- Following up infant bronchiolitis patients provided new evidence for and against the united airway disease hypothesis. [JOURNAL ARTICLE]
- Acta Paediatr 2016 Jul 29.
The united airway disease (UAD) hypothesis suggests that allergic rhinitis and asthma develop together. We evaluated the evidence for and against the UAD hypothesis at five to seven years of age after hospitalisation for bronchiolitis at less than six months.This study used prospective follow-up data for 102 children hospitalised for bronchiolitis under the age of six months. We included the presence of previous and current asthma, prolonged rhinitis and skin prick tests (SPT) to common inhaled allergens and lung function by impulse oscillometry (IOS) at five to seven years of age. Bronchial hyper-reactivity (BHR) was assessed using the exercise challenge test and bronchodilation test.Current asthma, but not previous transient asthma, was associated with prolonged rhinitis and a positive SPT. BHR, which reflected reactive airways, but not lung function, was associated with respiratory allergy, namely the combination of current asthma, prolonged rhinitis and a positive SPT.This post-bronchiolitis follow-up study suggested an association between respiratory allergy and reactive airways at five to seven years of age, which supported the UAD hypothesis. However, previous transient asthma and a reduction in lung function reduction did not support the hypothesis. This article is protected by copyright. All rights reserved.
- Crossing the threshold: can outcome data from food challenges be used to predict risk of anaphylaxis in the community? [JOURNAL ARTICLE]
- Allergy 2016 Jul 29.
There is increasing interest in using data from oral food challenges (OFC) performed under medical supervision to assist in allergy risk management, both in industry (allergen risk management) (1) and in the clinical management of the allergic individual (2). Data relating to the minimum eliciting dose (MED) needed to trigger symptoms can inform the need for precautionary allergen labelling (PAL) on food (1). However, given that "zero risk" for food-allergic individuals is not considered to be a realistic proposition (3), it is also important to consider the severity of symptoms which might be experienced: for example, a pragmatic approach, using a level of exposure that causes only minimal, transient oral symptoms in under 1% of the food-allergic population, may be acceptable to guide the use of PAL (4). However, there is often an assumption that individuals with a lower MED (i.e. who react to a lower doses of allergen) are at a greater risk of anaphylaxis (5). This article is protected by copyright. All rights reserved.
- House dust mite sublingual tablet is effective and safe in patients with allergic rhinitis. [JOURNAL ARTICLE]
- Allergy 2016 Jul 29.
House dust mite (HDM) is the major indoor allergen for allergic diseases such as allergic rhinitis (AR) and asthma. Although sublingual immunotherapy (SLIT) is a curative treatment for HDM-induced AR, data from large-scale studies are limited. We evaluated the efficacy and safety of HDM tablets in adolescent and adult patients (aged 12-64 years) with HDM-induced AR with or without intermittent asthma.In a double-blind trial in Japan, 968 subjects were randomized 1:1:1 to 300 index of reactivity (IR), 500 IR, or placebo groups. The primary endpoint was the Average Adjusted Symptom Score (AASS) in the last 8 weeks of the 52-week treatment. Secondary endpoints included individual nasal and ocular symptom scores, rescue medication use, and the Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) scores.The AASS in the last 8 weeks of treatment significantly improved in both the 300 IR and the 500 IR groups compared to that in the placebo group (p < 0.001). In the 300 IR group, the onset of action occurred at week 8-10. All four nasal symptoms significantly improved in both active treatment groups; rescue medication use and JRQLQ outcome improved in the 300 IR group. Most adverse events (AEs) were mild, and 16 serious AEs (SAEs) were reported; however, none of them were drug-related.One-year treatment with 300 IR and 500 IR HDM tablets was effective without major safety concerns. The recommended therapeutic dose for AR is 300 IR. This article is protected by copyright. All rights reserved.
- Clinical and immuno-proteomic approach on Lantana camara pollen allergy-a major health hazard. [Journal Article]
- Allergy Asthma Clin Immunol 2016.:33.
The incidence of allergic diseases is increasing gradually and is a global burden affecting the socio-economic quality of life. Identification of allergens is the first step towards paving the way for therapeutic interventions against atopic diseases. Our previous investigation figured out that total pollen load correlated significantly with the rise of respiratory allergy in a subtropical city in India. The most dominant pollen responsible for IgE sensitivity in most patients emerged to be from Lantana camara (LC) an obnoxious weed growing in and around suburban areas of West Bengal. In this study, we identified allergenic components from this shrub using an immunoproteomic approach.Determination of dominant pollen species was done using aerobiological sampling during two consecutive years and correlated with hospitalization and skin prick test. Serum was collected from LC positive patients and checked for in vitro allergenicity using ELISA and Histamine assay. Total proteome was profiled in SDS-PAGE, 2D PAGE and immunoblotted to detect IgE binding proteins which were further identified using mass spectrometry.Lantana camara pollen emerged as a significant contributor from the correlation study with hospital admission of the respiratory allergy sufferers and its extract demonstrated an elevated IgE response in ELISA and histamine release assay tests. Five IgE reactive bands/zones were observed in 1D blot which resolved to 12 allergo-reactive spots in the 2D blot. Mass spectrometric analysis identified nine spots that grouped into four diverse proteins. Pathogenesis-related Thaumatin-like protein was found to be one of the major allergens in Lantana camara.This is to our knowledge the first attempt to identify allergens from Lantana camara using a proteomic approach. The allergens identified thereof can be used to prepare hypoallergenic vaccine candidates and design immunotherapy trials against LC pollen and other aeroallergen carriers which are cross-reactive and harbor similar proteins.
- A positive methacholine challenge based on specific airway conductance: A case report. [Journal Article]
- Can J Respir Ther 2016; 52(2):53-5.
