Difficult Asthma Research Articles

Experience-based co-design to develop innovative telehealth physiotherapy interventions and resources for children and young people with asthma and dysfunctional breathing

Introduction Healthcare requires new technologies to deliver hybrid services. Before embedding health-delivery transformations including physiotherapy in asthma clinics, it is essential to give young people and their carers a voice to facilitate co-designing of services. Objective To co-design hybrid telehealth physiotherapy services and online resources for, and in partnership with, young people with asthma and dysfunctional breathing, and their families. Methods Experience based co-design study undertaken at a specialist paediatric difficult asthma clinic, including online service user focus groups and electronic questionnaires for service providers. Eight children aged between 11 and 17 years and their families and 11 members of the multi-disciplinary team (MDT) managing children with difficult asthma were recruited purposively. Results A series of seven online videos were created, topics included: how to support a breathless child, education on how we breathe, breathing patterns, symptom differentiation, breathlessness, rescue breathing techniques, and exercise. Each video has downloadable resources. Five children and four parents wrote blogs to share their experiences. A live online 12-week physiotherapy program was developed on a web-based platform www.beamfeelgood.com called Asthma Kids. Conclusion Co-design enabled partnership working to develop hybrid telehealth physiotherapy services and prototype interventions to support home practice for children with asthma and dysfunctional breathing.

Treating severe paediatric asthma with mepolizumab or omalizumab: a protocol for the TREAT randomised non-inferiority trial

IntroductionA minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death....

Introduction to food allergy

Food allergy is a common chronic disorder that affects infants, children, adolescents, and adults. The prevalence of food allergy has increased in recent decades throughout the world, not limited to Western countries. Since there is no treatment, this focuses on avoiding allergens, in addition to educating patients and caregivers in the emergency treatment of acute reactions, for example: application of epinephrine. Studies suggest that accidental reactions occur in about 45% of children with food allergies each year, although most reactions are mild or moderate in severity. Hospital admissions for food anaphylaxis vary from 4 to 20 per 100,000 inhabitants; Deaths are rare, with an estimated incidence of 0.03 to 0.3 per million people with food allergy. Death from food anaphylaxis is rare and appears to have remained stable, possibly due to increases in food allergen labeling, diagnostic services, rates of intramuscular epinephrine prescription, and awareness of food allergies. Omalizumab is a drug approved for several disorders (chronic hives or difficult asthma) and may help reduce symptoms associated with food allergy. The relative importance of alternative technologies, management strategies and policies for food allergy varies from one region to another, due to differences in the epidemiology, education, socioeconomic well-being, and cultural preferences of the population.

How Does Mild Asthma Differ Phenotypically from Difficult-to-Treat Asthma?

Despite most of the asthma population having mild disease, the mild asthma phenotype is poorly understood. Here, we aim to address this gap in knowledge by extensively characterising the mild asthma phenotype and comparing this with difficult-to-treat asthma. We assessed two real-world adult cohorts from the South of England using an identical methodology: the Wessex AsThma CoHort of difficult asthma (WATCH) (n=498) and a mild asthma cohort from the comparator arm of the Epigenetics Of Severe Asthma (EOSA) study (n=67). Data acquisition included detailed clinical, health and disease-related questionnaires, anthropometry, allergy and lung function testing, plus biological samples (blood and sputum) in a subset. Mild asthma is predominantly early-onset and is associated with type-2 (T2) inflammation (atopy, raised fractional exhaled nitric oxide (FeNO), blood/sputum eosinophilia) plus preserved lung function. A high prevalence of comorbidities and multimorbidity was observed in mild asthma, particularly depression (58.2%) and anxiety (56.7%). In comparison to difficult asthma, mild disease showed similar female predominance (>60%), T2-high inflammation and atopy prevalence, but lower peripheral blood/airway neutrophil counts and preserved lung function. Mild asthma was also associated with a greater prevalence of current smokers (20.9%). A multi-component T2-high inflammatory measure was comparable between the cohorts; T2-high status 88.1% in mild asthma and 93.5% in difficult asthma. Phenotypic characterisation of mild asthma identified early-onset disease with high prevalence of current smokers, T2-high inflammation and significant multimorbidity burden. Early comprehensive assessment of mild asthma patients could help prevent potential later progression to more complex severe disease.

