Outdoor pollen-related changes in lung function and markers of airway inflammation: A systematic review and meta-analysis.

BACKGROUND: Experimental challenge studies have shown that pollen can have early and delayed effects on the lungs and airways. Here, we qualitatively and quantitatively synthesize the evidence of outdoor pollen exposure on various lung function and airway inflammation markers in community-based studies. METHODS: Four online databases were searched: Medline, Web of Science, CINAHL and Google Scholar. The search strategy included terms relating to both exposure and outcomes. Inclusion criteria were human-based studies published in English that were representative of the community. Additionally, we only considered cross-sectional or short-term longitudinal studies which investigated pollen exposure by levels or season. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was conducted using random-effects models. RESULTS: We included 27 of 6551 studies identified from the search. Qualitative synthesis indicated associations between pollen exposure and predominantly type-2 inflammation in both the upper and lower airways, but little evidence for lung function changes. People with ever asthma and/or seasonal allergic rhinitis (SAR) were at higher risk of such airway inflammation. Meta-analysis confirmed a positive relationship between pollen season, eosinophilia and eosinophil cationic protein (ECP) in people with ever SAR but the results between studies were highly variable. Heterogeneity was reduced after further subgrouping by age, and the forest plots indicated that eosinophilic airway inflammation to outdoor pollen exposure increased with age. CONCLUSION: Among people with ever asthma and ever SAR, exposure to increased ambient pollen triggers type-2 upper and lower airway inflammation rather than a non-specific or innate inflammation. These findings can lead to the formulation of specific pollen immunotherapy for susceptible individuals. Future research should be directed towards investigating lagged associations and effect modifications using larger and more generalized populations. SYSTEMATIC REVIEW REGISTRATION: CRD42020146981 (PROSPERO).

Small airway dysfunction in patients with cough variant asthma: a retrospective cohort study.

BACKGROUND: Cough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness (BHR) and airway inflammatory subtypes between CVA and classic asthma (CA), and investigate the relationship between these markers to determine the accuracy as indicators of CVA. METHODS: A total of 825 asthmatic patients participated in the study and 614 were included. 614 patients underwent spirometry and a bronchial challenge with methacholine and 459 patients performed induction sputum cell test. RESULTS: The number of CVA patients showed less small airway dysfunction than those of CA patients (p < 0.005). The degree of small airways dysfunction was higher in the CA group compared with the CVA group (p < 0.001). Small airways dysfunction was severer in the eosinophilic airway inflammatory subtype compared with other subtypes (p < 0.05).The area under curve of MMEF, FEF50 and FEF75 (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD20 and 4.7% of sputum eosinophils was the best diagnostic value for CVA with an AUC of 0.582 and 0.575 (p = 0.001 and p = 0.005, respectively). CONCLUSIONS: The eosinophilic airway inflammatory subtype may be increased small airway dysfunction. The value of small airways, BHR and induction sputum cells in CVA prediction, which reflected significant, but not enough to be clinically useful.

Rho and Rac, but not ROCK, are required for secretion of human and mouse eosinophil-associated RNases.

BACKGROUND: Eosinophil-associated RNases (EARs) are stored preformed in eosinophil cytoplasmic secretory granules and have a key role in eosinophil effector functions in host defence and inflammatory disorders. However, the secretion mechanisms of EARs are poorly understood. OBJECTIVE: Our study aimed to understand the involvement of cytoskeleton machinery in EAR secretion. METHODS: Fresh human and mouse eosinophils were stimulated with CCL11, and the secretion of enzymatically active EARs was detected using an RNase activity assay. The involvement of cytoskeletal elements or microtubules was probed using specific inhibitors. RESULTS: We found that dynamic polymerization of microtubules and cytoskeletal elements, such as Rho and Rac, is required for chemokine-mediated EAR secretion from human and mouse eosinophils. However, inhibition of ROCK (Rho-associated protein kinase) increased EAR secretion in human and mouse eosinophils even in the absence of chemokine stimulation, suggesting ROCK negatively regulates EAR secretion. CONCLUSIONS: Collectively, these data suggest a cytoskeleton-dependent mechanism of EAR secretion from eosinophils, findings that are pertinent to host defence, allergy and other eosinophil-associated diseases.

