The effect of nasal provocation with a single-dose allergen on the physical and cognitive performance of patients with ragweed allergy.

Purpose This study aims to compare the impact of active allergic rhinitis on physical and cognitive abilities of trained allergic athletes to untrained allergic patients. Methods Cognitive, respiratory, and fitness functions were assessed before and after allergen exposure. Participants in both groups were provoked intranasally with ragweed allergen. Results The group of athletes revealed significantly higher average values in peak inspiratory flow and fitness index before and after provocation. In neuropsychological assessments, athletes performed significantly better after allergen provocation in complex working memory capacity. Due to single acute allergen exposure, the size of the nasal cavity and nasal inspiratory peak flow significantly decreased in both groups. The physical performance of both groups did not change after provocation. Executive functions and complex working memory capacity of athletes significantly improved resulting from provocation. Conclusions A single-shot allergen in high dose might cause an increase in mental concentration, which was more pronounced in the group of athletes. This study indicates that acute exposure to allergen cannot affect the physical performance and may result in increased mental focus in patients with allergy notwithstanding the declining respiratory functions.

Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes.

Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis due to inhalant allergens. We aimed to develop a reproducible technique for grass pollen nasal allergen challenge and to study biomarkers within nasal secretions. 20 Grass pollen allergic individuals underwent nasal challenges with purified Timothy grass allergen. An initial dose-titration challenge was used to determine dose-response characteristics. Subsequently, volunteers underwent 3 further challenges using individualised threshold doses. Symptom scores, visual analogue scores, and peak nasal inspiratory flow (PNIF) were recorded at baseline and up to 6h after challenge. Nasal secretions were collected at each time point using synthetic filter papers or absorptive polyurethane sponges and analysed for IL-4, -5, -10, -13, IFN-γ, Tryptase and Eosinophil Cationic Protein (ECP). Challenges gave reproducible symptom scores and decreased PNIF. Tryptase levels in nasal fluid peaked at 5 min after challenge and returned to baseline levels at 1h. ECP, IL-5, IL-13 and IL-4 levels were increased from 2-3 h and showed progressive increases to 5-6 h. Sponges proved the superior nasal fluid sampling technique. We have developed a reproducible nasal allergen challenge technique. This may be used as a surrogate clinical endpoint in trials assessing the efficacy of treatments for allergic rhinitis. Tryptase in local nasal secretions is a potential biomarker of the early phase response; ECP and the Th2 cytokines IL-5, -13 and -4 markers of late phase allergic responses. Our model allows correlation between clinical responses and local biomarkers following nasal allergen challenge.

Effect of natural seasonal pollen exposure and repeated nasal allergen provocations on elevation of exhaled nitric oxide.

BACKGROUND: Exhaled nitric oxide (FENO) is a marker for allergic airway inflammation. We wondered whether in patients with intermittent allergic rhinitis only (i) natural pollen exposure and (ii) artificial pollen exposure by repeated nasal allergen provocations may lead to an elevation of FENO. METHODS: In two prospective studies, we compared the FENO of nonatopic controls with the FENO of nonasthmatic individuals with mild intermittent rhinitis to tree and/or grass pollen. Study I: 13 atopic individuals and seven controls had measurements of FENO, blood eosinophils and eosinophilic cationic protein (ECP) before, during and after pollen season. Study II: 16 atopic individuals and 12 controls had nasal allergen provocations on four following days out of pollen season, with daily measurements of FENO before, 2 and 6 h after provocation, and determination of blood eosinophils, ECP and FEV1 at baseline, on days 5 and 10-12. RESULTS: Natural pollen exposure (study I) caused a significant elevation of FENO in allergic individuals. Nasal allergen provocations (study II) did not elicit a statistically significant rise neither of FENO nor of blood eosinophils between baseline and day 5. However, a subgroup of four individuals with a rise of blood eosinophils during nasal allergen provocations showed also a rise of FENO. CONCLUSIONS: We suppose that in allergic rhinitis a concomitant reaction of the bronchial system is dependent on a strong local inflammation leading to a generalized immune stimulation.