A 30-year-old Caucasian man presented to the pulmonary function laboratory for a methacholine challenge test. Following inhalation of the final dose of methacholine, the forced expiratory volume in 1 s (FEV1) was 8% below baseline. However, the patient complained of chest tightness and dyspnea, similar to the symptoms he experienced after running. Repeat specific airway conductance was found to be 73% below baseline, indicating marked airway hyper-responsiveness. Because the reduction in specific airway conductance was accompanied by familiar symptoms, the post-test probability of asthma increases, even in the absence of a 20% reduction in FEV1.
- Asthma-related emergency department use: current perspectives. [Journal Article, Review]
- Open Access Emerg Med 2016.:47-55.
Asthma is one of the most common chronic pediatric diseases. Patients with asthma often present to the emergency department for treatment for acute exacerbations. These patients may not have a primary care physician or primary care home, and thus are seeking care in the emergency department. Asthma care in the emergency department is multifaceted to treat asthma patients appropriately and provide quality care. National and international guidelines exist to help drive clinical care. Electronic and paper-based tools exist for both physicians and patients to help improve emergency, home, and preventive care. Treatment of patients with asthma should include the acute exacerbation, long-term management of controller medications, and controlling triggers in the home environment. We will address the current state of asthma research in emergency medicine in the US, and discuss some of the resources being used to help provide a medical home and improve care for patients who suffer from acute asthma exacerbations.
- Variations in pollen counts between Indianapolis, IN, and Dayton, OH, in spring 2013 and 2014. [JOURNAL ARTICLE]
- Ann Allergy Asthma Immunol 2016 Jul 25.
- Olfactory Impairment in Chronic Rhinosinusitis Using Threshold, Discrimination, and Identification Scores. [JOURNAL ARTICLE]
- Chem Senses 2016 Jul 28.
Differences in testing modalities and cut-points used to define olfactory dysfunction contribute to the wide variability in estimating the prevalence of olfactory dysfunction in chronic rhinosinusitis (CRS). The aim of this study is to report the prevalence of olfactory impairment using each component of the Sniffin' Sticks test (threshold, discrimination, identification, and total score) with age-adjusted and ideal cut-points from normative populations. Patients meeting diagnostic criteria for CRS were enrolled from rhinology clinics at a tertiary academic center. Olfaction was assessed using the Sniffin' Sticks test. The study population consisted of 110 patients. The prevalence of normosmia, hyposmia, and anosmia using total Sniffin' Sticks score was 41.8%, 20.0%, and 38.2% using age-appropriate cut-points and 20.9%, 40.9%, and 38.2% using ideal cut-points. Olfactory impairment estimates for each dimension mirrored these findings, with threshold yielding the highest values. Threshold, discrimination, and identification were also found to be significantly correlated to each other (P < 0.001). In addition, computed tomography scores, asthma, allergy, and diabetes were found to be associated with olfactory dysfunction. In conclusion, the prevalence of olfactory dysfunction is dependent upon olfactory dimension and if age-adjusted cut-points are used. The method of olfactory testing should be chosen based upon specific clinical and research goals.
- New insights into the stereochemical requirements of the bradykinin B1 receptor antagonists binding. [JOURNAL ARTICLE]
- J Mol Graph Model 2016 Jul 1.:184-196.
Bradykinin (BK) is a nonapeptide involved in several pathophysiological conditions including among others, septic and haemorrhagic shock, anaphylaxis, arthritis, rhinitis, asthma, inflammatory bowel disease. Accordingly, BK antagonists have long been sought after for therapeutic intervention. Action of BK is mediated through two different G-protein coupled receptors known as B1 and B2. Although there are several B1 antagonists reported in literature, their pharmacological profile is not yet optimal so that new molecules need to be discovered. In the present work we have constructed an atomistic model of the B1 receptor and docked diverse available non-peptide antagonists in order to get a deeper insight into the structure-activity relationships involving binding to this receptor. The model was constructed by homology modeling using the chemokine CXC4 and bovine rhodopsin receptors as template. The model was further refined using molecular dynamics for 600ns with the protein embedded in a POPC bilayer. From the refinement process we obtained an average structure that was used for docking studies using the Glide software. Antagonists selected for the docking studies include Compound 11, Compound 12, Chroman28, SSR240612, NPV-SAA164 and PS020990. The results of the docking study underline the role of specific receptor residues in ligand binding. The results of this study permitted to define a pharmacophore that describes the stereochemical requirements of antagonist binding, and can be used for the discovery of new compounds.
- The infant gut bacterial microbiota and risk of pediatric asthma and allergic diseases. [REVIEW, JOURNAL ARTICLE]
- Transl Res 2016 Jul 9.
Among the many areas being revolutionized by the recent introduction of culture-independent microbial identification techniques is investigation of the relationship between close contact with large animals, antibiotics, breast feeding, mode of birth, and other exposures during infancy as related to a reduced risk of asthma and allergic disease. These exposures were originally clustered under the "Hygiene Hypothesis" which has morphed into the "Microbiota Hypothesis". This review begins by summarizing epidemiologic studies suggesting that the common feature of these allergy risk-related exposures is their influence on the founding and early development of a child's gut microbiota. Next studies using culture-independent techniques are presented showing that the microbiota of children who have experienced the exposures of interest have altered gut microbiota. Finally, selected mouse and human studies are presented which begin to corroborate the protective exposures identified in epidemiologic studies by identifying mechanisms through which microbes can alter immune development and function. These microbially driven immune alterations demonstrate that microbial exposures in many cases could alter the risk of subsequent allergic disease and asthma. Hopefully, a better understanding of how microbes influence allergic disease will lead to safe and effective methods for reducing the prevalence of all forms of allergic disease.