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Background: Exposure to mosquitoes in the Tropics is perennial, and their somatic and saliva antigens have shown IgE binding capacity, although it is not clear whether this is due to cross-reactivity or primary sensitization. Inhalation of these allergens could trigger an allergic response. Objective: The aim of the study was to evaluate the clinical relevance of sensitization to Aedes aegypti in a group of patients with allergic rhinitis. Methods: A cross-sectional study with allergic rhinitis subjects and healthy controls sensitized to mosquito extract was performed. Sensitization to mosquito and house dust mites was evaluated using skin prick test (SPT) and antibody determination by ELISA. Nasal provocation test (NPT) with whole-body extract was used to determine clinical relevance. Results: Allergic rhinitis patients were more sensitized to mosquito extract than controls with (+) SPT (66.6% vs. 7.6%). From these (+) SPT patients, 44.5% had (+) NPT, and just two (11%) presented mono-sensitization to mosquito. Antibody reactivity was similar between patients and controls; however, (+) NPT patients showed a tendency to had higher levels of IgE and IgG4. Discussion: Mosquitoes are perennial in most tropical areas, and their body allergens could be associated with respiratory allergies. [ABSTRACT FROM AUTHOR]

Asthma is a heterogeneous disease in terms of both phenotype and response to therapy. Therefore, there is a great need for clinically applicable tools allowing for improved patient classification, and selection for specific management approaches. Some interventions are highly helpful in selected patients (e.g., allergen immunotherapy or aspirin desensitization), but they are costly and/or difficult to implement. Currently available biomarkers measurable in peripheral blood or exhaled air display many limitations for asthma phenotyping and cannot identify properly the specific triggers of the disease (e.g., aeroallergens or NSAID). The united airway concept illustrates the relevant epidemiological and pathophysiological links between the upper and lower airways. This concept has been largely applied to patient management and treatment, but its diagnostic implications have been less often explored. Of note, a recent document by the European Academy of Allergy and Clinical Immunology proposes the use of nasal allergen challenge to confirm the diagnosis of allergic asthma. Similarly, the nasal challenge with lysine acetylsalicylate (L-ASA) can be used to identify aspirin-sensitive asthma patients. In this review, we will summarize the main features of allergic asthma and aspirin-exacerbated respiratory disease and will discuss the methodology of nasal allergen and L-ASA challenges with a focus on their capacity to phenotype the inflammatory disease affecting both the upper and lower airways. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis is characterized by rhinorrhea, nasal congestion, sneezing and nasal pruritus. Group 2 innate lymphoid cells (ILC2s), CD4+ T cells and eosinophils in nasal mucosa are increased significantly after nasal allergen challenge (NAC). Effects of intranasal corticosteroids (INCS) on ILC2s remain to be investigated. Methods: Subjects (n = 10) with allergic rhinitis and mild asthma were enrolled in a single‐blind, placebo‐controlled, sequential treatment study and treated twice daily with intranasal triamcinolone acetonide (220 µg) or placebo for 14 days, separated by a 7‐day washout period. Following treatment, subjects underwent NAC and upper airway function was assessed. Cells from the nasal mucosa and blood, sampled 24 h post‐NAC, underwent flow cytometric enumeration for ILC2s, CD4+ T and eosinophil progenitor (EoPs) levels. Cell differentials and cytokine levels were assessed in nasal lavage. Results: Treatment with INCS significantly attenuated ILC2s, IL‐5+/IL‐13+ILC2s, HLA‐DR+ILC2s and CD4+ T cells in the nasal mucosa, 24 h post‐NAC. EoP in nasal mucosa was significantly increased, while mature eosinophils were significantly decreased, 24 h post‐NAC in INCS versus placebo treatment arm. Following INCS treatment, IL‐2, IL‐4, IL‐5 and IL‐13 were significantly attenuated 24 h post‐NAC accompanied by significant improvement in upper airway function. Conclusion: Pre‐treatment with INCS attenuates allergen‐induced increases in ILC2s, CD4+ T cells and terminal differentiation of EoPs in the nasal mucosa of allergic rhinitis patients with mild asthma, with little systemic effect. Attenuation of HLA‐DR expression by ILC2s may be an additional mechanism by which steroids modulate adaptive immune responses in the upper airways. [ABSTRACT FROM AUTHOR]

Bovine viral diarrhea is a widespread and economically important viral disease for livestock which can cause clinically diverse manifestations. The number of established BVDV subgenotypes has increased, not only the serological relationships of recently described subgenotypes but virulence and pathogenic characteristics have not yet been mostly elaborated. The dominant BVDV subgenotype in Turkiye was elaborated to be BVDV-1 l, that involves more than half of field strains and there is no scientific data to identify the pathogenicity of this strain so far. This study investigated the pathogenicity of a selected field strain (TR-72) from subgenotype BVDV-1 l. Experimental infection was implemented by intranasal inoculation of the strain TR-72 (10 ×105.5) to four young calves which were previously not vaccinated and were free both for BVDV antibodies and antigens. Clinical changes as well as blood parameters, body temperature, and viremia were monitored for 14 days. Only mild clinical signs associated with respiratory signs of BVDV infection were observed. Detected clinical signs included nasal discharge, conjunctivitis, cough, fatigue, high rectal temperature reaching 40.7 ℃, and white blood cell counts depression started from the 2nd day and 40.4% decreased between the 12th and 14th days post-infection (poi). The presence of viremia was investigated by virus isolation, RT-PCR, and real-time RT-PCR from blood samples. The efficiency of experimental infection was established not only by observed clinical signs but also by virus isolation from blood leukocytes between the 5th and 8th days poi., virus detection was obtained by real-time PCR between the 3rd − 13th days poi. Besides, the recorded mild clinical signs, high fever, long duration of viremia , and high decrease in blood parameters obtained in this study, it was shown that the noncytopathogenic BVDV-1 l strain TR-72 has a moderate virulence in naïve cattle. • Experimental infection was implemented by intranasal inoculation of the BVDV-1 l strain TR-72 to four young calves. • Blood parameters, body temperature, viremia, and virus shedding were monitored for 14 days. • Conjunctivitis, cough, fatigue, high rectal temperature reaching 40.7 ℃ and WBC depression above 40.4%. • Virus detection was achieved by real-time PCR between the 3rd − 13th days poi. • Recorded parameters showed that the BVDV-1 l strain TR-72 has a moderate virulence and can be used as a challenge virus. [ABSTRACT FROM AUTHOR]

Asthma is a heterogeneous disease in terms of both phenotype and response to therapy. Therefore, there is a great need for clinically applicable tools allowing for improved patient classification, and selection for specific management approaches. Some interventions are highly helpful in selected patients (e.g., allergen immunotherapy or aspirin desensitization), but they are costly and/or difficult to implement. Currently available biomarkers measurable in peripheral blood or exhaled air display many limitations for asthma phenotyping and cannot identify properly the specific triggers of the disease (e.g., aeroallergens or NSAID). The united airway concept illustrates the relevant epidemiological and pathophysiological links between the upper and lower airways. This concept has been largely applied to patient management and treatment, but its diagnostic implications have been less often explored. Of note, a recent document by the European Academy of Allergy and Clinical Immunology proposes the use of nasal allergen challenge to confirm the diagnosis of allergic asthma. Similarly, the nasal challenge with lysine acetylsalicylate (L-ASA) can be used to identify aspirin-sensitive asthma patients. In this review, we will summarize the main features of allergic asthma and aspirin-exacerbated respiratory disease and will discuss the methodology of nasal allergen and L-ASA challenges with a focus on their capacity to phenotype the inflammatory disease affecting both the upper and lower airways.

