BACKGROUND:Sensitisation to Lipid Transfer Proteins (LTP), usually ascertained by undertaking a test to the peach LTP allergen Pru p 3, is common but does not always indicate LTP allergy. Improving the diagnostic process would ensure the correct diagnosis and management of this complex condition. OBJECTIVES:To determine the diagnostic value of Pru p 3 and other LTP component allergens in UK adults. METHODS:A retrospective review was undertaken of adults referred to the Allergy Unit at the Royal Brompton & Harefield Hospitals (RBHT) London (UK), between 2012 and 2022 who were sensitised to Pru p 3. Those with a final diagnosis of LTP allergy were compared to those sensitized to Pru p 3 but not diagnosed with LTP allergy. RESULTS:Of 285 patients with a positive Pru p 3, 157 (55%) were diagnosed with LTP allergy. LTP allergic patients were more likely to have a higher level of Pru p 3, and a lower level of total IgE. The ratio of Pru p 3:total IgE was the most accurate diagnostic marker of LTP allergy, with a receiver operating characteristics AUC of 0.880. A diagnosis of LTP allergy was also significantly associated with sensitisation to the LTP in peanut (Ara h 9, p < 0.001), and hazelnut (Cor a 8, p < 0.001). CONCLUSION:Sensitisation to Pru p 3 may not always indicate an LTP allergy. Our data suggests that the Pru p 3:total IgE ratio, and sensitisation to Ara h 9 and Cor a 8 can support the diagnosis of LTP allergy in individuals sensitised to Pru p 3.

Sarcoidosis is an inflammatory, non-caseating granulomatous multisystem disease associated with JAK-STAT (Janus kinases-signal transducer and activator of transcription proteins) pathway activation. We present a patient with severe multi-systemic sarcoidosis who showed marked improvement with tofacitinib with regards to pulmonary, cutaneous, nasal and laryngeal disease. Tofacitinib prevented critical laryngeal stenosis from progressing to tracheostomy, induced regression of cutaneous lesions and improved pulmonary function in this steroid-resistant and immunosuppressive intolerant case. This case report supports further the role of JAK-inhibitors in the treatment of systemic sarcoidosis. Laryngoscope, 135:829-832, 2025.

PURPOSE OF REVIEW:Chronic rhinosinusitis (CRS) is a chronic inflammatory disorder of the sinonasal cavities classified into two major phenotypes: CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). The diagnosis of CRS is based on clinical symptoms associated with imaging and/or nasal endoscopy findings of mucosal inflammation. RECENT FINDINGS:Recently, novel biological therapies have emerged as therapeutic options for CRSwNP. Imaging is helpful in deciding whether surgery is likely to be beneficial and in guiding surgery. It can also help demonstrate a clinical response to medical therapy. However, specific guidelines concerning the role of imaging in CRwNP are lacking. SUMMARY:This article provides a comprehensive and critical multidisciplinary review of the role of conventional radiology, computed tomography (CT), and magnetic resonance imaging (MRI) in the diagnosis and characterization of CRSwNP. Since the complete characterization of nasal polyps on CT or MR images is very challenging, we provide a critical review of the best imaging methods and essential reporting elements used to assess nasal polyps.

For over 100 years, the only disease-modifying treatment option for IgE-mediated allergies has consisted in allergen immunotherapy (AIT). Lasting effectiveness upon cessation of years of treatment comes with safety and dosing issues impeding adoption. We present a new form of bioparticle-enhanced immunotherapy.

Background: Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n = 30), subcutaneous immunotherapy (SCIT) (n = 27), or sublingual immunotherapy (SLIT) (n = 27) and were then followed for 1 additional year.Objective: We used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response.Methods: We used longitudinal transcriptomic profiling of nasal brush and PBMC samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT. Trial Registration: ClinicalTrials.gov Identifier: NCT01335139, EudraCT Number: 2010-023536-16. Results: SCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes -0.133 to -0.640, false discovery rates [FDRs] <0.05). We observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (log2 fold changes 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (log2 fold changes -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and peak nasal inspiratory flow, indicating important links between treatment, module expression, and allergen response.Conclusions: Our results identify specific molecular responses of the nasal airway impacting barrier function, leukocyte migration activation, and mucus secretion that are affected by both SCIT and SLIT, offering potential targets to guide novel strategies for AIT. (J Allergy Clin Immunol 2023;152:1247-60.)

