Comparison of sensitization and prevalence of Japanese cedar pollen and mite-induced perennial allergic rhinitis between 2006 and 2016 in hospital workers in Japan.

BACKGROUND: The prevalence of allergic rhinitis (AR) is increasing worldwide, mainly due to an increase in antigen exposure. We conducted an epidemiological study involving the staff of the University of Fukui Hospital and its associated hospital in 2006. There were 1540 participants aged ≥20 years, and the rates of Japanese cedar (JC) pollinosis and mite-induced perennial allergic rhinitis (PAR) were 36.8% and 15.8%, respectively. In 2016, we conducted a second survey. METHODS: The rate of sensitization to JC pollen and mites and the prevalence of JC pollinosis and mite-induced PAR were analyzed based on data from questionnaires and antigen-specific immunoglobulin E (IgE) levels. RESULTS: In the present study, we analyzed data of 1472 participants aged between 20 and 59 years. Total sensitization to JC pollen and total prevalence of JC pollinosis were 57.8% (851/1472) and 40.8% (601/1472), respectively. Total sensitization to mites and total prevalence of mite-induced PAR were 41.4% (610/1472) and 18.8% (276/1472), respectively. Total prevalence of JC pollinosis and mite-induced PAR increased significantly over a decade. Among the 334 people who participated in the 2006 and 2016 cross-sectional studies, 13% of JC pollinosis and 36% of mite-induced PAR experienced remission. However, since the number of new onset cases was higher that the number of remission cases, a slight increase in prevalence was observed over a decade. CONCLUSIONS: The prevalence of JC pollinosis and mite-induced PAR continues to show increasing trends, accompanied by an increase in antigen exposure. The remission rate of JC pollinosis was particularly low.

Recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites.

BACKGROUND: N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity. OBJECTIVES: To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE. METHODS: One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology. HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif. Recombinant HHM proteins were analyzed regarding fold and aggregation by circular dichroism and gel filtration, respectively. IgE reactivity was assessed by ELISA, immunoblotting and quantitative ImmunoCAP measurements. IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes. RESULTS: HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins. The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates. IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2. CONCLUSION: Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.

The significance of the levels of IL-4, IL-31 and TLSP in patients with asthma and/or rhinitis.

AIM: To investigate the clinical significance of the levels of IL-4, IL-33 and thymic stromal lymphopoietin (TLSP) in patients with asthma and/or rhinitis, then do the simple verification in animals. METHODS: Levels of IL-4 IL-31, IL-33 and TLSP were detected by ELISA and real-time PCR in 64 asthma patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases), 64 rhinitis patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases), 64 asthma complicated with allergic rhinitis patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases) and 32 healthy controls. Then we detected the IL-4, IL-31, IL-33 and TLSP in the sensitized mice. RESULTS: Results showed that levels of IL-4, IL-31, IL-33 and TSLP in asthma and rhinitis patients, and those complicated with allergic rhinitis, had significant differences compared with the control group (p < 0.05). It was found that the indicators of mugwort and dust mite allergic patients were significantly higher than that of other allergic patients (p < 0.05). We got the same tendency in in vivo experiments. CONCLUSION: IL-4, IL-31, IL-33 and TSLP may be involved in the pathogenesis of asthma and rhinitis; dust mite and mugwort allergy could increase them significantly.

Comparison of serum concentrations of environmental allergen-specific IgE in atopic and healthy (nonatopic) horses.

Allergic responses in humans, horses and other species are mediated by immunoglobulin E (IgE) antibodies. Serum testing to detect allergen-specific IgE antibodies has been developed for dogs, cats and horses; this allows for the identification of allergens and determination of appropriate allergen- specific immunotherapies. This study compared serum allergen-specific IgE concentrations in atopic and healthy horses. The study was performed on Malopolski breed atopic (n=21) and nonatopic (n=21) clinically healthy horses. Allergen-specific IgE serum concentrations were measured in summer seasons of 2008-2015 using a monoclonal anti-IgE antibody. A Northern and Central European allergen panel containing mite, insect, mould and plant pollen allergens, including 15 tests of individual allergens and 5 tests of allergen mixtures was used. The mean allergen-specific IgE concentrations in the atopic and normal horse populations were compared. Among the atopic horses, the strongest positive reactions occurred against the storage mites Tyrophagus putrescentiae and the domestic mite Dermatophagoides farinae. The atopic horses also demonstrated high IgE concentrations against insects, particularly Tabanus sp., the plant pollens colza, cultivated rye and the mould pollen mixture Aspergillus/Penicillium. No horses in the atopic group were IgE-negative. Among all mite, insect, mould and some plant allergen groups the differences in mean specific IgE concentrations between allergic and healthy horses were significant. The mean IgE concentrations for most allergen groups were significantly higher in the atopic horses than in the healthy animals. However, a high incidence of positive reactions was observed in both healthy and allergic horses. Our results showed a high frequency of polysensitization in atopic horses.

