Search

Background: Bronchial thermoplasty (BT) is a bronchoscopic procedure for patients with severe uncontrolled asthma, but randomized controlled studies of its efficacy in severe asthma with frequent exacerbations are lacking. The current aim was to assess BT efficacy in this patient population., Methods: Thirty patients with asthma (GINA 5) who had experienced at least four severe exacerbations in the preceding year were randomized to BT (n = 15) or control groups (n = 15). All patients had four follow-up visits over the following 15 months, corresponding to 3, 6, 9, and 12 months after the last procedure for the BT group. The primary outcome was number of exacerbations at 15 months after inclusion (i.e. 12 months after bronchial thermoplasty)., Results: All but three patients had received an asthma biologic without receiving benefit. In the year preceding enrollment, patients in the BT group had an average of five exacerbations, compared with six among controls. For patients in the BT group, oral steroid intake was 9.3 mg/d, compared with 11.0 mg/d among controls. The BT group had 1.58 fewer severe exacerbations (mean, 6.09) compared with controls (mean, 8.28) in the 12-month period after the therapy (p = 0.047). Oral steroid intake during follow-up after BT was significantly lower in the BT group (ratio vs controls: 0.61; p = 0.0002). Quality-of-life measures between inclusion and the last visit were significantly improved in the BT group, but not among controls. Few mild to moderate adverse events were reported, and all were controlled within days., Conclusion: In patients with severe asthma and frequent severe exacerbations, BT significantly decreased the rate of severe exacerbations and oral steroid intake and led to improved quality of life during the 15 months after inclusion. BT appears to offer a therapeutic option for severe asthma with frequent exacerbations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pr F. De Blay reports financial support was provided by ADIRAL. Pr F. De Blay reports financial support was provided by SOS Oxygène. Pr F. De Blay reports financial support was provided by France Oxygen. Pr F. De Blay reports financial support was provided by Elivie SAS. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: The impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions., Objective: We aimed to assess predictive factors of the EAR and LAR and to evaluate the relation between rhinitis, conjunctivitis and asthma induced by cat allergen exposure in an environmental exposure chamber (EEC)., Methods: Data from two cohort studies involving asthmatic patients with cat allergy who performed a cat allergen exposure challenge in ALYATEC EEC were analysed. Spirometry, visual analogue scale (VAS) for asthma, VAS for rhinitis, Total Nasal Symptoms Score, Total Ocular Symptoms Score (TOSS), Rhinoconjunctivitis Total Symptoms Score and Abelson score were used to assess asthma, rhinitis and conjunctivitis during and after exposure., Results: An EAR occurred in 65.1% of patients, 32.1% of whom had a LAR. The diameter of the prick test to cat allergens and non-specific bronchial hypersensitivity level were independent risk factors for EAR (p < .05). No independent risk factors for LAR were identified. Rhinoconjunctivitis severity during exposure correlated with the asthma VAS during EAR and LAR (p < .05). Allergen exposure time needed to trigger an EAR correlated with the Abelson score during exposure (p < .05). The asthma VAS and TOSS during exposure correlated with faster LAR occurrence (p < .05)., Conclusion: Prick test size and non-specific bronchial hypersensitivity level were confirmed as independent predictive factors of EAR during allergen exposure in an EEC. This study demonstrated the relation between the severity of rhinitis, conjunctivitis and asthma induced by allergen exposure for both EAR and LAR., (© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

The environment of an asthmatic patient can contain numerous sources of pollutants that degrade the quality of indoor air and have major repercussions on the occurrence and control of asthma. Assessment and improvement of the quality of indoor air should be assigned a major role in pneumology and allergology consultations. Characterization of an asthmatic's environment entails a search for biological pollutants with mite allergens, mildew, and allergens resulting from the proximity of pets. It is important to evaluate the chemical pollution represented by exposure to volatile organic compounds, which are increasingly present in our lodgings. Active or second-hand smoking must in all circumstances be sought out and quantified. Assessment of the environment is mediated by several methods, of which the application depends not only on the pollutant sought out, but also on enzyme-linked immunosorbent assay (ELISA), which has an essential role in quantification of biological pollutants. Attempts at expulsion of the different indoor environment pollutants is mediated by indoor environment advisors, whose efforts are aimed at obtaining reliable evaluation and control of indoor air. Implemented as a form of tertiary prevention, their methods are conducive to improved asthma control, in adults as well as children., (Copyright © 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Humanized monoclonal anti-IgE antibody (omalizumab) has demonstrated efficacy in severe atopic asthma. However, few studies have assessed its efficacy in non-atopic and even less in T2-low severe asthma. The objective was to determinate the omalizumab response according to atopic status., Methods: This retrospective, real-world study was performed in the Chest Diseases Department of Strasbourg University Hospital from January 1, 2006, to June 30, 2017. The response to omalizumab was assessed in 139 patients 4, 6, and 12 months after treatment and compared to data collected prior to omalizumab initiation., Results: Forty-four patients (31.7%) had severe non-atopic asthma and 95 (68.3%) had a severe atopic asthma. In the non-atopic group, omalizumab significantly reduced the severe exacerbation rate by 44% (95% CI 18-64%, p  < 0.05), 43% (CI 95% 20-60%, p  < 0.05), and 54% (CI 95% 36-67%, p  < 0.05), at 4, 6 and 12 months, respectively. A trend toward improvement in FEV1, asthma control and oral corticosteroid use was also observed. These results were not significantly different from those obtained in atopic asthmatics except a more effective oral corticosteroid sparing in atopic group ( p  < 0.05). Similar reduction of severe exacerbation rates were observed in T2-low asthma subgroup (non-atopic, non-eosinophilic)., Conclusion: Omalizumab was effective in severe asthma, regardless of atopic status.