Value of Exhaled Nitric Oxide (FeNO) And Eosinophilia During the Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Hospital Admission.

The aim of this study was to analyze whether FeNO levels in acute exacerbation of COPD (AECOPD) with hospital admission have better diagnostic value than eosinophilia in blood, and to evaluate its usefulness in predicting a better clinical response. An observational prospective study of patients with AECOPD was carried out. FeNO determinations were made on arrival at the emergency room (ER), at discharge and during stability 3-6 months after discharge. Co-morbidities, bronchodilators, inhaled (IGC) and systemic (SGC) glucocorticoids, eosinophils, systemic inflammation markers (procalcitonin, C-reactive protein), eosinophil cationic protein, and total IgE were collected. Fifty consecutive patients (92% men, mean age 75 ± 6 years) were included in this study. Phenotypes were 26% Asthma-COPD Overlap Syndrome (ACOS), 42% chronic bronchitis (CB) and 32% emphysema. ACOS patients showed significantly higher levels of FeNO (73 ppb) and eosinophils (508 cells/mm3) than the rest (CB: 23 ppb, 184 cells/mm3, emphysema: 27 ppb, 159 cells/mm3; p < 0.05). A significant correlation between FeNO levels measured in ER and eosinophils was observed (r = 0.7; p < 0.001), but not at discharge or in stable phase. No significant association was found with parameters of systemic inflammation and mean stay. In conclusion, the determination of FeNO in AECOPD does not offer advantages over the evaluation of eosinophilia. These parameters rise at arrival in ER, descend at discharge, and remain unchanged in the stable phase. Both present similar diagnostic utility and are able to better identify the ACOS phenotype, which helps select a population that could benefit from a glucocorticoids therapy.

Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study.

RATIONALE: Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood. OBJECTIVE: To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects. METHODS: 18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points. RESULTS: Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells. CONCLUSION: Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust. TRIAL REGISTRATION NUMBER: NCT01792232.

Seasonal Local Allergic Rhinitis in Areas With High Concentrations of Grass Pollen.

BACKGROUND: Local allergic rhinitis (LAR) is a phenotype of allergic rhinitis characterized by the presence of a localized immune response in the nasal mucosa of patients with negative skin prick test (SPT) results and undetectable serum specific IgE (sIgE). It unknown whether LAR is limited to areas with low or moderate aeroallergen exposure. OBJECTIVE: To explore the presence of LAR and the clinical and immunological characteristics of this entity in geographic areas with high grass pollen loads. METHODS: A cross-sectional observational study was carried out in 2 hospitals in central Spain (Madrid and Ciudad Real). Sixty-one patients with seasonal rhinitis and negative SPT results and undetectable serum sIgE were evaluated using a clinical questionnaire, determination of serum total IgE, and a nasal allergen provocation test (NAPT) with Phleum species. The response to NAPT was monitored using assessment of nasal symptoms, acoustic rhinometry, and determination of sIgE, tryptase, and eosinophil cationic protein in the nasal cavity. RESULTS: Seasonal LAR was detected in 37 patients (61%) using the techniques described above. Eleven percent of patients with LAR were adolescents or children, and 14% reported onset of rhinitis in childhood. Most patients reported persistent-moderate seasonal nasal symptoms, and 41% reported worsening of the disease during the last 2 years. Conjunctivitis was the most common comorbidity, affecting 95% of cases. CONCLUSIONS: LAR to grass pollen is relevant in patients with seasonal symptoms indicative of allergic rhinitis but with a negative skin test result who live in areas with high allergenic pollen loads. This entity should be included the differential diagnosis of rhinitis.

IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (NPs) in Western populations is associated with TH2 cytokine polarization. IL-25, an IL-17 family cytokine, was recently reported to induce TH2-type immune responses and to contribute to several allergic diseases, such as atopic dermatitis and asthma. However, the role of IL-25 in Asian patients with nasal polyposis remains unclear. OBJECTIVE: We sought to determine the role of IL-25 in Asian patients with nasal polyposis and CRS. METHODS: We investigated IL-25 expression and its cellular origins in NPs of human subjects using immunohistochemistry (IHC), quantitative RT-PCR, and ELISA of NP tissues. Correlations between IL-25 expression and expression of other inflammatory markers in NP tissues were also explored. Anti-IL-25 neutralizing antibody was administered in an ovalbumin- and staphylococcal enterotoxin B-induced murine NP model to confirm the function of IL-25 during nasal polypogenesis. RESULTS: IL-25 expression was upregulated in NP mucosa from patients with CRS with NPs compared with uncinate process tissue from control subjects and those with CRS without NPs. Overexpression of epithelial IL-25 was confirmed by using IHC, and double IHC staining showed that tryptase-positive cells were one of the main sources of IL-25 among immune cells. Furthermore, IL-17 receptor B levels were also increased in immune cells of patients with NPs compared with those in control subjects. In NPs IL-25 mRNA expression positively correlated with the expression of several inflammatory markers, including T-box transcription factor, RAR-related orphan receptor C, GATA3, eosinophil cationic protein, TGF-ß1, and TGF-ß2. IL-25 was more abundant in the murine NP model compared with control mice, and similar correlations between IL-25 and inflammatory markers were observed in murine models. Anti-IL-25 treatment reduced the number of polyps, mucosal edema thickness, collagen deposition, and infiltration of inflammatory cells, such as eosinophils and neutrophils. This treatment also inhibited expression of local inflammatory cytokines, such as IL-4 and IFN-γ. Furthermore, expression of CCL11, CXCL2, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in the nasal mucosa was suppressed in the anti-IL-25-treated group. CONCLUSION: Our results suggest that IL-25 secreted from the sinonasal epithelia and infiltrating mast cells plays a crucial role in the pathogenesis of CRS with NPs in Asian patients. In addition, our results suggest the novel possibility of treating nasal polyposis with anti-IL-25 therapy.

Exploring new biological functions of amyloids: bacteria cell agglutination mediated by host protein aggregation.

Antimicrobial proteins and peptides (AMPs) are important effectors of the innate immune system that play a vital role in the prevention of infections. Recent advances have highlighted the similarity between AMPs and amyloid proteins. Using the Eosinophil Cationic Protein as a model, we have rationalized the structure-activity relationships between amyloid aggregation and antimicrobial activity. Our results show how protein aggregation can induce bacteria agglutination and cell death. Using confocal and total internal reflection fluorescence microscopy we have tracked the formation in situ of protein amyloid-like aggregates at the bacteria surface and on membrane models. In both cases, fibrillar aggregates able to bind to amyloid diagnostic dyes were detected. Additionally, a single point mutation (Ile13 to Ala) can suppress the protein amyloid behavior, abolishing the agglutinating activity and impairing the antimicrobial action. The mutant is also defective in triggering both leakage and lipid vesicle aggregation. We conclude that ECP aggregation at the bacterial surface is essential for its cytotoxicity. Hence, we propose here a new prospective biological function for amyloid-like aggregates with potential biological relevance.

Diesel exhaust exposure and nasal response to attenuated influenza in normal and allergic volunteers.

RATIONALE: Diesel exhaust enhances allergic inflammation, and pollutants are associated with heightened susceptibility to viral respiratory infections. The effects of combined diesel and virus exposure in humans are unknown. OBJECTIVES: Test whether acute exposure to diesel modifies inflammatory responses to influenza virus in normal humans and those with allergies. METHODS: We conducted a double-blind, randomized, placebo-controlled study of nasal responses to live attenuated influenza virus in normal volunteers and those with allergic rhinitis exposed to diesel (100 µg/m(3)) or clean air for 2 hours, followed by standard dose of virus and serial nasal lavages. Endpoints were inflammatory mediators (ELISA) and virus quantity (quantitative reverse-transcriptase polymerase chain reaction). To test for exposure effect, we used multiple regression with exposure group (diesel vs. air) as the main explanatory variable and allergic status as an additional factor. MEASUREMENTS AND MAIN RESULTS: Baseline levels of mediators did not differ among groups. For most postvirus nasal cytokine responses, there was no significant diesel effect, and no significant interaction with allergy. However, diesel was associated with significantly increased IFN-γ responses (P = 0.02), with no interaction with allergy in the regression model. Eotaxin-1 (P = 0.01), eosinophil cationic protein (P < 0.01), and influenza RNA sequences in nasal cells (P = 0.03) were significantly increased with diesel exposure, linked to allergy. CONCLUSIONS: Short-term exposure to diesel exhaust leads to increased eosinophil activation and increased virus quantity after virus inoculation in those with allergic rhinitis. This is consistent with previous literature suggesting a diesel "adjuvant" effect promoting allergic inflammation, and our data further suggest this change may be associated with reduced virus clearance.Clinical trial registered with www.clinicaltrials.gov (NCT00617110).