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Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the interaction between inflammatory cells and the neurogenic response, which is gender- related, and which may affect symptom profiles after challenges. Different regulation of neurogenic inflammation in females may have impact on symptoms and endotyping in respiratory disorders, not only in allergic rhinitis, but also asthma, chronic rhinosinusitis and irritant -induced cough. [ABSTRACT FROM AUTHOR]

Nasal and ocular challenges facilitate the evaluation of subjective and objective responses to defined allergen or irritant exposure. Nasal and ocular allergen challenges are the gold standard to diagnose allergic rhinitis and conjunctivitis, respectively, and aid in the evaluation of novel therapies in clinical trials. Additionally, nasal and ocular allergen challenges might help identify medically relevant allergens in clinical practice. Nonspecific or irritant challenges evaluate mucosal hyperreactivity. Direct mucosal challenges, which can be performed in an office or research setting, expose the participant to higher allergen doses than common in the natural environment. Park studies and environmental chambers, which are most practical in clinical trials, more closely simulate natural allergen exposure. International consensus guidelines for nasal and ocular challenges do not exist. Therefore the positivity criteria, methodologies, and extract or allergen preparations used in challenges vary in the literature. Regardless of these limitations, nasal and ocular challenges are helpful clinical and research tools for nasal and ocular diseases. [ABSTRACT FROM AUTHOR]

Background Low-molecular-weight ( LMW) and high-molecular-weight ( HMW) agents have been recognized as causes of occupational rhinitis ( OR). Immunological mechanisms underlying OR differ according to the type of exposure. While HMW agents act mainly through IgE-mediated mechanisms, LMW agents appear to act through both immunological and non-immunological mechanisms. Objective The objective of this study was to identify potential differences in the upper airways inflammatory response after exposure to LMW and HMW agents by specific inhalation challenge test ( SIC). Methods Nasal lavage ( NL) samples from 20 subjects who were exposed to HMW (n = 10, Group I) and LMW (n = 10, Group II) at their workplaces were collected after SIC with control and specific occupational agents. These samples were analysed for 47 inflammatory markers using multiplex bead technology. Results After exposure to specific agent, Group I exhibited higher concentrations of the following proteins compared to Group II: fibrinogen (median (interquartile range) Group I: 0.09 (0.00) μg/mL, Group II: 0.04 (0.05) μg/mL, P = .05); haptoglobin (Group I: 0.86 (0.01) μg/mL, Group II: 0.14 (0.20) μg/mL, P = .02); vascular cell adhesion molecule-1 ( VCAM-1) (Group I: 0.34 (0.67) ng/mL, Group II: 0.11 (0.11) ng/mL, P = .01); vascular endothelial growth factor ( VEGF) (Group I: 157.0 (154.0) pg/mL, Group II: 98.0 (20.25) pg/mL, P = .01); and vitamin D ( VDBP) (Group I: 0.06 (0.13) μg/mL, Group II: 0.03 (0.03) μg/mL, P = .04). No statistically significant differences in proteins profiles were observed between the groups after exposure to control agent. Also, subjects exposed to HMW agents showed a significant increase in NL levels of C-reactive protein compared to control-day exposure. Conclusions and clinical relevance Exposure to HMW and LMW agents by SIC induced a differential nasal airway response including acute-phase reactants proteins (fibrinogen, haptoglobin and CRP), cell adhesion molecules ( VCAM-1), endothelial growth factors ( VEGF) and VDBP. [ABSTRACT FROM AUTHOR]

Background. Bilateral nasal allergen provocation usually produces more pronounced obstruction of one nasal passage. It was found that this could be related to the stage of the nasal cycle before the provocation. objective. To discover whether the stage of the nasal cycle is decisive for asymmetry in congestive response observed during bilateral allergen nasal provocation. methods. Two bilateral nasal allergen provocations were performed in a group of 26 pollen-sensitive volunteers. Acoustic rhinometry measurements were taken during the nasal cycle, and then after the provocation. A cross-sectional area at the level of the inferior turbinate (CSA-2) was measured. Consecutive challenges were performed in the opposite phase of the nasal cycle: the side which had been wide just before the first challenge, was narrow before the second provocation. results. Asymmetry in CSA-2 reduction between the nasal passages was observed in most cases. Significant difference was observed between mean CSA-2 reduction rate (reactivity) of the side that responded with greater congestion, and the opposite side. No significant difference was found in mean CSA-2 reduction rate between the side which was narrow, and the side which was wide before provocation. conclusions. Asymmetry of congestive response during bilateral nasal allergen provocation is not dependent on the stage of the nasal cycle preceding the challenge.

Objective: Determine if the middle ear transmucosal nitrous oxide (N2O) exchange rate is affected by nasal inflammation caused by topical application of histamine. Methods: In a randomized, double-blind, crossover study, 20 adults were challenged intranasally with histamine (5 mg) and placebo on separate occasions. At each session, the subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes, 50% N2O:50% O2 for 20 minutes, and 100% O2 for 10 minutes. Throughout, heart rate, blood pressure, and blood O2 saturation were monitored, and bilateral middle ear pressure was recorded by tympanometry every minute. The primary outcome measure was the slope of the middle ear pressure-time function for the 50% N2O:50% O2 breathing period, which is a measure of the transmucosal N2O exchange-constant. The effects of challenge substance, session, and period on the measured vital signs and of treatment, session, ear disease history, and test ear on the pressure-time slopes were evaluated using repeated measures ANOVAs. Results: The post-challenge total symptom score and the slope of the middle ear pressure-time function were greater after histamine when compared to placebo challenge. Of the signs, only heart rate was affected, responding to challenge substance and study period. Conclusion: The transmucosal N2O exchange rate for the middle ear is increased during inflammation caused by nasal histamine exposure. [ABSTRACT FROM AUTHOR]

Background Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances has not been investigated to date. Objective To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet- APE < 3 kDa) on the human allergic immune response in vivo. Methods Birch and grass pollen allergic individuals underwent skin prick testing with allergen alone, allergen plus Bet- APE < 3 kDa, or allergen plus pre-identified candidate substances from low molecular pollen fraction. Nasal allergen challenges were performed in non-atopic and pollen allergic individuals using a 3 day repeated threshold challenge battery. Subjects were either exposed to allergen alone or to allergen plus Bet- APE< 3 kDa. Local cytokine levels, nasal secretion weights, nasal congestion and symptom scores were determined. Results Skin prick test reactions to pollen elicited larger weals when allergens were tested together with the low molecular weight compounds from pollen. Similar results were obtained with candidate pollen-associated lipid mediators. In nasal lining fluids of allergic patients challenged with allergen plus Bet- APE < 3 kDa, IL-8 and IgE was significantly increased as compared to allergen-only challenged patients. These patients also produced increased amounts of total nasal secretion and reported more severe rhinorrhea than the allergen-only challenged group. Conclusions Low molecular compounds from pollen enhance the allergen specific immune response in the skin and nose. They are therefore of potential clinical relevance in allergic patients. [ABSTRACT FROM AUTHOR]

