Nasal Challenge Test Research Articles

Role of specific immunoglobulin-E in chronic rhinosinusitis: Its clinical relevance according to nasal challenge test

BackgroundGuidelines for chronic rhinosinusitis (CRS) propose total IgE and eosinophils as important biomarkers to identify type-2 inflammation. Despite the fact that specific IgE (sIgE) have been identified as a clinical predictor in some type-2 diseases for different clinical outcomes, its role in CRS has yet to be explored in detail. ObjetiveTo describe systemic and local sIgE in CRS and explore its possible association with clinical outcomes using nasal challenge tests (NCT). MethodsIn CRS patients, we measure total IgE, serum sIgE (SsIgE) and nasosinusal sIgE (NsIgE) against 9 allergenic sources; Der p, Der f, Blo t, Can f, Fel d, Per a, grasses, Staphylococcus enterotoxin A, and B. NCT was done using the allergen with the higher sIgE prevalence (Der p). ResultsA total of 174 patients were included. Prevalence of SsIgE was 52.8% and NsIgE 46.5%; Der p was the principal allergen for SsIgE and NsIgE. The presence of nasal polyps, asthma comorbidity, NSAID hypersensitivity, and hyposmia, were significantly associated with the presence of SsIgE and NsIgE but not with total IgE. NCT-Der p was performed in 73 CRS patients, being positive in 33 (45.2%). SsIgE have the best diagnostic accuracy (79.4%) to predict NCT results (NsIgE 67.5% total IgE 52%). ConclusionSpecific IgE is a better biomarker in CRS than total IgE. Patients with clinically relevant SsIgE have a pheno-endotype associated with different clinical outcomes. Considering the clinical relevance of SsIgE demonstrated by NCT, interventions like allergen immunotherapy in CRS must be study.

Upcoming diagnostic modalities: Basophil activation test, CRD, and nasal challenge test

Upcoming diagnostic modalities: Basophil activation test, CRD, and nasal challenge test

Allergen challenge tests in allergen immunotherapy: State of the art.

Treatment effects in allergen immunotherapy (AIT) studies are based on symptomatic improvement, and evaluations of naturally exposed patients do often show weak efficacy. Allergen challenge tests, such as conjunctival (CAC), nasal (NAC), or bronchial (BAC) challenge tests, or challenges in allergen exposure chambers (AEC) are accepted by regulators for AIT phase II studies only. This review aims to describe different allergen challenge test methods, summarizes safety and limitations for each, and discusses their potential for use in AIT trials. Organ-specific allergen challenges provide information about individual reactivity, reaction threshold, and organ-specific efficacy of AIT. AECs, targeting all affected organs simultaneously, were developed to investigate disease mechanisms and treatment effects under controlled and reproducible conditions. A high level of standardization is existing for NAC only; in CAC and BAC, the toolbox is limited to subjective symptom scoring with no validated objective parameters identified yet. AECs are complex and heterogenous; correlation of systems and comparability of study data is claimed. All challenge methods are safe when conducted by experienced staff.

Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study

The efficacy of an allergen-specific IgG cocktail to treat cat allergy suggests that allergen-specific IgG may be a major protective mechanism elicited by allergen immunotherapy. Extending these findings, we tested a Bet v 1-specific antibody cocktail in birch-allergic subjects. This was a phase 1, randomized, double-blind, study with 2 parts. Part Aadministered ascending doses of the Bet v 1-specific antibody cocktail REGN5713/14/15 (150-900 mg) in 32 healthy adults. Part B administered a single subcutaneous 900-mg dose or placebo in 64 birch-allergic subjects. Total nasal symptom score response to titrated birch extract nasal allergen challenge and skin prick test (SPT) with birch and alder allergen were assessed at screening and days 8, 29, 57, and 113 (SPT only); basophil activation tests (n= 26) were conducted. Single-dose REGN5713/14/15 significantly reduced total nasal symptom score following birch nasal allergen challenge relative to baseline. Differences in total nasal symptom score areas under the curve (0-1 hour) for subjects treated with REGN5713/14/15 versus those given placebo (day 8: -1.17, P= .001; day 29: -1.18, P= .001; day 57: -0.85, P=.024) and titration SPT with birch difference in area under the curve of mean wheal diameters for subjects treated with REGN5713/14/15 versus placebo (all P< .001) were sustained for ≥2 months; similar results were observed with alder SPT. REGN5713/14/15 was well tolerated. Basophil responsiveness to birch-related allergens was significantly decreased in subjects treated with REGN5713/14/15 versus those given placebo on days 8, 57, and 113 (all P< .01). Single-dose REGN5713/14/15 was well tolerated and provided a rapid (1 week) and durable (2 months) reduction in allergic symptoms after birch allergen nasal allergen challenge, potentially offering a new paradigm for the treatment of birch allergy symptoms.