Cytokine expression in human dermal fibroblasts stimulated with eosinophil cationic protein measured by protein array.

BACKGROUND: Eosinophil cationic protein (ECP) was reported previously to be involved in allergic inflammation with cytotoxic activity. On the other hand, recent studies showed that ECP did not induce cell death but inhibited the growth of cancer-derived cells. Our previous study indicated that human ECP enhanced differentiation of rat neonatal cardiomyocytes and stress fiber formation in Balb/c 3T3 mouse fibroblasts, while the effects of human ECP on human fibroblasts are unknown. OBJECTIVE: The present study was performed to determine the effects of human ECP on cytokine expression in human fibroblasts by protein array. METHODS: The effects of recombinant human ECP (rhECP) on normal human dermal fibroblasts (NHDF) were examined by assaying cell growth. Furthermore, cytokine expression of NHDF stimulated by ECP, which could influence cell growth, was evaluated by protein array. RESULTS: ECP was not cytotoxic but enhanced the growth of NHDF. The peak rhECP concentration that enhanced the cell counts by 1.56-fold was 100 ng/mL, which was significantly different from cultures without ECP stimulation (ANOVA/ Scheffe's test, P < 0.05). Array analyses indicated that ciliary neurotrophic factor (CNTF), neutrophil-activating peptide (NAP)-2, and neurotrophin (NT)-3 were significantly upregulated in NHDF stimulated with 100 ng/mL ECP compared to those without stimulation. CONCLUSION: ECP is not cytotoxic but enhances the growth of NHDF. CNTF, NAP-2, and NT-3 were suggested to be involved in enhancing the growth of NHDF. These findings will contribute to determination of the role of ECP in allergic inflammation.

Structural determinants of the eosinophil cationic protein antimicrobial activity.

Antimicrobial RNases are small cationic proteins belonging to the vertebrate RNase A superfamily and endowed with a wide range of antipathogen activities. Vertebrate RNases, while sharing the active site architecture, are found to display a variety of noncatalytical biological properties, providing an excellent example of multitask proteins. The antibacterial activity of distant related RNases suggested that the family evolved from an ancestral host-defence function. The review provides a structural insight into antimicrobial RNases, taking as a reference the human RNase 3, also named eosinophil cationic protein (ECP). A particular high binding affinity against bacterial wall structures mediates the protein action. In particular, the interaction with the lipopolysaccharides at the Gram-negative outer membrane correlates with the protein antimicrobial and specific cell agglutinating activity. Although a direct mechanical action at the bacteria wall seems to be sufficient to trigger bacterial death, a potential intracellular target cannot be discarded. Indeed, the cationic clusters at the protein surface may serve both to interact with nucleic acids and cell surface heterosaccharides. Sequence determinants for ECP activity were screened by prediction tools, proteolysis and peptide synthesis. Docking results are complementing the structural analysis to delineate the protein anchoring sites for anionic targets of biological significance.

YKL-40 in induced sputum after allergen bronchial provocation in atopic asthma.

