Publications
322 results found
Boyle RJ, Shamji MH, 2023, Adrenaline auto-injectors for people at risk of anaphylaxis., Clin Exp Allergy, Vol: 53, Pages: 896-898
Sousa-Pinto B, Louis R, Anto JM, et al., 2023, Adherence to inhaled corticosteroids and long-acting β2-agonists in asthma: A MASK-air study., Pulmonology
INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting β2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.
Shamji MH, Boyle RJ, 2023, Immunotherapy and prevention of allergic diseases., Clin Exp Allergy, Vol: 53, Pages: 788-790
Sampath V, Shalakhti O, Veidis E, et al., 2023, Acute and chronic impacts of heat stress on planetary health., Allergy, Vol: 78, Pages: 2109-2120
Heat waves are increasing in intensity, frequency, and duration causing significant heat stress in all living organisms. Heat stress has multiple negative effects on plants affecting photosynthesis, respiration, growth, development, and reproduction. It also impacts animals leading to physiological and behavioral alterations, such as reduced caloric intake, increased water intake, and decreased reproduction and growth. In humans, epidemiological studies have shown that heat waves are associated with increased morbidity and mortality. There are many biological effects of heat stress (structural changes, enzyme function disruption, damage through reactive oxygen or nitrogen species). While plants and animals can mitigate some of these effects through adaptive mechanisms such as the generation of heat shock proteins, antioxidants, stress granules, and others, these mechanisms may likely be inadequate with further global warming. This review summarizes the effects of heat stress on plants and animals and the adaptative mechanisms that have evolved to counteract this stress.
Bousquet J, Sousa-Pinto B, Shamji MH, et al., 2023, Improvement of daily allergy control by sublingual immunotherapy: A MASK-air® study., Clin Exp Allergy, Vol: 53, Pages: 854-861
Altman MC, Segnitz RM, Larson D, et al., 2023, Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy, Journal of Allergy and Clinical Immunology, ISSN: 0091-6749
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. OBJECTIVE: The GRASS study was a randomized, double-blind, placebo-controlled trial of timothy grass allergic individuals who received 2 years of placebo (n=30), subcutaneous (SCIT) (n=27), or sublingual immunotherapy (SLIT) (n=27) and were then followed for 1 additional year. Here we used yearly biospecimens from the GRASS study to identify molecular mechanisms of response. METHODS: We utilized longitudinal transcriptomic profiling of nasal brush and peripheral blood mononuclear cell (PBMC) samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT. 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 (logFC) -0.133 to -0.640, FDRs <0.05). Interestingly, we observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (logFC 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 (logFC -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 responses, indicating important links among treatment, module expression, and allergen response. CONCLUSION: 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.
Kappen J, Diamant Z, Agache I, et al., 2023, Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper., Allergy
INTRODUCTION: In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add-on intervention to pharmacological treatment. AIT is a treatment with disease-modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. METHODS: The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. RESULTS: Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. CONCLUSION: This EAACI-PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT.
Shamji MH, Ollert M, Adcock IM, et al., 2023, EAACI guidelines on environmental science in allergic diseases and asthma - Leveraging artificial intelligence and machine learning to develop a causality model in exposomics, Allergy, Vol: 78, Pages: 1742-1757, ISSN: 0105-4538
Allergic diseases and asthma are intrinsically linked to the environment we live in and to patterns of exposure. The integrated approach to understanding the effects of exposures on the immune system includes the ongoing collection of large-scale and complex data. This requires sophisticated methods to take full advantage of what this data can offer. Here we discuss the progress and further promise of applying artificial intelligence and machine-learning approaches to help unlock the power of complex environmental data sets toward providing causality models of exposure and intervention. We discuss a range of relevant machine-learning paradigms and models including the way such models are trained and validated together with examples of machine learning applied to allergic disease in the context of specific environmental exposures as well as attempts to tie these environmental data streams to the full representative exposome. We also discuss the promise of artificial intelligence in personalized medicine and the methodological approaches to healthcare with the final AI to improve public health.
Krishna MT, Shamji MH, Boyle RJ, 2023, Allergy in India., Clin Exp Allergy, Vol: 53, Pages: 690-692
Bousquet J, Shamji MH, Anto JM, et al., 2023, Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report., Allergy, Vol: 78, Pages: 1758-1776
Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.
de Kam PJ, Zielen S, Bernstein JA, et al., 2023, Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy., Allergy
BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.