Changes in the cross-sections of the nasal cavity assessed by acoustic rhinometry in the study population as a guideline for attempts to standardize nasal provocation tests.

IntroductionA specific difficulty in the standardization of nasal allergen challenge tests as measured by acoustic rhinometry is the lack of reference values measured according to dependent changes, for example height and weight/height- or weight-dependent changes. Human growth and development rates and other changes the human body undergoes throughout the lifetime depend closely on the environment, sex, and race.AimTo assess selected anthropometric (body weight and height) and rhinometric (nasal cross-sectional areas) measurements concerning subject age and sex.Material and methodsThe study was conducted in 633 subjects selected in multistage, stratified sampling (324 females and 309 males). Body weight and height were measured with a sliding weight scale and height measure. Nasal cavity cross-sectional areas were measured via acoustic rhinometry.ResultsWe observed parallel increases in the evaluated anthropometric measurements and nasal cavity cross-sectional areas both in males and females aged ≤ 14 years, with the two sexes starting to differ significantly in terms of those measurements over the age of 14 (p < 0.0001; p < 0.000001). The evaluated rhinometric measurements showed a greater correlation with height than with body weight. The time of the most diversified and dynamic changes in anthropomorphic measurements was the age of > 12 years: with boys demonstrating significantly higher mean values of height and body weight than girls.ConclusionsHeight showed a better correlation with rhinometric measurements (cross-sectional area of the nasal cavity) in younger subjects (at their age of development) than in older ones.

Validity of Skin Prick Test to Bermuda Grass in a desert environment.

Background and aim:Skin prick test (SPT) with a wheal diameter of >3 mm, generally accepted as a positive, is most commonly use diagnostic tool for Allergic rhinitis. Aim was to validate wheal size of Skin Prick Test for the Bermuda grass, in desert environment, with positive Bermuda grass Nasal challenge in same environment.Methods:In 53 adults, mean age 33.43 ± 9.36 years, both gender (females: 33.96%), SPT positive on Bermuda grass with cut off wheal longest diameter of 3 mm, Bermuda grass nasal challenge test (bgNCT) was carried out. Response was assessed subjectively (scored) and objectively (PNIF). Safety profile was assessed by PEF measurement.Results:Mean weal size of SPT (mm) was bigger in bgNCT positive patients (n=47; 88.68%) 8 [4, 15] vs 5 [3, 6] (p<0.0001). ROC analysis showed Bermuda Grass SPT at the threshold of >6.5mm enabled identification of Bermuda challenge with sensitivity of 82.98% and specificity of 100.0% (area under the curve 0.9326, standard error 0.03528; 95% confidence interval (CI): 0.8635 to 1.002; p=0.0006203).Conclusions:A SPT wheal size ≥6.5mm might be considered as an appropriate wheal size for confirming Bermuda grass allergy in adults with SAR, avoiding the demanding, time consuming and often unavailable bgNCT, especially in patients eligible for allergen immunotherapy. In these patients, bgNCT is recommended if SPT wheal size is <6.5 mm. (www.actabiomedica.it)

Nasal specific IgE to Der p is not an acceptable screening test to predict the outcome of the nasal challenge test in patients with non-allergic rhinitis

ObjectivesNasal 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. MethodsWe 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). ResultsNsIgE 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. ConclusionsNsIgE 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.

Basophil sensitivity reflects long-term clinical outcome of subcutaneous immunotherapy in grass pollen-allergic patients.

