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The dural lymphatics develop mainly during the first postnatal month. Lymphatics may be shaped by immune activation when bacterial infection happens. BCG, a strong immune activator, is widely injected to newborns. Moreover, human beings are nasally exposed in daily life to bacterial stimuli. These background prompted us to investigate whether neonatal BCG injection combined with nasally exposure exerts an influence on dural lymphatics develop. Here, mice received a single dose intracutaneous (i.c.) BCG injection immediately after birth followed by repeated nasal BCG challenge once a day (i.c./nasal group). These mice had an accelerated dural lymphatics growth and increased levels of several cytokines and VEGFR-3. Furthermore, macrophages were identified as a key mediator of these alterations. Mice that received mere one dose i.c. BCG injection showed no significant alterations in these indexes. Additionally, mere repeated nasal BCG challenge induced similar effects to i.c./nasal challenge but with a slighter extent. Taken together, these findings show that repeated nasal BCG vaccination accelerates dural lymphatics development in neonatal mice, especially in the presence of neonatal i.c. BCG injection.

BACKGROUND The eye is especially susceptible to the symptoms of allergic rhinitis, itching (pruritus), tearing (epiphora) and redness (erythema) because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen on the conjunctival surface. These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction. A number of recently published clinical studies apparently support the positive effect of intranasal steroidal sprays on ocular allergy symptoms. The aim of the study is to evaluate the role of intranasal steroids in relieving ocular symptoms in allergic rhinitis. MATERIALS AND METHODS 60 subjects who had seasonal allergic rhinitis with ocular symptoms came to Outpatient Department of Chalmeda Anand Rao Hospital in the year 2015-2016. Randomly, each intranasal steroid is given to 12 patients to a total of 60 patients for 4 weeks 2 puffs in each nostril twice daily and the clinical response is observed. RESULTS A subjective improvement in ocular symptoms was observed in 11 of the 12 patients treated with fluticasone furoate, 8 of 12 patients with fluticasone propionate, 7 of the 12 patients with mometasone furoate, 6 of the 12 patients with beclomethasone and 6 of the 12 patients with budesonide. CONCLUSION Intranasal corticosteroids, which are used for seasonal allergic rhinitis with ocular symptoms are effective in controlling of ocular symptoms. Among these, intranasal corticosteroids, which are used for allergic rhinitis, fluticasone furoate is more effective in relieving ocular symptoms in our study.

Introduction Acoustic rhinometry as a simple and non-invasive method of evaluation of nasal patency is an important tool in the diagnosis of rhinologic and allergic disorders. The aim of the study was to attempt to evaluate the reaction of the nasal mucous membrane to a topically applied allergen by the measurement of the minimum cross-sectional area of the nose (MCA1 and MCA2). The study group consisted of 60 subjects (30 patients with diagnosed allergic rhinitis and 30 healthy ones). The method that was used in the study was acoustic rhinometry (Rhinometrics, Denmark 2001) assessed in a nasal challenge test. Results In the group with allergic rhinitis, significant changes of the surface of the cross-sectional area have been observed, and were measured from the 10th minute with the most significant changes achieved at the 15th and 20th minute of the test. Definitely, more relative reactivity was observed on the right side of the nasal cavity than on the left side (-13.76 ± 33.50 p

Objectives Nasal specific IgE (NsIgE) is the most common marker to identify type-2 inflammation in local allergic rhinitis (LAR). However, the comparison of NsIgE in different types of rhinitis, its frequency in tropical countries, and its diagnostic performance for predicting the outcome of a nasal challenge test (NCT) has had limited study. The main objective of this study was to explore the diagnostic performance of NsIgE to Dermatophagoides pteronyssinus (Der p) among different types of rhinitis and control subjects in a tropical population. Methods We evaluated the frequency of NsIgE, systemic atopy (serum sIgE and Skin Prick Test), and nasal eosinophils, and we performed nasal challenge tests (NCTs) with Der p in 3 groups of patients; rhinitis without atopy (RWoA) (n = 25), rhinitis with atopy (RWA) (n = 25), and control subjects (n = 18). Results NsIgE had a low sensitivity and specificity to predict a positive NCT in the RWoA group: 48% had NsIgE, but only 28% had a positive NCT. Among the RWA group 84% had NsIgE and 80% had a positive NCT; the association of NsIgE and positive NCT was high (>80%). In the control group 27.8% had NsIgE, but none had a positive NCT. Conclusions NsIgE performs poorly in predicting NCT results in patients with non-allergic rhinitis. More methodical investigations are needed in this complex area of rhinitis. In patients with allergic rhinitis, NsIgE was useful in predicting a positive nasal challenge, but not superior to the systemic atopic test.