Shamji MH, Boyle RJ, 2023, Novel diagnostics and therapeutic approaches for allergic diseases., Clin Exp Allergy, Vol: 53, Pages: 602-604
Beirag N, Varghese PM, Neto MM, et al., 2023, Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein., Viruses, Vol: 15
The complement system is a key component of the innate immune response to viruses and proinflammatory events. Exaggerated complement activation has been attributed to the induction of a cytokine storm in severe SARS-CoV-2 infection. However, there is also an argument for the protective role of complement proteins, given their local synthesis or activation at the site of viral infection. This study investigated the complement activation-independent role of C1q and C4b-binding protein (C4BP) against SARS-CoV-2 infection. The interactions of C1q, its recombinant globular heads, and C4BP with the SARS-CoV-2 spike and receptor binding domain (RBD) were examined using direct ELISA. In addition, RT-qPCR was used to evaluate the modulatory effect of these complement proteins on the SARS-CoV-2-mediated immune response. Cell binding and luciferase-based viral entry assays were utilised to assess the effects of C1q, its recombinant globular heads, and C4BP on SARS-CoV-2 cell entry. C1q and C4BP bound directly to SARS-CoV-2 pseudotype particles via the RBD domain of the spike protein. C1q via its globular heads and C4BP were found to reduce binding as well as viral transduction of SARS-CoV-2 spike protein expressing lentiviral pseudotypes into transfected A549 cells expressing human ACE2 and TMPRSS2. Furthermore, the treatment of the SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes with C1q, its recombinant globular heads, or C4BP triggered a reduction in mRNA levels of proinflammatory cytokines and chemokines such as IL-1β, IL-8, IL-6, TNF-α, IFN-α, and RANTES (as well as NF-κB) in A549 cells expressing human ACE2 and TMPRSS2. In addition, C1q and C4BP treatment also reduced SARS-CoV-2 pseudotype infection-mediated NF-κB activation in A549 cells expressing human ACE2 and TMPRSS2. C1q and C4BP are synthesised primarily by hepatocytes; however, they are also produced by macrophages, and alveolar type I
Bousquet J, Melén E, Haahtela T, et al., 2023, Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis, Allergy, Vol: 78, Pages: 1169-1203, ISSN: 0105-4538
Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
Boyle RJ, Shamji MH, 2023, Food anaphylaxis in older people., Clin Exp Allergy, Vol: 53, Pages: 488-490
Del Giacco S, Shamji M, Torres M, et al., 2023, EAACI-Kongress 2023, 9. – 11. Juni 2023, ISSN: 0344-5062
Sousa-Pinto B, Jácome C, Pereira AM, et al., 2023, Development and validation of an electronic daily control score for asthma (e-DASTHMA): a real-world direct patient data study., Lancet Digit Health, Vol: 5, Pages: e227-e238
BACKGROUND: Validated questionnaires are used to assess asthma control over the past 1-4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA). METHODS: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16-90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test-retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician. FINDINGS: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68-0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59-0&middo
Batard T, Canonica WG, Pfaar O, et al., 2023, Current advances in house dust mite allergen immunotherapy (AIT): Routes of administration, biomarkers and molecular allergen profiling., Mol Immunol, Vol: 155, Pages: 124-134
Allergy to house dust mites (HDM) is a perennial respiratory disease that affect more than half a billion people worldwide. Dermatophagoides pteronyssinus and D. farinae, two HDM species, are major sources of indoor allergens triggering allergic inflammation. Although symptomatic drugs are widely used to block the allergic reaction, allergen immunotherapy is the only curative treatment of IgE-mediated type I respiratory allergies. In this article, we review recent advances in various routes of allergen immunotherapy. We particularly focus on subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, used as a reference therapy since they have transformed allergic treatments by improving symptoms (asthma and rhinitis) as well as the quality of life of patients. We also highlight recent data in more exploratory routes (i.e., oral, intralymphatic, epicutaneous and intradermal) and discuss respective advantages of various route, as well as their foreseen modes of action. Finally, we provide an update on biomarkers as well as on the relevance of the molecular profiling of allergic individuals related to treatment efficacy or asthma prediction.
Boyle RJ, Flohr C, Shamji MH, 2023, Global trends in eczema prevalence during early life., Clin Exp Allergy, Vol: 53, Pages: 252-254
Magnan A, Nicolas J-F, Caimmi D, et al., 2023, Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy., J Pers Med, Vol: 13, ISSN: 2075-4426
Like in many fields of medicine, the concept of precision dosing has re-emerged in routine practice in allergology. Only one retrospective study on French physicians' practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT). Herein, we focus on key immune cells (i.e., dendritic cells, innate lymphoid cells, B and T cells, basophils and mast cells) involved in allergic disease and its resolution to further understand the effect of AIT on the phenotype, frequency or polarization of these cells. We strive to discriminate differences in immune responses between responders and non-responders to AIT, and discuss the eligibility of a non/low-responder subset for dose adaptation. A differential behavior in immune cells is clearly observed in responders, highlighting the importance of conducting clinical trials with large cohorts of well-characterized subjects to decipher the immune mechanism of AIT. We conclude that there is a need for designing new clinical and mechanistic studies to support the scientific rationale of dose adaptation in the interest of patients who do not properly respond to AIT.