Allergic rhinoconjunctivitis is a public health problem. Allergen Immunotherapy is an effective and safe treatment, that modifies the natural course of allergic disease and induces long-term tolerance. To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue. Adults suffering from allergic rhinoconjunctivitis due to grass pollen allergy were randomized to receive subcutaneous immunotherapy (n=18) or to an open control group (n=6). Patients reported daily symptom and medication scores and weekly rhinitis related quality of life scores during four pollen seasons. Biomarkers were measured every 3months for three years treatment and every 6months in the follow-up year. Nasal and cutaneous allergen challenge tests were performed annually. Leukocyte subsets were assessed in nasal mucosa biopsies at baseline and after treatment. Subcutaneous immunotherapy led to a 447-fold decrease in basophil sensitivity during the first treatment year. This remained 100-fold lower than baseline during the 3year-treatment period and 10-fold lower during the follow-up year (n=18, P=.03). Decrease in basophil sensitivity after three weeks of treatment predicted long-term improvement in seasonal combined symptom and medication scores (ῥ=-0.69, P=.0027) during three years of treatment. AUC of IgE-blocking factor correlated to nasal allergen challenge (ῥ=0.63, P=.0012) and SPT (ῥ=0.45, P=.03). Plasma cell numbers in the nasal mucosa increased during treatment (P=.02). Decrease in basophil sensitivity after three weeks of subcutaneous allergen immunotherapy predicted the clinical outcome of this treatment.

The Effect of Birch Pollen Immunotherapy on Apple and rMal d 1 Challenges in Adults with Apple Allergy

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.

Sensitization to Cat: When Is Nasal Challenge Needed?

Introduction: Although the skin prick test (SPT) is a reliable diagnostic tool in perennial allergic rhinitis (PER) for patients allergic to cats, the minimum necessary SPT wheal size required to distinguish cat sensitization from true allergy remains controversial. The cat nasal challenge test (cNCT) could be considered the gold standard for detecting true cat allergy. Aims: To assess the difference in the frequency of cNCT positivity between cat owners and non-owners and to determine an appropriate cut-off level for SPT wheal size in detecting positive cNCT in PER patients who are candidates for allergen immunotherapy (AIT) with cat allergen extracts. Subjects and Methods: cNCT in the form of a nasal spray was administered to 60 adult patients with PER, i.e., cat owners (n = 19) and cat non-owners (n = 41) with positive SPT to cat fur allergen (Diater, Spain). Subjective (total nasal symptom score [TNSS]) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal patency and nasal eosinophil count [NEo]) were used to assess the nasal response. Peak expiratory flow (PEF) was used as a safety parameter during cNCT. Results: No differences were obtained in SPT wheal size and cNCT positivity between cat owners and non-owners. Positive cNCT detecting true cat allergy could be predicted by a cat SPT wheal size > 6.5 mm with 71.11% sensitivity and 100% specificity. Conclusions: In adult patients with PER, the frequency of cat allergy was similar among cat owners and non-owners. A cat SPT wheal size ≥6.5 mm could be helpful in detecting true cat allergy by avoiding the demanding, time-consuming, and often unavailable cNCT when cat AIT is needed.

Role of nasal challenge and local eosinophilia in indirect exposure to cat in allergic rhinitis patients.

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.

Differences in the Nasal Inflammatory Response to Cynodon dactylon From Rural and Urban Areas in Patients With Allergic Rhinitis.

BackgroundEpidemiological and experimental studies suggest that air pollution has a negative impact on human health and modifies the environment. However, the clinical implications of changes in environmental allergens secondary to air pollution have been little studied.ObjectivesTo explore if the growth conditions of the Cynodon dactylon (rural vs urban area) modify the inflammatory response among patients with allergic rhinitis.Methodology: Two extracts were prepared for diagnostic test with Cyn d proteins obtained from rural and urban environment. Skin prick test (SPT), nasal challenge test (NCT), and eosinophil count in nasal mucus were performed in 3 groups: healthy subjects without rhinitis, rhinitis with (+) Cyn d, and rhinitis with (−) Cyn d.ResultsThere was a 97% concordance in the positive and negative results of the SPT with the 2 extracts. However, Cyn d-urban extract generated larger wheals (P = .03) and a higher number of patients with rhinitis presented a positive NCT to this extract (n = 7 vs 14, P = .04). Patients with positive NCT had a significant increase in eosinophils in mucus, but there was no difference between the extracts. The healthy controls did not react to the extracts tested in the skin or nasal test.ConclusionThe findings suggest that the growth conditions in urban area of Cynodon dactylon can generate changes in the protein extract and have clinical implications in patients with allergic rhinitis.

3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)- benzoic acid: a new cause of sensitiser induced occupational asthma, rhinitis and urticaria

Objectives3-(Bromomethyl)−2-chloro-4-(methylsulfonyl)-benzoic acid (BCMBA) has not previously been identified as a respiratory sensitiser. We detected two cases who presented respiratory and urticaria symptoms related to BCMBA and had positive skin prick...

Correlations of nasal responses to leukotriene D4 and histamine nasal provocation with quality of life in allergic rhinitis.