Role of Dau c 1 in three different patterns of carrot-induced asthma / Papel de Dau c 1 en tres modelos de asma inducida por zanahoria

Objective: To assess the role of Dau c 1 in three patients with carrot induced asthma. Material and methods: Patient 1 had asthma when handling raw carrots. Sensitization to pollens wasn't detected. Patient 2 had rhinoconjunctivitis due to grass and olive pollen allergy. She had asthma when handling raw carrots. Patient 3 was diagnosed of rhinoconjunctivitis and asthma due to allergic sensitization to mites, several pollens and cat. She had asthma due to raw carrot ingestion and inhalation. IgE immunobot analysis and ELISA inhibition assay were used to investigate the allergens and specific antibodies. Results: IgE Immunoblot Analysis: Dau c 1 from carrot extract and the recombinant rDau c 1 were recognized by IgE from patients 1 and 2. Band of Bet v 1 in birch pollen extract wasn't recognized. Patient 3 didn't recognize any of these allergens. Specific IgE to rDau c 1 was measured by ELISA. Specific IgE ELISA-inhibition with carrot as solid phase showed an intermediate inhibition (30 %) between carrot and rDau c 1 in patient 1; and a considerable inhibition (nearly 100 %) between carrot and rDau c 1 in patient 2. No inhibition was found in patient 3. Specific IgE ELISA inhibition between rDau c 1 and rBet v 1, employing rDau c 1 as solid phase was made in patients 1 and 2. Bet v 1 showed less than 40 % of inhibition of rDau c 1 in patient 1; and an intermediate inhibition (> 40 %) between rBet v 1 and rDau c 1 in patient 2. Conclusions: Airborne carrot allergens are able to sensitize without the implication of a previous pollen allergy. Dau c 1 was the main allergen in patient 2. In patient 1, there was a band of 30 kd that looks like the predominant allergen. Patients 1 and 2 were sensitized directly from carrot allergens. In patient 3, Dau c 1 isn't related to the carrot allergy. Allergy to carrot in patient 3 seems to be related to her allergy to different pollens; however, it wasn't related to birch pollen. Mediterranean countries didn't show the same patterns of food-related pollen allergy than Nordic countries

Objetivo: Valorar la responsabilidad del Dau c 1 en tres pacientes con asma causada por zanahoria. Material y métodos: El paciente 1 tenía asma cuando manejaba zanahorias crudas, en el que no se detectó sensibilización a pólenes. La paciente 2 tenía rinoconjuntivitis causada por polen de gramíneas y de olivo, y además presentaba asma cuando manejaba zanahorias crudas. La paciente 3 padecía rinoconjuntivitis y asma, estando sensibilizada a ácaros, varios pólenes y epitelio de gato, además tenía crisis de asma tras ingestión de zanahoria y también por inhalación al manejarla. La investigación de alergenos y anticuerpos específicos (IgE) se llevó a cabo con técnicas de immunoblot y ELISA-inhibición Resultados: Análisis de IgE por immunoblot: Dau c 1 de extracto de zanahoria y el recombinante rDau c 1 fueron reconocidos por la IgE de los pacientes 1 y 2, mientras que no se reconoció la banda de Bet v 1 del extracto de polen de abedul. En la paciente 3 no se reconoció ninguno de estos alergenos. La IgE específica para rDau c 1 se midió por ELISA-inhibición con zanahoria como fase sólida, mostrando una inhibición intermedia (30%) entre zanahoria y rDau c 1 en en el paciente 1 y una inhibición considerable (próxima al 100%) entre zanahoria y rDacu c 1 en la paciente 2. En la paciente 3 no se encontró ninguna inhibición. ELISA-inhibición IgE específica entre rDau c 1 y rBet v 1, empleando rDau c 1 como fase sólida, se realizó en los pacientes 1 y 2. Bet v 1 mostró menos del 40% de inhibición de rDau c 1 en el paciente 1, y una inhibición intermedia (>40%) entre rBet v 1 y rDau c 1 en la paciente 2. Conclusiones: Los alergenos de zanahoria son capaces de sensibilizar por inhalación, sin implicación previa del polen como alergeno. Dau c 1 fue el principal alérgeno en la paciente 2. En el paciente 1 hubo una banda de 30kd que parece ser el alergeno predominante. Los pacientes 1 y 2 se sensibilizaron directamente de los alergenos de la zanahoria. En la paciente 3 el Dau c 1 no parece estar relacionado con su proceso; en esta paciente la alergia a la zanahoria parece más relacionada con la alergia a diferen tes pólenes, aunque no parece que sea el polen de abedul. En los países mediterráneos no se encuentran los mismos patrones de alergia polen-alimentos que en los países nórdicos

Cough sensitivity in allergic rhinitis.