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., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 10 9 /L. Several of them also showed benefits on nasal polyps (NP), one of the most frequent comorbidities of the severe asthma, but comparative studies on their effectiveness in the association SAA-NP are currently lacking. The aim of this study is to compare the effectiveness of benralizumab, mepolizumab and omalizumab in patients with SAA-NP in real-life settings. A retrospective, observational, multicenter real-life study was realized including patients with SAA-NP treated by benralizumab, mepolizumab or omalizumab for 6 months. We analysed the nasal and respiratory symptoms, the number of asthma attacks and salbutamol use/week, acute sinusitis and severe exacerbation rates, the asthma control score, the lung function parameters, the NP endoscopic score, the sinus imaging and the blood eosinophil count 6 months before and after treatment. Seventy-two patients with SAA-NP were included: 16 treated by benralizumab, 21 by mepolizumab and 35 by omalizumab. After 6 months of treatment, almost all studied parameters were improved (except sinus imaging) with a greater effect of omalizumab on the nasal pruritus (p = 0.001) and more benefits of benralizumab on exacerbations rate, asthma attacks per week and lung function (all p < 0.05). Benralizumab and mepolizumab were more effective to improve the NP endoscopic score and the blood eosinophil count (both p < 0.001). All three biological therapies showed effectiveness by improving asthma and nasal outcomes in patients with SAA-NP. Several differences have been found that should be confirmed by larger comparative studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 0·59-0·68). They also displayed high test-retest reliability (intraclass correlation coefficients range 0·79-0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69-0·79; effect size measures range 0·57-0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61-0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68-0·78)., Interpretation: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation., Funding: None., Competing Interests: Declaration of interests IA is an associate editor for Allergy and Clinical and Translational Allergy journals. RAl reports personal fees from operation POCI-01–0145–36 FEDER-029130 (titled “mINSPIRE-mHealth to measure and improve adherence to medication in chronic respiratory diseases—generalisation and evaluation of gamification, peer support and advanced image processing technologies”), co-funded by European Regional Development Fund, Programa Operacional Competitividade e Internacionalização, Portugal 2020, and by Portuguese Funds through Fundação para a Ciência e a Tecnologia, outside the submitted work. SB-A reports grants from TEVA, and personal fees from Teva, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, and Mylan, outside the submitted work. L-PB reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis, and Sanofi-Regeneron; personal fees from AstraZeneca, Novartis, GlaxoSmithKline, Merck, Sanofi-Regeneron, Covis, and Sanofi, outside the submitted work; and is a member of the Chair of Global Initiative for Asthma (GINA) Board of Directors, President of the Global Asthma Organisation (Interasma), and is a member of the Canadian Thoracic Society Respiratory Guidelines Committee and Laval University Chair on Knowledge Transfer, and Prevention and Education in Respiratory and Cardiovascular Health. JB reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Purina, Sanofi-Aventis, Takeda, Teva, and Uriach; and other from Kyomed-Innov, outside the submitted work. GB reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Sanofi, outside the submitted work. RB reports grants to Mainz University Hospital from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche; and personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Novartis, Roche, Sanofi, and Teva, all outside the submitted work. LC reports personal fees from Thermofisher, Sanofi, Novartis, and AstraZeneca, outside the submitted work. AAC reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Eurofarma, GSK, Novartis, and Sanofi, outside the submitted work. FdB reports other grants from Novartis, ALK, Stallergenes, Regeneron, DBV, Sanofi, Boehringer, and AstraZeneca, outside the submitted work. PD reports non-financial support from AstraZeneca, Boehringer Ingelheim, Stallergenes, and ALK Abelló; and personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Stallergenes, ALK Abelló, and IQVIA, outside the submitted work. JAF reports grants from Astrazeneca and Mundipharma; and personal fees from AstraZeneca, Mundipharma, Sanofi, GSK, and Teva, outside the submitted work; and is co-founder of a company that develops mobile health technologies and has the copyright of the Control of Allergic Rhinitis and Asthma Test Patient-Reported Outcome Measurement. BG reports grants from AstraZeneca, Sanofi, Deva, Abdi Ibrahim, and Sandoz, outside the submitted work. TH reports personal fees from Orion Pharma, outside the submitted work. GJ reports personal fees from AstraZeneca, GSK, Chiesi, Novartis, and Laparcon; support from GSK, outside the submitted work; and is a member of European Respiratory Society Chair of Operational Committee International Respiratory Coalition. MJ reports personal fees from ALK-Abello, Allergopharma, Stallergenes, Anergis, Allergy Therapeutics, Leti, and HAL, during the conduct of the study; and personal fees from GSK, Novartis, Teva, Takeda, and Chiesi, outside the submitted work. LK reports grants from Allergopharma, MEDA/Mylan, ALK Abelló, LETI Pharma, Stallergenes, Sanofi, ASIT biotech, Lofarma Quintiles, AstraZeneca, GSK, and Inmunotk; and personal fees from Allergopharma, MEDA/Mylan, HAL Allergie, LETI Pharma, Sanofi, Allergy Therapeut, and Cassella Med, outside the submitted work; and is a member of Ärzteverband Deutscher Allergologen, Deutsche Gesellschaft für Hals-Nasen-Ohren, Deutsche Akademie für Allergologie und klinische Immunologie, Berufsverband der Hals-Nasen-Ohrenärzte, Gesellschaft für Pädiatrische Allergologie, andEuropean Academy of Allergy and Clinical Immunology. PK reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, FAES, Glenmark, Novartis, Polpharma, Boehringer Ingelheim, Teva, and Zentiva, outside the submitted work. MKup reports personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, Lekam, Alvogen, Emma, Nexter, Teva, Sanofi Aventis, and Berlin Chemie, outside the submitted work. VK reports non-financial support from Norameda and Berlin Chemie Menarini, outside the submitted work. DL-L reports personal fees from ALK, Allakos, Amstrong, Astrazeneca national and global, Chiesi, DBV Technologies, Grunenthal, GSK national and global, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot; and grants from Sanofi, Astrazeneca, Lilly, Pfizer, Novartis, Circassia, UCB, GSK, and Purina institute, outside the submitted work. RL reports personal fees from GSK and AZ; and grants from GSK, AZ, and Chiesi, outside the submitted work. NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, and Boehringer Ingelheim; and grants from Gerolymatos International SA and Capricare, outside the submitted work. AP reports grants from Chiesi, Astrazeneca, GSK, BI, Pfizer, Teva, and Sanofi; personal fees from CHIESI, Astrazeneca, GSK, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, BI, Menarini, Zambon, Mundipharma, Teva, Edmon Pharma, and MSD, outside the submitted work. OP reports grants from ALK Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding BV/HAL Allergie, Bencard Allergie/Allergy Therapeutics, Lofarma, Biomay, Circassia, ASIT Biotech Tools SA, Laboratorios LETI/LETI Pharma, Anergis SA, GlaxoSmithKline, Pohl-Boskamp, Inmunotek SL, and AstraZeneca; and personal fees from ALK-Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding BV/HAL Allergie, Bencard Allergie/Allergy Therapeutics, Lofarma, ASIT Biotech Tools SA, Laboratorios LETI/LETI Pharma, MEDA Pharma/MYLAN, Anergis SA, AstraZeneca, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, GlaxoSmithKline, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi-Aventis and Sanofi-Genzyme, Med Update Europe, streamedup!, John Wiley and Sons, AS, Paul-Martini-Stiftung, Regeneron Pharmaceuticals, RG Aerztefortbildung, Institut für Disease Management, Springer, IQVIA Commercial, Ingress Health, Wort & Bild Verlag, Verlag ME, and Procter & Gamble, outside the submitted work; and is a member of EAACI Excom, member of external board of directors Deutsche Gesellschaft für Allergologie und klinische Immunologie; and is a coordinator, main author, or coauthor of different position papers and guidelines in rhinology, allergology, and allergen immunotherapy. FSR reports speaker and advisory fees from AstraZeneca, Novartis, Sanofi, GSK, Teva, Kedrion, Takeda, LEO Pharma, and Lusomedicamenta, all outside the submitted work. NR reports grants from Boehringer Ingelheim, Novartis, GSK, and Pfizer; and personal fees from Boehringer Ingelheim, Novartis, GSK, AstraZeneca, Chiesi, Pfizer, Sanofi, Zambon, and MSD, outside the submitted work. JS reports grants from Sanofi; and personal fees from Sanofi, GSK, Novartis, AstraZeneca, MundiPharma, and Faes Farma, outside the submitted work. CSU reports personal fees from GSK, AZ, TEVA, Novartis, BI, Chiesi, Sanofi, Orion Pharma, and Covis Pharma; and grants from AZ, Novartis, BI, Sanofi, Orion Pharma, and Covis Pharma, outside the submitted work. OV reports grants from Astrazeneca and Chiesi, outside the submitted work. TZ reports grants from Novartis and Henkel; personal fees from Bayer Health Care, FAES, Novartis, Henkel, AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bencard, Berlin Chemie, HAL, Leti, Meda, Menarini, Merck, MSD, Pfizer, Sanofi, Stallergenes, Takeda, Teva, UCB, Kryolan, and L'Oréal, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE-sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate-to-severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite-driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long-term and costly management pathways., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