Occupational rhinitis is characterized by nasal congestion, rhinorrhea, nasal itching, and/or sneezing that occur secondary to exposures in the workplace. This disease can be classified into allergic or nonallergic subgroups based upon the underlying disease pathogenesis as well as the type of causative agent. While the true prevalence of occupational rhinitis is unknown, there are certain professions and occupational exposures that place workers at a higher risk for developing the disease. Additionally, occupational rhinitis can be associated with occupational asthma and upper airway symptoms may precede those of the lower respiratory tract. Taken together, occupational rhinitis is an important disease for study given its medical as well as socioeconomic implications. This review will focus on the classification of occupational rhinitis as well the prevalence, diagnosis, and treatment strategies. [ABSTRACT FROM AUTHOR]

Exposure to welding fumes is a recognized respiratory hazard. Occupational asthma but not occupational rhinitis has been documented in workers exposed to steel welding fumes. We report a 26-year-old male with work-related rhinitis symptoms as well as lower airways symptoms suggestive of occupational asthma and metal fume fever associated with exposure to steel welding fumes. The diagnosis of occupational rhinitis was confirmed by specific inhalation challenge. Am. J. Ind. Med. 57:1299-1302, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background. Bilateral nasal allergen provocation usually produces more pronounced obstruction of one nasal passage. It was found that this could be related to the stage of the nasal cycle before the provocation. Objective. To discover whether the stage of the nasal cycle is decisive for asymmetry in congestive response observed during bilateral allergen nasal provocation. Methods. Two bilateral nasal allergen provocations were performed in a group of 26 pollen-sensitive volunteers. Acoustic rhinometry measurements were taken during the nasal cycle, and then after the provocation. A cross-sectional area at the level of the inferior turbinate (CSA-2) was measured. Consecutive challenges were performed in the opposite phase of the nasal cycle; the side which had been wide just before the first challenge, was narrow before the second provocation. : Results. Asymmetry in CSA-2 reduction between the nasal passages was observed in most cases. Significant difference was observed between mean CSA-2 reduction rate (reactivity) of the side that responded with greater congestion, and the opposite side. No significant difference was found in mean CSA-2 reduction rate between the side which was narrow, and the side which was wide before provocation. Conclusions. Asymmetry of congestive response during bilateral nasal allergen provocation is not dependent on the stage of the nasal cycle preceding the challenge. [ABSTRACT FROM AUTHOR]

An accurate diagnosis of aeroallergen sensitization is pivotal to clinical practice and research. Given the recent technological advances in analyzing serum allergen-specific IgE, the question of which testing method, skin or serum testing, is superior in diagnosing allergic sensitization must be readdressed, as well as their value in predicting clinical disease. This review article provides a detailed summary of recent studies addressing these questions. Conclusively, most studies show substantial discordance between serum-specific IgE and skin testing results, suggesting that the two testing methods compliment each other and cannot be used interchangeably. On average, using only one testing method may misdiagnose every fourth allergically sensitized patient as non-sensitized. In addition, depending on the allergen tested, skin prick testing and serum-specific IgE testing appear to be the methods of choice in predicting outcomes of experimental allergen challenge, while intradermal testing is less contributory. [ABSTRACT FROM AUTHOR]

Background IgE-mediated allergic rhinitis to grass pollen can successfully be treated with either allergen immunotherapy tablets ( SLIT tablet) or SQ-standardized subcutaneous immunotherapy ( SCIT). The efficacy of these two treatment modalities for grass allergy is comparable, but the immunological mechanisms may differ. ClinicalTrials.gov ID: NCT01889875. Objectives To compare the immunological changes induced by SQ-standardized SCIT and SLIT tablet. Methods We randomized 40 individuals with grass pollen rhinitis into groups receiving SCIT, SLIT tablet, or neither and followed them for 15 months with regular serum measurements of specific Ig E, Ig G4, Ig E-blocking factor, facilitated antigen presentation ( FAP), and basophil activation test ( BAT). Nasal challenges were used to assess changes in nasal sensitivity. Results After 15 months of treatment Ig G4, Ig E-blocking factor, FAP, and BAT values differed significantly in both SCIT and SLIT-tablet treatment groups when compared to the control group. Both SCIT and SLIT-tablet groups were significantly different from the control group after 1-3 months of treatment. In general, the changes induced by SCIT reached twice that of SLIT tablet, with the exception of specific Ig E where SLIT tablet induced initial threefold increase compared with SCIT. A slight but significant increase in Ig E and BAT after season was seen only in the control group. Significant differences between SCIT and SLIT tablet were observed early, but the differences diminished with the length of treatment, especially for FAP inhibition. Conclusions Both SCIT and SLIT tablet induce significant changes in specific antibodies ( Ig E and Ig G4) and competition assays ( Ig E-blocking factor, FAP, and BAT). Overall, SCIT induced larger (two- to threefold) changes than SLIT tablet, with the exception of FAP, where SLIT tablet showed a gradual increase ending at the same level as SCIT. Maximal change was generally reached after 3 months' treatment. [ABSTRACT FROM AUTHOR]

Background Neurotrophins may play a role in the pathophysiology of allergic occupational rhinitis (OR). We sought to investigate whether an immediate allergic reaction that induces nasal inflammation is also able to induce changes in levels of brain-derived neurotrophic factor (BDNF) in nasal lavage (NAL) fluid from patients with allergic OR. Methods Ten patients sensitized to flour underwent control and active specific inhalation challenge (SIC) on consecutive days. Nasal response to SIC was monitored with acoustic rhinometry and symptoms recording. NAL was performed before and 30 minutes, 6 hours, and 24 hours after control and active challenge for the assessment of levels of BDNF and inflammatory cells in NAL fluid. Results In contrast to control day, flour challenge induced immediate clinical reactions in all subjects. After flour challenge, a significant increase in levels of BDNF in NAL fluid was observed at 6 hours after challenge ( p < 0.05). Also, a significant increase in the number of eosinophils in NAL fluid at 30 minutes ( p < 0.01), 6 hours ( p < 0.01), and 24 hours ( p = 0.05) postchallenge was observed. Also, levels of BDNF in NAL fluid were significantly higher at 30 minutes after flour challenge ( p = 0.02) in comparison to levels on the control day at the same postchallenge time. A marginally significant positive correlation between BDNF levels and eosinophil counts at 30 minutes ( r = 0.60, p = 0.06) and at 6 hours ( r = 0.50, p = 0.08) after flour challenge was noted. Conclusion We showed that BDNF is released in nasal fluid after SIC with flour. Results support the suggestion that neurotrophins may play a role in the pathogenesis of allergic OR. [ABSTRACT FROM AUTHOR]

