Impulsive simulation model for the dynamics of allergen immunotherapy

This study aims to analyze the effects of allergen immunotherapy, used to treat allergic symptoms such as pollen allergy. Mathematical models are used as a methodological approach to simulate from a system of impulsive differential equations the dynamics of the model. Immunotherapy is based of supplying small amounts of pollen to the patient, which leads to minimizing severe allergic symptoms when patients are subsequently exposed to higher amounts of pollen in the environment. Lymphocyte concentrations are considered state variables, allowing the behavior and efficacy of allergen immunotherapy to be identified. The manuscript proposes a method that allows to model mixed systems. Phenomena that present continuous times in some instants and discrete times in others, these are phenomena that are frequently found in the field of physics. Allergen immunotherapy is most effective when a treatment is created with pollen dose increments in a linear form.

Are Markers of Allergic Inflammation in Grass Pollen Allergy Influenced by H1 Antihistamines?

Soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) play important roles in allergic rhinitis (AR). Treatment with H1 antihistamines improves AR symptoms and in vitro reduces the levels of adhesion molecules. The aim of the study was to evaluate serum levels of ICAM-1 and VCAM-1 in patients with AR to grass pollen and their response to different H1 antihistamines. Material and methods: A total of 50 patients with grass pollen AR were clinically and biologically evaluated. ICAM-1 and VCAM-1 serum levels were evaluated during pollen season before and after treatment with levocetirizine and desloratadine through the ELISA method. Results: ICAM-1, VCAM-1, eosinophils, and total IgE were elevated in patients with AR, compared with healthy subjects. Both antihistamines improved specific symptoms of AR and increased patients’ quality of life during pollen season after one month of treatment. H1 antihistamines reduced VCAM-1, ICAM-1, and total IgE after one-month treatment but not significantly. Patients with increased baseline values tend to remain with increased values after one-month AH1 treatment. Conclusions: ICAM-1 and sVCAM-1 levels are higher in patients with grass pollen-induced AR than healthy controls during pollen exposure. Their serum levels tend to remain at high values during pollen season despite antihistaminic therapy.

Data Mining Methods to Detect Airborne Pollen of Spring Flowering Arboreal Taxa

Variations in the airborne pollen load are among the current and expected impacts on plant pollination driven by climate change. Due to the potential risk for pollen-allergy sufferers, this study aimed to analyze the trends of the three most abundant spring-tree pollen types, Pinus, Platanus and Quercus, and to evaluate the possible influence of meteorological conditions. An aerobiological study was performed during the 1993–2020 period in the Ourense city (NW Spain) by means of a Hirst-type volumetric sampler. Meteorological data were obtained from the ‘Ourense’ meteorological station of METEOGALICIA. We found statistically significant trends for the Total Pollen in all cases. The positive slope values indicated an increase in pollen grains over the pollen season along the studied years, ranging from an increase of 107 to 442 pollen grains. The resulting C5.0 Decision Trees and Rule-Based Models coincided with the Spearman’s correlations since both statistical analyses showed a strong and positive influence of temperature and sunlight on pollen release and dispersal, as well as a negative influence of rainfall due to washout processes. Specifically, we found that slight rainfall and moderate temperatures promote the presence of Pinus pollen in the atmosphere and a marked effect of the daily thermal amplitude on the presence of high Platanus pollen levels. The percentage of successful predictions of the C5.0 models ranged between 62.23–74.28%. The analysis of long-term datasets of pollen and meteorological information provides valuable models that can be used as an indicator of potential allergy risk in the short term by feeding the obtained models with weather prognostics.

