Skin Prick Automated Test device offers more reliable allergy test results compared to a manual skin prick test.

BACKGROUND: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of inhalant allergy. A novel device, SPAT or Skin Prick Automated Test, that enables more standardized allergy testing has been developed. Previous research has shown reduced intra-subject variability of histamine wheals by SPAT. OBJECTIVE: This study aimed to evaluate within-test agreement (% of patients with consistent test results) to detect sensitization to common inhalant allergens when a SPT is executed automated by SPAT or by manual SPT (SPMT) procedure. METHODS: The 110 volunteers prospectively enrolled underwent both SPAT and SPMT with 3 pricks of house dust mite, timothy grass and birch, 2 pricks of histamine and 1 prick of glycerol. The proportion of consistent (3x positive â€" 3 x negative) and inconsistent (2x positive/negative â€" 1x positive/negative) test results were analysed. RESULTS: The proportion of inconsistent test results was significantly lower in the SPAT compared to the SPMT group. The delta histamine to control pricks was significantly higher in SPAT compared to SPMT group. Coefficient of variation was lower in SPAT compared to SPMT for house dust mite, timothy grass, birch pollen. Visual analogue scale for discomfort was significantly lower in SPAT compared to SPMT group. CONCLUSION: SPAT showed a 34% reduction in the number of inconsistent test results compared to manual SPT with common inhalant allergens. Patient experience is significantly improved when an allergy test is performed by SPAT compared to a manual SPT.

Association between outdoor air pollution and chronic rhinosinusitis patient reported outcomes.

BACKGROUND: The aetiology of chronic rhinosinusitis (CRS) is multifactorial with a complex interplay between environmental, microbial endogenous and genetic factors. The impact of outdoor air pollution on prevalence or severity of CRS remains largely unknown. METHODS: Real-life geolocation data (2017-2018, Belgium) from 278 CRS patients (2576 health records) using the mySinusitisCoach mobile application were analysed to calculate the patients' individual exposure to outdoor air pollutants (ozone (O3), black carbon (BC), nitrogen dioxide (NO2) and particulate matter with diameter < 2.5 µm (PM2.5)) and to associate these pollutants with the patients' sinus related symptoms measured at multiple occasions by visual analogue scale (VAS). RESULTS: The adjusted seasonal model for the spring-summer (n = 1000 health entries, N = 83 patients) population revealed an increase of 6.07 (p < 0.0001) in overall CRS symptom scoring for an interquartile range (IQR) increase in exposure to O3 (26.9 µg/m3). An increase of 1.69 (p = 0.05) in total CRS symptom scoring was observed for an IQR increase of PM2.5 (7.1 µg/m3) exposure. Sex-stratified analysis in the spring-summer population showed significant interaction between air pollution and sex with male patients having higher total CRS symptom scores for an IQR increase in exposure to PM2.5 (3.52, p = 0.001), and O3 (8.33, p < 0.0001), while no significant association with symptom severity was seen in the female patients. In the analysis stratified by comorbid asthma, CRS patients with comorbid asthma had higher total CRS symptoms for an IQR increase in exposure to PM2.5 (2.58, p = 0.04) and O3 (7.72, p < 0.0001) while the patients without comorbid asthma had no significant symptom increases. CONCLUSION: Exposure to outdoor air pollution is associated with increased symptom severity in CRS patients. The extent to which CRS patients are sensitive to outdoor air pollution exposure varies per season and depends on their sex and comorbid asthma status. mHealth technology has the potential to reveal novel insights on the patients' exposome and disease severity in the real-life situation.

ARIA masterclass 2018: From guidelines to real-life implementation.

Over the past 20 years, ARIA (Allergic Rhinitis and its Impact on Asthma) has developed various guidelines for the treatment of allergic rhinitis (AR) and asthma multimorbidity. Over time, the ARIA initiative has evolved to ensure the highest level of bestpractices adoption in real life settings. It has evolved towards Integrated Care Pathways (ICPs) using mobile technology, and has now entered a new phase in which change management is key to provide an active and healthy life to all AR patients. With that in mind, the first ARIA masterclass was held on 12th September 2018 in Brussels, Belgium. The masterclass aimed at informing clinicians about the principles of change management, providing unbiased education on diagnosis and treatments, sharing the most recent research data on AR and multimorbidities, and creating a snowball effect to increase the adoption of best practices around the globe. This report provides an overview of the ARIA masterclass concept, summarizes the key lectures and discussions, and gives an outline of the future key development.

