New insights in the optimal diagnosis and management of food allergy.

Background: In recent years, food allergy has become a rising global epidemic, more so in Western countries. Although genetics may play a role in this increase, there are many other factors that have contributed to the upsurge. Recent research has shown that introducing allergenic foods to infants at an early age can reduce the risk of developing allergies to those foods. This is a substantial departure from traditional advice, which had recommended delaying the introduction of potential allergenic foods until a child was at least 1 year old and, in some cases, until the child was much older. Objective: The purpose of the present report is to review the epidemiology, mechanisms, and new prevention strategies for food allergies, and to discuss new treatment modalities associated with immune tolerance, which include the use of biologics as well as new forms of allergen immunotherapy (AIT) such as oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT), which have particular relevance for the allergist/immunologist. Results: Innovative developments in the treatment of food allergies have emerged through improved comprehension of immune tolerance and the induction of regulatory T (Treg) cells, the understanding of T-helper type 2 (Th2) cell-driven responses and their associated proinflammatory cytokine production, epitope mapping techniques, and the utilization of drugs such as monoclonal antibodies that target interleukin (IL) 4, IL-5, and IL-13 to disrupt Th2 cell-related pathways. In addition, there have been significant advancements in new forms AIT methods, which include OIT, SLIT, and EPIT. Conclusion: The present report reviews several of the many aspects of food allergy that have been impacted by this new knowledge and which have led to new insights for the optimal diagnosis and management of food allergy, and has had important implications for the diagnosis, treatment, prevention, and management of these conditions. The improved understanding of Treg-related mechanisms of immune tolerance and Th2 cell-driven responses associated with the production of proinflammatory cytokines associated with these responses, together with epitope mapping techniques, have played a crucial role in enhancing the diagnosis and management of food allergies. By identifying these variables, the allergist/immunologist is better equipped to tailor new diagnostic approaches and develop targeted therapies to significantly impact the lives of individuals affected by food allergies.

Salivary and serum IgA and IgG responses to SARS-CoV-2-spike protein following SARS-CoV-2 infection and after immunization with COVID-19 vaccines.

Background: Secretory immunoglobulin A (sIgA) plays an important role in antiviral protective immunity. Although salivary testing has been used for many viral infections, including severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), its use has not yet been well established with the SARS coronavirus 2 (SARS-CoV-2). Quantification of salivary IgA and IgG antibodies can elucidate mucosal and systemic immune responses after natural infection or vaccination. Here, we report the development and validation of a rapid enzyme-linked immunosorbent assay (ELISA) for anti-SARS-CoV-2 salivary IgA and serum IgG antibodies, and present quantitative results for immunized subjects both prior to or following COVID-19 infections. Objective: Total and serum SARS-CoV-2 spike-specific IgG responses were compared with salivary spike-specific IgA and IgG responses in samples obtained from patients recently infected with SARS-CoV-2 and from subjects recently immunized with COVID-19 vaccines. Methods: A total of 52 paired saliva and serum samples were collected from 26 study participants: 7 subjects after COVID-19 infection and 19 subjects who were uninfected. The ELISA results from these samples were compared with five prepandemic control serum samples. Total IgG and SARS-CoV-2 spike-specific IgG in the serum samples from the subjects who were infected and vaccinated were also measured in a commercial laboratory with an enzyme immunoassay. Results: A wide variation in antibody responses was seen in salivary and serum samples measured by both methods. Three groups of serum total and IgG spike-specific SARS-CoV-2 antibody responses were observed: (1) low, (2) intermediate, and (3) high antibody responders. A correlational analysis of salivary IgA (sIgA) responses with serum IgG concentrations showed a statistical correlation in the low and intermediate antibody responder groups but not in the high group (which we believe was a result of saturation). Conclusion: These preliminary findings suggest measuring salivary and serum IgG and IgA merit further investigation as markers of current or recent SARS-CoV-2 infections.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways.

BACKGROUND: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. OUTCOMES: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

Clinical reactivity to ingestion challenge with mixed mold extract may be enhanced in subjects sensitized to molds.

Manifestations of mold allergy are classically associated with inhalation of mold spores leading to symptoms of asthma and other respiratory illnesses. It is largely unknown, however, whether ingestion of aeroallergenic molds, mold spores, or other fungi found in food can also elicit hypersensitivity reactions in mold-sensitive individuals. The aim of this study was to evaluate the association between exposure to molds by oral challenge and elicitation of symptoms in mold- versus nonmold-sensitive individuals. Thirty-four adult atopic subjects were randomized into mold-sensitive groups based on skin test reactivity by skin percutaneous testing (SPT) and/or intradermal (ID) testing to a mixed mold (MM) extract preparation. All subjects underwent a single-blinded, placebo-controlled food challenge to the MM preparation. A modified scoring system was used to grade the clinical severity of symptoms elicited by challenge. All subjects tolerated challenges to the maximal oral mold dose concentration. However, higher symptom scores after challenge were found in mold-sensitive subjects compared with nonmold-sensitive subjects (p = 0.01). When mold-sensitive subjects were compared based on SPT and/or ID reactivity, higher symptom scores and lower symptom-eliciting concentrations of mold were associated with the SPT reactive subgroup compared with the subgroup with ID reactivity alone. In summary, based on our challenge results and scoring model, mold-sensitive subjects compared with nonmold-sensitive subjects experienced cumulatively higher symptom scores after oral challenge to an MM extract preparation. Future studies are warranted to confirm whether ingestion of aeroallergenic molds in food may be another contributor to symptoms in mold-sensitive individuals.

Inhaled mometasone furoate for the management of refractory oral corticosteroid-dependent asthma: a case report.

We report a case study of a 55-year-old white male with severe persistent refractory corticosteroid-dependent asthma receiving inhaled combination therapy with fluticasone propionate 500 mug and salmeterol 50 mug twice-daily in addition to 6-week cycles of oral corticosteroid treatment for the previous 7 months. The patient was switched to high-dose mometasone furoate delivered via a dry powder inhaler (660 mug twice-daily) for 6 weeks.Considerable improvement from baseline in peak expiratory flow, use of rescue medication, and asthma symptoms of coughing and wheezing was observed. The patient discontinued the oral corticosteroid after 1 week of high-dose mometasone furoate treatment. Plasma cortisol value at 8 a.m. was 8.4 mug/dL (normal range, 4.3-22.6 mug/dL) at week 6.