Nasal polyps, like asthma, have multiple phenotypes but are rarely malignant. Until recent decades, they were the preserve of the ear, nose, and throat surgeon, with operative removal being the main therapeutic option. Advances such as the sinus computed tomography scan, the nasendoscope, and endoscopic sinus surgery with resulting tissue examination have prompted research that has altered their management, particularly that of chronic rhinosinusitis with nasal polyposis (CRSwNP). CRSwNP is a heterogeneous inflammatory condition with bilateral nasal polyps in the mucosa of the nose and paranasal sinuses, predominantly mediated by type 2 inflammation and often associated with comorbid asthma and/or aspirin-exacerbated respiratory disease (AERD).1Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European position paper on rhinosinusitis and nasal polyps 2020.Rhinology. 2020; 51: 1-464Google Scholar,2Orlandi R. Kingdom T.T. Hwang P.H. Smith T.L. Alt J.A. Baroody F.M. International consensus in allergy and rhinology 2016 report: rhinosinusitis [special issue].Int Forum Allergy Rhinol. 2016; 6: S22-S209Crossref PubMed Scopus (607) Google Scholar As a result of symptoms of nasal obstruction and discharge, reduction in smell, taste, and sleep quality, CRSwNP has significant deleterious effects on quality of life and ability to function.2Orlandi R. Kingdom T.T. Hwang P.H. Smith T.L. Alt J.A. Baroody F.M. International consensus in allergy and rhinology 2016 report: rhinosinusitis [special issue].Int Forum Allergy Rhinol. 2016; 6: S22-S209Crossref PubMed Scopus (607) Google Scholar Pharmacotherapy is now the first-line treatment,1Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European position paper on rhinosinusitis and nasal polyps 2020.Rhinology. 2020; 51: 1-464Google Scholar with surgery reserved for individuals failing to respond. Nasal saline irrigation, topical corticosteroids, antileukotrienes, antibiotics, topical antihistamines, and topical diuretics have shown some therapeutic efficacy, whereas use of oral corticosteroids can both reduce polyp size and restore olfaction temporarily. None of these options is curative, and for many patients, despite continued therapy, symptomatic polyp recurrence will occur at some stage. Difficult-to-treat patients have a more severe disease requiring high systemic corticosteroid use and/or multiple sinonasal operations. These include, but are not limited to, phenotypes of CRSwNP such as AERD, allergic fungal rhinosinusitis, and eosinophilic granulomatosis with polyangiitis. CRSwNP can be associated with asthma, often severe, with similar underlying eosinophilic pathology,1Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European position paper on rhinosinusitis and nasal polyps 2020.Rhinology. 2020; 51: 1-464Google Scholar,2Orlandi R. Kingdom T.T. Hwang P.H. Smith T.L. Alt J.A. Baroody F.M. International consensus in allergy and rhinology 2016 report: rhinosinusitis [special issue].Int Forum Allergy Rhinol. 2016; 6: S22-S209Crossref PubMed Scopus (607) Google Scholar including type 2 innate lymphocytes.3Scadding G.K. Scadding G.W. Innate and adaptive immunity: ILC2 and Th2 cells in upper and lower airway allergic diseases.J Allergy Clin Immunol Pract. 2021; 9: 1851-1857Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar A more recent advance—the development of mAb drugs—is set to have a major impact on the treatment of CRSwNP, as it has already begun to do for asthma. These biologic inhibitors of key effectors of type 2 inflammation provide add-on therapy for patients with severe, uncontrolled CRSwNP, resulting in significant improvements in a proportion of patients, albeit at considerable financial cost.4Laidlaw T.M. Buchheit K.M. Biologics in chronic rhinosinusitis with nasal polyposis.Ann Allergy Asthma Immunol. 2020; 124: 326-332Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Understanding the endotype of responders and using this to predict responsive phenotypes is increasingly important. The predominance of eosinophilia and IL-5 in Western polyps suggested that monoclonals directed against the latter would prove therapeutic. This is the case for mepolizumab, which has been approved for CRSwNP by the US Food and Drug Administration. Monoclonals directed against IgE (omalizumab) and the IL-4 receptor α-subunit (IL-4Rα), which is common to both IL-4 and IL-13 receptors (dupilumab), also reduce nasal polyp size and symptoms, with studies of others directed against thymic stromal lymphopoietin awaited.4Laidlaw T.M. Buchheit K.M. Biologics in chronic rhinosinusitis with nasal polyposis.Ann Allergy Asthma Immunol. 2020; 124: 326-332Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar In the current issue of the Journal of Allergy and Clinical Immunology, Gevaert et al5Gevaert P. Saenz R. Corren J. Han J.K. Mullol J. Lee S.E. et al.Long-term efficacy and safety of omalizumab for nasal polyposis in an open-label extension study.J Allergy Clin Immunol. 2022; 149: 957-965Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar report on an open-label extension evaluating the efficacy, safety, and durability of responses to omalizumab in adults with CRSwNP who had completed the double-blinded POLYP 1 and POLYP 2 trials.6Gevaert P. Omachi T.A. Corren J. Mullol J. Han J. Lee S.E. et al.Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials.J Allergy Clin Immunol. 2020; 146: 595-605Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar Of the 265 participants from the original study, 249 either continued taking omalizumab or switched to omalizumab from placebo for 28 weeks, alongside ongoing use of nasal mometasone furoate. They were followed for a further 24 weeks after omalizumab discontinuation. The patients selected for these studies were moderately affected, with a nasal polyp score (NPS) of 5 or higher, moderate or severe nasal congestion, and 22-Item Sino-Nasal Outcome Test (SNOT-22) scores of 20 or higher; 59% of participants had undergone 1 or more sinus operations. Omalizumab had significantly reduced polyp and nasal congestion scores in blinded use.6Gevaert P. Omachi T.A. Corren J. Mullol J. Han J. Lee S.E. et al.Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials.J Allergy Clin Immunol. 2020; 146: 595-605Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar The open-label extension with omalizumab showed a further modest decrease in polyp and congestion scores from week 24 to week 52, suggesting that the full benefit of treatment is not reached until after 6 months. Discontinuation of omalizumab was associated with gradual increases in polyp and congestion scores, although not to pretrial levels, by week 72. Extrapolation of the data suggests a prolonged rather than a permanent disease-modifying effect. The estimated reduced need for surgery (defined by an NPS of 4 or lower and improvement of 8.9 points or more in SNOT-22 score) was found in a quarter of those treated with omalizumab. Quality of life showed a 28.47-point improvement in SNOT-22 score (>3 times the minimally clinically important difference) after 52 weeks of omalizumab therapy. Although loss of smell improved, it remained within the anosmic range. Asthma, mostly mild to moderate, was present in 57.0% of patients. The improvement in Asthma Quality of Life Questionnaire score at week 52 just exceeded the minimally clinically important difference (0.5 points) in patients who switched to omalizumab from placebo (0.52 points) and was higher (0.95 points) in those who continued taking omalizumab, suggesting that asthma outcomes also improved with longer treatment. Patients with comorbid asthma and AERD, compared with patients with neither, had similar mean improvements in polyp and congestion scores at week 52.5Gevaert P. Saenz R. Corren J. Han J.K. Mullol J. Lee S.E. et al.Long-term efficacy and safety of omalizumab for nasal polyposis in an open-label extension study.J Allergy Clin Immunol. 2022; 149: 957-965Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar These results add to the data from the original studies,6Gevaert P. Omachi T.A. Corren J. Mullol J. Han J. Lee S.E. et al.Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials.J Allergy Clin Immunol. 2020; 146: 595-605Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar suggesting additional improvements beyond 6 months of treatment and no immediate return of symptoms on discontinuation of treatment. Omalizumab is therefore an effective treatment for CRSwNP. The question is when should it, and other biologics, be used? Approximately 2% to 4% of the population have CRSwNP, and these drugs are expensive. Guidelines for biologic use are available. The European Position Paper on Rhinosinusitis and Nasal Polyps 20201Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European position paper on rhinosinusitis and nasal polyps 2020.Rhinology. 