Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond.

Anaphylaxis is a severe, acute, life-threatening multisystem allergic reaction resulting from the release of a plethora of mediators from mast cells culminating in serious respiratory, cardiovascular and mucocutaneous manifestations that can be fatal. Medications, foods, latex, exercise, hormones (progesterone), and clonal mast cell disorders may be responsible. More recently, novel syndromes such as delayed reactions to red meat and hereditary alpha tryptasemia have been described. Anaphylaxis manifests as sudden onset urticaria, pruritus, flushing, erythema, angioedema (lips, tongue, airways, periphery), myocardial dysfunction (hypovolemia, distributive or mixed shock and arrhythmias), rhinitis, wheezing and stridor. Vomiting, diarrhea, scrotal edema, uterine cramps, vaginal bleeding, urinary incontinence, dizziness, seizures, confusion, and syncope may occur. The traditional (or classical) pathway is mediated via T cells, Th2 cytokines (such as IL-4 and 5), B cell production of IgE and subsequent crosslinking of the high affinity IgE receptor (FcεRI) on mast cells and basophils by IgE-antigen complexes, culminating in mast cell and basophil degranulation. Degranulation results in the release of preformed mediators (histamine, heparin, tryptase, chymase, carboxypeptidase, cathepsin G and tumor necrosis factor alpha (TNF-α), and of de novo synthesized ones such as lipid mediators (cysteinyl leukotrienes), platelet activating factor (PAF), cytokines and growth factors such as vascular endothelial growth factor (VEGF). Of these, histamine, tryptase, cathepsin G, TNF-α, LTC4, PAF and VEGF can increase vascular permeability. Recent data suggest that mast cell-derived histamine and PAF can activate nitric oxide production from endothelium and set into motion a signaling cascade that leads to dilatation of blood vessels and dysfunction of the endothelial barrier. The latter, characterized by the opening of adherens junctions, leads to increased capillary permeability and fluid extravasation. These changes contribute to airway edema, hypovolemia, and distributive shock, with potentially fatal consequences. In this review, besides mechanisms (endotypes) underlying IgE-mediated anaphylaxis, we also provide a brief overview of IgG-, complement-, contact system-, cytokine- and mast cell-mediated reactions that can result in phenotypes resembling IgE-mediated anaphylaxis. Such classifications can lead the way to precision medicine approaches to the management of this complex disease.

The Effect of Broccoli Sprout Extract on Seasonal Grass Pollen-Induced Allergic Rhinitis.

Patients exposed to pollutants are more likely to suffer from allergic rhinitis and may benefit from antioxidant treatment. Our study determined if patients diagnosed with grass-induced allergic rhinitis could benefit from broccoli sprout extract (BSE) supplementation. In total, 47 patients were confirmed with grass-induced allergic rhinitis and randomized to one of four groups: group 1 (nasal steroid spray + BSE), group 2 (nasal steroid spray + placebo tablet), group 3 (saline nasal spray + BSE) and group 4 (saline nasal spray + placebo tablet). Peak Nasal Inspiratory Flow (PNIF), Total Nasal Symptoms Scores (TNSS) and nasal mucus cytokine levels were analyzed in samples collected before and after the 3-week intervention. Comparing before and after the intervention, PNIF improved significantly when comparing Groups 1 and 2, vs. placebo, at various time points (p ≤ 0.05 at 5, 15, 60 and 240 min) following nasal challenge, while TNSS was only statistically significant at 5 (p = 0.03), 15 (p = 0.057) and 30 (p = 0.05) minutes. There were no statistically significant differences in various cytokine markers before and after the intervention. Combining nasal corticosteroid with BSE led to the most significant improvement in objective measures.

Asthma in the older adult.

