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Objectives: Innate lymphoid cells (ILCs) secrete cytokines, such as IFN‐γ, IL‐13 and IL‐17, which are linked to chronic obstructive pulmonary disease (COPD). Here, we investigated the role of pulmonary ILCs in COPD pathogenesis. Methods: Lung ILC subsets in COPD and control subjects were quantified using flow cytometry and associated with clinical parameters. Tissue localisation of ILC and T‐cell subsets was determined by immunohistochemistry. Mice were exposed to air or cigarette smoke (CS) for 1, 4 or 24 weeks to investigate whether pulmonary ILC numbers and activation are altered and whether they contribute to CS‐induced innate inflammatory responses. Results: Quantification of lung ILC subsets demonstrated that ILC1 frequency in the total ILC population was elevated in COPD and was associated with smoking and severity of respiratory symptoms (COPD Assessment Test [CAT] score). All three ILC subsets localised near lymphoid aggregates in COPD. In the COPD mouse model, CS exposure in C57BL/6J mice increased ILC numbers at all time points, with relative increases in ILC1 in bronchoalveolar lavage (BAL) fluid. Importantly, CS exposure induced increases in neutrophils, monocytes and dendritic cells that remained elevated in Rag2/Il2rg‐deficient mice that lack adaptive immune cells and ILCs. However, CS‐induced CXCL1, IL‐6, TNF‐α and IFN‐γ levels were reduced by ILC deficiency. Conclusion: The ILC1 subset is increased in COPD patients and correlates with smoking and severity of respiratory symptoms. ILCs also increase upon CS exposure in C57BL/6J mice. In the absence of adaptive immunity, ILCs contribute to CS‐induced pro‐inflammatory mediator release, but are redundant in CS‐induced innate inflammation. [ABSTRACT FROM AUTHOR]

Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy. Type 2‐targeting biologics such as anti‐IgE, anti‐IL4Rα, anti‐IL5, and anti‐IL5Rα have entered the market for selected pheno/endotypes of asthma patients and may soon also become available for CRSwNP patients. Given the high prevalence of chronic respiratory diseases and the high cost associated with biologics, patient selection is crucial in order to implement such therapies into chronic respiratory disease care pathways. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized a multidisciplinary Expert Board Meeting to discuss the positioning of biologics into the care pathways for CRSwNP patients with and without comorbid asthma. [ABSTRACT FROM AUTHOR]

An editorial is presented on the second Rhinology Future Debate which took place in Brussels, Belgium in December 2017 which brought together key experts in the field of respiratory diseases. Topics discussed include Lessons from biologicals in asthma for ENT physicians, Positioning Dymista in Allergic Rhinitis treatment and Nasal turbinate as therapeutic target in patients with turbinate‐induced nasal symptoms.

Summary: Background: Clinical and experimental studies have identified a crucial role for IL‐33 and its receptor ST2 in allergic asthma. Inhalation of traffic‐related pollutants, such as diesel exhaust particles (DEP), facilitates the development of asthma and can cause exacerbations of asthma. However, it is unknown whether IL‐33/ST2 signalling contributes to the enhancing effects of air pollutants on allergic airway responses. Objective: We aim to investigate the functional role of IL‐33/ST2 signalling in DEP‐enhanced allergic airway responses, using an established murine model. Methods: C57BL/6J mice were exposed to saline, DEP alone, house dust mite (HDM) alone or combined DEP+HDM. To inhibit IL‐33 signalling, recombinant soluble ST2 (r‐sST2) was given prophylactically (ie, during the whole experimental protocol) or therapeutically (ie, at the end of the experimental protocol). Airway hyperresponsiveness and the airway inflammatory responses were assessed in bronchoalveolar lavage fluid (BALF) and lung. Results: Combined exposure to DEP+HDM increased IL‐33 and ST2 expression in lung, elevated inflammatory responses and bronchial hyperresponsiveness compared to saline, sole DEP or sole HDM exposure. Prophylactic interference with the IL‐33/ST2 signalling pathway impaired the DEP‐enhanced allergic airway inflammation in the BALF, whereas effects on lung inflammation and airway hyperresponsiveness were minimal. Treatment with r‐sST2 at the end of the experimental protocol did not modulate the DEP‐enhanced allergic airway responses. Conclusion: Our data suggest that the IL‐33/ST2 pathway contributes to the onset of DEP‐enhanced allergic airway inflammation. [ABSTRACT FROM AUTHOR]

