Identification by cluster analysis of patients with asthma and nasal symptoms using the MASK-air® mHealth app

peer reviewedBackground: 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. © 2022 Sociedade Portuguesa de Pneumologi

Superparamagnetic iron oxide nanoparticles conjugated to a grass pollen allergen and an optical probe.

In this study we report the development of a bioconjugate between superparamagnetic iron oxide nanoparticles and Phl p5a (one of the major allergens from grass pollen). The bioconjugate also contains an optical probe (Alexa647) conjugated to the nanoparticle via biotinstreptavidin association. We show that this conjugate has a range of features that makes it a very promising candidate to image the localization of this allergen in vivo: (a) upon conjugation to the iron oxide nanoparticles, the allergen retains its ability to interact with IgE antibodies; (b) the magnetic properties of the iron oxide core of this bioconjugate are suitable for MR imaging; and (c) Alexa647 fluorophore retains its emission properties once attached to the iron oxide nanoparticles, yielding a dual modality MRI-optical probe

Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody

The calcium-binding 2EF-hand protein Phl p 7 from timothy grass pollen is a highly cross-reactive pollen pan-allergen that can induce severe clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7-specific IgG4 antibody (mAb102.1F10) was isolated from a patient who had received grass pollen-specific immunotherapy (SIT).We studied epitope specificity, cross-reactivity, affinity and cross-protection of mAb102.1F10 towards homologous calcium-binding pollen allergens. Sequence comparisons and molecular modelling studies were performed with ClustalW and SPADE, respectively. Surface plasmon resonance measurements were done with purified recombinant allergens. Binding and cross-reactivity of patients’ IgE and mAb102.1F10 to calcium-binding allergens and peptides thereof was studied with quantitative RAST-based methods, in ELISA, basophil activation and IgE-facilitated allergen presentation experiments. Allergens from Timothy grass (Phl p 7), Alder (Aln g 4), Birch (Bet v 4), Turnip rape (Bra r 1), Lamb′s quarter (Che a 3) and Olive (Ole e 3, Ole e 8) showed high sequence similarity and cross-reacted with allergic patients’ IgE. mAb102.1F10 bound the C-terminal portion of Phl p 7 in a calcium-dependent manner. It cross-reacted with high affinity with Ole e 3 whereas binding and affinity to the other allergens was low. mAb102.1F10 showed limited inhibition of patients’ IgE binding and basophil activation. Sequence comparison and surface exposure calculations identified three amino acids likely to be responsible for limited cross-reactivity.Our results demonstrate that a small number of amino acid differences among cross-reactive allergens can reduce the affinity of binding by a SIT-induced IgG and thus limit cross-protection

Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy

International audienceLike 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

Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL-4: A randomized controlled trial.

BACKGROUND: Allergen immunotherapy is currently the only disease-modifying treatment available for allergic rhinitis and allergic asthma. OBJECTIVES: We sought to evaluate the induction of sustained tolerance to allergen when anti-IL-4 was combined with a suboptimal course of grass pollen subcutaneous immunotherapy (SCIT) using the allergen-induced skin late-phase response (LPR) and exploratory immune monitoring as surrogate markers of therapeutic response. METHODS: In this randomized, double-blind, 3-group parallel design trial, 37 participants with seasonal allergic rhinitis received suboptimal SCIT (30,000 standardized quality units) in combination with anti-IL-4 (VAK694) and suboptimal SCIT (30,000 standardized quality units) plus placebo antibody or double placebo (placebo SCIT and placebo antibody) restricted to 13 weeks before the grass pollen season. The primary end point was the size of the LPR at 12 months. Exploratory end points included measures of the immunomodulatory activity of treatment by using IL-4 and IL-10 FluoroSpot assays, flow cytometry of T cells, and measurement of IgE, IgG4, and facilitated antigen binding. RESULTS: Both active treatment arms led to a substantial and sustained reduction of the LPR with no additional suppression with addition of anti-IL-4. Treatment with anti-IL-4 and SCIT compared with SCIT alone led to a sustained reduction in allergen-specific IL-4-producing cell counts (P < .01). Both active treatment arms led to induction of dual IL-4/IL-10-producing cells during the pollen season. CONCLUSION: The combination of anti-IL-4 with SCIT provided no additional benefit over SCIT alone in suppressing the allergen-induced skin LPR. A larger trial is needed to assess whether the observed ex vivo downregulation of TH2 responses might translate into clinical benefit

The Role of Mobile Health Technologies in Stratifying Patients for AIT and Its Cessation: The ARIA-EAACI Perspective

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many international or national practice guidelines have been produced, but the evidence-based method varies and they do not usually propose care pathways. The present article considers the possible role of mobile health in AIT for allergic rhinitis/asthma. There are no currently available validated biologic biomarkers that can predict AIT success, and mobile health biomarkers have some relevance. In the current article, the following aspects will be discussed: patient stratification for AIT, symptom-medication scores for the follow-up of patients, clinical trials, as well as the approach of the European Academy of Allergy and Clinical Immunology. © 2021 American Academy of Allergy, Asthma & Immunolog