Background: Platelet-activating factor (PAF) is a lipid mediator produced by most inflammatory cells. Clinical and experimental findings suggest that PAF participates in allergic rhinitis (AR) pathogenesis. The aim was to assess the PAF ability to induce clinical response in nasal airway after local stimulation. Method: Ten nonatopic healthy volunteers (HVs) and 10 AR patients out of pollen season were enrolled. PAF increasing concentrations (100, 200, and 400 nM) were instilled into both nasal cavities (0, 30, and 60 minutes, respectively). Nasal symptoms (congestion, rhinorrhea, sneezing, itching, and total 4 symptom score and nasal volume between the 2nd and 5th cm (Vol2-5) using acoustic rhinometry (AcR), were assessed at -30, 0, 30, 60, 90, 120, and 240 minutes. Result: PAF increased individual and total nasal symptom score in both HVs and seasonal AR (SAR) patients from 30 to 120 minutes (maximum score at 120′, p < 0.05). Nasal obstruction was the most relevant and lasting nasal symptom. PAF also induced a significant reduction of Vol2-5 at 90′ (27%), 120′ (38.7%), and 240′ (36.4%). No differences in the response to PAF nasal challenge were observed between HVs and SAR subjects in either clinical symptoms or AcR. Conclusion: This is the first description of PAF effects on human nasal mucosa using a cumulative dose schedule and evaluated by both nasal symptoms and AcR. Nasal provocation with PAF showed long-lasting effects on nasal symptoms and nasal obstruction in HVs and in patients with SAR. Nasal challenge may be a useful tool to investigate the role of PAF in AR and the potential role of anti-PAF drugs. [ABSTRACT FROM AUTHOR]

Background: The safety and utility of nasal provocation tests with lysine-aspirin (L-ASA) in the diagnosis of aspirin-intolerant asthma (AIA) have previously been described in a short series of patients. Objectives: To describe the clinical features and safety of an L-ASA challenge test in patients with AIA. Methods: We evaluated 72 patients (79% women), with a mean ± SD age of 47.9 ± 14.5 years. All patients were submitted to an L-ASA nasal provocation test (29 mg in each nostril) under acoustic rhinometry (AcR) control. Symptom score (0-3), visual analogical scale and nitric oxide determinations were performed at baseline and at 15, 30,60 and 90 min. A decrease in nasal volume of at least 25% was considered a positive test. Nasal nitric oxide (nNO) and forced expiratory volume in 1 s were measured. Results: Nasal congestion and rhinorrhea represented 51 and 32%, respectively, of total symptoms. According to AcR data, the L-ASA challenge test was positive in 20% of patients at 15 min, an additional 36% were positive at 30 min, 18% at 60 min, and the remaining 26% at 90 min. nNO nasal values decreased but did not reach statistical significance. No pulmonary or systemic reactions were observed. Conclusions: Symptoms of nasal congestion associated with the reduction in nasal volume measured by AcR are the most useful parameters for establishing the diagnosis of AIA using the L-ASA nasal challenge. The method is very well tolerated and can be safely used even in patients with severe asthma. [ABSTRACT FROM AUTHOR]

Background: Nasal nitric oxide (nNO) levels after nasal lysine acetylsalicylic acid (lys-ASA) challenge have not been determined. This study was designed to determine a pattern of changes after lys-ASA challenge in aspirin-exacerbated respiratory disease (AERD) patients and to evaluate the usefulness of nNO measurements in the assessment of lys-ASA nasal challenge outcome. Methods: Eighteen patients with aspirin hypersensitivity, nasal polyps, and asthma were included. Aspirin-tolerant control groups consisted of 10 healthy volunteers without asthma and nasal polyps and 10 patients with nasal polyps without asthma. All subjects underwent nasal challenge with lys-ASA. nNO was measured before and 1, 2, 4, and 24 hours after control solution and lys-ASA administration. Results: A significant fall in nNO levels was noted in AERD patients with a positive result to challenges at time points 1 hour (p = 0.0033), 2 hours (p = 0.0033), and 3 hours (p = 0.026) after lys-ASA. A trend toward higher nNO concentrations was observed after lys-ASA challenge at the 2-hour (p = 0.018) and 4-hour (p = 0.018) time points compared with baseline in subjects with AERD and a clinically negative result to the challenge. No significant changes in nNO levels after the challenge were observed in control groups. The combined increase and decrease in nNO levels gave the sensitivity as 0.94 and specificity 1.00 at best. Conclusion: nNO levels decrease after lys-ASA nasal challenge in subjects with AERD and a clinically positive result of the challenge. An unexpected trend toward an increase in nNO levels is observed in subjects with AERD and a clinically negative result of the challenge. [ABSTRACT FROM AUTHOR]

The workplace is emerging as an increasingly important venue for the development of rhinitis and asthma. There is no question that allergic diseases of the respiratory tract caused by occupational exposure are on the increase. The clinician's diagnostic index of suspicion must be high so that a diagnosis of occupational rhinitis and/or asthma can be made in a timely fashion. Altering the environment of the workplace or removing the patient from that workplace may spare the patient permanent damage. [ABSTRACT FROM AUTHOR]

Epidemiologic studies have shown an association between mouse allergen exposure and asthma morbidity among urban populations, but confirmatory challenge studies in community populations have not been performed. This study was designed to examine the clinical relevance of mouse sensitization using a nasal challenge model. Forty-nine urban adults with asthma underwent skin-prick testing (SPT) and intradermal testing (IDT) with mouse epithelia extract. A positive SPT was defined as a net wheal size ≥3 mm and a positive IDT was defined as a net wheal size ≥6 mm using a 1:100 dilution of extract (1:10 w/v was obtained from Greer Laboratories (Lenoir, NC) as a single lot [Mus m 1 concentration = 2130 ng/mL]). Mouse-specific IgE (m-IgE) was measured by ImmunoCAP (Phadia, Uppsala, Sweden). Nasal challenge was performed with increasing concentrations of mouse epithelia extract and symptoms were assessed by visual analog scale. A positive challenge was defined as a 20-mm increase in the scale. The age range of the 49 participants was 18-50 years; 41% were men and 86% were black. Fourteen participants were SPT+ to mouse, 15 participants were SPT- but (IDT+), and 20 participants were negative on both SPT- and IDT- (SPT-/IDT-). Sixty-four percent of the SPT+ group, 40% of the IDT+ group, and 20% of the SPT-/IDT- group had a positive nasal challenge. Sixty-seven percent (10/15) of those who were either SPT+ or m-IgE+ had a positive nasal challenge. SPT or the combination of SPT plus m-IgE performed best in diagnosing mouse allergy. The great majority of mouse-sensitized urban adults with asthma appear to have clinically relevant sensitization. Urban adults with asthma should be evaluated for mouse sensitization using SPT or SPT plus m-IgE testing. [ABSTRACT FROM AUTHOR]

Background Although nasal challenge with allergen has often been used to evaluate the efficacy of therapeutic modalities used for the treatment of allergic rhinitis, the reproducibility of this model in quantitatively evaluating efficacy has not been rigorously examined. Objective To examine the reproducibility of the suppressive effects of an intranasal corticosteroid on the clinical and biochemical outcomes of a nasal allergen challenge during two identical treatment periods using the same subjects. Methods In a single-blind study, 25 seasonal allergic subjects with positive skin tests to grass or ragweed were studied outside of their pollen season. Subjects underwent a baseline, three-dose allergen challenge. Beginning 1 week later, subjects received two 7-day courses of intranasal beclomethasone (168 μg b.i.d.) separated by a 1-month washout period. Nasal challenges with allergen were performed after each treatment period. The nasal allergic response was evaluated by counting sneezes, recording symptom scores and measuring levels of albumin (an index of vascular permeability), lysozyme (an index of serous glandular secretion) and kinins (proinflammatory peptides) in recovered nasal lavages. Results Compared with the baseline challenge, each course of beclomethasone significantly reduced sneezing, symptom scores, albumin and kinins, but not lysozyme. Reproducibility analysis of the net changes from diluent challenge in the two beclomethasone treatment periods, showed the following intraclass correlation coefficients: sneezing (0.92), lysozyme (0.82), symptom scores (0.72), albumin (0.64) and kinins (0.28). Conclusion We conclude that the nasal challenge model is a reproducible method to evaluate the efficacy of anti-allergic medications. For nasal corticosteroid trials, sneezing, symptom scores and albumin levels are recommended as the most reproducibly suppressive outcome measures. Cite this as: D. Proud, D. K. Riker and A. Togias, Clinical & Experimental Allergy, 2010 (40) 738–744. [ABSTRACT FROM AUTHOR]