Patient Advisory Board for Chronic Rhinosinusitis - A EUFOREA initiative.

Despite the high prevalence of chronic rhinosinusitis (CRS) and its impact on patients' quality of life, no European patient organization that advocates for patients with CRS currently exists. To fill this gap and give a voice to CRS patients, EUFOREA has created a patient advisory board, whose goal is to better understand the real-life needs of patients, to raise awareness at political level and to involve patients in the development of novel integrated solutions to accelerate access to accurate diagnosis and treatments. This report summarizes the key discussion points from the kick-off meeting of the board on the 8th June 2018 and provides an outline of the key objectives for the future.

Probiotics for the airways: Potential to improve epithelial and immune homeostasis.

Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefit on the host. The therapeutic effects of probiotics have been mostly studied in the gastrointestinal tract, but recent evidence points toward the potential of these bacteria to prevent and/or treat chronic airway diseases. In this review, possible mechanisms of action of probiotics in the airways are described, with a particular focus on their capacity to modulate the epithelial barrier function and their mode of interaction with the immune system. Indeed, probiotic bacteria, mostly lactobacilli, can promote the expression and regulation of tight junctions and adherence junctions, resulting in the restoration of a defective epithelial barrier. These bacteria interact with the epithelial barrier and immune cells through pattern recognition receptors, such as Toll-like receptors, which upon activation can stimulate or suppress various immune responses. Finally, the clinical potential of probiotics to treat inflammatory diseases of the upper and lower respiratory tract, and the difference between their mode of application (eg, oral or nasal) are discussed here.

Mechanisms of exercise-induced bronchoconstriction in athletes: Current perspectives and future challenges.

The evidence of exercise-induced bronchoconstriction (EIB) without asthma (EIBwA ) occurring in athletes led to speculate about different endotypes inducing respiratory symptoms within athletes. Classical postulated mechanisms for bronchial obstruction in this population include the osmotic and the thermal hypotheses. More recently, the presence of epithelial injury and inflammation in the airways of athletes was demonstrated. In addition, neuronal activation has been suggested as a potential modulator of bronchoconstriction. Investigation of these emerging mechanisms is of major importance as EIB is a significant problem for both recreational and competitive athletes and is the most common chronic condition among Olympic athletes, with obvious implications for their competing performance, health and quality of life. Hereby, we summarize the latest achievements in this area and identify the current gaps of knowledge so that future research heads toward better defining the etiologic factors and mechanisms involved in development of EIB in elite athletes as well as essential aspects to ultimately propose preventive and therapeutic measures.

MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite-allergic rhinitis.

BACKGROUND: Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate [FP]) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. METHODS: A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction in nasal flow upon cold dry air exposure. The effects of AZE ± FP on barrier integrity and airway inflammation were studied in a murine model of HDM-induced NHR and on reduced activation of murine sensory neurons and human mast cells. RESULTS: MP29-02 but not placebo reduced NHR (P < .0001 vs P = .21), levels of substance P (P = .026 vs P = .941), and ß-hexosaminidase (P = .036 vs P = .632) in human nasal secretions. In wild-type C57BL6 mice, the reduction in ß-hexosaminidase levels (P < .0001) by AZE + FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage (P = .0012) and completely reversed eosinophilic inflammation (P = .0013). In vitro, repeated applications of AZE + FP desensitized sensory neurons expressing the transient receptor potential channels TRPA1 and TRPV1. AZE + FP reduced MC degranulation to the same extent as AZE alone. CONCLUSION: MP29-02 treatment reduces inflammatory mediators and NHR in AR. The effects of AZE + FP on MC degranulation, nasal epithelial barrier integrity, and TRP channels provide novel insights into the pathophysiology of allergic rhinitis.

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.

Nasal symptoms, epithelial injury and neurogenic inflammation in elite swimmers.