The objective of this study was to evaluate capsaicin cough sensitivity in pollen sensitive patients with allergic rhinitis at the time of grass pollen season and out of it. Cough reflex sensitivity was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Capsaicin aerosol in doubled concentrations (from 0.02 to 200 micromol) was inhaled by a single breath. Two groups of pollen sensitive rhinitis subjects and a group of healthy controls were studied. The C2 for the 23 pollen sensitive patients of the first group, studied out of pollen season (January-February), was 0.22 micromol/l (0.06-0.76) (geometric mean + 95% CI), which was substantially lower than the 4.29 micromol/l (2.54-7.26) in 24 healthy volunteers (P=0.0001). In another group of 15 pollen sensitive patients, C2 was 0.84 micromol/l (0.14-5.20) out of pollen season and 0.11 micromol/l (0.03-0.33) during the pollen season (May-June) (P=0.04). We conclude that pollen-sensitive subjects who suffer of seasonal allergic rhinitis have significantly greater capsaicin cough sensitivity, regardless of them being in or out of pollen season. Subclinical inflammatory changes in the lower airways are probably responsible for this effect.

Bilateral nasal allergen provocation monitored with acoustic rhinometry. Assessment of both nasal passages and the side reacting with greater congestion: relation to the nasal cycle.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Superoxide dismutase failed to attenuate allergen-induced nasal congestion in ragweed-sensitized dogs.

We hypothesized that augmentation of antioxidant defenses with exogenous superoxide dismutase (SOD), an enzyme that provides an initial defense against oxidative injury, would attenuate allergen-induced nasal congestion in the canine model of allergic rhinitis. Nasal congestion was evaluated by the measurements of nasal resistance and the volume of the nasal passage. In five nonsensitized dogs, 30,000 U of SOD from bovine erythrocytes delivered by aerosol to the nasal passages before histamine challenge reduced the histamine-induced nasal congestion. At 30 min postchallenge, nasal resistance was 1.14 +/- 0.2 cmH2O.l(-1).min(-1) in the saline pretreatment study vs. 0.36 +/- 0.02 cmH2O.l(-1).min(-1) in the SOD pretreatment study (P < 0.05), and volume of nasal passage was 10.9 +/- 0.5 cm3 vs. 17.4 +/- 1.3 cm3 (P < 0.05), respectively. In five sensitized dogs, however, neither an analogous pretreatment with SOD nor intranasal aerosolized pretreatment with 30,000 U of SOD conjugated to polyethylene glycol attenuated ragweed-induced nasal congestion. Also, systemic application of SOD did not attenuate responses to challenges with histamine and ragweed in nonsensitized and sensitized dogs, respectively. The antioxidant-induced attenuation of nasal congestion in nonsensitized dogs confirms validity of the model and indicates the involvement of free radical-mediated damage in the genesis of the histamine-induced congestion. In sensitized dogs, the data do not support the hypothesis that oxidative stress is a clinically significant component of acute ragweed-induced nasal congestion. The data do not support the use of SOD for acute protection against allergic rhinitis.

Specific nasal provocation tests in patients hypersensitive to mould allergens.