On March 29, 2017, a European Summit on the Prevention and Self-Management of Chronic Respiratory Diseases (CRD) was organized by the European Forum for Research and Education in Allergy and Airway Diseases. The event took place in the European Parliament of Brussels and was hosted by MEP David Borrelli and MEP Sirpa Pietikainen. The aim of the Summit was to correspond to the needs of the European Commission and of patients suffering from CRD to join forces in Europe for the prevention and self-management. Delegates of the European Rhinologic Society, European Respiratory Society, European Academy of Allergy and Clinical Immunology, European Academy of Paediatrics, and European Patients Organization EFA all lectured on their vision and action plan to join forces in achieving adequate prevention and self-management of CRD in the context of Precision Medicine. Recent data highlight the preventive capacity of education on optimal care pathways for CRD. Self-management and patient empowerment can be achieved by novel educational on-line materials and by novel mobile health tools enabling patients and doctors to monitor and optimally treat CRDs based on the level of control. This report summarizes the contributions of the representatives of different European academic stakeholders in the field of CRD. [ABSTRACT FROM AUTHOR]

Background An important percentage of subjects diagnosed with chronic upper airway disease report alcohol-induced worsening of their symptoms. The prevalence and characteristics of respiratory reactions provoked by alcohol-containing drinks have not been fully investigated yet. Objective The aim of this study was to estimate the prevalence and characteristics of alcohol hyper-responsiveness in patients with chronic airway disease and healthy controls. Furthermore, nasal inflammation was evaluated in nasal polyp patients with and without hyper-responsiveness. Methods We evaluated the prevalence and characteristics of alcohol-induced respiratory complaints in 1281 subjects. Chronic rhinosinusitis with nasal polyps (CRSwNP) patients with and without NSAID exacerbated respiratory disease (NERD), chronic rhinosinusitis patients without nasal polyps (CRSsNP), allergic rhinitis (AR) patients and healthy controls were approached by means of a questionnaire. Inflammatory markers (eosinophilic cationic protein (ECP), IL-5, IgE, SAE-specific IgE, IL-17, TNFα and IFNγ) in tissue were then compared between alcohol hyper-responsive and non-hyper-responsive CRSwNP patients. Results The highest prevalence of nasal and bronchial alcohol hyper-responsiveness was observed in patients with NERD, followed by CRSwNP, and less frequent in CRSsNP, AR and healthy controls. Alcohol hyper-responsiveness is significantly more prevalent in CRSwNP patients suffering from recurrent disease and in patients with severe symptomatology. In nasal tissue of the hyper-responsive CRSwNP group, we observed significantly higher nasal levels of the eosinophilic biomarker ECP. Conclusion and Clinical Relevance Nasal hyper-responsiveness to alcohol is significantly more prevalent in severe eosinophilic upper airway disease. [ABSTRACT FROM AUTHOR]