Predictors of Airway Hyperresponsiveness in Symptomatic Children with Normal Spirometry and Suspicious of Possible Asthma

<b><i>Background:</i></b> Asthma diagnosis may be challenging particularly in patients with mild symptoms without an obstructive pattern in spirometry. Detection of airway hyperresponsiveness (AHR) by a positive methacholine challenge (MCC) is still an important diagnostic tool to confirm the presence of asthma with reasonable certainty. However, it is time consuming and could be exhausting for patients. We aimed to identify the predictive factors for AHR in children with respiratory symptoms without obstructive pattern in spirometry. <b><i>Methods:</i></b> Data from children who had undergone MCC were analyzed retrospectively. The demographic features of patients along with laboratory results were collected. <b><i>Results:</i></b> A total of 123 children with a median age of 10.5 years were enrolled. AHR was detected in 81 children (65.8%). The age of the children with AHR was significantly younger. The prevalences of aeroallergen sensitization, nocturnal cough, wheezing, and a baseline forced expiratory flow at 75% of vital capacity (FEF₇₅) &#x3c;65% were significantly more frequent in children with AHR. Multivariate logistic regression analysis revealed age, ever wheezing, nocturnal cough, tree pollen allergy, and FEF₇₅ &#x3c;65% as independent predictors of AHR. A weighted clinical risk score was developed (range, 0–75 points). At a cutoff point of 35, the presence of AHR is predicted with a specificity of 90.5% and a positive predictive value of 91.5%. <b><i>Conclusion:</i></b> In children suspected of having asthma, but without an obstructive pattern in the spirometry, combining independent predictors, which can be easily obtained in clinical practice, might be used to identify children with AHR.

The Fusion Protein rFlaA:Betv1 Modulates DC Responses by a p38-MAPK and COX2-Dependent Secretion of PGE2 from Epithelial Cells

Developing new adjuvants/vaccines and better understanding their mode-of-action is an important task. To specifically improve birch pollen allergy treatment, we designed a fusion protein consisting of major birch pollen allergen Betv1 conjugated to the TLR5-ligand flagellin (rFlaA:Betv1). This study investigates the immune-modulatory effects of rFlaA:Betv1 on airway epithelial cells. LA-4 mouse lung epithelial cells were stimulated with rFlaA:Betv1 in the presence/absence of various inhibitors with cytokine- and chemokine secretion quantified by ELISA and activation of intracellular signaling cascades demonstrated by Western blot (WB). Either LA-4 cells or LA-4-derived supernatants were co-cultured with BALB/c bone marrow-derived myeloid dendritic cells (mDCs). Compared to equimolar amounts of flagellin and Betv1 provided as a mixture, rFlaA:Betv1 induced higher secretion of IL-6 and the chemokines CCL2 and CCL20 from LA-4 cells and a pronounced MAPK- and NFκB-activation. Mechanistically, rFlaA:Betv1 was taken up more strongly and the induced cytokine production was inhibited by NFκB-inhibitors, while ERK- and p38-MAPK-inhibitors only suppressed IL-6 and CCL2 secretion. In co-cultures of LA-4 cells with mDCs, rFlaA:Betv1-stimulated LA-4 cells p38-MAPK- and COX2-dependently secreted PGE2, which modulated DC responses by suppressing pro-inflammatory IL-12 and TNF-α secretion. Taken together, these results contribute to our understanding of the mechanisms underlying the strong immune-modulatory effects of flagellin-containing fusion proteins.

Thunderstorm allergy and asthma: state of the art

Thunderstorm-triggered asthma (TA) can be defined as the occurrence of acute asthma attacks immediately following a thunderstorm during pollen seasons. Outbreaks have occurred across the world during pollen season with the capacity to rapidly inundate a health care service, resulting in potentially catastrophic outcomes for allergicpatients. TA occurs when specific meteorological and aerobiological factors combine to affect predisposed atopic patients with IgE-mediated sentitization to pollen allergens. Thunderstorm outflows can concentrate aeroallergens, most commonly grass pollen but also other pollens such as Parietaria and moulds in TA, at ground level to release respirable allergenic particles after rupture by osmotic shock related to humidity and rainfall. Inhalation of high concentrations of these aeroallergens by sensitized individuals can induce early asthmatic responses which can be followed by a late inflammatory phase. There is evidence that, during pollen season, thunderstorms can induce allergic asthma outbreaks, sometimes also severe asthma crisis and sometimes deaths in patients suffering from pollen allergy. It has been observed that changes in the weather such as rain or humidity may induce hydratation of pollen grains during pollen seasons and sometimes also their fragmentation which generates atmospheric biological aerosols carrying allergens. Asthma attacks are induced for the high concentration at ground level of pollen grains which may release allergenic particles of respirable size after rupture by osmotic shock. In other words, it is a global health problem observed in several cities and areas of the world that can strike without sufficient warning, inducing sometimes severe clinical consequences also with deaths of asthma patients. Due to constant climate change, future TA events are likely to become more common, more disastrous and more unpredictable, as a consequence it is important to have deep knowledge on this topic to prevent asthma attacks. Other environmental factors, such as rapid changes in temperature and agricultural practices, also contribute to causing TA.

