eight members of the two crews had at least two assessments. Mean upper and lower respiratory symptom scores were higher postfire compared to preseason (P < 0.001). The mean forced expiratory volume in 1 second was lower postfire compared to preseason (P < 0.001) and then recovered by postseason. Individual increases in sputum and nasal ECP and MPO from preseason to postfire were all significantly associated with postfire respiratory symptom scores. Wildland firefighting was associated with upper and lower respiratory symptoms and reduced forced expiratory volume in 1 second. Within individuals, symptoms were associated with increased ECP and MPO in sputum and nasal lavage fluid. The long-term respiratory health impact of wildland firefighting, especially over multiple fire seasons, remains an important concern.

Correlation of Quality of Life with Clinical Parameters and Eosinophilic Cation Protein Levels in Children with Allergic Rhinoconjunctivitis

Background: Systemic and mucosal roles of eosinophils in the pathogenesis of allergic rhinoconjunctivitis (AR) are known. The aim of this study was to investigate the relationship of clinical parameters and quality of life with eosinophilic cationic protein (ECP) in grass pollen-sensitive children with seasonal AR. Methods: This study included 31 children with AR and 18 healthy controls aged between 5 and 15 years. ECP levels in nasal lavage fluid and serum were measured. AR symptom scores were calculated and the pediatric rhinoconjunctivitis quality of life questionnaire (PRQLQ) was filled in for all patients. Results: Mean serum and nasal ECP levels (ng/ml) were significantly higher in the patient group (p < 0.05 for both). In the AR group, the mean clinical symptom score was 7.3 ± 2.2, while the total PRQLQ score, activity limitation, symptoms and emotional function domains were 2.5 ± 0.9, 3.0 ± 1.1, 2.5 ± 1.2 and 2.6 ± 1.1, respectively. The total clinical symptom score and disease duration showed a significant correlation with the total PRQLQ score (p = 0.00 and 0.003, respectively). However, neither nasal lavage nor serum ECP levels were significantly correlated with symptom score, duration of disease, PRQLQ total score or domains (p > 0.05 for all). Conclusion: These results may indicate the absence of a correlation between clinical status and quality of life and levels of ECP in tissues with allergic inflammation.

Mediator measurements after daily instillation of allergen: Increased IL-5 and decreased IFN-gamma

This study was designed to measure symptoms, IL-4, IL-5, IFN-gamma, and eosinophilic cationic protein (ECP) in nasal secretions from subjects experiencing an artificial allergy season and to look for evidence of priming. Clinically relevant allergen was administered intranasally out of season to 12 asymptomatic individuals with seasonal allergic rhinitis. These individuals were then randomized to receive allergen or saline daily for the next 7 days. Nasal secretions and scrapings of nasal epithelium were obtained at baseline (day 1), 24 hours after the initial allergen administration (day 2), and 24 hours after the last instillation of allergen or saline (day 9). Nasal symptom scores (p < 0.0002), IL-5 mRNA (p = 0.03), and ECP (p < 0.02) increased after receiving the first challenge (day 2 compared with day 1). In the six subjects randomized to receive seven sequential daily challenges with allergen, symptom scores remained elevated (p < 0.02), IL-5 protein increased (p = 0.02), and IFN-gamma (p = 0.02) levels decreased (day 9 compared with day 1). In the six subjects randomized to receive seven sequential daily challenges with placebo, symptom scores, IL-5, and IFN-gamma levels were not significantly different (day 9 compared with day 1). Compared with the findings at day 2 (n = 12), the treated subjects (n = 6) had no further increase in symptoms but did show a further increase in IL-5 (p = 0.01) and a decrease in IFN-gamma (p = 0.02) at day 9. Daily instillation of moderate doses of allergen intranasally is characterized by persistent symptoms, elevation of IL-5, and reduced levels of IFN-gamma.

Bronchial responsiveness in bakery workers: relation to airway symptoms, IgE sensitization, nasal indices of inflammation, flour dust exposure and smoking