BACKGROUND: In the case of allergies to outdoor mould spores and plant pollen allergens, which are often concomitant, doubts may arise as to the role of mould allergens in inducing specific clinical manifestations. Establishing their significance is crucial for qualifying the patient for specific immunotherapy. This information also helps to reduce the percentage of therapeutic failures. MATERIAL/METHODS: The study population comprised 31 patients with seasonal allergic rhinitis who were allergic to both plant pollen allergens and mould spores. In each patient we performed a skin prick test, sIgE level determination, and a specific nasal provocation test using mould allergens, according to standard allergological diagnostic procedure, and the results were objectified using acoustic rhinometry. RESULTS: Positive NPT results were obtained in 22 patients. The positive results were more frequent in persons allergic to Cladosporium herbarum (92.3%) than in those allergic to Alternaria alternata (55.5%); these differences were statistically significant (p = 0.039). No differences were found between the two subgroups in terms of the sIgE levels (p = 0.13). In the study group as a whole, a high correlation between the results of acoustic rhinometry and the intensity of clinical manifestations was observed after administration of the NPT (correlation coefficient of 0.9). The correlation between the sIgE levels and the results of the skin prick tests and the NPT was much lower (0.48 and 0.66, respectively). CONCLUSIONS: The specific nasal provocation test is a safe and easy diagnostic modality, and acoustic rhinometry provides a good method of measuring it.

Nasal provocative test in patients allergic to pollen.

Nasal provocative test (NPT) can be defined as a method for recreating upper respiratory tract response to natural allergens or irritants. It can be used in solving nasal patophisiology problems: establishing whether and how the patient's nose is sensitive to antigens or irritants; quantitative evaluation of sensitivity; establishing factors influencing sensitivity. This method is employed to confirm clinical diagnosis in cases where difficulties arise in interpretation of diagnostic tests. The study based on nasal provocative tests establish an allergy to pollen in cases of pollinosis, and select appropriate components for the desensitising vaccine. Sample group included 53 patients, 29 were females and 24 were males, aged 15-42 years, selected from 1,021 patients diagnosed between 1999-2002 in the Allergology Department of the ENT Department of the MMI. The sample patients were diagnosed based on additional tests with allergic inflammation of the nasal mucosa caused by allergy to pollen of such plants as birch, grass, rye, mugwort and plantain. Research methods included: subjective physical examination, prick tests, total and specific IgE levels in serum, nasal provocative tests and rhinomanometric examination. Allergen solution was administered onto the mucosa with a calibrated atomiser. NPT solutions containing pollen of birch, grass, rye, mugwort and plantain were used. Provocative test was considered positive if, following allergen provocation, rhinomanometric examination revealed an increase in respiratory resistance by at least 40 % in comparison with the control test. On the basis of the study, 2 conclusions were drawn: 1) Nasal provocative test is an essential element in diagnostics of allergic nasal obstruction. 2) Rhinomanometry, as an objective method of examining nasal patency, is crucial for evaluating the nasal provocative test.

Do tryptase, ECP and specific IgE measurement by nasal incubation increase the specific nasal provocation test sensitivity?

The specific Nasal Provocation Test (sNPT) is a third level diagnostic tool. Fitted to reproduce natural exposure condition to pick the responsible allergen for nasal symptoms out, it is applied when prick test and RAST responses are doubtful. SNPT results have been evaluated measuring nasal resistance (anterior rhinomanometry) and nasal symptoms (clinical score), reaching 50% of sensitivity. This study focused on the determination of allergic response markers, triggered by nasal challenge: tryptase levels in the nose, specific IgE and ECP (Eosinophil Cationic Protein). The aim was to increase sNPT sensitivity. Twenty patients suffering from allergic rhinitis and 16 age-matched-nonallergic subjects were enrolled in the study. Tryptase, specific IgE and ECP were determined in nasal mucosa applying a new method, based on in situ incubation, before and after sNPT. The latter was performed following a standardized method. Tryptase levels increased in 13 patients (65%), were unchanged in four patients (20%), and slightly decreased in three patients (15%). The increase recorded was significant in mite allergic patients (p=0.005), but not significant (p> 0.05) in pollen allergic patients. ECP values increased in 13 patients (65%), were unchanged in two patients (10%), and highly decreased in five patients (25%). ECP increase was not significant (p> 0.05). Specific IgE levels increased in seven patients (35%), were unchanged in 11 patients (55%) and decreased in two patients (10%). The IgE increase was significant in pollen-allergic patients (p<0.05), while it was not significant in mite-allergic patients (p>0.05). Tryptase, ECP, and specific IgE were not detected in the control group. The data obtained showed a positive sNPT response in 12 patients (60%). Comparing our results with those derived from classical-parameter employment, we gathered an improvement of 10%. On the basis of the usual parameters, in fact, we recorded 50% positivity, while the use of mediators provided an additional 10% improvement in sNPT sensitivity: taking together the usual parameters and nasal allergic mediators values, we reached an sNPT over-all sensitivity of 85%.