2020; 51: 1-464Google Scholar concluded that they are indicated in patients with bilateral nasal polyps who had undergone sinus surgery or were not fit for it and met 3 of the following 5 criteria: (1) evidence of type 2 disease (tissue eosinophil counts ≥ 10/hpf or blood eosinophil concentrations ≥ 250/μL or total IgE concentration ≥ 100), (2) need for at least 2 courses of systemic corticosteroids per year or long-term (>3 months) low-dose systemic steroids or contraindication to systemic steroids, (3) significantly impaired quality of life defined by a SNOT-22 score of 40 or higher, (4) anosmia on smell test, and (5) comorbid asthma needing regular inhaled corticosteroids. The European Position Paper on Rhinosinusitis and Nasal Polyps steering group additionally identified cutoffs for “severe” CRSwNP, specifically, a Visual Analogue Scale score of 7 or higher, SNOT-22 score of 40 or higher, and NPS of 5 or higher. Similar criteria have typically been used when recruiting participants for clinical trials of biologics in treatment of CRSwNP. Other therapeutic options, such as antileukotrienes, macrolides, and aspirin desensitization in patients with AERD, may be considered before use of a monoclonal in appropriate patients. Recent evidence suggests that dupilumab is cost-effectively used as rescue therapy where needed following aspirin desensitization in AERD.7Yong M. Wu Y.Q. Howlett J. Ballreich J. Walgama E. Thamboo A. Cost-effectiveness analysis comparing dupilumab and aspirin desensitization therapy for chronic rhinosinusitis with nasal polyposis in aspirin-exacerbated respiratory disease.Int Forum Allergy Rhinol. 2021; 11: 1626-1636Crossref PubMed Scopus (8) Google Scholar Occasionally, allergen-specific immunotherapy, which does have long-term posttherapy benefit, may be appropriate in cases in which polyps are allergen-driven, as in central compartment atopic disease.8Marcus S. Schertzer J. Roland L.T. Wise S.K. Levy J.M. DelGaudio J.M. Central compartment atopic disease: prevalence of allergy and asthma compared with other subtypes of chronic rhinosinusitis with nasal polyps.Int Forum Allergy Rhinol. 2020; 10: 183-189Crossref PubMed Scopus (27) Google Scholar Concomitant asthma is a factor promoting use of a biologic. A combined upper and lower airway scoring system is needed, as is a willingness of regulatory authorities to consider both diseases together in future trials. Other outstanding questions include how best to judge the response to biologics; how long to continue treatment; when or if to combine surgery with biologic use; and of course, which biologic is likely to give the best result. This latter question remains inconclusively answered in asthma and now in CRSwNP, and it is unlikely to be investigated in head-to-head trials. This leaves indirect comparisons and real-world clinical data as the means for answering this question. With regard to the latter, polyp immunopathology, endotype, phenotype, and relevant biomarkers should now be captured wherever biologics are being extensively used. A widely adopted definition of responsiveness is needed to define responder factors and enable accurate choice of future therapy, particularly now that 3 monoclonals (mepolizumab, omalizumab, and dupilumab) have satisfied the US Food and Drug Administration criteria for use in CRSwNP. Table I gives our ideas on a simple system for decision-making regarding biologic use.Table ISuggested considerations for using biologics in CRSwNPWhen to begin a biologicWhen to continue a biologicMajor considerations:Evidence of type 2 inflammatory polyps (≥1 of: eosinophils on polyp histology; peripheral blood eosinophilia ≥0.3 × 109/L; clear [systemic] steroid-responsiveness)Significant impairment of quality of life (SNOT-22 score ≥40 points) despite good concordance with intranasal corticosteroids (unless contraindicated) and previous surgery (if patient is a viable candidate) and use of systemic corticosteroids for nasal disease in the past 12 mo (unless contraindicated)Additional considerations:Impact of loss of smell (eg, on profession)Sleep-disordered breathingComorbid asthma (but severe asthma should be considered for a biologic on its own merit)Failed or contraindicated or unavailable trial of aspirin desensitization if patient has AERDSteroid side effects/contraindications (reduced bone density, cataract, glaucoma)Relative costs of available drugsMajor considerations:Improved quality of life (≥2 × MCID on SNOT-22) and/or ≥50% reduction in systemic corticosteroid use (without further surgery)Additional considerations:Significant improvement in nasal obstruction, allowing nasal breathing and refreshing sleepReduction in polyp size compared with baseline of ≥2 on Meltzer 8-point bilateral grading systemImprovement in sense of smell (at least out of anosmic range)Improved asthma controlTwo major criteria are a sine qua non for consideration of biologic use. Additional criteria provide more pressure in cases in which such therapies are cost-limited. A score of 1 point for each of these could be given, followed by a threshold for use in a particular society determined, taking into account the relative costs of the available drugs. Continuation of the biologic should occur only when its efficacy is of clinically significant benefit to the patient and/or society. Change of polyp grade is not a useful measure, whereas upper airway patency and the ability to nose breathe, smell, taste. and sleep well are all useful. Reduction in systemic corticosteroid use is also an important variable. One point could be given for all of the criteria, after which a threshold is determined based on circumstances. This simple system would allow identification of good responders and nonresponders. Collaborative efforts using clinical data and polyp immunohistology might then permit maximally effective future use of biologic tools.MCID, Minimal clinically important difference. Open table in a new tab Two major criteria are a sine qua non for consideration of biologic use. Additional criteria provide more pressure in cases in which such therapies are cost-limited. A score of 1 point for each of these could be given, followed by a threshold for use in a particular society determined, taking into account the relative costs of the available drugs. Continuation of the biologic should occur only when its efficacy is of clinically significant benefit to the patient and/or society. Change of polyp grade is not a useful measure, whereas upper airway patency and the ability to nose breathe, smell, taste. and sleep well are all useful. Reduction in systemic corticosteroid use is also an important variable. One point could be given for all of the criteria, after which a threshold is determined based on circumstances. This simple system would allow identification of good responders and nonresponders. Collaborative efforts using clinical data and polyp immunohistology might then permit maximally effective future use of biologic tools. MCID, Minimal clinically important difference. The role of biologics in CRSwNP will evolve and needs continued investigation and monitoring. Widespread use in nationalized health care systems will require evidence of cost-effectiveness. Currently, they are the future of management for severe type 2 upper and lower airway disease. But watch out for other forms of precision medicine, such as Janus kinase–selective inhibitors.9Traves P.G. Murray B. Campigotto F. Galien R. Meng A. Di Paolo J.A. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib.Ann Rheum Dis. 2021; 80: 865-875Crossref PubMed Scopus (35) Google Scholar With upadacitinib having shown greater efficacy than dupilumab in atopic dermatitis,10Blauvelt A. Teixeira H.D. Simpson E.L. Papp K.A. Pangan A.L. Blauvelt A. et al.Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-severe atopic dermatitis: a randomized clinical trial.JAMA Dermatol. 2021; 157: 1047-1055Crossref PubMed Scopus (50) Google Scholar might these oral, small molecule inhibitors be the next CRSwNP therapy? Long-term efficacy and safety of omalizumab for nasal polyposis in an open-label extension studyJournal of Allergy and Clinical ImmunologyVol. 149Issue 3PreviewChronic rhinosinusitis with nasal polyps (CRSwNP) frequently remains uncontrolled despite maximal medical therapy and sinonasal surgery, presenting several unmet needs and challenges. Omalizumab previously demonstrated efficacy in CRSwNP in duplicate phase 3, randomized, placebo-controlled trials (POLYP 1, POLYP 2). Full-Text PDF Open Access