Background: Lipoxins represent a group of lipoxygenase derived eicosanoids which, in contrast to leukotrienes, are potent anti-inflammatory mediators. The aim of our study was to determine lipoxin A4 (LXA4) and leukotriene C4 (LTC4) levels in nasal lavages after intranasal challenge with aspirin in aspirin intolerant (AIA) in comparison to aspirin tolerant (ATA) asthmatics and after allergen challenge in patients suffering from allergic rhinitis. Methods: Twelve AIA, 8 ATA and 20 allergic patients were challenged with placebo, 16 mg of lysine-aspirin (Lys-ASA) or allergen (grasses). Nasal lavages were collected and eicosanoids’ levels were determined using ELISA. Results: Clinically positive Lys-ASA challenge in AIA resulted in influx of leukocytes (eosinophils and basophils) to nasal secretions and increase of LTC4 to 106.82 pg/ml ( P < 0.05 vs baseline (26.58 pg/ml)) on first hour after the challenge. We did not observe any differences in LTC4 level before and after ASA challenge in ATA. In AIA group the mean level of LXA4 was 43 ± 21.5 pg/ml after placebo and decreased in 2 h after Lys-ASA challenge (29 ± 17 pg/ml, P = 0.015). We found an increase in LXA4 in ATA after ASA provocation as compared to placebo (33 ± 16 pg/ml vs 52 ± 31 pg/ml, P = 0.046). In atopic patients baseline level of LXA4 was 33.49 ± 16.95 pg/ml with no difference after the clinically positive allergen challenge (36.22 ± 13.26 pg/ml, P = 0.23). Conclusions: Results of our study confirm that AIA have diminished LXs’ biosynthesis capacities in vivo after ASA challenge. Taking into consideration anti-inflammatory properties of lipoxins this phenomenon may be partially responsible for the development of chronic inflammation in AIA patients. [ABSTRACT FROM AUTHOR]

Background: Eye symptoms frequently occur in patients with allergic rhinitis and are among the most bothersome symptoms. Intranasal steroids have been shown to reduce ocular symptoms associated with allergic nasal symptoms, even though they do not reach the eye. Objective: To elucidate a mechanism to explain these observations. Methods: We performed a double-blind, placebo-controlled, crossover experiment in 20 subjects with seasonal allergic rhinitis. Nasal antigen challenge was performed consecutively for 3 days after 1 week of treatment with either placebo or fluticasone furoate nasal spray (FFNS). Subjects recorded their nasal and ocular symptoms, and nasal secretions were quantified. Nasal scrapings to quantify eosinophils were obtained before each antigen challenge. Results: Nasal challenge with antigen led to sneezing, a nasonasal, and a nasal-ocular reflex. Priming in the number of sneezes, contralateral nasal secretion weights, and total eye symptoms were observed. Treatment with FFNS reduced sneezing, the nasonasal and nasal-ocular reflexes, and the amount of eosinophils in nasal secretions. Conclusions: We confirmed that a nasal-ocular reflex follows nasal challenge with allergen and that it can contribute to the ocular symptoms associated with allergic rhinitis. FFNS reduced eosinophil infiltration, priming, and ocular symptoms. Furthermore, our results support a mechanism by which control of eye symptoms can be achieved during nasal administration of an intranasal steroid in patients with seasonal allergic rhinitis. [Copyright &y& Elsevier]

The aim of this study was to examine the effects of persulphate on the nasal mucosa and on the immune cells in hairdressers suffering from bleaching powder associated rhinitis (BAR) versus subjects with rhinitis not previously exposed to bleaching powder. Fifteen hairdressers (S) with BAR, 14 without symptoms (WS) and 12 atopics (A) with rhinitis but without exposure to bleaching powder were studied. Each performed a nasal challenge with persulphates. Effect parameters were symptom score, acoustic rhinometry, albumin in nasal lavage, subpopulations of lymphocytes in blood and specific serum antibodies. The S group had a post-challenge increase in nasal symptoms and nasal lavage albumin. The A group reacted to a lesser intent. The S and A groups showed an increase in Th1 cells. An HLA class II cell expression was noticed in both groups of hairdressers. No evidence of a type 1 reaction (immediate type) to persulphate was noticed. Persulphate challenge affects hairdressers with BAR, but also atopics. The reaction may be driven by a Th1 cell activation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Few studies have yet addressed the effects of di(2-ethylhexyl) phthalate (DEHP) in house dust on human nasal mucosa. OBJECTIVES: We investigated the effects of house dust containing DEHP on nasal mucosa of healthy and house dust mite (HDM)–allergic subjects in a short-term exposure setting. METHODS: We challenged 16 healthy and 16 HDM-allergic subjects for 3 hr with house dust at a concentration of 300 µg/m3 containing either low (0.41 mg/g) or high (2.09 mg/g) levels of DEHP. Exposure to filtered air served as control. After exposure, we measured proteins and performed a DNA microarray analysis. RESULTS: Nasal exposure to house dust with low or high DEHP had no effect on symptom scores. Healthy subjects had almost no response to inhaled dust, but HDM-allergic subjects showed varied responses: DEHPlow house dust increased eosinophil cationic protein, granulocyte-colony--stimulating factor (G-CSF), interleukin (IL)-5, and IL-6, whereas DEHPhigh house dust decreased G-CSF and IL-6. Furthermore, in healthy subjects, DEHP concentration resulted in 10 differentially expressed genes, whereas 16 genes were differentially expressed in HDM-allergic subjects, among them anti- Müllerian hormone, which was significantly up-regulated after exposure to DEHPhigh house dust compared with exposure to DEHPlow house dust, and fibroblast growth factor 9, IL-6, and transforming growth factor-β 1, which were down-regulated. CONCLUSIONS: Short-term exposure to house dust with high concentrations of DEHP has attenuating effects on human nasal immune response in HDM-allergic subjects, concerning both gene expression and cytokines. [ABSTRACT FROM AUTHOR]