BACKGROUND: A high burden of lower airway symptoms is found in elite swimmers. To what extent elite swimmers suffer from upper airway symptoms and how these associate with nasal inflammation is less clear. We here aimed to evaluate upper airway symptoms and nasal inflammation in elite athletes. METHODOLOGY: Elite swimmers, indoor athletes and age-matched controls were recruited. Upper airway symptoms were assessed by sino-nasal outcome test (SNOT)-22 questionnaire. Visual Analogue score (VAS) for nasal symptoms as well as neurogenic and inflammatory mediators in nasal fluid were assessed at baseline, immediately and 24-hours after sport-specific training. The effect of hypochlorite on nasal epithelial cells was evaluated in vitro. RESULTS: Baseline SNOT-22 and VAS for nasal itch and impaired smell were significantly higher in swimmers compared to controls. Nasal substance P and uric acid levels were increased in elite swimmers 24-hours after swimming compared to baseline. In elite swimmers, uric acid levels 24-hours post-exercise correlated with baseline SNOT-22. As increased symptoms and inflammation were found in swimmers but not in indoor athletes, we hypothesized that hypochlorite exposure might be the underlying mechanism. In vitro, the highest dose of hypochlorite decreased nasal epithelial cell integrity and induced release of uric acid. CONCLUSION: Upper airway symptoms are frequently reported in elite swimmers. Intensive swimming resulted in a delayed increase of epithelial injury and neurogenic inflammation.

mySinusitisCoach: patient empowerment in chronic rhinosinusitis using mobile technology.

Mobile health technology is emerging to take a prominent position in the management of chronic diseases. These technologies aim at enhancing patient empowerment via education and self-management. To date, of all the different apps available for patients with sinus disease, none were developed by medical experts dealing with chronic rhinosinusitis (CRS). The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) has undertaken a multi-stakeholder approach for designing, developing and implementing a tool to support CRS patients in monitoring their symptoms and to provide patients with a digital support platform containing reliable medical information about their disease and treatment options. mySinusitisCoach has been developed by medical experts dealing with CRS in close collaboration with patients, primary care physicians and community pharmacists, meeting the needs of both patients and health care providers. From a research perspective, the generation of real life data will help to validate clinical studies, patient stratification and improve understanding of the socio-economic impact of CRS, thereby paving the way for better treatment strategies.

Real-life study showing uncontrolled rhinosinusitis after sinus surgery in a tertiary referral centre.

RATIONALE: The European Position Paper on Sinusitis (EPOS) guidelines provide composite criteria to evaluate chronic rhinosinusitis (CRS) control, taking into consideration the severity of patients' symptoms, aspect of nasal mucosa and medical intake as parameters of CRS control. OBJECTIVES: To study the degree of CRS control using novel EPOS control criteria at 3-5 years after a functional endoscopic sinus surgery (FESS) and correlate these data to symptoms scores. METHODS: Adult CRS patients (n = 560) who had undergone bilateral FESS for chronic inflammatory sinonasal disease 3-5 years prior to the study were included. Patients received a postal questionnaire asking for control items according to EPOS control criteria, visual analogue scale (VAS) scores for total and individual sinonasal symptoms, sinonasal outcome test (SNOT)-22 and Short Form (SF)-36 questionnaires. MEASUREMENTS AND MAIN RESULTS: About 19.5% of CRS patients were well controlled, with 36.8% of patients being partly controlled and 43.7% uncontrolled. The levels of control corresponded to mean total VAS, SNOT-22 and SF-36 scores. Subgroup analysis revealed that female gender, aspirin intolerance and revision FESS were associated with higher prevalence of uncontrolled CRS, whereas allergy, asthma and smoking status did not alter the percentage of patients in each category of control. In 81 patients attending the outpatient clinic, nasal endoscopy changed classification in only four patients (4.9%). CONCLUSIONS: Based on the novel EPOS control criteria, at least 40% of CRS patients are uncontrolled at 3-5 years after FESS. Therefore, better treatment strategies leading to higher disease control are warranted in CRS care.