Effects of a Cloth Panel Containing a Specific Ore Powder on Patients with Chamaecyparis obtusa (Cypress) Pollen Allergy

Pollen allergy to Japanese cedar and cypress is a serious illness that impairs daily life and sleep, especially during pollen season. We have reported that placing a cloth panel containing a specific natural ore powder (CCSNOP) in a room may alleviate the symptoms of hay fever and may also benefit the immune system. This ore is from the Aso mountain range, a volcano on Kyushu Island in the southwestern part of Japan. The purpose of this study was to verify the effect of CCSNOP on cypress pollen. Thirty-one double-blind tests, which investigated cedar pollen allergies, were conducted from February to March 2018 and have already been reported. After this, in early April, 10 of these cases were recruited and all had CCSNOP installed in their bedrooms. Before that, various symptoms and changes in medication were recorded in a “Symptom Diary” and included a mood survey by a questionnaire, stress test using saliva amylase, changes in cypress-specific immunoglobulins IgE and IgG4 by blood sampling, and eosinophil changes. In addition, changes in 29 types of cytokines were investigated. Exposure to CCSNOP relieved symptoms and subjects decreased their intake of medication. There was no change in mood or stress, but eosinophil levels tended to decrease. Although there were no statistical changes in cypress-specific IgE or IgG4, an increase in the former and a decrease in the latter were observed in some individuals during the period of pollen dispersal. Furthermore, levels of GM-CSF and IL8 decreased significantly after use of CCSNOP. The CCSNOP was shown to be effective against cypress pollen allergy, and future investigations will be necessary to observe the long-term effects of CCSNOP.

Isotretinoin-associated exercise-induced anaphylaxis in a patient with birch pollinosis and soybean sensitization: case presentation and literature review

Background Peanut and soybean allergies are listed as contraindication in the package leaflet of isotretinoin, a widely used treatment of acne vulgaris. Cross-reactivity between PR10-proteins in peanut, tree nuts, and soybean is particularly common in patients with birch pollinosis and may lead to anaphylactic reactions in sensitized patients after intake of soybean oil containing isotretinoin capsules. Case presentation Here, we describe a young man with hazelnut and birch pollen allergy, who experienced exercise-induced anaphylaxis after isotretinoin intake on the third day of treatment. A complete allergy work-up was carried out, and sensitization to both peanut and soybean PR10-proteins was confirmed. However, oral provocation with isotretinoin remained negative in the absence of intense physical activity and longterm treatment was well tolerated. Conclusion To our knowledge, this is the first report of an exercise-induced anaphylaxis due to isotretinoin therapy. Our literature review to assess tolerability of isotretinoin in patients allergic to peanut, tree nuts or soybean revealed only one other case of anaphylaxis in a cashew-nut allergic patient sensitized to soybean PR10-protein Gly m 4. While there are no reports on soybean allergic patients treated with isotretinoin, the vast majority of peanut or tree nut allergic patients tolerated isotretinoin. Therefore, we conclude that sensitization to soybean, peanut or tree nuts should not preclude isotretinoin therapy. Particular caution is however warranted in patients with soybean sensitization. Pre-treatment oral challenges with isotretinoin may be recommended and physicians should be aware of the potential role of cofactors.