[An analysis of clinical and imaging characteristics of atopic myelitis].

OBJECTIVE: To study the clinical and imaging characteristics of Chinese atopic myelitis (AM) patients. METHODS: Three diagnosed AM patients were retrospectively analyzed for the clinical data, serum IgE level, antigen specific IgE, cerebrospinal fluid, spinal MRI and therapeutic efficacy profiles. RESULTS: All the three patients were male and presented as subacute AM with the onset at 25, 47 and 49 years old respectively. Two patients were allergic to pollen and other drugs, while another patient suffered from allergic rhinitis. Elevated serum total IgE and mite antigen specific IgE were found in all cases. Paraesthesia in limb extremities and positive Lhermitte sign were the main clinical features, while no optic, motor, urinary and defecation disturbance were found. Oligoclonal banding of cerebrospinal fluid and serum aquaporin 4 (AQP4) antibody were both negative in all cases. Spinal MRI showed lesions were hypointense on T1 and hyperintense on T2 at the posterior column of T2-3 segment with abnormal enhancement in case 1, hypointense on T1 and hyperintense on T2 at C2/3 segment with mild swelling in case 2 and hypointense on T1 and hyperintense on T2 at C3-5 segments with swelling and abnormal enhancement in case 3. Vitamin B were used in one patient, while the other two patients improved after the treatment with high-dose corticosteroids. CONCLUSIONS: Subacute myelitis predominantly presents as paraesthesia in limb extremities with elevated serum total IgE and mite antigen specific IgE, while severe motor disorders are rare. Swelling and abnormal enhancement lesions at the posterior column of cervical cord are the common imaging features. Treatment with corticosteroids is recommended to be sustained for 3-6 months.

Assessment of serum levels of allergen-specific immunoglobulin E in different seasons and breeds in healthy horses.

The present study was designed to asses specific IgE towards environment allergens in 42 healthy horses. Determination of this immunoglobulin in serum serve as diagnostic tools in allergic diseases to improve efficacy of the treatment and proper allergen selection to specific immunotherapy. Serum levels of allergen specific IgE were measured with equine monoclonal antibody, using 15 individual and 5 mix allergens in North European Panel. The study revealed season dependent increased levels of allergen specific IgE in normal horses. It is noteworthy that healthy horses show high percentage of positive reactions, most commonly towards to domestic mites D. farinae (80%), D. pteronyssinus (35.71%) and storage mites T. putrenscentiae (42.86%), Acarus siro (40.48%). These allergens play an important role in equine, canine and feline atopic dermatitis. We also demonstrated high IgE levels in the group of horse specific insect allergens. Tabanus sp. (35.71%), Culicoides sp. (28.57%) and Simulium sp. (26.19%) were the most frequent insect positive reaction allergens. No positive reactions in all groups of allergens were found in winter season, low and merely detectable levels of antibodies have been found relating to D. farianae and T. putrescentiae allergen. We observed elevated mould-IgE levels in horses that live in stables, while outdoor living horses showed very low levels. Amongst all positive reactions we observed only weak and moderate reactions but no strong positive reactions were found. No significant differences were observed between three breeds of horses with the exception of moulds and D. pteronyssinus allergens.