BACKGROUND: Serum chitinase-like proteins such as YKL-40 in asthmatic patients are known to positively correlate with disease severity but controversy remains regarding their role. The allergen bronchial provocation test (ABPT) can induce allergic airway inflammation in individuals with atopic asthma. OBJECTIVE: To evaluate the induction and kinetics of YKL-40 during allergen-induced airway inflammation in atopic asthmatics. METHODS: Thirteen patients were enrolled from May to November 2008. They all underwent ABPT with Dermatophagoides farinae crude extract. Induced sputums (IS) and serum were collected 3 times: 7 days before ABPT (baseline), 7 hours after ABPT, and 24 hours after ABPT. We examined the cytology of induced sputum (IS) and measured levels of YKL-40, interleukin (IL) 4, IL-5, IL-13, IL-33, tumor necrosis factor (TNF) alpha, and eosinophilic cationic protein (ECP) in IS and/or serum. RESULTS: Following ABPT, total inflammatory cells, eosinophils, and neutrophils increased in a time-dependent manner in IS. YKL-40 levels were increased in IS but not in serum at 7 or 24 hours after ABPT (P=.011 and P=.006, respectively). Similarly to YKL-40, IL-5 and ECP levels were also increased in IS at 7 and 24 hours after ABPT (P=.011 for IL-5 and P=.006 for ECP). Overall, YKL-40 levels were well correlated with ECP levels in IS (p=0.576, P<.001). CONCLUSIONS: YKL-40 levels increased immediately in IS but not in the serum of atopic asthmatics. The correlation between YKL-40 levels and ECP in IS suggests that YKL-40 may play a pathophysiologic role in human atopic asthma.

Biology of the eosinophil.

In this review, we aim to put in perspective the biology of a multifunctional leukocyte, the eosinophil, by placing it in the context of innate and adaptive immune responses. Eosinophils have a unique contribution in initiating inflammatory and adaptive responses, due to their bidirectional interactions with dendritic cells and T cells, as well as their large panel of secreted cytokines and soluble mediators. The mechanisms and consequences of eosinophil responses in experimental inflammatory models and human diseases are discussed.

Eosinophilic gastroenteritis due to allergy to cow's milk.

Eosinophilic gastroenteritis is an uncommon condition that is characterized by infiltration of the gastrointestinal tract by eosinophils. We report the case of a 24-year-old woman who presented 4 episodes of eosinophilic gastroenteritis. Skin prick tests and patch tests with different allergens were all negative. The patient's eosinophil cationic protein (ECP) level was very high. Given that one of the most common causes of this condition is allergy to cow's milk, ECP levels were determined during a diet with and without cow's milk. ECP levels were considerably elevated during the diet with milk, although they returned to normal values several months after milk was withdrawn. The favorable clinical outcome and normalization of ECP levels point to a very probable association with cow's milk in the eosinophilic gastroenteritis presented by our patient.

Exhaled nitric oxide is associated with allergic inflammation in children.

Exhaled nitric oxide (eNO) has been proposed as a noninvasive marker of airway inflammation in asthma. In asthmatic patients, exhaled NO levels have been shown to relate with other markers of eosinophilic recruitment, which are detected in blood, sputum, bronchoalveolar lavage fluid and bronchial biopsy samples. The purpose of this study was to assess the possible relationship between eNO and allergic inflammation or sensitization in childhood asthma and allergic rhinitis. Subjects consisted of 118 asthmatic children, 79 patients with allergic rhinitis, and 74 controls. Their age ranged from 6 to 15 yr old. eNO level, peripheral blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE level and specific IgE levels were measured. Methacholine challenge test and allergic skin prick test for common allergens were performed in all subjects. Atopic group (n = 206, 44.48 ± 30.45 ppb) had higher eNO values than non-atopic group (n = 65, 20.54 ± 16.57 ppb, P < 0.001). eNO level was significantly higher in patients with asthma (42.84 ± 31.92 ppb) and in those with allergic rhinitis (43.59 ± 29.84 ppb) than in healthy controls (27.01 ± 21.34 ppb, P < 0.001) but there was no difference between asthma and allergic rhinitis group. eNO also had significant positive correlations with Dermatophagoides pteronyssinus IgE level (r = 0.348, P < 0.001), Dermatophagoides farinae IgE level (r = 0.376, P < 0.001), and the number of positive allergens in skin prick test (r = 0.329, P = 0.001). eNO had significant positive correlations with peripheral blood eosinophil count (r = 0.356, P < 0.001), serum total IgE level (r = 0.221, P < 0.001), and ECP (r = 0.436, P < 0.001). This study reveals that eNO level is associated with allergic inflammation and the degree of allergic sensitization.

Effects of antisense interleukin-5 gene transferred by recombinant adeno-associated virus to allergic rats.