If allergen immunotherapy (AIT) is to be considered as a treatment option for allergic asthma, it must undergo the same developmental steps as other antiasthmatic drugs. The bronchial allergen challenge model has demonstrated excellent negative predictive value for the development of new therapies for asthma. Subcutaneous immunotherapy appears to have a clinical and significant effect on the early asthmatic response to mite, cat, and birch and grass pollens in children and adults. Use of AIT in children with asthma is widely practiced but not supported by as strong a level of evidence as in adults. House dust mite sublingual immunotherapy tablets demonstrate efficacy in asthma exacerbations and other outcomes when used as add-on therapy in adult patients. Using a biologic to improve the patient's lung functions and asthma control before initiating AIT can transform unsuitable candidates for AIT into appropriate candidates. Because AIT is a form of personalized medicine, phenotyping the most suitable patient is necessary. Field studies of adults and children have suggested that polysensitized patients with rhinitis and Global Initiative for Asthma class 2 to class 4 asthma appear the most likely to be good responders. We hypothesized that AIT responders are those who demonstrate a high eosinophilic response to natural or experimental exposure., (Copyright © 2022. Published by Elsevier Inc.)

Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials. The need for further validation in comparison with field exposure is clearly mandated. On this basis, the European Academy of Allergy and Clinical Immunology (EAACI) initiated a Task Force in 2015 charged to gain a better understanding of how AECs can generate knowledge about respiratory allergies and can contribute to the clinical development of treatments. Researchers working with AECs worldwide were asked to provide technical information in eight sections: (i) dimensions and structure of the AEC, (ii) AEC staff, (iii) airflow, air processing, and operating conditions, (iv) particle dispersal, (v) pollen/particle counting, (vi) safety and non-contamination measures, (vii) procedures for symptom assessments, (viii) tested allergens/substances and validation procedures. On this basis, a minimal set of technical requirements for AECs applied to the field of allergology is proposed., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports., Objective: We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents., Methods: In this retrospective multicenter study, OEB was defined by (1) a fall in FEV 1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness., Results: An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%)., Conclusions: This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Viral infections are known to exacerbate asthma in adults. Previous studies have found few patients with asthma among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia cases. However, the relationship between SARS-CoV-2 infection and severe asthma exacerbation is not known., Objective: To assess the frequency of asthma exacerbation in patients with asthma hospitalized for SARS-CoV-2 pneumonia and compare symptoms and laboratory and radiological findings in patients with and without asthma with SARS-CoV-2 pneumonia., Methods: We included 106 patients between March 4 and April 6, 2020, who were hospitalized in the Chest Diseases Department of Strasbourg University Hospital; 23 had asthma. To assess the patients' asthma status, 3 periods were defined: the last month before the onset of COVID-19 symptoms (p1), prehospitalization (p2), and during hospitalization (p3). Severe asthma exacerbations were defined according to Global INitiative for Asthma guidelines during p1 and p2. During p3, we defined severe asthma deterioration as the onset of breathlessness and wheezing requiring systemic corticosteroids and inhaled β2 agonist., Results: We found no significant difference between patients with and without asthma in terms of severity (length of stay, maximal oxygen flow needed, noninvasive ventilation requirement, and intensive care unit transfer); 52.2% of the patients with asthma had Global INitiative for Asthma step 1 asthma. One patient had a severe exacerbation during p1, 2 patients during p2, and 5 patients were treated with systemic corticosteroids and inhaled β2 agonist during p3., Conclusions: Our results demonstrate that patients with asthma appeared not to be at risk for severe SARS-CoV-2 pneumonia. Moreover, SARS-CoV-2 pneumonia did not induce severe asthma exacerbation., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations., Objective: To assess changes in asthma control between baseline and 12 months of treatment., Methods: Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447)., Results: Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm 3 was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators., Conclusion & Clinical Relevance: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia., (© 2020 John Wiley & Sons Ltd.)

Allergy is a hypersensitivity reaction induced by immunological mechanisms. In asthma, allergy has a complex role and is usually IgE mediated. Allergy must be evaluated during the work up but evidence of IgE sensitivity does not mean that allergens play a role in the pathophysiology of the disease. The clinical relevance of the sensitivity has to be considered. This paper describes current available tools to screen for IgE sensitivity, allergen exposure and their role in asthma., (Copyright © 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Environmental Exposure Chamber (EEC) should have standardized and controlled allergenic and non-allergenic exposures to perform reproducible clinical studies. The aim was to demonstrate that mite exposure in the Alyatec ® EEC could induce early (EAR) and/or late asthmatic reactions (LAR) in at least 60% of subjects allergic to mite. Methods: The EEC has a volume of 147-m 3 with 20 seats. The nebulized particle number, airborne Der p1, endotoxins, and volatile organic compound (VOC) concentrations were measured. Twenty-four asthmatics allergic to mite were randomly exposed to 15, 25, and 46 ng/m 3 Der p1. Specificity was assessed in not mite-sensitized asthmatics. Results: No significant endotoxin or VOC contamination was measured. The mean inter-assay CVs were 12.5% for the airborne particle number and 28.7% for airborne Der p1 concentrations. For the three Der p1 concentrations, at least 88% of the subjects developed EAR and/or LAR, and at least 46% developed a dual response. No reaction occurred with placebo or in the control group. No severe bronchial reaction occurred. Conclusions: The Alyatec ® EEC demonstrated a tight control of allergenic and non-allergenic exposures. The EEC was clinically validated, with airborne Der p1 levels close to levels found in natural settings.