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.

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.

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.

Background and objective Safer and less time-consuming alternatives to single-blind placebo-controlled oral challenge (SBPCOC) have been sought for the diagnosis of aspirin-exacerbated respiratory disease (AERD). Nasal challenges with various nonsteroidal anti-inflammatory drugs and assessment methods have been developed. Objective: Our objective was to evaluate the utility and safety of nasal ketorolac challenge (NKC) using acoustic rhinometry in patients with suspected AERD. Methods The study population comprised 36 patients with suspected AERD. NKC was performed with placebo (saline) and 13 mg of ketorolac sprayed as aerosol into both nostrils. A positive challenge result was defined as an increase of ≥30% in nasal symptoms (recorded using a visual analog scale) and a 30% drop in the sum of the volumes of both nasal cavities at 2-8 cm. Patients with a negative NKC result underwent SBPCOC with aspirin (cumulative dose of 750 mg). Results A naso-ocular reaction during NKC was detected in 21 patients. Four patients also developed mild asthma exacerbations (although only 1 experienced a decrease in FEV1 >15%). No other significant adverse events occurred. The remaining 15 patients with a negative NKC result had a negative response during aspirin SBPCOC. Conclusions NKC assessed using acoustic rhinometry is a reliable method for the study of patients with AERD. We suggest that NKC assessed with acoustic rhinometry was useful and safe for selection of candidates for safe oral aspirin challenge.

Clin. Otolaryngol. 2010, 35, 462–467 Objectives: To assess the correlation between acoustic rhinometry and visual analogue scale endpoints in the context of nasal challenge with occupational agents. Design: Prospective controlled study. Setting: University teaching hospital. Participants: Sixty-seven subjects with a history of work-related rhinitis and asthma symptoms. Main outcomes measures: Subjects underwent nasal challenge with control and specific agent on consecutive days. Nasal congestive response to challenge was monitored by acoustic rhinometry and visual analogue scale. Results: Results showed no correlation between visual analogue scale and acoustic rhinometry measurements at baseline on the control (r = −0.13, P = 0.3) and active (r = 0.14, P = 0.2) challenge days. No correlation was found between acoustic rhinometry and visual analogue scale when analysing all measurements obtained at all times after challenge with the control and active agent (control: r = 0.09, P = 0.04; active: r = 0.001, P = 0.9). The correlation between acoustic rhinometry and visual analogue scale was good and significant (r = −0.62, P = 40% from baseline values. Conclusions: We showed that the correlation between acoustic rhinometry and subjective nasal patency was poor on steady conditions. However, a significant correlation was observed in those cases showing a greater nasal congestive response after challenge measured by acoustic rhinometry.