Asthma is a chronic inflammatory disease characterized by variable airflow limitation and airway hyperresponsiveness. A plethora of immune and structural cells are involved in asthma pathogenesis. The roles of neutrophils and their mediators in different asthma phenotypes are largely unknown. Neutrophil extracellular traps (NETs) are net-like structures composed of DNA scaffolds, histones and granular proteins released by activated neutrophils. NETs were originally described as a process to entrap and kill a variety of microorganisms. NET formation can be achieved through a cell-death process, termed NETosis, or in association with the release of DNA from viable neutrophils. NETs can also promote the resolution of inflammation by degrading cytokines and chemokines. NETs have been implicated in the pathogenesis of various non-infectious conditions, including autoimmunity, cancer and even allergic disorders. Putative surrogate NET biomarkers (e.g., double-strand DNA (dsDNA), myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (CitH3)) have been found in different sites/fluids of patients with asthma. Targeting NETs has been proposed as a therapeutic strategy in several diseases. However, different NETs and NET components may have alternate, even opposite, consequences on inflammation. Here we review recent findings emphasizing the pathogenic and therapeutic potential of NETs in asthma.

The allergen provocation test is an established model of allergic airway diseases, including asthma and allergic rhinitis, allowing the study of allergen-induced changes in respiratory physiology and inflammatory mechanisms in sensitised individuals as well as their associations. In the upper airways, allergen challenge is focused on the clinical and pathophysiological sequelae of the early allergic response, and is applied both as a diagnostic tool and in research settings. In contrast, bronchial allergen challenge has almost exclusively served as a research tool in specialised research settings with a focus on the late asthmatic response and the underlying type 2 inflammation. The allergen-induced late asthmatic response is also characterised by prolonged airway narrowing, increased nonspecific airway hyperresponsiveness and features of airway remodelling including the small airways, and hence allows the study of several key mechanisms and features of asthma. In line with these characteristics, allergen challenge has served as a valued tool to study the cross-talk of the upper and lower airways and in proof-of-mechanism studies of drug development. In recent years, several new insights into respiratory phenotypes and endotypes including the involvement of the upper and small airways, innovative biomarker sampling methods and detection techniques, refined lung function testing as well as targeted treatment options further shaped the applicability of the allergen provocation test in precision medicine. These topics, along with descriptions of subject populations and safety, in line with the updated Global Initiative for Asthma 2021 document, will be addressed in this review.