Associations of Breathing Pattern Disorder and Nijmegen Score With Clinical Outcomes in Difficult-to-Treat Asthma

BackgroundBreathing pattern disorder (BPD) reflects altered biomechanical patterns of breathing that drive breathing difficulty and commonly accompanies difficult-to-treat asthma. Diagnosis of BPD has no gold standard, but Nijmegen Questionnaire (NQ) >23 is commonly used. ObjectivesWe sought to advance clinical characterisation of BPD and better understand clinical utility of NQ in difficult asthma, in patients from the Wessex AsThma CoHort of difficult asthma (WATCH) study. MethodsAssociation between demographic and clinical factors in difficult asthma and BPD, ascertained by clinical diagnosis (yes/no, n=476), by NQ scores (≤23: normal (no suggestion of BPD) and >23: abnormal (suggested BPD), n=372, as well as the continuous raw NQ scores) were assessed in univariate models to identify significant risk factors associated with the three BPD outcomes. For the clinician-diagnosed and NQ-based BPD, associations of continuous factors were assessed using independent samples t-test or Mann-Whitney U test as appropriate for the data distribution or by Spearman correlation test. Dichotomous associations were evaluated using chi-squared tests. Multivariable logistic (dichotomous outcomes) and linear regression models (continuous outcomes) were developed to identify predictive factors associated with clinician-diagnosed and NQ-based BPD, dichotomous and continuous. Patients with data on NQ scores were grouped into NQ quartiles (low, moderate, high, and very high). The patterns of association of the quartiles with four health-related questionnaire outcomes were assessed using linear regression analyses. ResultsMultivariable regression identified that clinically diagnosed BPD was associated with female sex (OR 1.85; 95% CI 1.07, 3.20), comorbidities (rhinitis (OR 2.46; 95% CI 1.45, 4.17), GORD (OR 2.77; 95% CI 1.58, 4.84), ILO (OR 4.37; 95% CI 2.01, 9.50) and any psychological co-morbidity (OR 1.86; 95% CI 1.13, 3.07)) and healthcare usage (exacerbations (OR 1.07; 95% CI 1.003, 1.14) and previous ICU admissions (OR 2.03; 95% CI 1.18, 3.47)). Abnormal NQ-based BPD diagnosis was associated with history of eczema (OR 1.83; 95% CI 1.07, 3.14), GORD (OR 1.94; 95% CI 1.15, 3.27) or any psychological comorbidity (OR 4.29; 95% CI 2.64, 6.95) at multivariable regression. Differences between clinical and NQ-based BPD traits were also found with 42% discordance in BPD-state between these definitions. Multivariable linear regression analysis with NQ as a continuous outcome showed positive association with worse asthma outcomes (admission to ICU, p=0.037), different phenotypic traits (female sex p=0.001, ever smoker, p=0.025)) and greater multimorbidity (GORD, p=0.002, sleep apnoea, p=0.040, any psychological comorbidity, p<0.0001). ConclusionBPD is associated with worse health outcomes and negative health impacts in difficult asthma within a multimorbidity disease model. It therefore merits better recognition and prompt treatment. Clinical diagnosis and NQ offer different perspectives on BPD, so this goal may be best addressed by considering clinical features alongside magnitude of NQ.

Management of comorbidities in difficult and severe asthma.

Difficult-to-treat and severe asthma are challenging clinical entities. In the face of suboptimal asthma control, the temptation for clinicians is to reflexively escalate asthma-directed therapy, including increasing exposure to corticosteroids and commencement of costly but potent biologic therapies. However, asthma control is objectively and subjectively assessed based on measurable parameters (such as exacerbations or variability in pulmonary physiology), symptoms and patient histories. Crucially, these features can be confounded by common untreated comorbidities, affecting clinicians' assessment of asthma treatment efficacy.

Comprehensive Characterization of Difficult-to-Treat Asthma Reveals Near Absence of T2-Low Status.