Summary Introduction. Sensitization to cat allergens is common worldwide. Currently, there is a trend towards costly and often unavailable diagnostic analysis. Objectives. The aim is to assess the reliability of skin prick test (SPT) and serum specific IgE (ssIgE) to cat sensitization, by performing nasal challenge test (NCT) in a community with low cat ownership but common presence of stray cats. Patients and methods. Forty-one pa-tients with perennial allergic rhinitis (AR) who were mono or polysensitized (including cat) were included. We had 31 cat non-owners and 10 present cat owners. SPT (> 5 mm / diameter), ssIgE (≥ 0.70 IU/ml), nasal smear for eosinophil (Eo) and NCT were compared between groups. Outcomes included nasal challenge score, nasal Eo positivity, peak inspiratory and expiratory flow (PIF and PEF) 2 and 8 hours after the NCT, and were compared to baseline. Results. Baseline SPT wheal size and ssIgE level were similar in both groups. NCT positivity was more frequent in cat owners. The strongest nasal reaction was on the top concentration in both groups. Nasal Eo positivity in cat owners was higher before and 2 hours after NCT, but similar to non-owners at last measurement. NCT positive cat non-owners had bigger SPT wheal size than NCT negative non-owners, but smaller than NCT positive cat owners. In contrast to PEF, a significant fall in PIF was noticed in both groups. Mono and polysensitised patients showed similar NCT positivity. Conclusion. Stray cats may pose a relevant risk of developing perennial AR. Regardless of cat ownership status, SPT and ssIgE should be the first diagnostic tool. Nasal Eo and NCT seem to be good diagnostic tools in cat non-owners if diagnosis is elusive.

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-β1, 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.

Background The ability of prick puncture skin test (PPST) results and the presence of serum specific IgE (sIgE) to Dermatophagoides pteronyssinus to predict positive or negative nasal challenge (NC) results has not been determined in older adults. Objective To determine if allergy skin test and/or serum sIgE is diagnostic of allergic rhinitis in older adults. Methods Forty-eight adults (20 younger and 28 older) with rhinitis underwent NC to D pteronyssinus 1 to 4 weeks after PPST and sIgE to D pteronyssinus . Patients were not aware of their in vivo or in vitro results at the time of their NC. Results Fourteen of 48 adults (10 younger and 4 older) were NC positive. The positive predictive values for older adults with positive NC results ranged from 28.57% to 42.86% for PPST and was 16.67% for sIgE. In contrast, positive predictive values in younger adults ranged from 76.92% to 100% for PPST and was 100% for sIgE. However, negative PPST results and sIgE had high predictive values for a negative NC result to D pteronyssinus in older adults (90.48%-95.24% for PPST and 89.47% for sIgE). Conclusions Although PPST and sIgE negative results were good predictors of negative NC outcomes, neither positive PPST results nor serum sIgE to D pteronyssinus predicted positive NC results in older adults. PPST and sIgE to D pteronyssinus were excellent predictors of both positive and negative NC outcomes in younger adults.

RESTRITO Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2012-07-31T18:56:49Z No. of bitstreams: 1 DD.pdf: 265590 bytes, checksum: 6e3d0b1a12f7db40dd1f418bd2029edb (MD5) Made available in DSpace on 2012-07-31T18:56:49Z (GMT). No. of bitstreams: 1 DD.pdf: 265590 bytes, checksum: 6e3d0b1a12f7db40dd1f418bd2029edb (MD5) Previous issue date: 2006 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.