[Mold hypersensitivity in children with frequent respiratory tract infection and prolonged cough attacks]. / Sik solunum yolu enfeksiyonu ve uzamis öksürük ataklari olan çocuklarda küf duyarliligi

OBJECTIVES: This study aims to investigate pollen, mite and mold sensitivities among children with frequent respiratory tract infection living in damp apartments and to evaluate the effects of separated parents, education status, ethnicity, the presence of siblings, and their atopy status on the development of atopy. PATIENTS AND METHODS: Between June 2012 and September 2013, 63 children (28 girls, 35 boys; mean age 80.2 years; range 24 to 97 years) who were admitted to Acibadem Bodrum Hospital with at least six respiratory tract infection per year with mold exposure and prolonged cough attacks and underwent skin prick test (SPT) were included. Skin prick test-positive patients were further divided into groups according to the upper respiratory tract (URT) or lower respiratory tract (LRT) involvement and were assessed for mold, mite and pollen sensitivities. RESULTS: One-third of the patients were SPT positive. The parents of these patients had physician-diagnosed allergy (p<0.05). Most patients with mite sensitivity presented with URT and LRT findings (p<0.05). Pollen-sensitive patients had predominantly URT findings (p<0.05). All children with mold sensitivity presented with LRT findings (p<0.05). CONCLUSION: Atopic children may experience more frequent LRT symptoms when exposed to molds than non-atopic children. Mold exposure may also cause inflammation at LRT without causing immunoglobulin E-dependent sensitization.

Topical application of Rosa multiflora root extract improves atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice.

The roots of Rosa multiflora THUNB. (RM) has been used in oriental traditional medicines as remedies for scabies, rheumatic arthralgia and stomatitis which were practicably related with today's inflammatory and allergic diseases. In the present study, we evaluated whether RM root extract (RME) and its major constituent, 2-(3,4-dihydroxyphenyl)-6-(4-hydroxyphenyl)-8-(2,4-dihydroxyphenyl)-2,3-trans-6,7-cis-7,8-trans-3,4,7,8-tetrahydro-2H,6H-pyrano[2,3-f] chromene-3,7,9-triol (RM-3) belongs to condensed tannins, improve atopic dermatitis (AD)-like skin lesions in NC/Nga mice induced by mite antigen. Topical application of RME as well as RM-3 improved skin severity and suppressed mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) on skin tissues, in addition, significantly reduced T helper 2 (Th2) immune responses via interleukin 10 (IL-10) up-regulation. Thus, RME, contains lots of condensed tannins such as RM-3 which possesses potent anti-inflammtory and immune-modulatory effects, may be useful for treatment of skin allergies and can be developed as new alternative herbal therapy against AD.

[The analysis of the allergens in 576 patients with allergic rhinitis in Qingyang of Gansu Province].

OBJECTIVE: To investigate the allergens distribution of 576 allergic rhinitis patients in Qingyang, and to provide basic epidemiologic information for the prevention and treatment of allergic rhinitis. METHOD: Skin prick test was done to all the 576 patients with allergic rhinitis with 28 kinds of allergens. RESULT: Four hundred and eighty cases (83.3%) showed positive reaction to at least one allergen of 28 allergens. The most common allergens were Magwort (73.3%), Giant Ragweed (55.0%) Tree II (51.7%), Tree I (48.3%) Dermatophagoides farinae (43.3%) and Dermatophagoides pteronyssinus (36.7%). Moreover. the positivity decreased with age. There was no difference between male and female. CONCLUSION: The study shows that Magwort. Giant ragweed and tree II are the most important allergens on Qingyang district.

Immunotherapy is allergen-specific: a double-blind trial of mite or timothy extract in mite and grass dual-allergic patients.

BACKGROUND: One hundred years ago, Noon [Lancet 1911;1:1572-1573], using conjunctival provocation testing (CPT), was the first to demonstrate the effectiveness of subcutaneous immunotherapy (SCIT) in grass-allergic subjects with hay fever. In this centenary year, we present data that, by use of CPT and allergen-specific IgG, replicate this observation and additionally confirm the allergen specificity of SCIT by using a double-blind design employing either grass or mite SCIT in dual grass- and mite-allergic individuals. METHODS: Twenty adults (11 females) with perennial rhinoconjunctivitis and exacerbation of symptoms during the grass pollen season and in the autumn had immediate skin and conjunctival sensitivity and raised specific IgE to both Dermatophagoides farinae and Phleum pratense. Participants were randomly assigned to either timothy or D. farinae immunotherapy for 3 years. CPT and specific IgG tests to both allergens were performed annually. After 3 years, subjects gave their blinded overall evaluation. RESULTS: Six mild-to-moderate general reactions occurred in 2 timothy- and 4 mite-treated patients. Four of these patients and 2 other patients withdrew from the study. Seven patients in each group completed the study. After 3 years of immunotherapy, the timothy CPT threshold concentration had increased 16- fold in timothy-treated patients (p < 0.05; between-group change, p < 0.05). The increase in the mite CPT threshold in mite- compared to grass-treated patients was 31-fold (p < 0.05). The overall assessment of conjunctival sensitivity was highly significant in favour of treatment (p < 0.015), as was that of allergen-specific IgG (p < 0.0001). CONCLUSIONS: Allergen immunotherapy is allergen species-specific, as judged by decreased conjunctival sensitivity and changes in allergen-specific IgG concentrations.