Background: The impact of poor diet on growth and development in children with a food allergy is well-recognized and researched. Food allergy is an increasing problem in adults, as are food intolerances. Another issue is the rising number of individuals adopting a vegetarian or vegan lifestyle. Studies evaluating the diet of adolescents and adults with food allergy against controls suggest their dietary intakes are similar. We wished to evaluate all patients attending a food allergy clinic to determine whether there were dietary and nutritional differences between those with a food allergy or a food intolerance. Methods: All adults newly referred to a secondary care food allergy clinic in a UK hospital, in a 1-month period, were included in the study. Prior to their appointment, those who consented to take part had their height and weight documented and an assessment made of their habitual food intake. Their subsequent diagnosis was reviewed, and results for those with a confirmed diagnosis of food allergy were compared to those with a food intolerance or where the cause of symptoms was unknown. Results: Thirty subjects were recruited, with full results available for 29 subjects, 15 of whom (52%) were diagnosed with a new/existing food allergy (FA). For the whole cohort, dietary intake was sufficient for protein, and most vitamins and minerals, whereas energy, carbohydrate, unsaturated fat and fiber intakes were well-below the reference range. Those with a FA had lower intakes of iron, zinc and vitamin B12 compared to those with no FA. In addition, iron and energy intakes were depleted in those avoiding nuts, and wheat avoidance was linked to a lower intake of riboflavin. Conclusion: The results from this small exploratory study suggest that whilst the majority of nutrients in the diet are sufficient in adults presenting to the food allergy clinic, intakes of energy and fiber may be below the reference range. Those with a food allergy are more likely to have a reduced intake of iron, zinc and vitamin B12. As others have demonstrated, the exclusion of specific food groups can also affect nutritional intakes.