BackgroundThe symptoms of allergic rhinitis (AR) greatly affect the quality of life (QoL) in the patients with AR. The correlations of nasal response to leukotriene D4 (LTD4) and histamine nasal provocation with health related QoL in AR are not clear.ObjectiveTo evaluate the correlations of nasal response to LTD4 and histamine nasal challenge with QoL in AR.MethodsPatients randomly underwent LTD4 and histamine nasal challenge tests, completed the rhinoconjunctivitis quality of life questionnaire (RQoLQ), and rating the symptom severity score (total symptom score 4, TSS4) in the previous week. The correlations between nasal challenge tests induced nasal responses and QoL in RQoLQ were analyzed.ResultsA total of 25 eligible AR patients enrolled and finished both LTD4 and histamine nasal challenge and completed the questionnaire of RQoLQ. Histamine nasal challenge induced sneezing, increased nasal resistant were correlated with most of the dimensions (general, practical, nasal, eye problems, and quality of sleep, p < 0.05), while LTD4 nasal challenge induced sneeze, increased nasal resistant only correlated with nasal and ocular problems. On the contrary, the severity of the sneeze assessed by TSS4, was not correlated with QoL, while the severity of rhinorrhea, congestion, and nasal pruritus were correlated with nasal and practical problems, and nasal congestion was also correlated with ocular problems (r = 0.60, p = 0.01).ConclusionLTD4 and histamine nasal challenge induced nasal responses were correlated with different clinical symptoms severity and QoL, which can be used as a good diagnosis and evaluation methods for the management of AR.

Najmniejsze przekroje poprzeczne jamy nosa w ocenie donosowej próby prowokacyjnej z alergenem

IntroductionAcoustic 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. ResultsIn 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<0,05; -14.26±28.648 p<0,05). ConclusionA response to the topically applied allergen was observed mainly in the area of the head of the inferior nasal concha as compared to the area located in the nasal vestibule.

Basophil activation testing in diagnosis and monitoring of allergic disease – an overview

The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. Through the development of flow cytometry, discovery of activation markers such as CD63 and markers identifying basophil granulocytes, the basophil activation test (BAT) has become a pervasive test. BAT measures basophil response to allergen crosslinking IgE on between 150 and 2,000 basophil granulocytes with remarkable analytical sensitivity in < 0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In patients with food-, insect venom-, and drug allergy and patients with chronic urticaria BAT can be part of the diagnostic evaluation in addition to history, skin prick testing, and specific IgE determination. BAT may also be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment, or in the natural resolution of allergy. The test may use fewer resources and be more reproducible than oral, sting, nasal or bronchial challenge testing. BAT may be useful before challenge testing as it is less stressful for the patient and avoids severe allergic reactions. It may be useful before challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. This article provides an overview of the practical and technical details as well as the utility of BAT in diagnosis and management of allergic diseases.

Basophil activation testing in diagnosis and monitoring of allergic disease – an overview

The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. Through the development of flow cytometry, discovery of activation markers such as CD63 and markers identifying basophil granulocytes, the basophil activation test (BAT) has become a pervasive test. BAT measures basophil response to allergen crosslinking IgE on between 150 and 2,000 basophil granulocytes with remarkable analytical sensitivity in < 0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In patients with food-, insect venom-, and drug allergy and patients with chronic urticaria BAT can be part of the diagnostic evaluation in addition to history, skin prick testing, and specific IgE determination. BAT may also be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment, or in the natural resolution of allergy. The test may use fewer resources and be more reproducible than oral, sting, nasal or bronchial challenge testing. BAT may be useful before challenge testing as it is less stressful for the patient and avoids severe allergic reactions. It may be useful before challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. This article provides an overview of the practical and technical details as well as the utility of BAT in diagnosis and management of allergic diseases.

A novel and well tolerated mite allergoid subcutaneous immunotherapy: evidence of clinical and immunologic efficacy.