Resume Nasofibroscopes et optiques rigides se sont banalises. Ils ont revolutionne l'abord clinique de la pathologie nasale. Parallelement, l'evolution des imperatifs medico-legaux et de securite impose des contraintes de desinfection et sterilisation indissociables de leur utilisation quotidienne. La radiographie standard (« face haute » et « Blondeau ») garde l'avantage de la rapidite et de la simplicite dans l'exploration des cavites sinusiennes. La numerisation y ajoute une meilleure qualite et une plus faible irradiation. Cependant, la tomodensitometrie (TDM) detient ici la place de choix : deux plans de coupes sont necessaires : frontal et transversal. Le contraste iode est reserve a l'etude des tumeurs ou des complications de la pathologie inflammatoire. La dose d'irradiation et le risque de cataracte restent faibles. L'endoscopie virtuelle est un developpement dont l'interet pratique reste a evaluer. Seul le bilan de lesions tumorales justifie le complement d'imagerie qu'apporte l'imagerie par resonance magnetique (IRM). La rhinometrie acoustique mesure de facon fiable et non invasive les dimensions des cinq premiers centimetres des fosses nasales (avant et apres vasoconstricteurs). La mesure du debit nasal inspiratoire de pointe (DNIP) est particulierement simple et economique. Elle reste encore sous-utilisee en comparaison avec ses indications potentielles. La rhinomanometrie, plus souvent anterieure que posterieure, a du mal a confirmer sa place reelle en rhinologie clinique quotidienne. L'etude de la fonction mucociliaire repose sur une mesure de clairance plus ou moins sophistiquee (saccharine, colorant, isotopes). L'etude du battement ciliaire in vitro est un examen reserve pour l'instant a la recherche d'un syndrome de dyskinesie ciliaire. Cette meme etude in vivo reste actuellement au stade experimental. L'etude ultrastructurelle (microscopie electronique) est indispensable au diagnostic de dyskinesie ciliaire primitive. La cytologie nasale selon qu'elle est realisee sur un mouchage, un lavage, une aspiration, une empreinte, un frottis, un brossage ou un grattage concerne des sous-compartiments cellulaires differents. Les resultats en termes de compte cellulaire total ou de comptage differentiel sont differents. En pratique clinique, pour l'instant, seule l'eosinophilie secretoire (plus de 10 a 20 % selon les auteurs) a une reelle incidence diagnostique en l'absence d'allergie. D'un point de vue bacteriologique, le prelevement des fosses nasales permet d'identifier une flore commensale assez riche. La ponction de la cavite maxillaire, sinon le prelevement au meat moyen (fiabilite de 70 a 80 %) montre la flore en cause dans les sinusites, avec plus de polymicrobisme et d'anaerobie dans les sinusites chroniques. La presence de champignons dans le mucus nasal, parfois importante, ne permet pas actuellement de leur attribuer ou non un role pathogene. La mesure de la concentration de monoxyde d'azote nasale (NO nasal) fait l'objet de nombreux travaux de recherche. Aucune utilisation clinique n'est actuellement demontree. Les tests de provocation nasale (TPN) utilisent des methodes d'evaluation variees : clinique, rhinomanometrie, rhinometrie acoustique, voire cytologie. Ces tests realises avec des pneumallergenes souffrent actuellement d'un manque de standardisation. Les TPN pharmacologiques ou physicochimiques restent du domaine de la recherche. Enfin, pour un meilleur rendement de l'analyse anatomopathologique, il convient, des le conditionnement du prelevement d'envisager les techniques d'analyse necessaires (analyse standard, immunomarquage, biologie moleculaire).

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 30 ) 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 PC30 were 26.5, 27.4 and 38.7% for PIFR, AR and Rhino, respectively. For AMP challenge, the PC 30 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.

BACKGROUND: Topical corticosteroid therapy reduces symptoms and nasal mucosal inflammatory cells in patients with allergic rhinitis. Usually patients are advised to start their medication (1 week) before the beginning of the pollen season. The effect of pretreatment with a topical corticosteroid on unchallenged nasal mucosa is not well documented. OBJECTIVES: The purpose of this study was to investigate, in a double-blind, placebo-controlled study, the effect of 6 weeks' pretreatment with 200 microg twice daily fluticasone propionate on nasal symptoms and inflammatory cell numbers after nasal allergen provocation in patients with seasonal allergic rhinitis. METHODS: Nineteen patients with grass pollen-induced allergic rhinitis were treated for a 6-week period out of the grass pollen season. After completing the treatment period, patients were challenged with grass pollen. Nasal mucosal biopsy specimens were taken 5 times in every patient. In nasal mucosa changes in numbers of T cells, B cells, mast cells, eosinophils, macrophages, and Langerhans' cells were investigated. RESULTS: After 4 weeks of treatment but before allergen provocation, significantly fewer epithelial Langerhans' cells, macrophages, mast cells, T cells, and eosinophils were found in the fluticasone propionate group compared with those found in the placebo group. In the lamina propria significantly fewer Langerhans' cells and eosinophils were found in the fluticasone propionate group. Cell influx in nasal mucosa after allergen provocation was significantly inhibited in the fluticasone propionate group compared with that in the placebo group for epithelial Langerhans' cells, mast cells, macrophages, and T cells and for lamina propria eosinophils, mast cells, Langerhans' cells, macrophages, and T cells. CONCLUSIONS: Fluticasone propionate is effective in reducing early- and late-phase nasal symptoms. Topical corticosteroid treatment reduces inflammatory cells in unchallenged nasal mucosa