Background The genus Senecio is the largest genus of the family Asteraceae (Compositae). The allergenicity of Senecio has not been assessed previously. Objective The aim of this study was to investigate the allergens of Senecio jacobea pollen and to determine their immunological characteristics and clinical relevance. Methods Fifty patients with rhinoconjunctivitis and a positive skin prick test (SPT) to Senecio were recruited. The clinical relevance of this pollen was assessed by means of a nasal provocation test (NPT). Allergens were characterized by one-dimensional electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis and immunoblotting. Furthermore, characterization and identification of the allergens were performed by mass spectrometry (MS). In vitro inhibition tests were performed to evaluate cross-reactivity with other pollen. Results Three predominant allergens, both in the intensity of reaction and the frequency of recognition by human-allergic sera, were 59 (60%), 42 (50%) and 31 kDa (50%). The two-dimensional analysis allowed the identification of several allergens. One spot around 42 kDa was identified as a protein homologous to pectate lyase and three other spots were homologous to malate dehydrogenase by MS. S. jacobea proteins showed cross-reactivity with other proteins of the Asteraceae family and also with Parietaria judaica. This was demonstrated by immunoblotting and ELISA inhibition studies. Conclusion S. jacobea constitute a newly discovered allergenic source. It shows cross-reactivity with other members of the Asteraceae plant family as well as with P. judaica. [ABSTRACT FROM AUTHOR]

Background: Mouse sensitization is assessed by using skin testing and serum levels of mouse allergen-specific IgE (m-IgE). However, it is unknown whether a positive skin test response or m-IgE result accurately identifies those with clinically relevant mouse sensitization. Objective: We sought to compare skin testing and m-IgE measurement in the diagnosis of mouse allergy. Methods: Sixty-nine mouse laboratory workers underwent skin prick tests (SPTs), intradermal tests (IDTs), and serum IgE measurements to mouse allergen, followed by nasal challenge to increasing concentrations of mouse allergen. Challenge response was assessed by nasal symptom score. Results: Thirty-eight women and 31 men with a mean age of 30 years were studied. Forty-nine workers reported mouse-related symptoms, of whom 10 had positive m-IgE results and 12 had positive SPT responses. Fifteen had negative SPT responses but positive IDT responses. Positive nasal challenges were observed in 70% of workers with positive m-IgE results, 83% of workers with positive SPT responses, 33% of workers with negative SPT responses/positive IDT responses, and 0% of workers with negative IDT responses. SPTs performed best, having the highest positive and negative predictive values. Among participants with a positive challenge result, those with a positive SPT response or m-IgE result had a significantly lower challenge threshold than those with a positive IDT response (P = .01). Workers with a positive challenge result were more likely to have an increase in nasal eosinophilia after the challenge compared with those with a negative challenge result (P = .03). Conclusions: SPTs perform best in discriminating patients with and without mouse allergy. Mouse-specific IgE and IDTs appear to be less useful than SPTs in the diagnosis of mouse allergy. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Ocular symptoms occur in &thksim;40% of patients with allergic rhinitis. The purpose of this study was to determine whether nasal challenge with antigen induces a nasal-ocular reflex. We performed a double-blind crossover trial in 20 subjects. A nasal challenge with antigen was performed in one nostril, and the response was assessed in both nostrils and both eyes. Subjects were treated before challenge with either placebo or azelastine, an H1-antihistamine. Nasal challenge with antigen led to a nasonasal reflex and a nasal-ocular reflex as manifested by an increase in symptoms and secretion weights. Treatment with azelastine reduced both reflexes. A nasal-ocular reflex follows nasal challenge with antigen and probably contributes to the ocular symptoms associated with allergic rhinitis. [ABSTRACT FROM AUTHOR]

Although cysteinyl-leukotriene receptor antagonists were recently approved for use in allergic rhinitis (AR), there has been no study to date investigating their application in children. The aim was to evaluate whether montelukast provides any benefit in nasal allergen challenge-induced symptoms in children, and whether it could improve the control provided by an antihistamine during pollen season. Two randomized studies, one a double-blind, placebo-controlled, nasal allergen challenge study and one an open-label, cross-over, parallel-group clinical study, were performed in 18 (11.7 ± 0.7 years) and 32 children (10.5 ± 0.5 years), respectively, with grass pollen allergy. In the first study, the effect of a single dose of montelukast and its combination with loratadine were compared with placebo on nasal responses induced by allergen challenge. In the second study, the additive effect of montelukast to loratadine was tested in an open-label cross-over clinical study. In the challenge study, early-phase and late-phase nasal reactions peaked at 15 min and 4 h after the challenge respectively. During the early phase, combination improved total nasal symptoms (p = 0.004) during the first hour and sneezing (p = 0.012) at 15 min compared with placebo group. During the late phase, montelukast (p = 0.017) and combination (p = 0.011) caused less nasal obstruction at 4 h and combination caused less sneezing at 6 h (p = 0.015). In the clinical trial, montelukast provided protection on seasonal increase in pulmonary symptoms [0 (0, 14) vs. 6.5 (0, 27.7); p = 0.016] and on the decrease in FEF25−75 [−0.09 (−0.34, 0.17) vs. −0.28 (−0.66, 0.02); p = 0.002]. However, there was no improvement in nasal symptoms and flows. Although we showed protection against nasal challenge-induced congestion with montelukast, we were not able to show the same in the clinical study possibly because of low pollen counts and mildness of the symptoms of the patients with AR. However, montelukast provided better control of pulmonary symptoms and protection from seasonal decrease in lung function, indicating its potential therapeutic benefit in children with AR. [ABSTRACT FROM AUTHOR]

Background: Cold, dry air (CDA) can cause symptoms of rhinitis and obstructive airway responses. The pathophysiology of these reactions is not understood. One hypothesis is that the respiratory mucosa of individuals with CDA sensitivity cannot compensate for the loss of water that occurs on exposure to the stimulus, leading to epithelial damage. Objective: To test for an association between nasal reactions to CDA and the number of epithelial cells recovered in nasal fluids. Methods: Ten CDA-sensitive subjects received nasal provocations with CDA and warm, moist air; 10 CDA-insensitive subjects received CDA; and 10 subjects with allergic rhinitis received allergen and diluent challenges. Nasal lavage cytology was performed at baseline and after the challenge. Symptoms were recorded and histamine, [3H]-N-α-tosyl-L-arginine methyl ester-esterase activity, tryptase, and albumin were assayed in nasal lavages. Results: A 6-fold increase in nasal lavage epithelial cells was found in the CDA-sensitive group after CDA (P < .01), but not after warm, moist air. No changes were observed in the CDA-insensitive group, or after allergen or diluent in allergic rhinitis. Conclusion: Epithelial cell shedding accompanies clinical responses to CDA in the human nose. This supports the hypothesis that the airway mucosa of CDA-sensitive individuals cannot compensate for the water loss that occurs under extreme conditions leading to epithelial damage. Clinical implications: A defect in mucosal water homeostasis may need to be considered in individuals who get excessive nasal symptoms when exposed to cold and dry, windy environment. [Copyright &y& Elsevier]

Oral allergy syndrome (OAS) is often associated with pollen-induced rhinitis, and there are preferential associations between causative substances. If OAS and rhinitis are both immunoglobulin (Ig)E-mediated and there are cross-reacting proteins, it is expected that similar reactions can be elicited in the nose and mouth. In order to test this hypothesis we performed a series of‘cross-challenges’ with foods and pollens in both the nose and the mouth.Nine patients with ascertained OAS due to vegetables and rhinitis due to pollens were studied. On the first day a nasal challenge with pollen extracts and an oral challenge with fresh food was carried out. After a week, washout nasal challenge with food and an oral challenge with pollens were performed. Immediate symptoms, mucosal tryptase and soluble eosinophil cationic protein (ECP) were assessed after each challenge.The administration of pollen into the nose and food into the mouth elicited symptoms as expected, but the cross-challenge had no clinical effect. In parallel, tryptase and ECP increased after nasal challenge with pollens, whereas foods did not elicit a measurable response.The cross-reactivity between foods and pollens, when evaluated at the shock organ, was not clinically evident. This data can be explained with a low concentration of cross-reagent epitopes in pollen extracts and food homogenized because of degradation. The different behaviour upon challenge suggests that different immunological mechanisms may act in the nose and mouth. [ABSTRACT FROM AUTHOR]