Background: Air cleaners have been promoted for respiratory allergic disease prevention, but there is no clear clinical proof of their efficacy in allergic asthma., Objective: To examine the efficacy of a new air cleaner on early and late asthmatic responses in cat-allergic patients., Methods: This randomized, cross-over, double-blind placebo-controlled study enrolled 24 cat-asthmatic patients with GINA 1 asthma. At baseline, participants were exposed to 40 ng/m 3 of airborne cat allergen for a maximum of 2 hours in ALYATEC ® environmental exposure chamber (EEC). All participants were subsequently randomized into two groups that were exposed to cat allergen, either with active then placebo air cleaners or with placebo then active air cleaners with a 3-week interval in the EEC. This study was registered under number (NCT03928561)., Results: Fewer patients experienced an EAR with active air cleaners (seven patients; 29.17%) than placebo (21 patients; 87.50%). The response incidence was lower with active than with placebo air cleaners. A Cox model demonstrated a significant treatment effect (hazard ratio, 0.10; P = .002). Active air cleaners also prevented late asthmatic response: four patients (16.67%) had a late asthmatic response with active air cleaners compared to 11 patients (45.83%) with placebo (Prescott test P = .002). Active air cleaners also decreased the maximal severity of bronchial response (FEV1 decrease of 17.24% with active vs 25.62% with placebo air cleaners; P = .001)., Conclusions: Our present results demonstrated that Intense Pure Air XL ® air cleaners significantly prevented early and late asthmatic responses among cat-allergic asthmatics during cat allergen exposure in the ALYATEC ® EEC., (© 2019 John Wiley & Sons Ltd.)

Background and Objective: Omalizumab is a human anti-IgE antibody approved for the treatment of severe allergic asthma (SAA). However, its effectiveness in SAA associated with chronic rhinosinusitis with nasal polyposis (CRSNP+) is less well documented. Objective: The aim of this study was to evaluate the real-life effectiveness of omalizumab in patients with SAA and CRSNP+ who tolerated and did not tolerate aspirin., Methods: We performed a retrospective, observational, multicenter, real-life study of patients with SAA and CRSNP+ treated with omalizumab for 6 months. Asthma outcome parameters (symptoms, number of salbutamol rescues/wk, number of moderate/severe exacerbations, Asthma Control Test score, and lung function), sinonasal outcome parameters (symptoms, number of episodes of acute rhinosinusitis, sinus computed tomography images, nasal polyps endoscopy score), and serum eosinophil levels were analyzed 6 months before and after treatment with omalizumab., Results: Twenty-four adult patients were included (9 with documented aspirin intolerance). All respiratory parameters were significantly improved by the treatment. In parallel, a significant improvement was observed in sinonasal clinical outcomes and sinus computed tomography images, with no major effect on the nasal polyps endoscopy score. The serum eosinophil count decreased significantly after 6 months of treatment with omalizumab., Conclusion: Treatment of SAA with omalizumab improves the outcome of associated CRSNP+, thus supporting the concept of a "one airway disease".

The seventh "Future of the Allergists and Specific Immunotherapy (FASIT)" workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the "Therapy Allergen Ordinance" in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future., (© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.)

Background: The clinical efficacy of controlling environmental allergens as a component of allergic asthma treatment remains controversial. Multifaceted allergen reductions appeared to be the most efficient methods. However, they require home visits with indoor technicians., Objective: To examine the characteristics of indoor environments that might be related to symptoms of children and adult patients with mite allergic rhinitis and/or asthma., Methods: We included 315 patients allergic to house dust mites with rhinitis and/or asthma who had been visited at home by 2 medical indoor environment counselors (MIECs) from the Strasbourg University Hospital between January 2007 and June 2015. In a cluster analysis, we analyzed 42 characteristics of respiratory symptoms, dwelling characteristics, and indoor pollutants in this population., Results: Three clusters were defined among the patients. Cluster 1 included 55 patients, all with rhinitis, 32% with asthma, and all living in an urban area. Clusters 2 and 3 included 86 and 174 patients, respectively. The important factors in these 2 clusters were asthma incidence and exposure to different indoor pollutants, such as indoor perfumes, cleaning products, and tobacco smoke., Conclusion: Our results underlined the variability of indoor environments and the importance of MIEC home visits to investigate individual patient environments and propose an appropriate avoidance management plan. Our results showed that sensitization to mite and exposure to indoor chemical pollutants were associated with severe asthma., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rhinitis and asthma are common diseases that are strongly linked from both the epidemiological and patho-physiological point of view. A precise aetiological diagnosis is required in order to optimize treatment. Nasal provocation tests (NPT) determine precisely the role of the allergen in the initiation of the symptoms of rhinitis particularly when the history does not produce convincing evidence of the clinical relevance of an allergen. It may also have important consequences for the choice of an allergenic immunotherapy. NPT are not standardized but simple methods based on international recommendations provide us with good diagnostic accuracy. In this paper, we will discuss the practical aspects of NPT as well as the clinical or research situations where they may be useful for the respiratory physician., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

