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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.

BACKGROUND: Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances hasn't been investigated to date. OBJECTIVE: To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet-APE

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.

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.

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.

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.

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

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.

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

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.

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.

In this two-stage, double-blind study, we evaluated the effects of different dosages of oxatomide (1 and 2 mg/kg/day) on nasal provocation and skin reaction wheal induced by grass-pollen challenge. Children with a positive history of allergic rhinoconjunctivitis and positive responses to skin prick test and nasal provocation test to grass pollen were studied out of season. The results obtained with 1 mg/kg/day of oxatomide demonstrated no significant difference in wheal areas and nasal secretion induced by allergen challenge between treated and untreated patients. The administration of 2 mg/kg/day demonstrated a significant suppression in wheal reaction and nasal secretion induced by specific challenge.

Radioallergosorbent test (RAST), skin test and nasal challenge (provocative) test are used to identify allergen of nasal allergy. We have compared the results of tests to evaluate the methods and to establish appropriate indications for their use.House dust extract is a mixture of numerous allergenic components, mainly mites' component, so there seems to be a close correlation between sensitivities to house dust and mites. One hundred and sixty-two patients were tested with a battery of Dermatophagoides pteronyssinus (D1), Dermatophagoides farinae (D2), house dust by Greer Labos (H1), and house dust by Hollister-Stier Labos. (H2) We found 96% agreement of IgE antibodies to D1 and D2, 92% agreement for D2 and HI and 95% agreement for H1 and H2. We performed provocative tests with house dust by Torii Co. in Japan in 16 skin test-positive but RAST-negative and one skin test-negative but BAST-positive individuals. Twelve of these 17 patients had a nasal response. These results show that house dust in Japan probably contains more components of mites than does that in the United States.In cases of Japanese cedar (Cryptomeria japonica) pollinosis, there is much closer correlation between skin tests and RAST. Thirteen RAST-negative but skin testpositive patients had seasonal symptoms.RAST shows no false positive but sometimes shows false negative results.It therefore follows that RAST should be ordered only after a careful history and physical examination. As a screening test, RAST is too expensive, and excessive use of it should be condemned.

In a double-blind placebo-controlled trial of tyrosine-absorbed Dermatophagoides pteronyssinus vaccine no improvement was seen in 45 patients with asthma sensitive to house dust mite. In particular there was no significant improvement in symptom scores, spirometry, and skin and nasal challenge test results. Some patients in other studies have benefited from doses of vaccine much stronger than those now commercially available, but the incidence of side effects has also been high.

There are no data concerning the significance of allergen specific nasal challenge to latex (ASNCL) in the pediatric population and the effect of mometasone furoate nasal spray [(MFNS), topic corticosteroid exerting a potent anti-inflammatory activity] in children with latex allergic rhinitis. The aims of this study are: to investigate the clinical and immune pathological effects of ASNCL in children with latex allergy; to study the effects of MFNS pre-medication on the clinical and immune pathological effects of ASNCL in children with latex allergy. Thirteen children [6 male and 7 female, mean (SD) age 9.6 (2.9) years] with latex allergy and seven children [3 male and 4 female, mean (SD) age 9.9 (3.8) years] without latex allergy underwent ASNCL. Nasal symptoms were recorded, nasal lavage fluid was collected to measure tryptase, eosinophil cationic protein (ECP), interleukin-5, interferon-γ levels, and spirometric test was performed for each patient without or with pre-medication with MFNS. ASNCL induced a clinical allergic response and increased tryptase levels only in children with latex allergy. No serious adverse events occurred after ASNCL. MFNS pre-medication reduced both tryptase and ECP levels only in children with latex allergy. ASNCL is a simple, reliable and useful tool to make or confirm the diagnosis of nasal symptoms due to latex; it allows us to study both clinical symptoms and local immunological changes. MFNS pre-medication before an ASNCL may prevent some immunological responses induced by ASNCL without clinical allergic modifications.

Background: Nasal lysine aspirin (Lys-ASA) challenge is an alternative to oral and bronchial challenges in the diagnosis of hypersensitivity to acetylsalicylic acid (ASA) and other non-steroid anti-inflammatory drugs (NSAIDs). The aim of the study was to evaluate the sensitivity and specificity of acoustic rhinometry as an objective method of evaluation of nasal Lys-ASA challenge. Material and methods: We enrolled 20 patients with ASA-induced asthma confirmed by oral challenge (ASA-S group), 5 patients with allergic rhinitis without hypersensitivity to NSAIDs, and 5 healthy individuals (ASA-NS group). All the subjects underwent challenge with placebo (0.9% NaCl) or 14.4 mg of Lys-ASA applied in a spray into both nostrils (total dose: 16 mg of ASA). Measurements of nasal volume bilaterally were performed with an acoustic rhinometer before and 1, 2, 4, and 24 hours after the challenge. For further calculations we used the sum of both nasal volumes at 2 to 5 cm from the nostrils. Results: The mean total nasal volume in the AIA group before and 1, 2, 4, and 24 hours after the challenge was 7.75, 6.21, 7.11, 7.12, and 7.24 cm3 following placebo, respectively, and 7.24, 5.77, 6.31, 6.27, and 6.98 cm3 following Lys-ASA, respectively (p = 0.048 and p = 0.02 at 2 and 4 hours, Lys-ASA vs. placebo, Wilcoxon test). With the cutoff value of nasal volume reduction of 10%, the test sensitivity was 70%, the specificity was 60%, the positive predictive value was 77.78%, and the negative predictive value was 50% at 1 hour after the challenge. Conclusions: Acoustic rhinometry with the measurement of nasal volume at 2 to 5 cm from the nostrils proved insufficiently sensitive or specific to be used as the sole method for evaluation of nasal Lys-ASA challenge.

Background: A proportion of patients allergic to birch pollen are also allergic to pit fruit. The objective of this study was to investigate the effect of immunotherapy with birch pollen on birch-pollen-related apple allergy. Method: Patients with birch pollen immunotherapy underwent a skin-prick test with birch pollen, apple and rMal d 1, global assessments and nasal challenges with birch pollen, open food challenge with apple and a double-blind, placebo-controlled test with rMal d 1 at the start of and during the immunotherapy. Measurements of specific IgE in response to Bet v 1 and rMal d 1 and IgG4 in response to Bet v 1 and rMal d 1 took place. Results: Six of eight patients demonstrated an improvement of nasal challenge test results and all patients improved on global assessment during the immunotherapy. The median oral dose of apple required to elicit a reaction increased but was not statistically significant. The patients showed a decrease in skin-prick test values in response to birch pollen (1.05 to 0.36), apple (0.78 to 0.25) and rMal d 1 (0.51 to 0.10) with p-values of 0.04, 0.03 and 0.06, respectively and a decrease of specific IgE in response to Bet v 1 (10.66 kU/L to 5.19 kU/L) and rMal d 1 (0.99 to 0.61 kU/L) with p-values of 0.01 and 0.05, respectively. Only the median specific IgG4 value to Bet v 1 increased from 0.05 to 1.85 mg/L (p-value of 0.02) and not to IgG4 rMal d 1 (0.07 to 0.08 kU/L). Conclusion: The beneficial effects of immunotherapy for birch pollen were accompanied by a limited effect on apple allergy.