Multicenter clinical trials on a novel polyherbal formulation in allergic rhinitis.

Allergic rhinitis is the most frequently occurring immunological disorder. It affects men, women and children and represents significant cost in terms of suffering and loss of productivity. Allergy is termed as an excessive reaction to an environmental allergen. Pollen, mold, dust, mite and animal allergens that contact the nasal or eye lining cause sneezing, nasal congestion and itchy, watery, swollen, red eyes. Although a broad spectrum of therapeutic options is available, the treatment of allergic rhinitis appears to be far from satisfactory. A novel polyherbal formulation (PF; Aller-7/NR-A2) comprising seven medicinal herbal extracts was assessed in a multicenter clinical trial involving 545 patients (321 males and 224 females) aged 18-59 years for 12 weeks to evaluate its clinical efficacy in patients suffering from allergic rhinitis. A total of 171 patients participated in double-blind, randomized, placebo-controlled studies in three centers, while 374 patients were included in the open-label studies in 11 centers. The three major symptoms (sneezing, rhinorrhea and nasal congestion) of allergic rhinitis were significantly reduced. Significant improvement was also observed in absolute eosinophil count, mucociliary clearance time, peak expiratory flow rate and peak nasal flow rate. No serious adverse events that warranted cessation of treatment were observed. Minor adverse effects were noted in both the treatment and placebo groups. Thus, this study demonstrates that Aller-7/NR-A2 is well tolerated and efficacious in patients with allergic rhinitis.

Validation of an environmental exposure unit for controlled human inhalation studies with grass pollen in patients with seasonal allergic rhinitis.

BACKGROUND: There is an increasing need for allergen inhalation systems to perform basic clinical research and test anti-allergic drugs under well-controlled conditions. This requires stability of environmental conditions like temperature and humidity, as well as allergen concentration and reproducible induction of allergic symptoms. OBJECTIVE: The aim of this study was to validate an environmental exposure unit for controlled human pollen inhalation studies in participants with seasonal allergic rhinitis. METHODS: Temperature, relative humidity, and air flow rate were kept constant with an air conditioning system. Pollen atmosphere was generated using a specially designed feeding system and monitored online by laser counter and offline using rotating rod samplers. Efficacy (total nasal symptom score, nasal air flow rate, nasal secretion) and safety (lung function) parameters were evaluated at different pollen concentrations and repeated allergen challenges. RESULTS: Temperature, humidity, and air flow rate in the environmental exposure unit remained constant within a range of <2%. The spatial distribution and the temporal stability of the pollen concentration varied only slightly over 4 h (+/-10% and <4%, respectively). Dose-dependent induction of allergic rhinitis symptoms, reduction in nasal air flow rate, and increase in nasal secretion were observed over time. These effects were reproducible from day to day. Lung function remained clinically normal at all concentrations and from day to day. CONCLUSIONS: Thus, pollen exposure in the environmental exposure unit is an effective, reproducible, safe, and suitable method for single-centre clinical studies on the efficacy of anti-allergic treatment or basic clinical research.

In vitro and in vivo allergenicity of recombinant Bet v 1 compared to the reactivity of natural birch pollen extract.

BACKGROUND: Diagnostic procedures using natural extracts show only limited quantitative correlation between in vivo and in vitro results. Highly pure recombinant allergens might show more predictive findings. OBJECTIVE: The aim of this study was to compare natural birch pollen extract (BPE) and recombinant Betula verrucosa (rBet v 1) for their diagnostic value comparing skin prick tests (SPTS) and nasal provocation tests (NPTS) with specific IgE in the serum. METHODS: Thirty-four patients allergic to birch pollen and five healthy controls were investigated. SPT and NPT were performed with BPE and rBet v 1 at different concentrations. Specific serum IgE was measured by the Pharmacia CAP system. RESULTS: Commercial BPE and rBet v 1 (10 micro g/mL) were able to elicit similar allergenic reactions in vivo and IgE binding in vitro. SPT reflects immediate-type allergy as determined by NPT to a higher degree than specific IgE, for both reagents. To cause allergic reactions in NPT, higher amounts of rBet v 1 were needed than for skin tests and the sensitivity was lower than with BPE. CONCLUSION: rBet v 1 alone is sufficient for a reliable diagnosis of birch pollen allergy in most patients and induces comparable skin test reactivity as BPE, but less allergic reactions in nasal provocations.

Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal responsiveness in seasonal allergic rhinitis.

BACKGROUND: Butterbur (BB) or Petasites hybridus, a herbal remedy, exhibits in vitro inhibition of cysteinyl leukotriene biosynthesis. However, no placebo-controlled studies have been performed to evaluate the effectiveness of BB on objective outcomes such as nasal provocation testing in seasonal allergic rhinitis (SAR). METHODS: Twenty patients with grass-pollen-sensitized SAR were randomized in a double-blind, cross-over manner to receive for 2 weeks either BB 50 mg twice daily or placebo (PL) twice daily during the grass pollen season. Nasal adenosine monophosphate (AMP) challenge (the primary outcome) was administered as a single 400 mg/mL dose after each randomized treatment. RESULTS: Spontaneous recovery following AMP challenge (area under the response time profile curve as % x min+/-SEM) was significantly attenuated (P=0.028) with BB (584+/-289) compared to PL (1438+/-240); mean difference: 854 (95% CI 95-1614), and the maximum % peak nasal inspiratory flow reduction from baseline following AMP challenge was significantly blunted (P=0.036) with BB (30+/-4) compared to PL (43+/-5); mean difference: 13 (95% CI 1-25). CONCLUSIONS: BB exhibited protection against AMP-induced nasal responsiveness during the grass pollen season in sensitized patients. This is turn may explain its potential clinical efficacy in patients with SAR.

Comparison of cedar pollen-induced allergic rhinitis in passively and actively sensitized guinea pigs.

We have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an H1 antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized.

A multicenter trial of specific local nasal immunotherapy.

OBJECTIVE: To assess the efficacy and safety of specific local nasal immunotherapy (LNIT) in powder form in patients with allergic rhinitis, using subjective and objective parameters. STUDY DESIGN: A double-blind randomized multicenter trial of 102 patients with allergic rhinitis who were treated with specific LNIT for 8 consecutive months. METHODS: After identifying allergens with the skin prick test and sensitization threshold dose with the specific nasal provocation test, 102 patients were selected, of whom 55 were allergic to mites and 47 were allergic to Graminaceae or Parietaria pollen. The specific treatments were self-administered using an insufflator in two phases (phase 1: increasing doses; phase: 2, maintenance dose). Patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test results confirmed that this difference was statistically significant. The rhinomanometric analysis gave positive results for the treated group mainly in LNIT for mites. No differences in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is effective for allergic rhinitis and appears to offer considerable advantages over other hyposensitization methods. It can be done at home, patient compliance is good, and the treatment is safe.

[Comparative study of the effect of vasoconstrictive and balsamic agents in the decongestant nasal test]. / Studio comparativo degli effetti di sostanze vasocostrittrici e balsamiche nel test di decongestione nasale.

The authors report a study of 60 subjects with mono or bilateral nasal obstruction of different etiologies (30 vasomotor rhinopathy, 30 septum deviations) evaluating the decongestion action of a vasoconstrictor. This substance for topic use was administered in pill form both in association with and without different balsamic substances. The patients underwent subjective evaluation using a visual analogy scale (VAS) and an objective test such as active anterior rhinomanometry (AAR) and acustic rhinometry (AR). All evaluations were performed under basal conditions and after the nasal decongestion test (NDT). The results were processed in order to evaluate: a) relationships between the subjective results (VAS) and the objective instrumental tests (AAR and AR); b) the mechanism by which the balsamic substances affect the symptoms. The purpose was to evaluate exactly how important balsamic substances are in topic vasoconstrictor preparations. Finally, an attempt was made to confirm the importance of the nasal decongestion test to provide a concise diagnostic picture and a suitable medical or surgical approach to "nasal obstruction" symptoms. Among other things, the results underline the importance of objective methods; thanks to their reliability they now provide an essential support in the surgical indications and in following-up every nasal obstruction treatment, even as regards forensic medicine. From a strictly pharmacological point of view, whether associated with balsamic substances or not, vasoconstrictors give similar results with all evaluation methods. On the other hand, the balsamic action is limited to a subjective sensation of increased nasal air flow stemming from the stimulation of cutaneous thermoreceptors in the vestibule. Although this sensation does not correspond to an objective reduction in nasal resistance, it cannot be neglected in the treatment of obstructive symptoms where the psychological component can play an important role.