Programmed cell death-1 expression correlates with disease severity and IL-5 in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Programmed cell death-1 (PD-1) is a negative regulator of T-cell responses. Expression of PD-1 and its ligands PD-L1 and PD-L2 in chronic rhinosinusitis with nasal polyps (CRSwNP) is poorly studied. METHODS: Expression of PD-1, PD-L1, PD-L2, TGF-ß, IL-5, and IL-10 mRNA was measured by real-time quantitative PCR on tissue homogenates of patients with CRSwNP (n = 21) and healthy controls (n = 21) and on primary epithelial cells. Disease severity was scored using the Lund-Mackay scores of maxillofacial computed tomography (CT) scans. Expression of PD-1 and PD-L1/L2 was evaluated at the cellular and tissue levels (n = 6) by flow cytometry and immunohistochemistry. RESULTS: Programmed cell death-1 mRNA expression was increased in tissue homogenates from patients with CRSwNP compared with controls, irrespective of the atopy status. Importantly, expression of PD-1 correlated with the total CT scan scores (r = 0.5, P = 0.02). Additionally, a significant association was found between PD-1 mRNA and expression of IL-5 mRNA in control nasal tissue (r = 0.95, P < 0.0001) and in CRSwNP (r = 0.63, P = 0.002). PD-1 was expressed on different subsets of T cells and CD11b- dendritic cells. Both PD-1 and its ligands were expressed on primary epithelial cells from control nasal tissue and nasal polyp tissue. CONCLUSIONS: Higher PD-1 expression was found in CRSwNP than in nasal tissue from controls. This was associated with disease severity and tissue IL-5 expression but unrelated to the patients' atopy status.

Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement.

Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment.

Non-allergic rhinitis: Position paper of the European Academy of Allergy and Clinical Immunology.

This EAACI position paper aims at providing a state-of-the-art overview on nonallergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as nonallergic noninfectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug-induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called "entopy" or local allergic rhinitis (LAR). We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research.

Rhinology Future Debates, an EUFOREA Report.

The first Rhinology Future Debates was held in Brussels in December 2016, organized by EUFOREA (European Forum for Research and Education in Allergy and Airways diseases). The purpose of these debates is to bring novel developments in the field of Rhinology to the attention of the medical, paramedical and patient community, in a highly credible and balanced context. For the first time in Rhinology, a peer to peer scientific exchange with key experts in the field of rhinology and key medical colleagues from leading industries let to a brainstorming and discussion event on a number of hot issues in Rhinology. Novel developments are presented by key experts from industry and/or key thought leaders in Rhinology, and then followed by a lively debate on the potential positioning of new developments in care pathways, the strengths and weaknesses of the novel development(s), and comparisons with existing and/or competing products, devices, and/or molecules. As all debates are recorded and distributed on-line with limited editing (www.rhinology-future.com), EUFOREA aims at maximizing the education of the target groups on novel developments, allowing a critical appraisal of the future and a more rapid implementation of promising novel tools, techniques and/or molecules in clinical practise in Europe. The next Rhinology Future debate will be held in Brussels in December 2017.

Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo.

BACKGROUND: α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. OBJECTIVE: This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis. METHODS: MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. RESULTS: We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.

Restoring airway epithelial barrier dysfunction: a new therapeutic challenge in allergic airway disease.

An intact functional mucosal barrier is considered to be crucial for the maintenance of airway homeostasis as it protects the host immune system from exposure to allergens and noxious environmental triggers. Recent data provided evidence for the contribution of barrier dysfunction to the development of inflammatory diseases in the airways, skin and gut. A defective barrier has been documented in chronic rhinosinusitis, allergic rhinitis, asthma, atopic dermatitis and inflammatory bowel diseases. However, it remains to be elucidated to what extent primary (genetic) versus secondary (inflammatory) mechanisms drive barrier dysfunction. The precise pathogenesis of barrier dysfunction in patients with chronic mucosal inflammation and its implications on tissue inflammation and systemic absorption of exogenous particles are only partly understood. Since epithelial barrier defects are linked with chronicity and severity of airway inflammation, restoring the barrier integrity may become a useful approach in the treatment of allergic diseases. We here provide a state-of-the-art review on epithelial barrier dysfunction in upper and lower airways as well as in the intestine and the skin and on how barrier dysfunction can be restored from a therapeutic perspective.

Damage-associated molecular pattern and innate cytokine release in the airways of competitive swimmers.