BACKGROUND AND OBJECTIVE: The accumulation of eosinophils in airways is an important characteristic of asthma. The process is primarily mediated by interleukin-5 (IL-5) secreted by Th2 lymphocytes. This study explored a new approach to asthma therapy in which allergic rats were transfected with the IL-5 antisense gene delivered by the recombinant adeno-associated virus (rAAV-ASIL-5). METHODS: The viral vector rAAV-ASIL-5 was constructed and the IL-5 antisense gene transfected into allergic rats. The levels of IL-5, IgE, eotaxin and eosinophilic cationic protein (ECP) in sera and bronchoalveolar lavage fluid (BALF) were measured by ELISA. The inflammatory responses in lung tissues were evaluated by histological study. RESULTS: The levels of IL-5 protein in serum and BALF were significantly decreased in the allergic rats treated with rAAV-ASIL-5 (P < 0.05). Serum ovalbumin-specific IgE was reduced in treated rats compared with untreated rats (P < 0.05). rAAV-ASIL-5 treatment also reduced eosinophils in the peripheral blood and BALF, as well as the ECP and eotaxin levels in serum and BALF (P < 0.05). There was significantly less inflammation in the lungs of rAAV-ASIL-5-treated rats than in those of untreated rats. No obvious pathological damage to the kidneys and livers of the rats treated with rAAV was observed. CONCLUSIONS: Treatment with rAAV-ASIL-5 inhibited the accumulation of eosinophils and airway inflammation in the rat model of allergic asthma by suppressing IL-5 production. These results suggest that rAAV-ASIL-5-based gene therapy may be used for the treatment of allergic asthma.

Local allergic rhinitis: concept, clinical manifestations, and diagnostic approach.

Local allergic rhinitis is a newly described type of rhinitis involving nasal production of specific immunoglobulin (slg) E antibodies in the absence of atopy. It can affect patients previously diagnosed with non-allergic rhinitis. Evidence for this entity is supported by clinical symptoms, local production of slgE, a type 2 helperT cell inflammatory pattern in nasal secretions during natural exposure to aeroallergens, and a positive response to nasal allergen provocation with local nasal production of slgE to aeroallergens, tryptase, and eosinophil cationic protein (ECP). Based on these new findings, an advanced diagnostic approach is proposed in patients with symptoms suggestive of allergic rhinitis but negative results in skin prick test and serum slgE determination. Detection of local slgE in nasal secretions during natural exposure to aeorallergens and a positive nasal allergen provocation test with local production of tryptase, ECP, and slgE are useful for detecting patients with local allergic rhinitis.

Nasal inflammatory mediators and specific IgE production after nasal challenge with grass pollen in local allergic rhinitis.

BACKGROUND: Evidence exists of a new form of local allergic rhinitis (LAR) with local production of specific IgE (sIgE) and a positive response to nasal allergen provocation test (NAPT) in patients previously diagnosed with idiopathic rhinitis. However, the immunologic mechanisms involved are still poorly understood. OBJECTIVE: We explored the involvement of nasal sIgE, eosinophil, and mast cell activation in the response to NAPT with grass pollen (NAPT-grass) in a group of patients already classified with LAR. METHODS: Out-of-spring NAPT-grass was performed in 30 patients with LAR and 30 healthy controls. Nasal symptoms, acoustic rhinometry, and nasal lavage were performed at baseline and 15 minutes and 1, 6, and 24 hours post-NAPT. Tryptase, eosinophilic cationic protein (ECP), and total and sIgE to grass pollen were measured in nasal lavage by immunoassays. RESULTS: NAPT-grass was positive in all patients with LAR. We detected significant increases of tryptase and ECP in 40% and 43%, respectively, at 15 minutes and 1, 6, and 24 hours post-NAPT compared with baseline (P < .05). sIgE was increased in 30%, with significant increases at 1 and 6 hours (P < .05) and 24 hours (P = .002) post-NAPT. The maximum release of tryptase was detected 15 minutes after NAPT, whereas the maximum release of ECP and sIgE was detected 24 hours after challenge. NAPT-grass was negative in all healthy controls, with no increase in tryptase, ECP, total IgE, or sIgE. CONCLUSION: These results demonstrate that patients with LAR had local production of sIgE and mast cell/eosinophil activation induced by nasal exposure to grass pollen.