BACKGROUND:Allergen-specific immunotherapy is a disease-modifying treatment that induces long-term T-cell tolerance.OBJECTIVE:We sought to evaluate the role of circulating CXCR5+PD-1+ T follicular helper (cTFH) and T follicular regulatory (TFR) cells following grass pollen subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) and the accompanying changes in their chromatin landscape.METHODS:Phenotype and function of cTFH cells were initially evaluated in the grass pollen-allergic (GPA) group (n = 28) and nonatopic healthy controls (NAC, n = 13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cTFH and TFR cells were further enumerated in NAC (n = 12), GPA (n = 14), SCIT- (n = 10), and SLIT- (n = 8) treated groups. Chromatin accessibility in cTFH and TFR cells was assessed by assay for transposase-accessible chromatin sequencing (ATAC-seq) to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT, and SLIT groups.RESULTS:cTFH cells were shown to be distinct from TH2- and TH2A-cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B-cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cTFH-cell proliferation in the GPA group but not in the NAC group (P < .05). cTFH cells were higher in the GPA group compared with the NAC group and were lower in the SCIT and SLIT groups (P < .01). Time-dependent induction of IL-4, IL-21, and IL-6 was observed in nasal mucosa following intranasal allergen challenge in the GPA group but not in SCIT and SLIT groups. TFR and IL-10+ cTFH cells were induced in SCIT and SLIT groups (all, P < .01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups.CONCLUSIONS:For the first time, we showed dysregulation of cTFH cells in the GPA group compared to NAC, SCIT, and SLIT groups and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following allergen-specific immunotherapy in cTFH and TFR cells.