Objective: The older adult population is increasing worldwide, and a significant percentage has asthma. This review will discuss the challenges to diagnosis and management of asthma in older adults. Data Sources: PubMed was searched for multiple terms in various combinations, including asthma, older adult, elderly, comorbid conditions, asthma diagnosis, asthma treatment, biologics and medication side effects, and adverse events. From the search, the data sources that were utilized included peer reviewed scholarly review articles, peer reviewed scientific research articles, and peer reviewed book chapters. Study Selections: Study selections that were utilized included peer reviewed scholarly review articles, peer reviewed scientific research articles, and peer reviewed book chapters. Results: Asthma in older adults is frequently underdiagnosed and has higher morbidity and mortality rates compared to their younger counterparts. A detailed history and physical examination as well as judicious testing are essential to establish the asthma diagnosis and exclude alternative ones. Medical comorbidities, such as cardiovascular disease, cognitive impairment, depression, arthritis, gastroesophageal reflux disease (GERD), rhinitis, and sinusitis are common in this population and should also be assessed and treated. Non-pharmacologic management, including asthma education on inhaler technique and self-monitoring, is vital. Pharmacologic management includes standard asthma therapies such as inhaled corticosteroids (ICS), inhaled corticosteroid-long acting ß-agonist combinations (ICS-LABA), leukotriene antagonists, long acting muscarinic antagonists (LAMA), and short acting bronchodilators (SABA). Newly approved biologic agents may also be utilized. Older adults are more vulnerable to polypharmacy and medication adverse events, and this should be taken into account when selecting the appropriate asthma treatment. Conclusions: The diagnosis and management of asthma in older adults has certain challenges, but if the clinician is aware of them, the morbidity and mortality of this condition can be improved in this growing population.

Understanding the relationship among pharmacoadherence measures, asthma control test scores, and office-based spirometry.

BACKGROUND: This study used accepted asthma metrics and pharmaceutical claim data to develop a new asthma metric as a possible surrogate for spirometry and to better assess asthma control. OBJECTIVE: To develop and validate a new asthma metric called the Rescue Index (RI) based on ß(2)-agonist dispensings and to test the feasibility of a multivariate model to construct a global asthma metric called the Asthma Control Index (ACI). METHODS: This prospective, observational, multicenter cohort study was conducted at the Naval Medical Center San Diego (NMCSD) and at the Phoenix VA Health Care System (PVAHCS). Pharmacy claim data were correlated with the ACT, Medication Adherence Report Scale for Asthma (MARS-A), and spirometry using univariate and multivariate analyses. RESULTS: A total of 263 individuals enrolled in the study, and 95 (PVAHCS) and 156 (NMCSD) individuals completed the study. In the PVAHCS, the ACT correlated with the asthma medication ratio (AMR) (ρ = 0.37, P < .001) and inversely correlated with the RI (ρ = -0.33, P = .001), the RI inversely correlated with forced expiratory volume in 1 second (FEV(1)) (ρ = -0.22, P = .03) and the FEV(1) to forced vital capacity ratio (ρ = 0.22, P = .03). In the NMCSD population, the ACT correlated with the MARS-A (ρ = 0.23, P = .006), FEV(1) did not correlate with ACT (ρ = 0.09, P = .25) or MARS-A (ρ = 0.16, P = .047) but directly correlated with the RI (ρ = 0.19, P = .03). The AMR was strongly inversely correlated with RI in both populations (-0.74, P < .001 in the PVAHCS group and -0.78, P < .001 in the NMCSD group). When multivariate models were applied to the NMCSD and PVAHCS groups, the combination of RI and MARS-A was the best predictor of spirometry. CONCLUSION: The RI shows promise as a new asthma metric because it correlated with AMR in both cohorts. However, because RI correlated with adult spirometry and ACT only, further validation studies are needed before RI may be included in an ACI metric.

Metabolic testing in the office.

The three most commonly used metabolic tests are the Resting Metabolic Rate, Anaerobic Threshold Testing, and V.O2max. For several decades, these metabolic tests have been confined to the setting of university-based physiology laboratories and cardiopulmonary environments, i.e., metabolic carts in the intensive care units. The information gathered is used as a research and clinical tool in evaluating metabolic activity in a variety of physiological states from a body at rest, to exercise (aerobic and anaerobic), in certain medical states like illness, fed/starvation, and medicinal or supplementation affective states. Over the last decade, as technology has improved, so have the metabolic testing carts. They have become widely available for mainstream use by a variety of health care professionals. The purpose of this article is to review these three tests and how they may be useful in a medical practice.