Allergy to house dust mite is one of the most common causes of allergic rhinitis. A novel tyrosine-adsorbed, modified allergen product, Acarovac Plus, developed for the treatment of perennial mite allergy seeks to address the underlying cause of allergic rhinitis in this instance. One of two dosing regimens may be used, either the Conventional Regimen or the Cluster Regimen. We sought to compare the efficacy and safety of a specific immunotherapy, developed for the treatment of perennial mite allergy, administered under a Conventional and Clustered dosing schedule in patients with persistent allergic rhinitis. Thirty adult patients, between 18 and 65 years old, with allergic rhinitis and/or asthma secondary to hypersensitivity to Dermatophagoides pteronyssinus were administered with either conventional or cluster initial regime, with a final visit one week after the last dose administration. The efficacy to the Conventional and Cluster regimens was measured using a Nasal Challenge Test monitoring clinical symptoms and peak nasal inspiratory flow. Total IgE, serum-specific inmunoglobulins (IgE and IgG4) to Dermatophagoides pteronyssinus and relevant cytokines (IFN-γ, IL-4, IL-5, IL-10 and IL-13) were assessed. A Satisfaction Questionnaire (TSQM) was completed after each patient's final visit. The tolerability of the vaccine was assessed monitoring adverse reactions. No adverse events were recorded in either conventional or cluster regime. The specific Nasal Challenge Test led to a decrease in symptom scores and a significant decrease in mean nasal peak inspiratory flow drop was recorded in both dosing regimen groups. A significant increase in IgG4-specific antibody titres was assessed. No significant changes were observed in concentrations of total IgE, specific IgE or cytokines (IFN-γ, IL-4, IL-5, IL-10 and IL-13). Patients declared themselves most satisfied in relation to “Secondary effects”, with high overall satisfaction in both groups. Cluster and conventional specific immunotherapy resulted in no adverse reaction(s) and led to similar improvements in immunological parameters, clinical efficacy (Nasal Challenge Test) and high overall satisfaction.

Intranasal influenza vaccination using a new synthetic mucosal adjuvant SF-10: induction of potent local and systemic immunity with balanced Th1 and Th2 responses.

We found previously that bovine pulmonary Surfacten® used in newborns with acute respiratory distress syndrome is a safe and efficacious antigen vehicle for intranasal vaccination. The objective of this study was to industrially produce a synthetic adjuvant mimicking Surfacten® for clinical use without risk of bovine spongiform encephalopathy. We selected three Surfacten lipids and surfactant protein (SP)-C as essential constituents for adjuvanticity. For replacement of the hydrophobic SP-C, we synthesized SP-related peptides and analyzed their adjuvanticity. We evaluated lyophilization to replace sonication for the binding of influenza virus hemagglutinin (HA) to the synthetic adjuvant. We also added a carboxy vinyl polymer (CVP) to the synthetic adjuvant and named the mixture as SF-10 adjuvant. HA combined with SF-10 was administered intranasally to mice, and induction of nasal-wash HA-specific secretory IgA (s-IgA) and serum IgG with Th1-/Th2-type cytokine responses in nasal cavity and virus challenge test were assessed. Intranasal immunization with HA-SF-10 induced significantly higher levels of anti-HA-specific nasal-wash s-IgA and serum IgG than those induced by HA-poly(I:C), a reported potent mucosal vaccine, and provided highly efficient protection against lethal doses of virus challenge in mice. Anti-HA-specific serum IgG levels induced by HA-SF-10 were almost equivalent to those induced by subcutaneous immunization of HA twice. Intranasal administration of HA-SF-10 induced balanced anti-HA-specific IgG1 and IgG2a in sera and IFN-γ- and IL-4-producing lymphocytes in nasal cavity without any induction of anti-HA IgE. The results suggest that HA-SF-10 is a promising nasal influenza vaccine and that SF-10 can be supplied in large quantities commercially.

Occupational rhinitis caused by concurrent * sensitization to two different allergens

Exposure to wheat flour and guar gum is a well-known cause of occupational respiratory allergies among workers in the food processing industry. To date, there have been no reports of occupational rhinitis (OR) caused concurrently by two different allergens present in the workplace. To report a case of OR likely to be induced concurrently by exposure to wheat flour and guar gum in a mid-40s male employed in the food processing industry. Allergy tests and nasal challenge tests were performed to investigate and confirm the diagnosis of OR. We discuss potential mechanisms involved in the observed dual sensitization. The patient showed positive responses to wheat and guar gum extracts on skin prick testing. The total IgE was 1680 kU/l (0-100 kU/l). The diagnosis of OR was confirmed by nasal challenge tests with wheat flour and guar gum on different days. In contrast to the control day, the challenge with flour and guar gum induced an immediate clinical reaction associated with a decrease in nasal volume measured by acoustic rhinometry. The patient was advised to avoid exposure to wheat and guar gum, which resulted in a gradual resolution of nasal symptoms. Co-sensitization and cross-reactivity are possible mechanisms involved in cases of concurrent sensitization to related and unrelated allergens in patients complaining of work-related rhinitis symptoms.