Purpose of review This article explores recent findings on the involvement of innate immunity in allergic airways disease, concentrating on allergic rhinitis. Recent findings We speculate on the ways in which environmental influences act to initiate inflammation and on how these may have altered in recent decades. Improved understanding of the mechanisms involved may reveal future possibilities for therapy. Summary The complex nature of immunity - both innate and acquired - in airways disease has implications for prevention and for therapy and requires further elucidation.

Introduction: There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). Objective: We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial. Methods: Nasal fluid and serum were obtained yearly (perprotocol population, n = 84). TGP-specific IgA(1), IgA(2), IgG(4), IgG, and IgE were measured in nasal fluids by ELISA. TGPspecific IgA(1), IgA(2), and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG(4) were measured in sera by ELISA and ImmunoCAP, respectively. Results: At years 2 and 3, TGP-IgA(1/2) levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA(1), 2.0- and 1.8-fold for IgA(2), respectively; all P<.01). TGP-IgA(1) level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P<.001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG(4) level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P<.01). Serum IgG(4) levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9-fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P<.05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P = .04) and placebo (3.1-fold; P = .02). IgA to TGP and IgE and IgG(4) to TGP components stratified participants according to treatment group and clinical response. Conclusions: The observed induction of IgA(1/2) in SLIT and IgG(4) in SCIT suggest key differences in the mechanisms of action.

Advances in our understanding of the immune system, with the recent discovery of a parallel set of innate T lymphocytes, the innate lymphocytes (ILCs), have led to a reassessment of the pathogenesis of allergic and eosinophilic airway disorders, including allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps. We review current understanding of both elements of type-2 inflammatory responses and their relative influence in these common conditions and consider possible impacts of this on treatment selection. (C) 2021 American Academy of Allergy, Asthma & Immunology

INTRODUCTION:Food hypersensitivity (FHS), including food allergy, coeliac disease and food intolerance, is a major public health issue. The Food Standards Agency (FSA), an independent UK Government department working to protect public health and consumers' wider interests in food, sought to identify research priorities in the area of FHS.METHODS:A priority setting exercise was undertaken, using a methodology adapted from the James Lind Alliance-the first such exercise with respect to food hypersensitivity. A UK-wide public consultation was held to identify unanswered research questions. After excluding diagnostics, desensitization treatment and other questions which were out of scope for FSA or where FSA was already commissioning research, 15 indicative questions were identified and prioritized by a range of stakeholders, representing food businesses, patient groups, health care and academia, local authorities and the FSA.RESULTS:295 responses were received during the public consultation, which were categorized into 70 sub-questions and used to define 15 key evidence uncertainties ('indicative questions') for prioritization. Using the JLA prioritization framework, this resulted in 10 priority uncertainties in evidence, from which 16 research questions were developed. These could be summarized under the following 5 themes: communication of allergens both within the food supply chain and then to the end consumer (ensuring trust in allergen communication); the impact of socio-economic factors on consumers with FHS; drivers of severe reactions; mechanism(s) underlying loss of tolerance in FHS; and the risks posed by novel allergens/processing.DISCUSSION:In this first research prioritization exercise for food allergy and FHS, key priorities identified to protect the food-allergic public were strategies to help allergic consumers to make confident food choices, prevention of FHS and increasing understanding of socio-economic impacts. Diagnosis and treatment of FHS was not considered in this prioritization.

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