The effect of bilateral nasal provocation on nasal mucosa measured with the use of acoustic rhinometry (AR) can be assessed for both nasal passages or for the side responding with greater congestion. Assessment of changes in nasal congestion during the nasal provocation test (NPT) can be affected by the nasal cycle (NC). The aim of this study was to find out the most accurate method to evaluate changes observed during bilateral nasal provocation.Cross-sectional areas (CSA) at the level of inferior nasal turbinate (CSA-2) were recorded by AR in 26 volunteers with allergic rhinitis during the NC for 5–7 h and subsequently during NPT. The risk of spontaneous total and unilateral CSA-2 decrease was established.Sensitivity of the NPT assessment for the total CSA-2 and for the side responding with greater congestion was evaluated at chosen thresholds. These thresholds were selected in a way that the risk levels of spontaneous decrease of unilateral and total CSA-2 were equal.The assessment of the total CSA-2 was found to be more sensitive than the assessment of the side responding with greater congestion. The highest sensitivity and specificity of the test was achieved by using a combination of both assessments. Optimum thresholds of the CSA-2 decrease for assessment at 15 min after provocation, with this method, were 27% and 40% for the side responding with greater congestion and for the total CSA-2, respectively.Recognition of the risk of spontaneous unilateral and total CSA-2 decreases enables introduction of combined assessment of bilateral NPT. This assessment seems to be the most accurate method for evaluation of the test results. [ABSTRACT FROM AUTHOR]

The effects of single or combined histamine H1-receptor and leukotriene CysLT1-receptor antagonism on nasal adenosine monophosphate (AMP) challenge in allergic rhinitis are unknown. We elected to study the effects of usual clinically recommended doses of fexofenadine (FEX), montelukast (ML) and FEX + ML combination, compared with placebo (PL), on nasal AMP challenge in patients with persistent allergic rhinitis. Twelve patients with persistent allergic rhinitis (all skin prick positive to house dust mite) were randomized in a double-blind cross-over fashion to receive for 1 week either FEX 180 mg, ML 10 mg, FEX 180 mg + ML 10 mg combination, or PL, with nasal AMP challenge performed 12 h after dosing. There was a 1-week washout period between each randomized treatment. The primary outcome measure was the maximum percentage peak nasal inspiratory flow (PNIF) fall from baseline over a 60-min period after nasal challenge with a single 400 mg ml−1 dose of AMP. The area under the 60-min time–response curve (AUC) and nasal symptoms were measured as secondary outcomes. There was significant attenuation ( P < 0.05) of the mean maximum percentage PNIF fall from baseline after nasal AMP challenge vs. PL, 48; with FEX, 37; 95% confidence interval for difference 2, 20; ML, 35 (4, 22); and FEX + ML, 32 (7, 24). The AUC (%.min) was also significantly attenuated ( P < 0.05) vs. PL, 1893; with FEX, 1306 (30, 1143); ML, 1246 (214, 1078); and FEX + ML, 1153 (251, 1227). There were no significant differences for FEX vs. ML vs. FEX + ML comparing either the maximum or AUC response. The total nasal symptom score (out of 12) was also significantly improved ( P < 0.05) vs. PL, 3.3; with FEX, 2.1 (0.3, 2.0); ML, 2.0 (0.5, 1.9); and FEX + ML, 2.5 (0.1, 1.4). FEX and ML as monotherapy significantly attenuated the response to nasal AMP challenge and improved nasal symptoms compared with PL, while combination therapy conferred no additional benefit. [ABSTRACT FROM AUTHOR]

There are presently no placebo-controlled data regarding the effects of butterbur (BB) on subjective and objective outcomes in patients with perennial allergic rhinitis. We performed a placebo-controlled evaluation of the effects of BB and fexofenadine (FEX) on subjective and objective outcomes in patients with perennial allergic rhinitis. Sixteen patients with perennial allergic rhinitis and house dust mite sensitization were randomized in double-blind cross-over fashion to receive for 1 week either BB 50 mg twice daily, FEX 180 mg once daily and placebo (PL) once daily, or PL twice daily. The peak nasal inspiratory flow (PNIF) response to adenosine monophosphate (AMP) challenge administered as a single 400 mg/mL dose was measured over a 60-min period after challenge, and domiciliary total nasal symptom score was recorded. Pre-challenge values for mean±SEM PNIF (L/min) were not significantly different comparing all groups; BB (138±8), FEX (140±9), and PL (138±8). The maximum % PNIF fall from baseline after nasal AMP challenge was significantly attenuated ( P<0.05) compared to PL (46±3), with BB (34±3) and FEX (39±3). The area under the 60-min time–response curve (%.min) was also significantly attenuated ( P<0.05) compared to PL (1734±156), with BB (1052±258) and FEX (1194±161). There was also a significant reduction ( P<0.05) in total nasal symptom score with BB (1.8±0.4) and FEX (1.8±0.4), compared to PL (2.8±0.5). There were no significant differences between BB and FEX for any outcomes. BB and FEX, in comparison to PL, were equally effective in attenuating the nasal response to AMP and in improving nasal symptoms, highlighting a potential role for BB in the treatment of allergic rhinitis. [ABSTRACT FROM AUTHOR]

There are no data directly comparing the relative efficacy of modern H1-antihistamines in allergic rhinitis using nasal provocation challenge. We elected to study the comparative effectiveness of usual clinically recommended doses of desloratadine (DES), fexofenadine (FEX), and levocetirizine (LEV), on nasal adenosine monophosphate (AMP) challenge in patients with perennial allergic rhinitis (PAR). 16 patients with PAR were randomized in double-blind cross-over fashion to receive single doses of DES 5 mg, FEX 180 mg, LEV 5 mg, or placebo (PL), with nasal AMP challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after nasal AMP challenge. Pre-challenge values (mean±SEM) for PNIF (L/min) were not significantly different comparing all groups; DES (129±9), FEX (128±11), LEV (128±13), and PL (128±12). The maximum % PNIF fall from baseline over 60 min after nasal AMP challenge was significantly attenuated ( P<0.05) compared to PL (50±4), with DES (32±5), FEX (36±4), and LEV (36±4). The area under the 60-min time–response curve (%.min) was also significantly attenuated ( P<0.05) compared to PL (2110±268), with DES (1126±285), FEX (1225±255), and LEV (1261±194). There were no significant differences between the three H1-antihistamines for any outcomes. DES, FEX, and LEV were equally effective in attenuating the response to nasal AMP challenge. However, further long-term studies will be required to study their comparative effects on nasal symptoms, quality of life, as well as on nasal inflammatory cells. [ABSTRACT FROM AUTHOR]