The Fernand Widal syndrome is a set of associations between asthma, nasal polyposis and aspirin sensitivity. Selective cyclo-oxygenase 2 (COX 2) inhibitors are recognized as being a therapeutic alternative in cases needing analgesic or anti-inflammatory treatment. In a retrospective study, we have compiled data concerning oral provocation tests (OPT) undertaken with celecoxib, one of most the selective COX 2 inhibitors, in eight patients with the Fernand Widal syndrome. They were compared with twenty-seven control patients with sensitivity to aspirin or non-steroidal anti-inflammatories, manifesting as asthma, urticaria or rhino-conjunctivitis. Four patients with the Fernand Widal syndrome developed bronchospasm after taking the usually recommended daily dose of celecoxib while all the control patients tolerated it. The Fernand Widal patients who reacted during the OPT had a lower threshold of reactivity to aspirin, a more severe reaction with aspirin, and/or more severe asthma. In patients with the Fernand Widal syndrome, celecoxib is not always a possible alternative to non-steroidal anti-inflammatory drugs. Its introduction must be carried out in a hospital environment under medical supervision., (Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Introduction: Vocal cord dyskinesia or vocal cord dysfunction (VCD) is characterized by intermittent abnormal adduction of the vocal cords leading to airflow limitation at the level of the larynx, in the absence of local organic disease. It may occur in isolation or in association with asthma. The pathophysiology is complex and poorly understood. Wheeze, stridor or apparent upper airway obstruction are the most common symptoms. It occurs in a wide age range, more commonly in women, and diagnosis is often delayed and leads to unnecessary treatments (intubation, tracheostomy and high dose steroids)., Methods: A retrospective study of 15 cases of VCD (8 cases of isolated VCD and 7 cases of VCD with associated asthma) describing the main clinical features and the diagnosis strategy., Results: Apparent upper airway obstruction, with or without associated asthma, requires an ear nose and throat examination with laryngoscopy to confirm the paradoxical adduction of the vocal cords during an acute episode of dyspnoea or during a provocation test with triggers like exercise or exposure to irritants, and for the purpose of differential diagnosis., Conclusions: VCD remains under-appreciated and misdiagnosed, often by mimicking asthma with which it can be associated. A delayed diagnosis by emergency specialists, pulmonologists and ear nose and throat surgeons leads to unnecessary treatments and morbidity before specific therapy can be given., (Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: It is known that asthma is related to obesity but also to small birthweight. The objective of this study was to clarify this issue by assessing the putative relationship between the changes in corpulence between birth and childhood as assessed by body mass index (BMI) and asthma phenotypes., Methods: The following status in corpulence was assessed in 7781 schoolchildren using quartile of BMI at birth and at around 10 (9-11 years): underweight at birth and at around 10, underweight at birth and overweight at around 10, overweight at birth and underweight at around 10, overweight at birth and at around 10, and the reference group constituted by all the other children in whom corpulence changes were not extreme. Determination of asthma phenotypes (allergic, non-allergic, and exercise-induced asthma) was based on a clinical examination including skin prick tests, an exercise challenge test, and a questionnaire., Results: The risk of allergic asthma was higher in children with persistent underweight, children with persistent overweight, and children becoming markedly more corpulent. In boys, the risk of allergic asthma was significantly higher for the less corpulent children at birth, regardless of whether they remained so or become overweight. In girls, the risk of allergic asthma was significantly higher in those with persistent overweight. There were no significant associations between BMI changes and non-allergic and exercise-induced asthma., Conclusions: We observed that some extreme changes in BMI, persistent underweight, and persistent overweight in childhood increased the risk of allergic asthma., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The SQ house dust mite (HDM) SLIT-tablet (ALK, Denmark) addresses the underlying cause of HDM respiratory allergic disease, and a clinical effect has been demonstrated for both HDM allergic rhinitis and allergic asthma. Here, we present pooled safety data from an adult population with HDM respiratory allergy, with particular focus on the impact of asthma on the SQ HDM SLIT-tablet tolerability profile., Methods: Safety data from 2 randomised double-blind, placebo-controlled clinical trials were included: MT-04: 834 adults with HDM allergic asthma not well controlled by inhaled corticosteroids and with HDM allergic rhinitis, and MT-06: 992 adults with moderate-to-severe HDM allergic rhinitis despite the use of allergy pharmacotherapy and with or without asthma., Results: The proportion of subjects experiencing adverse events (AEs) was greater in the active treatment group (12 SQ-HDM; 73% of subjects) compared to placebo (53%). The most common treatment-related AEs were local allergic reactions. No AEs were reported as systemic allergic reactions. Regardless of asthma status, most AEs were mild or moderate (>97% of AEs) and the frequency of serious AEs was low. Subgroup analysis revealed no statistically significant difference in the risk of experiencing moderate or severe treatment-related AEs for subjects with asthma compared to subjects without asthma (p = 0.88). In addition, subjects with partly controlled or uncontrolled asthma were no more likely to experience moderate or severe treatment-related AEs than subjects with controlled asthma (p = 0.42)., Conclusion: The SQ HDM SLIT-tablet is well tolerated, and the safety profile was comparable for subjects with HDM respiratory allergic disease irrespective of asthma status., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Triggers and precipitating factors as well as comorbid conditions are associated with asthma and severe asthma. They interfere with the potential to control the disease and represent an additional burden for the patients. Allergen exposure is well known to induce loss of control and exacerbations. Comorbid conditions belong to various fields of medicines including cardiovascular diseases, osteoporosis, obesity and sleep apneas and GERD. They should be diagnosed and treated for themselves according to the best state of the art. Their precise role et their contribution to severe asthma pathophysiology is largely unknown and longitudinal cohort studies are needed to better understand and treat the patients with severe asthma., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Importance: The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma., Objectives: To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid (ICS) reduction period., Design, Settings, and Participants: Double-blind, randomized, placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites. The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products, and with HDM allergy-related rhinitis. Key exclusion criteria were FEV1 less than 70% of predicted value or hospitalization due to asthma within 3 months before randomization. Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50% for 3 months and then completely withdrawn for 3 months., Interventions: 1:1:1 randomization to once-daily treatment with placebo (n = 277) or HDM SLIT tablet (dosage groups: 6 SQ-HDM [n = 275] or 12 SQ-HDM [n = 282]) in addition to ICS and the short-acting β2-agonist salbutamol., Main Outcomes and Measures: Primary outcome was time to first moderate or severe asthma exacerbation during the ICS reduction period. Secondary outcomes were deterioration in asthma symptoms, change in allergen-specific immunoglobulin G4 (IgG4), change in asthma control or asthma quality-of-life questionnaires, and adverse events., Results: Among 834 randomized patients (mean age, 33 years [range, 17-83]; women, 48%), 693 completed the study. The 6 SQ-HDM and 12 SQ-HDM doses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo (hazard ratio [HR]: 0.72 [95% CI, 0.52-0.99] for the 6 SQ-HDM group, P = .045, and 0.69 [95% CI, 0.50-0.96] for the 12 SQ-HDM group, P = .03). The absolute risk differences based on the observed data (full analysis set) in the active groups vs the placebo group were 0.09 (95% CI, 0.01-0.15) for the 6 SQ-HDM group and 0.10 (95% CI, 0.02-0.16) for the 12 SQ-HDM group. There was no significant difference between the 2 active groups. Compared with placebo, there was a reduced risk of an exacerbation with deterioration in asthma symptoms (HR, 0.72 [95% CI, 0.49-1.02] for the 6 SQ-HDM group, P = .11, and 0.64 [95% CI, 0.42-0.96] for the 12 SQ-HDM group, P = .03) and a significant increase in allergen-specific IgG4. However, there was no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. There were no reports of severe systemic allergic reactions. The most frequent adverse events were mild to moderate oral pruritus (13% for the 6 SQ-HDM group, 20% for the 12 SQ-HDM group, and 3% for the placebo group), mouth edema, and throat irritation., Conclusions and Relevance: Among adults with HDM allergy-related asthma not well controlled by ICS, the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction, with an estimated absolute reduction at 6 months of 9 to 10 percentage points; the reduction was primarily due to an effect on moderate exacerbations. Treatment-related adverse events were common at both active doses. Further studies are needed to assess long-term efficacy and safety., Trial Registration: clinicaltrialsregister.eu Identifier: 2010-018621-19.

Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach-in a limited number of patients and controls-to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology.