Bronchial hyperresponsiveness (BHR) is common in bakery workers. The relation between bronchial responsiveness measured with a tidal breathing method and smoking, airway symptoms, IgE-sensitization, nasal indices of inflammation and flour dust exposure have been studied with bronchial responsiveness expressed as a continuous outcome. Bakery workers (n = 197) were subjected to interviews, questionnaires, allergy tests, workplace dust measurements and bronchial metacholine provocation. Eosinophil cationic protein (ECP) and alpha(2)-macroglobulin were measured in nasal lavage. Bronchial responsiveness was expressed as slope(conc), a measurement based on regressing the per cent reduction in FEV(1) at each provocation step. BHR expressed as slope(conc) was associated with smoking (P = 0.009), asthma symptoms at work (P = 0.001), and occupational IgE sensitization (P = 0.048). After adjusting for baseline lung function the association between BHR and IgE sensitization was no longer present. We demonstrated an association between nasal ECP and BHR (slope(conc) < 3: P = 0.012), but not to alpha(2)-macroglobulin in nasal lavage. No association was seen between BHR and current exposure level of flour dust, number of working years in a bakery or a history of dough-making. BHR is related to baseline lung function, work-related asthma symptoms, smoking and nasal eosinophil activity, but not to occupational IgE sensitization and current flour dust exposure when measured with metacholine provocation. The slope(conc) expression seems to be a useful continuous outcome in bronchial responsiveness testing.

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.

Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis

Allergic rhinitis is an IgE-mediated inflammatory disease of the nasal mucosa, which is usually diagnosed by typical symptoms, positive skin tests, and/or serum specific IgE antibodies to allergens. Despite suggestive symptoms of allergic rhinitis, some patients have a negative diagnostic test for atopy. To evaluate in the nose the inflammatory response, specific IgE to Dermatophagoides pteronyssinus (DP), and the response to a nasal allergen provocation test with DP (NAPT-DP), in patients with persistent nonallergic rhinitis (PNAR) compared with patients with persistent allergic rhinitis (PAR) and healthy controls. Fifty patients with PNAR, 30 with PAR to DP, and 30 healthy controls were studied by determining the nasal leukocyte-lymphocyte phenotype by flow cytometry (CD16, CD8, CD4, CD33, CD3, and CD45), nasal eosinophil cationic protein (ECP), albumin, total and specific IgE to DP, and NAPT-DP. The PNAR patients showed a similar leukocyte-lymphocyte phenotype in nasal lavage to the PAR patients and was different to the healthy controls. Within the PNAR group, 54% showed a positive NAPT-DP, with 22% of these having nasal specific IgE to DP. These data support the hypothesis that in persistent nonallergic rhinitis some patients may have local inflammation, nasal IgE production, and a positive response to a nasal allergen provocation test despite no evidence of systemic atopy. Further research is needed to evaluate the influence of other perennial allergens and/or immunologic mechanisms. The local production of IgE antibodies without systemic detection is a condition that should be considered in patients with PNAR.

Polyposis nasi - Besserung der Lebensqualität durch Leukotrien-Rezeptorantagonisten

Sulfido-Leukotrienes are important inflammatory mediators of bronchial asthma, intolerance of acetylsalicylic acid (ASA), polyposis nasi and allergic rhinitis. Receptorantagonists like Montelukast constitute a well-established asthma- and ASA intolerance-therapy. The aim of our study was to evaluate changes in patients Health-Related-Quality-of-Life (HRQL) during Montelukast-monotherapy of nasal polyposis. The study was performed in a prospective, double blind and placebo-controlled matter. The study included 30 patients of our ENT outpatient's dept. (77 % male, mean age 49 yrs), suffering from nasal polyposis grade II to IV. Polyps were endoscopically graded, nasal Eosinophilic Cationic Protein (ECP) was measured, and HRQL-score was taken prior to and four weeks after Montelukast-(0 - 0 - 10 mg) compared to placebo. An established HRQL-questionnaire - including 25 items, summarized in 6 symptom-groups - was used. Given was a symptom-score of 1 (not troubled) to 4 (extremely troubled). Patients treated with Montelukast improved their nasal symptoms (Delta HRQL-score 0.58 +/- 0.94, P < 0.01), practical problems (Delta HRQL-score 0.42 +/- 0.71, P < 0.05), headaches (Delta HRQL-score 0.38 +/- 0.56, P < 0.05), non-nasal symptoms (Delta HRQL-score 0.35 +/- 0.92, P < 0.05), sleep (Delta HRQL-score 0.26 +/- 0.71) and emotional problems (Delta HRQL-score 0.18 +/- 0.75). Intranasal ECP (Delta 210.67 ng/ml +/- 332.68) and polyp grading (Delta 0.72 +/- 1.77) tended to improve as well, but did not reach statistical significance. Patients treated with placebo revealed no significant changes neither in HRQL-score, ECP, nor polyp grading. Montelukast-therapy of nasal polyposis significantly improved patient's HRQL in 4 out of 6 symptom-groups. Measuring HRQL proofed to constitute a more sensitive tool than looking at eosinophilic parameters of inflammation or polyp size.