Nasal challenge with allergen or mediators is a useful model to understand the pathophysiology of allergic rhinitis. Some mechanisms have thereby been clearly clarified. Different methods have been proposed to mimic the natural allergen exposure and to measure the clinical and biological responses. Nasal challenges can also be used in clinical practice, mainly when there is a discrepancy between results of skin tests and in vitro or when occupational allergens are involved. Nasal challenges are also valuable to assess the efficacy of specific immunotherapy or some drugs.

Background: A link ("naso-bronchial reflex") between nasal and bronchial reactivity seems to exist. The effect of nonspecific nasal challenge (standing for the exposure to irritative stimuli at the workplace) on lung function indices and nonspecific bronchial reactivity is not known. Methods: In 80 healthy workers (age: 36.0 +/- 8.6 years) continuously exposed to acceptable levels of different respiratory irritants (for more than 2 years) nasal challenge was performed by spraying doubling concentrations of histamine (0.0625-16.0 mg/mL, doses of histamine: 7.8 mu g-2.08 mg) into each nostril. Before and immediately after nasal challenge spirometry and the bronchoprovocation test with histamine (0.5-128 mg/mL) was performed Results: Although nasal challenge with histamine had not reduced airway caliber (before nasal challenge vs, following nasal challenge: FEV1 3.8 +/- 0.8 vs. 3.7 +/- 0.8 L, and MEF50 4.3 +/- 1.4 vs. 4.3 +/- 1.4 L/s, mean +/- SD, respectively), it had significantly reduced nonspecific bronchial reactivity in 30.2% of the irritant-exposed subjects. Conclusions: Nasal challenge with histamine decreases nonspecific bronchial reactivity in workers occupationally exposed to respiratory irritants. Thus, a methodological implication would be that these two tests should not be performed consecutively in less than 2 hr in the same subjects.

Numerous studies have compared the duration of the cutaneous effect of cetirizine and loratadine. We assessed their nasal effects 24 hours after administration in patients with allergic rhinitis, using a randomized, double-blind, crossover, placebo-controlled trial. Nasal challenge was performed by nebulization of increasing doubling dosages of histamine (0.04-1.28 mg/nostril) in 12 patients (seven males, five females, aged 31 +/- 7 years). Nasal airway resistance was measured by posterior rhinomanometry 24 hours after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline nasal airway resistance was identical on all study days (2.86 +/- 0.10 cm H2 O/L per second). Twenty-four hours after intake, the dose-response curve of nasal obstruction to histamine was significantly lower after treatment with cetirizine compared with placebo (P0.05). However, although the curve was lower on loratadine than on placebo, the curves did not differ significantly. In conclusion, our study shows significant efficacy of cetirizine, but not of loratadine, in the nose at 24 hours after a single dose. This suggests that the nasal action of cetirizine is longer lasting than that of loratadine in patients with allergic rhinitis.

Background Platelet-activating factor (PAF) is produced by most inflammatory cells and it is involved in inflammatory and allergic reactions. We aimed to assess the anti-PAF effects of rupatadine and levocetirizine in the upper airways. Findings Healthy volunteers (HV, N = 10) and seasonal allergic rhinitis (SAR, N = 10) asymptomatic patients were treated out of the pollen season with either rupatadine 20 mg, levocetirizine 10 mg, or placebo once a day during 5 days prior to the PAF nasal challenge. Total 4-nasal symptom score (T4SS) and nasal patency (Vol2-5, by acoustic rhinometry) were assessed from 0 to 240 minutes after a repeated PAF challenge. In SAR patients but not in HV, both rupatadine and levocetirizine showed a trend to decrease PAF-induced T4SS from 60 to 120 minutes. Rupatadine but not levocetirizine caused a significant reduction (p