Background: The prevalence of asthma and allergy has recently risen among children. This increase in prevalence might be related to various factors, particularly diet. The aim of this study is to assess the prevalence and association of asthma and allergic sensitization with dietary factors in the French Six Cities Study., Methods: Cross-sectional studies were performed among 7432 schoolchildren aged 9-11 years in Bordeaux, Clermont-Ferrand, Créteil, Marseille, Reims, and Strasbourg. Parental questionnaires, based on the International Study on Asthma and Allergies in Childhood (ISAAC), were used to collect information on allergic diseases and potential exposure factors including a food frequency questionnaire to evaluate dietary habits. Skin prick testing to common allergens for allergic sensitization and bronchial hyper-responsiveness (BHR) testing to exercise were performed. Confounders control was performed with multiple logistic regressions., Results: Asthma symptoms, asthma and allergic sensitization were more prevalent in boys than in girls and were more prevalent in the South than in the North of France. After adjustment for confounders, fruit juice intake was associated with a low prevalence of lifetime asthma (ORa [95 % CI]; 0.73 [0.56-0.97]), butter intake was positively associated with atopic wheeze (1.48 [1.07-2.05]) and having lunch at the canteen 1-2 times/week compared to never or occasionally was associated with a lower prevalence of past year wheeze (0.71 [0.52-0.96]), lifetime asthma (0.76 [0.60-0.96]) and allergic sensitization (0.80 [0.67-0.95]). Meat intake was inversely related to past year wheeze among atopic children (0.68 [0.50-0.98]) while fast food consumption and butter intake were associated with an increase prevalence of asthma (2.39 [1.47-3.93] and 1.51 [1.17-2.00] respectively). Fish intake was associated with a lower prevalence of asthma among non-atopic children (0.61 [0.43-0.87]. None of the dietary factors was associated with BHR., Conclusions: Diet is associated with wheeze, asthma and allergic sensitization but not with BHR in children. These results provide further evidence that adherence to a healthy diet including fruits, meat and fish seems to have a protective effect on asthma and allergy in childhood. However, prospective and experimental studies are needed to provide causal evidence concerning the effect of diet on asthma and atopy.

Background: Exacerbations are a key outcome in clinical research, providing patient-relevant information about symptomatic control, health state and disease progression. Generally considered as an episode of (sub)acute deterioration of respiratory symptoms, a precise, clinically useful definition is needed for use in clinical trials., Aim and Methods: Focussing on moderate exacerbations, this opinion piece reviews landmark trials and current guidelines to provide a practical definition of a moderate exacerbation. Specifically, we adapt the ATS/ERS consensus statement of terminology Reddel et al. (2009) [1] which provides a conceptual (or 'theoretical') definition for moderate exacerbations, to an operational (or 'practical') criterion suitable for use in clinical research., Results: The proposed definition for a moderate exacerbation requires ≥1 of the following criteria combined with a change in treatment: a) nocturnal awakening(s) due to asthma requiring SABA for 2 consecutive nights or an increase of ≥0.75 from baseline in daily symptom scores on 2 consecutive days; b) increase from baseline in occasions of SABA use on 2 consecutive days (minimum increase: 4 puffs/day); c) ≥20% decrease in PEF from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline and/or d) visit to the emergency room/trial site for asthma treatment not requiring systemic corticosteroids., Conclusion: A clinically and patient-relevant, operational definition of moderate exacerbations is needed. The proposed definition has been endorsed by the EMA Scientific Advice Working Party in 2011and needs to be trialled in forthcoming clinical studies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: In a 1999 survey, community pharmacists from the Alsace region of France had a reasonably good knowledge of asthma treatment and prevention, but their skill in the use of asthma inhalation devices left room for improvement. Since then, health authorities have encouraged the involvement of community pharmacists in patient care and education in order to improve asthma control. The aim of this study was to assess the change in the knowledge of asthma management and inhaler technique skills of community pharmacists in the same geographic area after a 10-year interval., Methods: In 2009, 86 randomly selected community pharmacists from the Alsace region answered a standardized questionnaire about their theoretical knowledge of and practical attitude toward asthma management and inhaled delivery systems, following which their skills in the use of four inhalation devices (pressurized metered-dose inhaler (pMDI) with/without a spacer, breath-actuated pMDI and dry powder inhaler (DPI)) were evaluated., Results: Very few pharmacists were required to manage an acute asthma exacerbation at the pharmacy, but all responded well by administering a short-acting inhaled β2-agonist. Theoretical knowledge of asthma management (criteria of severity of asthma exacerbation, guidelines and drugs triggering asthma exacerbations) was still average. Compared with 1999, they were twice as confident in demonstrating inhaler use, and their skills in using the pMDI, breath-actuated pMDI and DPI had improved significantly (p < 0.001)., Conclusions: Since 1999, pharmacists' skill in the use of inhalers has improved, but theoretical knowledge of asthma management is still average, pointing to the importance of continuing pharmaceutical education.

Introduction: In a double-blind, placebo-controlled trial (EudraCT identifier: 2006-001795-20), the standardised quality (SQ) house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) was investigated., Method: The trial included 604 subjects, ≥14 years, with mild-moderate HDM allergic asthma. Subjects were randomised 1:1:1:1 to 1, 3 or 6 SQ-HDM or placebo once daily. The primary endpoint was reduction in inhaled corticosteroid (ICS) after one year. ICS reduction, asthma quality of life questionnaire (AQLQ) and asthma control questionnaire (ACQ) score was analysed post hoc in a subgroup with daily ICS use of 400-800 μg and ACQ score of 1-1.5, corresponding to partly controlled asthma (N = 108)., Results: The trial met its primary endpoint. In the subgroup, the difference between placebo and 6 SQ-HDM in change from baseline in daily ICS use was 327 μg (p < 0.0001), while it was 0.52 (p = 0.010) for AQLQ. The treatment effect on ICS reduction and AQLQ was increased for the subgroup versus the residual population (ICS reduction: p < 0.001); AQLQ: p = 0.044)., Conclusion: In this subgroup, including only patients with partly controlled asthma, the benefit of 1 year of treatment with SQ HDM SLIT-tablet was significantly higher than for the less severe full population, both in terms of increased asthma control and improved quality of life., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Investigations meeting current standards are limited for the effect of house dust mite (HDM) allergy immunotherapy in asthmatic patients., Objective: This trial investigated the efficacy and safety of a standardized quality (SQ; allergen standardization method proprietary to the trial sponsor) HDM SLIT-tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease. This publication reports the results of the endpoints related to asthma., Methods: Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were randomized 1:1:1:1 to double-blind daily treatment with one of 3 active doses (1, 3, or 6 SQ-HDM) or placebo. Their use of inhaled corticosteroid (ICS) was standardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control. The primary end point was a reduction in ICS dose from the individual subject's baseline dose after 1 year of treatment., Results: The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg (P = .004). Relative mean and median reductions were 42% and 50% for 6 SQ-HDM and 15% and 25% for placebo, respectively. No statistically significant differences were observed for the other assessed asthma parameters, reflecting the intended controlled status of the trial subjects. The most common adverse events were local reactions in the mouth. The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo., Conclusion: Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control. All active doses were well tolerated., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: An increased incidence of asthma has been reported among healthcare workers. The role of quaternary ammonium compounds (QACs), commonly used in cleaning/disinfection products, has not been clearly defined. The aim of this study was to analyse associations between asthma and occupational exposure to disinfectants, especially QACs., Methods: The study was performed on a stratified random sample of the various healthcare departments of 7 healthcare settings. The study included: questionnaire, physical examination and specific IgE assays. Occupational exposure assessment was performed by means of a work questionnaire, workplace studies and a review of products ingredients. Data were analysed by logistic regression., Results: Response rate was 77%; 543 workers (89% female) participated; 37.1% were registered nurses (RNs), 16.4% auxiliary nurses (ANs), 17.3% cleaners; 32.8% were atopic. 335 participants were exposed to QACs. Nursing professionals reported a significantly higher risk of reported physician-diagnosed asthma and, for RNs, of nasal symptoms at work than administrative staff working in healthcare sector. This risk was particularly marked during disinfection tasks and when exposure to QACs. Exposure to QACs increased significantly the risk of reported physician-diagnosed asthma and nasal symptoms at work (adjusted OR = 7.5 and 3.2, respectively). No significant association was found with other exposures such as latex glove use, chlorinated products/bleach or glutaraldehyde., Conclusion: RNs and ANs presented a higher risk of reported asthma than administrative staff. The highest risk was associated with tasks involving dilution of disinfection products by manual mixing, suggesting possible exposure to repeated peaks of concentrated products known to be strong respiratory irritants. Workplace interventions should be conducted to more clearly determine QAC exposure and improve disinfection procedures., (© 2013 John Wiley & Sons Ltd.)