Effects of aging on the natural history of seasonal allergic rhinitis in middle-aged subjects in South chiba, Japan.

BACKGROUND: The natural history of allergic rhinitis has been examined in a few longitudinal studies. The purpose of the study was to investigate the course, development and remission of seasonal allergic rhinitis (SAR) over 10 successive years in middle-aged subjects. METHODS: An annual questionnaire survey on allergic rhinitis symptoms combined with an examination of specific IgE has been undertaken in a rural town in south Chiba since 1995. The analyzed subjects were 703 residents who underwent every examination in 1995, 2004 and 2005. In the last 15 years, the annual pollen count in Chiba was highest in 2005. RESULTS: The sensitization rates to cedar pollen decreased with age in the same subject groups over 10 years, but the prevalence of SAR was higher in 2005 compared with 1995. Of the 52 subjects with SAR in 1995, the symptoms had disappeared in 10 subjects in 2005. Specific IgE had converted to negative or borderline in 4 of these patients, had decreased but was still positive in 4 and was increased or unchanged in 2. During the 10-year period, 22 subjects developed SAR, of whom 12 had increased specific IgE and 10 had similar or decreased specific IgE in 2005. CONCLUSION: SAR induced by cedar pollen takes a chronic course in the majority of middle-aged patients in south Chiba, Japan. The prevalence of SAR increased over 10 years due to a high level of pollen exposure. Changes in specific IgE were not directly associated with the development or remission of SAR.

[The analysis on the allergen test of the allergic rhinitis with 1564 cases in Changji district].

OBJECTIVE: To investigate the allergen distribution of subjects suffered from the allergic rhinitis in Changji district. METHOD: Skin prick test was employed on all the 1 564 sufferers by 17 sorts of allergic stock solution, with the physiological saline to be the negative control and the histamine to be the positive control. RESULT: The positive rate of allergen citanest was 85.17%. Furthermore, Chenopodium and Lupulus, as the main allergen substances, were found out to be the highest positive rate among 1332 subjects who were detected to be positive, with pollen of trees following. Whereas, the positive rate of allergic rhinitis caused by dust mite, fungus and canine epidermis was relatively low. CONCLUSION: The main allergens of the allergic rhinitis in Changji district are Chenopodium and Lupulus, similar as the dust mite. The allergen prick test, which is characterized as accuracy, sensitiveness and fastness, is an essential way to seek and screen those allergens. Thus, it can provide scientific instruction to the prevention of the allergic rhinitis in Changji district.

Allergens and their role in the allergic immune response.

Allergens are recognized as the proteins that induce immunoglobulin E (IgE) responses in humans. The proteins come from a range of sources and, not surprisingly, have many different biological functions. However, the delivery of allergens to the nose is exclusively on particles, which carry a range of molecules in addition to the protein allergens. These molecules include pathogen-associated molecular patterns (PAMPs) that can alter the response. Although the response to allergens is characterized by IgE antibodies, it also includes other isotypes (IgG, IgA, and IgG4), as well as T cells. The challenge is to identify the characteristics of these exposures that favor the production of this form of response. The primary features of the exposure appear to be the delivery in particles, such as pollen grains or mite feces, containing both proteins and PAMPs, but with overall low dose. Within this model, there is a simple direct relationship between the dose of exposure to mite or grass pollen and the prevalence of IgE responses. By contrast, the highest levels of exposure to cat allergen are associated with a lower prevalence of IgE responses. Although the detailed mechanisms for this phenomenon are not clear, it appears that enhanced production of interleukin-10 in response to specific Fel d 1 peptides could influence the response. However, it is striking that the animal sources that are most clearly associated with decreased responses at high allergen dose are derived from animals from which humans evolved more recently (∼65 million years ago). Although the nose is still recognized as the primary route for sensitization to inhalant allergens, there is increasing evidence that the skin is also an important site for the generation of IgE antibody responses. By contrast, it is now evident that delivery of foreign proteins by the oral route or sublingually will favor the generation of tolerance.