We have previously shown that unilateral nasal challenge with antigen causes an increase in the number of eosinophils in the ipsilateral maxillary sinus. Here we aimed to determine whether there was an eosinophil response in the contralateral maxillary sinus after unilateral nasal challenge with antigen. Twenty subjects with a history of seasonal allergic rhinitis and a positive nasal challenge to ragweed or grass allergens were studied outside of their allergy season. Catheters were placed in both maxillary sinuses and the subjects were challenged with antigen via the left nostril. The subjects recorded nasal symptoms before and after each allergen challenge and hourly for 8 h afterward. We performed nasal lavages of the nose and sinuses at the same time as symptoms were recorded. The lavages were analyzed for the number of eosinophils and levels of albumin. Subjects showed a symptomatic response to challenge accompanied by an influx of eosinophils into the nose and increased vascular permeability. The number of eosinophils increased in both maxillary sinuses. The total change from diluent in eosinophils during the late phase response was higher in the ipsilateral maxillary sinus (median = 8,505; range = 0–100,360) compared with the contralateral sinus (median = 1,596; range = −13,527–93,373; P = 0.03). We conclude that eosinophils increase in both maxillary sinuses after unilateral nasal challenge. We speculate that a central neurologic reflex initiated in the nose by the nasal challenge contributes to the bilateral eosinophil response in the maxillary sinuses. We further speculate that, since there are more eosinophils in the ipsilateral compared with the contralateral maxillary sinus, there is also an axonal reflex into the ipsilateral maxillary sinus that contributed to the eosinophil response.

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.

The purpose of the study was to develop a suitable natural rubber latex (NRL) antigen powder and a control material for the nasal application of the test reagent and to evaluate the nasal provocation test (NPT) response pattern in latex allergic and nonlatex allergic subjects with a suspicion of latex-induced rhinitis. A questionnaire was completed among health care workers (n = 268) in one hospital. Seven health care workers who had upper respiratory symptoms associated with daily usage of latex gloves were examined by using skin prick test (SPT), NPT, and sinus plain X-ray. NRL allergen for the nasal challenge was collected from surgical gloves. The powder was obtained by washing the gloves, freeze-drying the solution, and the powder was then used in NPT. As a negative control, clean corn starch powder was applicated on nasal mucous. SDS-PAGE analysis of the NRL test powder was performed. After the nasal challenge, one of seven workers showed rhinorrhea, a significant increase in nasal obstruction, and in the amount of nasal secretion in NPT. This patient also showed a positive SPT to NRL allergens and an elevated NRL specific IgE level in her serum. In six patients NPT, SPT, and specific IgE for latex were negative. SDS-PAGE analysis of the glove powder showed a major NRL antigen, with molecular weight of 14 kDa. The NPT may be used in persons with a suspicion of latex-induced rhinitis and borderline skin and humoral test results for NRL and in subjects with heavy glove powder-associated nasal symptoms but negative skin and humoral tests for latex. Only well known test reagents should be used in NPT.

Allergic rhinitis affects individuals in multiple environmental settings. We hypothesized that the environmental conditions of temperature and humidity had no effect on the early response to nasal challenge with antigen. To test this hypothesis, we selected 16 subjects with allergic rhinitis and challenged them intranasally with either ragweed or grass antigen after they were acclimatized for 1 hour in an environmental chamber to the following conditions: 4°C and 30% relative humidity (RH) (cold and dry environment), 22°C and 50% RH (normal indoor environment), and 37°C and 90% RH (hot and humid environment). The subjects remained in the chamber and were challenged with three increasing doses of antigen. Their response was measured by counting the number of sneezes and measuring the levels of histamine, N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity, albumin, and lacto ferrin in recovered nasal lavage fluids. The levels of TAME-esterase activity and albumin were significantly less during exposure to hot, humid conditions compared to normal or cold, dry environments. The other parameters were also less, although they did not reach statistical significance. We conclude that the temperature and humidity of inspired air affect the immediate allergic response. The mechanism for this reduction needs to be elucidated.