Severe asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic lung diseases with a clear need for development of new and more efficient therapy. In preclinical research, the mouse model has been instrumental in advancing our knowledge of the biology and immunology. However, it has been proven rather difficult and time consuming to develop new treatments that can impact on the clinical course of these diseases. Many challenges need to be overcome for upgrading the quality of currently available experimental disease models in order to enhance the translation rate of basic research to clinical practice. Establishment of transgenic mouse overexpressing disease-causing genes may provide tools to discover new pathological pathways and to evaluate the possibility of molecular targeted therapy in chronic lung diseases. Personalized medicine, if developed, might be the solution for 'disease heterogeneity' and for improving clinical outcome. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Long-acting inhaled bronchodilators are central in the symptomatic treatment of patients with chronic obstructive pulmonary disease (COPD). Until now the only long-acting inhaled anticholinergic drug available in the clinic is tiotropium bromide. WHAT THIS STUDY ADDS • Aclidinium bromide is a new anticholinergic drug. In normal volunteers inhalation of this compound induced a long-lasting bronchodilation and offered protection against the bronchoconstrictor effect of inhaled methacholine. Aclidinium bromide is now being developed as a long-acting anticholinergic for patients with COPD. AIM Aclidinium bromide is a muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This phase I trial in healthy subjects investigated the bronchodilator activity of aclidinium and its ability to reduce methacholine-induced bronchoconstriction. METHODS This double-blind, partial-crossover study randomized 12 subjects to treatment with single doses of aclidinium (50, 300 or 600 µg) or placebo. Drug activity was assessed for 24 h after administration by specific airway conductance (sGaw), airways resistance (Raw) and bronchial responsiveness (PC35 sGaw methacholine). RESULTS Aclidinium significantly increased sGaw compared with placebo at all assessments and doses (sGaw mean ± SD AUC (l kPa−1 h) for placebo 24.4 ± 4.37, for 50 µg 29.0 ± 7.08, for 300 µg 31.2 ± 6.68 and for 600 µg 32.7 ± 7.95) ( P < 0.009), except 50 µg at 1 and 24 h. Significant decreases in Raw were observed with aclidinium 300 and 600 µg compared with placebo at all assessments (Raw mean ± SD AUC (kPa s−1 l−1 h) for placebo 7.7 ± 3.46, for 300 µg 5.8 ± 2.33, for 600 µg 6.3 ± 3.11) ( P < 0.04) except 600 µg at 24 h. Differences between aclidinium 300 and 600 µg vs. placebo in PC35 doubling concentration were significant at all assessments (mean ± SD AUC (mg ml−1 h) for placebo 100.0 ± 30.27, for 50 µg 117.2 ± 33.33, for 300 µg 168.9 ± 28.66 and for 600 µg 179.1 ± 15.73 ( P < 0.0001). For all endpoints, there was a significant difference between aclidinium 50 µg and the higher doses ( P < 0.0001). Aclidinium was not detected in plasma and was well tolerated. CONCLUSION Aclidinium produced statistically significant and sustained bronchodilation over 24 h, suggesting long-acting efficacy and providing a rationale for future studies in patients with COPD. [ABSTRACT FROM AUTHOR]

Asthma is a disease associated with inflammation, airway hyperresponsiveness (AHR) and airflow limitation. Clinical diagnosis and management of asthma often relies on assessment of lung function and symptom control, but these factors do not always correlate well with underlying inflammation. Bronchial challenge tests (BCTs) assess AHR, and can be used to assist in the diagnosis and management of asthma. Data presented at the symposium 'Use of inhaled mannitol for assessing airways disease' organised by the Allied Respiratory Professionals Assembly (9) of the European Respiratory Society (ERS) at the ERS Congress, Berlin 2008. Indirect challenge tests such as exercise testing, hypertonic saline or adenosine 5′-monophosphate (AMP) are more specific though less sensitive than direct challenge tests (such as methacholine) for identifying patients with active asthma. Indirect BCTs may be used to diagnose exercise-induced bronchoconstriction or AHR consistent with active asthma, to evaluate AHR that will respond to treatment with anti-inflammatory drugs and to determine the effectiveness and optimal dosing of such therapy. An ideal indirect challenge test should be standardised and reproducible, and the test result should correlate with the degree of airway inflammation. The mannitol BCT provides a standardised and rapid point-of-need test to identify currently active asthma, and is clinically useful in the identification of patients with asthma who are likely to benefit from inhaled corticosteroid therapy. In the future, mannitol BCT may be added to lung function and symptom assessment to aid in the everyday management of asthma. Please cite this paper as: Porsbjerg C, Backer V, Joos G, Kerstjens HAM and Rodriguez-Roisin R. Current and future use of the mannitol bronchial challenge in everyday clinical practice. The Clinical Respiratory Journal 2009; 3: 189-197. [ABSTRACT FROM AUTHOR]

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)