[Survey on the distribution of common allergens responsible for cases with allergic rhinitis in Tianjin district].

OBJECTIVE: To investigate the distribution of common allergens responsible for cases with allergic rhinitis in Tianjin district. METHOD: A total of 676 cases who are diagnosed with allergic rhinitis in Tianjin district, underwent a skin prick tests with 23 kinds of inhaling allergens and 20 kinds of ingestive ones. The samples were stratified on four age group. Then, an analysis was made to determine the distributive characteristics of allergens responsible for difference groups. RESULT: Among the surveyed local 676 cases with allergic rhinitis, higher positive rates was all inhaling group of allergens. CONCLUSION: It is concluded that the mostly responsible common allergens for attacks of allergic rhinitis among local cases in Tianjin district are mites, flowers pollen in inhaling group of allergens.

How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement.

Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom-medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.

Role of immunmodulators in allergen-specific immunotherapy.

Allergen-specific immunotherapy (SIT) is the only causal treatment of allergic disorders and therefore a cornerstone in the management of respiratory allergy. SIT is effective in patients with allergic rhinitis and mild-to-moderate allergic asthma. Successful treatment is associated with decrease in allergic symptoms of the upper and lower airways. The most relevant limitation in the daily routine is the restricted use of SIT in patients with moderate-to-severe allergic asthma. A strategy to overcome this limitation is to combine SIT with immunmodulators. One example of a recently developed immunmodulator is Omalizumab, a humanized, monoclonal anti-IgE antibody that binds to circulating IgE molecules, thus interrupting the allergic cascade downstream the IgE production of B cells. Up to now, four clinical trials have been performed, which all showed that the combination of Omalizumab and SIT is safe and clinically more effective than SIT alone. Moreover, administration of Omalizumab prior to SIT reduces the risk of SIT-related systemic reactions. Omalizumab and SIT are also effective in patients with mild-moderate allergic asthma. In conclusion, the use of Omalizumab as an additive immunmodulator improves safety and efficacy and might be a useful approach to broaden the indication of specific immunotherapy in allergic patients.

Topical application of Rehmannia glutinosa extract inhibits mite allergen-induced atopic dermatitis in NC/Nga mice.

AIM OF THE STUDY: Rehmannia glutinosa is known in Asia as a traditional herbal medicine with anti-inflammatory properties. Atopic dermatitis (AD) is an inflammatory skin disease associated with enhanced T-helper 2 (Th2) lymphocyte responses to allergens that results in elevated serum IgE levels and leukocyte infiltration. Although some studies have shown that Rehmannia glutinosa extract (RGE) has anti-inflammatory and anti-allergic activities, these properties have not been demonstrated in AD. This study investigated the effectiveness of RGE as a therapeutic candidate in an AD model as well as its underlying mechanism of action. MATERIALS AND METHODS: The effects of RGE on mite allergen (Dermatophagoides farinae)-treated NC/Nga mice were evaluated by skin symptom severity, ear thickness, production of serum IgE and histamine, and expression of cytokines, chemokines, and adhesion molecules in the ear lesions. In addition, the levels of thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), and regulated on activation, normal T cell expressed and secreted (RANTES) produced in both TNF-α- and IFN-γ-stimulated human keratinocytes were investigated by enzyme-linked immunosorbent assay (ELISA). RESULTS: RGE treatment of NC/Nga mice significantly reduced dermatitis scores, ear thicknesses, and serum histamine levels. Histological analyses demonstrated decreased thickening of the epidermis/dermis as well as dermal infiltration by inflammatory cells. In the ear lesions, mRNA expression levels of IL-4, TNF-α, VCAM-1, and ICAM-1 were inhibited by RGE treatment. RGE also suppressed the production of TARC, MDC, and RANTES in both the ear lesions and keratinocytes. CONCLUSIONS: RGE inhibits the development of AD in NC/Nga mice by suppressing the expression of cytokines, chemokines, and adhesion molecules.