Allergic rhinitis is a common disorder and involves the reaction to environmental allergens with resultant nasal and eye symptoms. The pathophysiologic mechanisms of the eye symptoms in allergic conjunctivitis include a direct effect on the eye by deposited allergen and indirect effects related to the deposition of allergen in the nasal mucosa. One of these proposed mechanisms is the existence of a nasal-ocular reflex whereby the nasal allergic reaction leads to an afferent reflex response, the efferent limb of which results in eye symptoms. Among the treatments available for allergic rhinitis, intranasal steroids are most efficacious for nasal symptoms and have also shown sizeable efficacy related to eye symptoms. We speculated that the effect of intranasal steroids on eye symptoms in allergic rhinitis was related to their inhibition of the nasal-ocular reflex and present data previously generated from our laboratory to support this assumption in a nasal challenge model. Keywords: Nasal-ocular reflex, allergic rhinoconjuctivitis, nasal challenge, intranasal steroids

Recently, several studies have revealed a subset of patients who have positive nasal provocation to allergens despite having a negative skin prick test. It has been hypothesized that these patients have localized allergic rhinitis. However, the prevalence varies greatly, ranging from 0% to 100% of skin test–negative individuals. This wide range in prevalence is likely related to differences in methodology, including differences in allergen manufacturers, concentrations, and numbers of allergens tested and, perhaps most importantly, criteria for a positive nasal challenge. Despite the evidence to date, many challenges exist with regard to the concept of localized nasal allergy. Further studies will be required to further define the immunopathology, prevalence, practical diagnostic tests, and management.

Background The majority of allergic asthmatic patients are sensitised to several aeroallergens. Discrimination of the clinically relevant allergen is essential for the correct use of immunotherapy. Objective To investigate nasal challenge and its role in screening clinically relevant allergens in asthmatic children. Methods Aeroallergen nasal challenge was performed in five different groups of patients (asthma; asthma & rhinitis; rhinitis; atopic controls; and non-atopic controls). Differences between groups after challenge were evaluated by means of spirometry and acoustic rhinometry. Results Nasal challenge was performed in 125 patients, 25 per group. The positive nasal response of immediate type was recorded in 21 patients with asthma only (P

Ocular symptoms occur in approximately 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 H(1)-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.

Summary We evaluated the effect of pre-treatment with 1 and 2 mg b.i.d. of ketotifen on the early response to nasal challenge in a double-blind cross-over trial. Weekly nasal challenges were performed in 10 allergic subjects after 1 hr and 1, 2, 3 and 4 weeks of ketotifen administration. The response to nasal challenge was monitored by counting the number of sneezes, the assessment of subjective symptoms, and by measuring the levels of histamine and TAME-esterase activity in recovered nasal lavages. The number of sneezes diminished significantly after a single dose of drug with both the 1 and 2 mg doses. Prolonged pre-treatment did not improve the results. The levels of histamine and TAME-esterase activity in recovered nasal lavages were not changed significantly by either pre-treatment at either dose. Although the number of subjects was small, our data suggest that ketotifen diminishes allergic symptomatology by its antihistaminic properties rather than by inhibiting histamine release from mast cells. As we did not look into the effects of ketotifen on other products generated by mast cells (prostanoids, leukotrienes and tryptase), we cannot fully rule out an effect on mast cells.

Background Patients with seasonal allergic rhinitis (SAR) may have symptoms triggered by environmental changes and irritants exposure in the absence of allergen. It is hypothesized that level of hyperreactivity in mixed rhinitis is related the inflammation in the late phase response, stimulation of sensory nerves and transient receptor potential (TRP) channels. The study was done to compare subjective and objective response to the low-dose allergen, histamine and hypertonic saline challenge, with subjective responsiveness to common irritants.