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Previous research indicates that diesel exhaust particles (DEP) can augment allergen- driven allergic responses. In vivo nasal challenge offers a practical method to characterize variation in response to pulmonary toxicants and immunogens. We investigated the reproducibility of responses to determine whether susceptibility to DEP''s adjuvant effects is intrinsic or extrinsic. Eighteen nonsmoking rhinitic volunteers with positive skin tests to ragweed were randomly assigned to allergen/placebo or allergen + DEP nasal challenge; after 30 days, the other “arm” was completed. We replicated the procedure 30 days later. Nasal washes were performed after challenge, and allergen-specific IgE and cytokines were measured by ELISA. Repeated challenge with allergen+DEP, but not allergen/placebo, produced reproducible responses for IgE, IL-4, and INF-γ. DEPs ability to enhance allergic responses was highly reproducible within individuals and was independent from response to allergen, suggesting that susceptibility to DEPs adjuvant effects is an intrinsic trait that can be quantified using combined allergen + DEP challenges. [Copyright &y& Elsevier]

Background: Adenosine monophosphate (AMP) acts by releasing inflammatory mediators from mast cells and may be used for bronchial and nasal provocation tests. The aim of the present study was to determine whether AMP could be used in a dose-response manner to evaluate nasal function and to evaluate the reproducibility of nasal function measurements with nasal challenge testing using histamine and AMP in patients with perennial allergic rhinitis. Methods: Nine patients were challenged on three separate occasions for each challenge with doubling doses of either histamine (0.25-8 mg/mL) or AMP (25-800 mg/mL). Challenge measurements were made of peak inspiratory flow rate (PIFR), acoustic rhinometry (AR) and rhinomanometry (Rhino). The provocation concentration (PC[SUB30]) was calculated in order to produce: (i) a 30% fall in PIFR; (ii) a 30% fall in AR and (iii) a 30% increase in nasal airway resistance in Rhino and a symptom score of 10 (of 40). The mean intrasubject coefficient of variation (CV) was calculated for baseline and the corresponding PC. Results: Baseline CV prior to histamine were 15.1, 19.6 and 15.8 for PIFR, AR and Rhino, respectively; prior to AMP, baseline CV were 12.7, 19.6 and 10.6% for PIFR, AR and Rhino, respectively. For histamine challenge, the PC[SUB30] were 26.5, 27.4 and 38.7% for PIFR, AR and Rhino, respectively. For AMP challenge, the PC[SUB30] CV values were 46.2, 30.8 and 49.5% for PIFR, AR and Rhino, respectively. There was no significant difference in the provocative dose required to cause a predetermined change in response or the response at 1 mg/mL histamine and 100 mg/mL AMP. Conclusions: Adenosine monophosphate may be used as a challenge agent for nasal challenge testing, although it results in greater variability than histamine. [ABSTRACT FROM AUTHOR]

Aims To evaluate the role of AMP nasal challenge as a measure of short-term treatment response in patients receiving intranasal corticosteroids. Adenosine monophosphate (AMP) challenge has been shown to be a good inflammatory surrogate in the lower airways, but it has not been properly evaluated as a nasal challenge test. Methods Fourteen patients with perennial allergic rhinitis (PAR) were randomized to receive 2 weeks treatment with placebo (PL) or 200 µg intranasal mometasone furoate (MF) once daily in a randomized single-blind crossover study. AMP (25–800 mg ml-1 ) and histamine (0.25–8 mg ml-1 ) nasal challenge testing were performed after each treatment period with 30% decrease in minimal cross-sectional area (MCA). Domiciliary symptom data were collected. Results There was a significant (P < 0.05) improvement in PC 30 MCA and nasal volume with AMP but not with histamine comparing MF vs PL. This amounted to a 2.8 (95% CI 1.5, 4.0) and 0.7 (95% CI -0.5, 1.9) doubling-dose change for AMP and histamine challenges, respectively. There were significant (P < 0.05) improvements in nasal symptoms and quality of life. Conclusions AMP nasal challenge using acoustic rhinometry may be a useful test to assess short-term treatment response in patient with PAR. [ABSTRACT FROM AUTHOR]

Summary Background Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability. Objective To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction. Methods Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively. Results All 10 patients tolerated the highest accumulated dose, 8.124 µg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined. Conclusion The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction. [ABSTRACT FROM AUTHOR]

BackgroundInhalation of hot, humid air (HHA: 37 °C, > 95% relative humidity (RH)) partially inhibits the early response to nasal challenge with antigen. ObjectiveTo investigate whether HHA inhibited the late-phase response to nasal challenge with antigen and increased hyper-responsiveness of the nasal mucosa to histamine. MethodsTwenty subjects with seasonal allergic rhinitis, outside of their allergy season, participated in a randomized, 2-way cross-over study. The subjects continuously breathed room air (25 °C, 30% RH) or HHA delivered via a face mask during the entire experiment. Subjects were challenged intranasally with antigen 1 h after beginning conditioning. The response was monitored by symptoms and nasal lavage at 2-h intervals after the last antigen challenge. Eight hours after antigen challenge, nasal challenge with histamine was performed. ResultsExposure to HHA significantly increased nasal mucosal temperature from baseline without affecting nasal secretion osmolality. HHA significantly inhibited antigen-induced sneezes, congestion, pruritus, and human serum albumin levels during the early response to antigen challenge. HHA exposure, however, was associated with an 8-fold increase in the eosinophil influx and a 15-fold increase in the levels of eosinophil cationic protein during the late-phase response compared to room air. There were no significant differences in nasal hyper-responsiveness to histamine during either exposure. ConclusionHHA partially decreases the early response to nasal challenge with antigen, but dramatically increases eosinophil influx. Increasing eosinophil number had no effects on the hyper-responsiveness to histamine. We speculate that the physical conditions of air differentially impact the stages of allergic inflammation. [ABSTRACT FROM AUTHOR]

Background: The clinical safety of sublingual immunotherapy (SLIT) has been repeatedly confirmed; nevertheless, the possible onset of local oral symptoms is still a concern, and nothing is known about the pathogenesis of this effect. We aimed to determine whether the administration of SLIT in allergic children can evoke an IgE-mediated reaction, by measuring the levels of sublingual tryptase and ECP. Methods: Thirty children (7–12 years old) with allergic rhinitis/asthma due to grass pollen were prescribed SLIT. In these children, an allergen-specific nasal challenge was performed, and nasal tryptase and ECP were measured before and after. Sublingual ECP and tryptase were also assessed before the SLIT, after 1 month, and after 6 months of treatment. Ten matched allergic children and 10 healthy ones served as controls for the baseline levels of sublingual ECP and tryptase. Results: The levels of nasal tryptase and ECP significantly increased after nasal challenge (P<0.001), whereas no change during the SLIT course (at the beginning, after 1 month, and after 6 months) could be detected in sublingual tryptase either before or after SLIT administration. The sublingual ECP significantly decreased after 6 months of SLIT. The baseline levels of nasal tryptase and ECP were significantly higher in allergic subjects than in healthy controls, as was the level of sublingual ECP. Conclusions: In the presence of an IgE-mediated reaction (ASNC), a significant increase of tryptase and ECP can be seen. When SLIT is administered, such a phenomenon does not occur; therefore, SLIT does not elicit any IgE reaction in the mouth. It is noteworthy that allergic subjects display higher levels of nasal ECP and tryptase than healthy subjects, even when symptom-free, and these observations may indicate the presence of subclinical inflammation. [ABSTRACT FROM AUTHOR]