Professional and domestic cleaning is associated with work-related asthma (WRA). This position paper reviews the literature linking exposure to cleaning products and the risk of asthma and focuses on prevention. Increased risk of asthma has been shown in many epidemiological and surveillance studies, and several case reports describe the relationship between exposure to one or more cleaning agents and WRA. Cleaning sprays, bleach, ammonia, disinfectants, mixing products, and specific job tasks have been identified as specific causes and/or triggers of asthma. Because research conclusions and policy suggestions have remained unheeded by manufactures, vendors, and commercial cleaning companies, it is time for a multifaceted intervention. Possible preventive measures encompass the following: substitution of cleaning sprays, bleach, and ammonia; minimizing the use of disinfectants; avoidance of mixing products; use of respiratory protective devices; and worker education. Moreover, we suggest the education of unions, consumer, and public interest groups to encourage safer products. In addition, information activities for the general population with the purpose of improving the knowledge of professional and domestic cleaners regarding risks and available preventive measures and to promote strict collaboration between scientific communities and safety and health agencies are urgently needed., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: This study examined the hypothesis that emotion and conduct problems (ECPs) may modify the relationships between ambient air pollutants and childhood asthma and eczema., Methods: In the cross-sectional study, 4209 French schoolchildren (aged 10e12 years) were investigated between March 1999 and October 2000. Ambient air pollutants exposures were estimated with dispersion modeling. Health outcomes and ECPs were evaluated by validated questionnaires, completed by the parents. Marginal models were used to analyze the relationships of exposures to ambient air pollutants and/or ECPs to asthma phenotypes and current eczema, adjusting for potential confounders., Results: In our population, interactions were found between ECPs and exposures to ambient air pollutants (benzene, carbon monoxide, nitrogen dioxide, nitrogen oxides, particulate matter with an aerodynamic diameter below 10 mm, volatile organic compounds) (P < .20). In addition, ECPs were related to current wheezing (adjusted prevalence odds ratio [aOR], 2.35; 95% confidence interval [CI], 1.59e3.47), current doctor-diagnosed asthma (aOR, 1.82; 95% CI, 1.25e2.66), and current eczema (aOR, 2.21; 95% CI, 1.61e3.02). Children with ECPs had 1.17e1.51 times higher aORs for the associations between ambient air pollutants and asthma phenotypes and current eczema than those without ECPs., Conclusions: ECPs may modify the relationships between ambient air pollutants and childhood asthma and eczema., (2013 Elsevier Inc. All rights reserved.)

We investigated the relationships of behavioural problems as assessed using the standardized Strengths and Difficulties Questionnaire (SDQ) to asthma in view of improving asthma management. Six thousand eight hundred and eighty children (mean age 10.4 years, male: 49%) were recruited in the French 6 Cities Study. Children with abnormal or borderline emotional symptoms (internalizing problems) or conduct problems (externalizing problems) were more asthmatic than others (P < 0.01). Compared to being normal, abnormal emotional symptoms or conduct problems were found to be related to mild-to-moderate persistent asthma (logistic model adjusted odds ratio = 1.55 (95% CI = 1.26-1.90) and 1.42 (95% CI = 1.17-1.71), respectively) and to early-onset asthma (Cox's model Adjusted Hazard Risk = 1.60 (95% CI = 1.27-2.01) and 1.34 (95% CI = 1.05-1.70). Borderline conduct problems were found to be negatively related to parents' knowledge on how to prevent asthma attacks, compared to normal conduct problems [adjusted OR = 0.51 (95% CI = 0.31-0.85)]. Further data are needed to better understand the involvement of behavioural problems in childhood asthma according to phenotypes., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: While up to 50% of patients with severe asthma have no evidence of allergy, IgE has been linked to asthma, irrespective of atopic status. Omalizumab, an anti-IgE monoclonal antibody, is reported to significantly benefit a subset of patients with severe, persistent, allergic asthma. Therefore, we investigated whether omalizumab has biologic and clinical effects in patients with refractory nonatopic asthma., Methods: Forty-one adult patients who, despite daily treatment with or without maintenance oral corticosteroids, had severe, nonatopic, refractory asthma according to GINA (Global Initiative for Asthma) step 4, were randomized to receive omalizumab or placebo in a 1:1 ratio. The primary end point was the change in expression of high-affinity IgE receptor (FcεRI) on blood basophils and plasmacytoid dendritic cells (pDC2) after 16 weeks. The impact of omalizumab on lung function and clinical variables was also examined., Results: Compared with placebo, omalizumab resulted in a statistically significant reduction in FcεRI expression on basophils and pDC2 (P &lt; .001). The omalizumab group also showed an overall increase in FEV1 compared with baseline (+250 mL, P = .032; +9.9%, P = .029). A trend toward improvement in global evaluation of treatment effectiveness and asthma exacerbation rate was also observed., Conclusions: Omalizumab negatively regulates FcεRI expression in patients with severe nonatopic asthma, as it does in severe atopic asthma. Omalizumab may have a therapeutic role in severe nonatopic asthma. Nonetheless, our preliminary findings support further investigation to better assess the clinical efficacy of omalizumab., Trial Registry: ClinicalTrials.gov; No.: NCT01007149; URL: www.clinicaltrials.gov and European Clinical Trials Database, EudraCT; No.: 2009-010937-38; URL: https://www.clinicaltrialsregister.eu.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Relationships between indoor air quality (IAQ) found in schools and the allergic and respiratory health of schoolchildren have been insufficiently explored. A survey was conducted in a large sample of classrooms of primary schools in France to provide objective assessments of IAQ to which young schoolchildren are exposed in classrooms, and to relate exposure to major air pollutants found in classrooms to asthma and allergies of schoolchildren., Methods: Concentrations of fine particles with aerodynamic diameter ≤2.5 μm (PM(2.5)), nitrogen dioxide (NO(2)) and three aldehydes were objectively assessed in 401 randomly chosen classrooms in 108 primary schools attended by 6590 children (mean age 10.4 years, SD ±0.7) in the French 6 Cities Study. The survey incorporated a medical visit including skin prick testing (SPT) for common allergens, a test for screening exercise-induced asthma (EIA) and a standardised health questionnaire completed by parents., Results: Children were differently exposed to poor air quality in classrooms, with almost 30% being highly exposed according to available standards. After adjusting for confounders, past year rhinoconjunctivitis was significantly associated with high levels of formaldehyde in classrooms (OR 1.19; 95% CI 1.04 to 1.36). Additionally, an increased prevalence of past year asthma was found in the classrooms with high levels of PM(2.5) (OR 1.21; 95% CI 1.05 to 1.39), acrolein (OR 1.22; 95% CI 1.09 to 1.38) and NO(2) (OR 1.16; 95% CI 0.95 to 1.41) compared with others. The relationship was observed mostly for allergic asthma as defined using SPT. A significant positive correlation was found between EIA and the levels of PM(2.5) and acrolein in the same week., Conclusions: In this random sample, air quality in classrooms was poor, varied significantly among schools and cities, and was related to an increased prevalence of clinical manifestations of asthma and rhinitis in schoolchildren. Children with a background of allergies seemed at increased risk.