U E S D A Y 839 Evaluation of in Vivo and in Vitro Responses to Nole e1 in Systemic and Local Allergic Rhinitis Paloma Campo, MD, PhD, Carmen M. Rondon Segovia, MD, Mayte Villalba, PhD, Cristobalina Mayorga, PhD, M. J. Sanchez-Quintero, BS, Oscar Palomares, PhD, Luisa Galindo, RN, Lidia Melendez, Lab. Tech., Jose Luis Rodriguez-Bada, Lab. Tech., Miguel Blanca, MD, PhD; Allergy Service Carlos Haya Hospital, Malaga, Spain, Carlos Haya Hospital, Malaga, Spain, Department of Biochemistry and Molecular Biology, Faculty of Chemistry, Madrid, Spain, Research Laboratory, Carlos Haya Hospital, Malaga, Spain, Research Laboratory, Hospital Carlos Haya, Malaga, Spain. RATIONALE: The aim of this study is evaluating in vivo and in vitro responses to purified allergen nOle e1 in local allergic rhinitis (LAR) compared to systemic allergic rhinitis (SAR). METHODS: nOle e1 was purified from olive tree pollen by RP-HPLC chromatography. Subjects with positive skin prick test (SPT), specific IgE (sIgE) to olive >0.35 kU/L, and positive nasal challenge with commercial olive pollen extract were recruited (SAR subjects). Also, subjects with negative SPT, sIgE to olive _ 2 SI). Ethical committee approved the study. RESULTS: Six SAR subjects and 4 LAR subjects were selected for the study. SPTwith nOle e1 was positive in 100% SAR subjects and all LAR subjects had negative skin tests. All SAR and LAR subjects had positive responses to nOle e1 nasal challenge. Of SAR subjects, 100% of them had positive BATwith whole commercial olive extract and 75% with nOle e1. LAR subjects showed a 75% positive BAT responses to whole commercial olive extract but no positive responses to nOle e1. CONCLUSIONS: Subjects with LAR showed positive responses to nOle e1 in vivo. In vitro responses to whole olive pollen extract were detected in a significant percentage of subjects with LAR.

Background Changes in nasal nitric oxide (nNO) levels after nasal lysine aspirin (lys-ASA) challenge have not been determined. Methods Fourteen patients with aspirin induced asthma (AIA) with or without nasal polyps with aspirin were included to the study. Hypersensitivity had to be confirmed by positive result of oral aspirin challenge Ten healthy subjects served as the control group. 12 mg of lys-ASA were applied unilaterally. Nasal symptoms were assessed using visual analogue scale (VAS) and nNO and peak nasal inspiratory flow (PNIF) measurements were performed before and 1, 2, 4 and 24 hours after the challenge. The result of the challenge was considered as positive when at least 20% fall of PNIF as well as 20% increase of total VAS score were observed. Results Ten patients (71.4%) had clinically positive result of the challenge. We observed significant fall in nNO levels in AIA patients after 1 and 2 hours after the challenge (653. 1 ± 420. 2 at baseline versus 490. 3 ± 456. 0; P = 0.0029 and 439. 9 ± 556. 4 ppb; P = 0.0076; respectively). The decrease in nNO level was more pronounced in patients with clinically positive result of the challenge (510. 1 ± 212. 5 at baseline versus 283. 3 ± 173. 4; P = 0.005; 159, 6 ± 166,1; P = 0.005 and 331. 0 ± 312.0 ppb; P = 0.037 after 1, 2 and 3 hours, respectively). In 4 subjects with clinically negative result of the challenge we noticed a trend towards higher nNO concentrations after lys-ASA challenge (1010. 8 ± 625. 2 at baseline vs 1341. 3 ± 670. 5 ppb after 4 hours). No significant changes in nNO levels after the challenge were observed in healthy controls. Conclusions NO levels decrease after lys-ASA nasal challenge in subjects with AIA and clinically positive nasal provocation. An unexpected trend towards increase in nNO levels was observed in subjects with AIA and clinically negative provocation Potential usefulness of nNO measurement in aspirin nasal provocation needs further evaluation.