BACKGROUND: Daily intensive exercise by elite athletes can result in exercise-induced asthma especially in elite swimmers and this may be linked to epithelial damage. OBJECTIVE: To study airway epithelial damage and release of damage-associated molecular patterns (DAMPs) after intensive exercise in elite athletes and controls. METHODS: We recruited competitive swimmers (n = 26), competitive indoor athletes (n = 13) and controls (n = 15) without any history of asthma. Lung function was measured before, immediately after and 24 h after a 90-min intensive exercise protocol. Sputum induction was performed at baseline and 24 h after exercise. Exercise-induced bronchoconstriction (EIB) was assessed by the eucapnic voluntary hyperventilation test. RESULTS: Baseline sputum uric acid, high mobility group box-1, CXCL8 mRNA, sputum neutrophils and serum Clara cell protein-16 (CC-16) were significantly higher in competitive swimmers compared with controls. Intensive swimming for 90 min resulted in an increase of sputum IL-1ß, IL-6 and TNF mRNA in competitive swimmers, and of sputum IL-6 mRNA and sputum neutrophils in controls. Although all participants were asymptomatic, seven competitive swimmers, one indoor athlete and one control met the criteria for EIB. CONCLUSION: Our findings show that the intensive training combined with exposure to by-products of chlorination induces airway epithelial damage in competitive swimmers. This is associated with increased damage-associated molecular patterns, innate cytokine release and neutrophilic airway inflammation.

Sputum cytokine mapping reveals an 'IL-5, IL-17A, IL-25-high' pattern associated with poorly controlled asthma.

BACKGROUND AND OBJECTIVE: Asthma is a heterogeneous disease with various clinical, inflammatory and molecular phenotypes. We studied sputum cytokine mRNA expression patterns in an unselected group of adult asthma patients to characterize the underlying inflammatory process. METHODS: Differential cell counts and cytokine mRNA (quantified by real-time PCR) were analysed on sputum from 40 controls and 66 asthmatic adults. A 'cytokine-high' profile was defined if mRNA levels for that particular cytokine exceeded the 90th percentile value in the control population. Radar graphs were used to visualize cytokine profiles. RESULTS: Sputum mRNA analysis confirmed heterogeneity of cytokine patterns among patients. Thirty-six patients (55%) had a Th2 cytokine pattern: 'IL-5-high' (n = 13), 'IL-4-high' (n = 17) or 'IL-4- and IL-5-high' (n = 6). The 'IL-5-high' asthma profile (n = 13) coincided with the 'IL-25-high' (10/13) and surprisingly also with the 'IL-17A-high' (11/13) profile. The 'IL-5-/IL-25-/IL-17A-high profile was different from the 'IL-4-high' pattern. Patients with the 'IL-5, IL-17A, IL-25-high' pattern had significantly worse lung function parameters. Uncontrolled asthmatics [Asthma Control Test (ACT) < 20] had higher sputum IL-5, IL-17A and IL-25 mRNA levels compared to controlled asthmatics (P = 0.002; P = 0.002; P = 0.066) and uncontrolled asthma is more common among 'IL-5- and IL-17A-high' asthmatics compared to 'IL-5-, IL-17A-low' asthmatics (χ(2) = 3.7, P = 0.027; relative risk (RR): 1.8, 95% CI = 1.1-3.1). CONCLUSIONS AND CLINICAL RELEVANCE: Patients with the 'IL-5, IL-17A, IL-25-high' airway inflammatory pattern are often uncontrolled asthmatics, despite daily treatment. It seems worthwhile to evaluate whether measuring sputum cytokine levels might be used to assess the response to increased doses of steroids in patients with asthma.

Real-life studies and registries of severe asthma: The advent of digital technology.

Severe asthma is a chronic and heterogeneous disease that negatively affects the quality of life of our patients and health care utilization. Given the remaining burden of uncontrolled disease in many of these patients, better understanding of its epidemiology, disease mechanisms, effectiveness of novel therapies such as biologics are still highly needed. Asthma treatment guidelines are largely informed by randomized controlled trials (RCTs) and meta analyses of RCTs, however inclusion criteria of many efficacy RCTs of asthma treatments often exclude a high number of patients with asthma in the community. Data from real-life studies and registries of severe asthma can complement efficacy studies by not only providing evidence on how a treatment performs in everyday clinical practice, post marketing safety information, data to support subsequent clinical trial design, but also helping to delineate the natural history of a disease and supporting important translational research endeavors. In the current review, we summarise available national and international collaborative studies and registries, the variables studies and the novel data and insights they provide. The key source of information for most asthma registries are real-life data from patient's electronic health records. Advent of digital technology in collecting data and their analysis is obvious and we draw attention to generation of new knowledge from registries of severe asthma to improve current diagnostic and therapeutic guidelines and asthma control.