Shamji MH, Boyle RJ, 2023, Biological therapy practice, biomarkers of severe asthma and novel approaches for attaining immunomodulation in upper airway disease., Clin Exp Allergy, Vol: 53, Pages: 130-131
The hybrid rDer p 2231 stimulated in PBMCs isolated from atopic patients, higher levels of IL-2, IL-10, IL-15 and IFN-γ, as well as lower levels of IL-4, IL-5, IL-13, TNF-α and GM-CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies, which blocked the IgE binding to the parental allergens in serum of atopic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL-10 and IFN-γ and decreased the secretion of IL-4 and IL-5, when compared to parental allergens and D. pteronyssinus extract. (7).
Layhadi J, Moya R, Tan TJ, et al., 2023, Single-cell RNA-Seq identifies precise tolerogenic cellular and molecular pathways induced by depigmented-polymerized grass pollen allergen extract, Journal of Allergy and Clinical Immunology, Vol: 151, Pages: 1357-1370.e9, ISSN: 0091-6749
Background:Immunological mechanism of action of allergoids remains poorly understood. Previous models of allergenicity and immunogenicity have yielded sub-optimal knowledge of these immunotherapeutic vaccine products. Novel single-cell RNA-seq technology offers a bridge to this gap in knowledge.Objective:To identify the underpinning tolerogenic molecular and cellular mechanisms of depigmented-polymerized Phleum pratense extract.MethodsThe molecular mechanisms underlying native Phleum pratense (Phl p), depigmented Phl p (DPG-Phl p), and depigmented-polymerized (DPG-POL-Phl p) allergoid were investigated using scRNA-seq. Allergen-specific Th2A, Tfh and IL-10+ Breg cells were quantified by flow cytometry in PBMCs from 16 grass pollen allergics (GPA) and 8 non-atopic controls (NAC). The ability of Phl p, DPG-Phl p and DPG-POL-Phl p to elicit FcεRI and FcεRII-mediated IgE responses was measured by basophil activation test and IgE-FAB assay.Results:ScRNA-seq analysis revealed that DPG-POL-Phl p downregulated genes associated with Th2 signaling, induced functional Tregs exhibiting immunosuppressive roles through CD52 and Siglec-10, modulated genes encoding immunoproteasome that dysregulate the processing and presentation of antigens to T cells and promoted a shift from IgE towards an IgA1 and IgG responses. In GPA, DPG-POL-Phl p exhibited reduced capacity to elicit proliferation of Th2A, IL-4+ Tfh and IL-21+ Tfh cells whilst being the most prominent at inducing CD19+CD5hiIL-10+ and CD19+CD5hiCD38intCD24intIL-10+ Breg cell subsets compared to Phl p (all, P<.05). Furthermore, DPG-POL-Phl p demonstrated a hypoallergenic profile through basophil activation and histamine release compared to Phl p (31.54-fold, P<.001).Conclusions:ScRNA-seq provides an in-depth resolution of the mechanisms underlying the tolerogenic profile of DPG-POL-Phl p.