In vivo diagnostic procedures: skin testing, nasal provocation, and bronchial provocation.

In vivo challenge procedures can be very useful in the analysis of allergic symptoms. Skin testing has a high degree of sensitivity and specificity for determining antigens that cause allergic disease. However, positive skin tests do not necessarily indicate that a specific allergen causes symptoms specific for a certain organ. Nasal and whole lung provocation testing can help define relevant allergens that cause rhinitis or asthma symptoms. These tests are safe when performed properly under close medical supervision and have predictive values that make them useful diagnostic tools.

[Cell response in the nasal mucosa in patients with hay fever during plant pollen season]. / Odpowiedzi komórkowe blony slzowej nosa u chorych z pylkowica w okresie pylenia roslin.

The aim of the present study was to determine whether different reactions of the nasal mucosa can be a result of a natural provocation with allergen. During the pollen season of anemorphilous plants the nasal mucosa may trigger the following reactions allergic inflammation or non-specific secretion.

Specific nasal provocation test with powder allergen.

Reported here are the results of a large-scale trial conducted under the guidance of Prof. Giovanni Motta, which I coordinated. A total of 656 patients with nasal hyperreactivity were recruited in 51 Italian centres (18 in the north of Italy, 20 in central Italy and 13 in the south). The trial's results were as follows. 1) A clear clinical prevalence of sensitization to different allergens in the different areas of Italy, which could be roughly classified thus: a) in Northern Italy birch and grasses were in the main species; b) in Central Italy mites prevailed but oleaceae were also significant; c) in Southern Italy parietaria and oleaceae were the prevailing species. 2) Most cases were sensitive to several allergens, although a considerable proportion (22%) actually presented reactions only to one allergen and those responding account of the patients sensitive to only one allergen and those responding to a main allergen, the proportion of patients reacting clinically to only one allergen rises to 64%. 4) The specific nasal provocation test (sNPT) offers specificity comparable to in vivo diagnostic methods such as the prick test, and in vitro methods such as RAST, but is much more sensitive. 5) The sNPT can be done in any season. 6) The sNPT is highly specific below a threshold value of nasal reactivity, which can be identified for each allergen studied and expressed in Allergenic Units. 7) In patients in whom the prick test shows multiple sensitivity, the specific NPT identifies the allergen presumably responsible for the nasal reactions (main allergen). In the light of these findings double-blind specific immunotherapy was started, to last 1 year, in 107 patients (49 given placebo and 58 active treatment), with nasal allergy to grasses, parietaria and mites. The results of this treatment were as follows: 74.1% of patients presented a reduction in nasal resistance, measured by dynamic anterior rhinomanometry, indicating relief of nasal obstruction; mucociliary transport time became normal in 81% of patients, meaning that rhinorrhoea had become less marked; there was significant rise in the nasal reactivity threshold in 74.1% of patients, illustrating the degree of desensitization achieved; nasal IgA increased by 62.5% of patients and IgG in 55.2% indicating improvement in the local immunological picture. No such improvements were detectable in the patients given placebo. In conclusion, therefore, the findings of this trial in allergic rhinitis underline that the specific NPT proved more sensitive than other in vivo and in vitro diagnostic methods and is unquestionably a fundamental investigational approach for assessing nasal allergies, identifying the allergens causing the symptoms and setting up rational local immunotherapy. The sNPT also showed the efficacy of specific intranasal immunotherapy.