Provocation and challenge tests have been used to understand the pathobiology of asthma, to facilitate diagnosis and to assess therapeutic efficacy and dosage. Current challenge tests expose the patient to 'natural conditions', for example, in an allergen chamber. For determining drug efficacy in asthma, allergen challenge has a moderate positive predictive value and an excellent negative predictive value. The best challenge tests are standardized, and the best bronchial challenge tests use a large allergen particle size. Allergen provocation tests are safe when performed by experienced investigators., (© 2011 John Wiley & Sons A/S.)

Background: It is documented that omalizumab treatment reduces the cell surface expression of immunoglobulin E high-affinity receptor (FcɛRI) on several cell types. This has not been investigated in patients with uncontrolled severe persistent allergic asthma., Methods: In a double-blind, randomized, placebo-controlled study, patients with severe allergic asthma uncontrolled by high dose inhaled corticosteroids and long-acting β(2)-agonist received either omalizumab (n = 20) or placebo (n = 11) over 16 weeks at appropriate doses and frequencies. Baseline and end of study (week 16) FcɛRI expression on basophils and plasmacytoid dendritic cells was determined by flow cytometry for the primary endpoint. Secondary efficacy endpoints included asthma control and lung function as part of an initial investigation into the use of FcɛRI expression as a marker of response., Results: In the omalizumab group, and with respect to placebo, FcɛRI expression was significantly reduced at end of study on basophils (-82.6%, p < 0.01) and plasmacytoid dendritic cells (-44.2%, p = 0.029). FcɛRI expression reduction was not found to be correlated with clinical response., Conclusions: Long-term omalizumab treatment induced reduction of FcɛRI expression on circulating basophils and plasmacytoid dendritic cells. These changes were not associated with those of clinical features related to severe asthma, which does not support further investigation into its use as a predictive marker of response., Trial Registration: The study was registered with ClinicalTrials.gov (identifier: NCT00454051) and the European Clinical Trials Database, EudraCT (identifier: 2006-003591-35)., (Copyright © 2010. Published by Elsevier Ltd.)

Background: Allergic sensitization to Alternaria has been related to asthma in various studies, but its association with allergic rhinitis is still controversial., Objectives: The aim of this study was to assess at the population level the relationships in childhood between Alternaria sensitization and 'past-year rhinoconjunctivitis' (PYRC), 'ever hay fever' (EHF) and 'ever allergic rhinitis caused by allergens other than pollens' (EAR) according to the presence or the absence of asthma., Methods: This study is part of the Six Cities Study, the French contribution to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II. Children underwent skin prick test (SPT) to Alternaria and parents filled a standardized medical questionnaire., Results: Some 6726 children with a mean age of 10 years were examined. The overall prevalence of Alternaria sensitization was 2.8%, 0.8% for monosensitization. Prevalences of symptoms in sensitized children were 27.7% for PYRC, 27.0% for EHF and 30.4% for EAR. Adjusted Odds Ratios (OR) between Alternaria sensitization and allergic rhinitis phenotypes were 2.34 (95% confidence interval: 1.51-3.63) for PYRC, 2.40 (1.65-3.50) for EHF and 2.95 (2.05-4.23) for EAR. The relationship still remained in the case of monosensitization to Alternaria for both PYRC and EAR when excluding the asthmatic children [OR = 3.87 (1.54-9.78) and 2.88 (1.10-7.55) respectively]., Conclusion: In our population-based sample of children, we found a link between Alternaria sensitization and allergic rhinitis, independently of asthma, which is compatible with the mechanisms of deposition of Alternaria in the upper airways.

Since tropomyosin is cross reactive in many arthropods, it was assumed that this highly conserved protein could be responsible for cross reactions in house dust mite (HDM) allergic patients who experienced adverse reactions after crustacean and mollusc ingestion. Here we report two clinical cases where the role of tropomyosin is a matter of debate. In the first case, the clinical history, as well as the results of in vivo and in vitro investigations, are in favour of a shrimp allergy without any snail allergy in a patient sensitized to HDM. In the second, the clinical history and the cutaneous tests are in favour of an allergy to snails without any allergy to shrimps in a patient suffering from HDM allergies. The clinical presentation is different in shrimp and snail allergies. In shrimp allergy, symptoms are mainly urticaria or angio-oedema. In snail allergies, adverse reactions are especially severe asthma. Shrimp tropomyosin is a dominant allergen in crustaceans whereas has a much less prominent role in HDM sensitization. Cross reactivities between HDM and snails have been confirmed by inhibition experiments. However, tropomyosin appears to be a minor allergen or even is not involved in snail allergy. It is necessary to clarify the allergens shared between HDMI and snails. The effects of HDM immunotherapy in snail allergy are questioned. Knowledge of taxonomy can contribute to more precise evaluation of cross reactivities between crustaceans and molluscs.