Pablo-Torres C, Izquierdo E, Tan TJ, et al., 2023, Deciphering the role of platelets in severe allergy by an integrative omics approach, ALLERGY, ISSN: 0105-4538
Bousquet J, Anto JM, Sousa-Pinto B, et al., 2023, Digitally-enabled, patient-centred care in rhinitis and asthma multimorbidity: The ARIA-MASK-air((R)) approach, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 13
Boyle RJ, Shamji MH, 2023, What does Clinical and Experimental Allergy mean by Trusted Evidence in Allergy'?, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 4-6, ISSN: 0954-7894
Agache I, Shamji MH, Kermani NZ, et al., 2023, Multidimensional endotyping using nasal proteomics predicts molecular phenotypes in the asthmatic airways, Journal of Allergy and Clinical Immunology, Vol: 151, Pages: 128-137, ISSN: 0091-6749
BACKGROUND: Unsupervised clustering of biomarkers derived from non-invasive samples such as nasal fluid is less evaluated as a tool for describing asthma endotypes. OBJECTIVE: To evauate whether protein expression in nasal fluid would identify distinct clusters of asthmatics with specific lower airway molecular phenotypes. METHODS: Unsupervised clustering of 168 nasal inflammatory and immune proteins and Shapley values was used to stratify 43 severe asthmatic patients (ENDANA) using a two 'modelling blocks' machine learning (ML) approach. This algorithm was also applied to nasal brushings transcriptomics from U-BIOPRED. Feature reduction and functional gene analysis were used to compare proteomic and transcriptomic clusters. Gene set variation analysis (GSVA) provided enrichment scores (ESs) of the ENDANA protein signature within U-BIOPRED sputum and blood. RESULTS: The nasal protein ML model identified two severe asthma endotypes, which were replicated in U-BIOPRED nasal transcriptomics. Cluster 1 patients had significant airway obstruction, small airways disease, air trapping, decreased diffusing capacity and increased oxidative stress, although only 4/18 were current smokers. Shapley identified 20 cluster-defining proteins. Forty-one proteins were significantly higher in Cluster 1. Pathways associated with proteomic and transcriptomic clusters were linked to Th1, Th2, neutrophil, JAK-STAT, TLR and infection activation. GSVA analysis of the nasal protein and gene signatures were enriched in subjects with sputum neutrophilic/mixed granulocytic asthma and in subjects with a molecular phenotype found in sputum neutrophil-high subjects. CONCLUSIONS: Protein or gene analysis may indicate molecular phenotypes within the asthmatic lower airway and provide a simple, non-invasive test for non-T2 asthma that is currently unavailable.
Bousquet J, Sousa-Pinto B, Anto JM, et al., 2023, Identification by cluster analysis of patients with asthma and nasal symptoms using the MASK-air® mHealth app., Pulmonology, Vol: 29, Pages: 292-305
BACKGROUND: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. METHODS: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. FINDINGS: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. INTERPRETATION: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.
Shamji MH, Boyle RJ, 2022, Mepolizumab for eosinophilic chronic rhinosinusitis, loss of smell and challenges with accessibility to allergen immunotherapy, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 1358-1360, ISSN: 0954-7894
Tan TJ, Delgado-Dolset MI, Escribese MM, et al., 2022, Biomarkers of AIT: Models of prediction of efficacy, Allergologie, Vol: 45, Pages: 857-867, ISSN: 0344-5062
Allergic rhinitis is an IgE-mediated inflammation that remains a clinical challenge, affecting 40% of the UK population with a wide range of severity from nasal discomfort to life-threatening anaphylaxis. It can be managed by pharmacotherapeutics and in selected patients by allergen immunotherapy (AIT), which provides long-term clinical efficacy, especially during peak allergy season. However, there are no definitive biomarkers for AIT efficacy. Here, we aim to summarize the key adaptive, innate, humoral, and metabolic advances in biomarker identification in response to AIT. Mechanisms of efficacy consist of an immune deviation towards TH1-secreting IFN-γ, as well as an induction of IL10+ cTFR and TREG have been observed. TH2 cells undergo exhaustion after AIT due to chronic allergen exposure and correlates with the exhaustion markers PD-1, CTLA-4, TIGIT, and LAG3. IL10+ DCREG expressing C1Q and STAB are induced. KLRG1+IL10+ILC2 were shown to be induced in AIT in correlation with efficacy. BREG cells secreting IL-10, IL-35, and TGF-β are induced. Blocking antibodies IgG, IgA, and IgG4 are increased during AIT; whereas inflammatory metabolites, such as eicosanoids, are reduced. There are multiple promising biomarkers for AIT currently being evaluated. A panomic approach is essential to better understand cellular, molecular mechanisms and their correlation with clinical outcomes. Identification of predictive biomarkers of AIT efficacy will hugely impact current practice allowing physicians to select eligible patients that are likely to respond to treatment as well as improve patients' compliance to complete the course of treatment.
Agache I, Zemelka-Wiącek M, Shamji MH, et al., 2022, Immunotherapy: State-of-the-art review of therapies and theratypes., J Allergy Clin Immunol, Vol: 150, Pages: 1279-1288
Through its disease-modifying potential, immunotherapy is the keystone to curing allergic diseases. Allergen immunotherapy, applied for more than a century, is currently supported by novel modalities such as mAb-based therapies or small molecules targeting the key nodes of the allergic inflammation network. In this review, a summary of the most significant advances in immunotherapy is presented, addressing not only novel approaches to stratifying patients but also major controlled clinical trials and real-world evidence that strengthen the role of immunotherapy in the treatment of allergies.
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