Asthma is conventionally stratified as type 2 inflammation (T2)-high or T2-low disease. Identifying T2 status has therapeutic implications for patient management, but a real-world understanding of this T2 paradigm in difficult-to-treat and severe asthma remains limited. To identify the prevalence of T2-high status in difficult-to-treat asthma patients using a multicomponent definition and compare clinical and pathophysiologic characteristics between patients classified as T2-high and T2-low. We evaluated 388 biologic-naive patients from the Wessex Asthma Cohort of difficult asthma (WATCH) study in the United Kingdom. Type 2-high asthma was defined as 20 parts per billion or greater FeNO , 150 cells/μL or greater peripheral blood eosinophils, the need for maintenance oral corticosteroids, and/or clinically allergy-driven asthma. This multicomponent assessment identified T2-high asthma in 93% of patients (360 of 388). Body mass index, inhaled corticosteroid dose, asthma exacerbations, and common comorbidities did not differ by T2 status. Significantly worse airflow limitation was found in T2-high compared with T2-low patients (FEV1/FVC 65.9% vs 74.6%). Moreover, 75% of patients defined as having T2-low asthma had raised peripheral blood eosinophils within the preceding 10 years, which left only seven patients (1.8%) who had never had T2 signals. Incorporation of sputum eosinophilia 2% or greater into the multicomponent definition in a subset of 117 patients with induced sputum data similarly found that 96% (112 of 117) met criteria for T2-high asthma, 50% of whom (56 of 112) had sputum eosinophils 2% or greater. Almost all patients with difficult-to-treat asthma have T2-high disease; less than 2% of patients never display T2-defining criteria. This highlights a need to assess T2 status comprehensively in clinical practice before labeling a patient with difficult-to-treat asthma as T2-low.

Nebulized caffeine alleviates airway hyperresponsiveness in a murine asthma model.

The clinical definition of "difficult asthma" has expanded recently to include an ever-growing subset of patients with symptoms that cannot be controlled by conventional means, forcing the medical community to develop innovative therapeutics. Beneficial effects of coffee for subjects with asthma, primarily the effect of methylxanthine components, have long been described. Methylxanthines, including theophylline and caffeine, inhibit phosphodiesterases and downstream cAMP signaling to prevent mast cell degranulation while promoting immunomodulation (Peleman RA, Kips JC, Pauwels RA. Clin Exp Allergy 28: 53-56, 1998; Deshpande DA, Wang WCH, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JSK, Liggett SB. Nat Med 16: 1299-1304, 2010). Caffeine is also a bitter taste receptor agonist, binding to taste-sensing type 2 receptors (TAS2R) before releasing calcium to hyperpolarize airway smooth muscle membranes, inducing bronchodilation (Workman AD, Palmer JN, Adappa ND, Cohen NA. Curr Allergy Asthma Rep 15: 72, 2015; Devillier P, Naline E, Grassin-Delyle S. Pharmacol Ther 155: 11-21, 2015). Theophylline is conventionally used to treat asthma, whereas, according to the literature, the dosage required for orally administered caffeine has yielded modest improvement (Alfaro TM, Monteiro RA, Cunha RA, Cordeiro CR. Clin Respir J 12: 1283-1294, 2018). We sought to determine whether aerosolization of ultrafine caffeine particles (2.5-4 μm) directly to the lungs of susceptible A/J mice challenged with methacholine would improve pulmonary function via forced oscillation technique. In addition, we assessed whether nebulization of caffeine leads to changes in lung pathophysiology and bronchoalveolar lavage cell profiles. We found that mice that received aerosolized caffeine had statistically significant decreases in maximum airway resistance [6.3 vs. 3.9 cmH2O·s/mL at 62.5 mg/mL caffeine; confidence interval (CI) = -4.3, -0.4; P = 0.02] and significant delays in the time required to reach maximum resistance compared with that of controls (64.7 vs. 172.1 sec at 62.5 mg/mL caffeine, CI = 96.0, 118.9; P < 0.0001). Nebulized caffeine yielded a consistent effect on airway hyperresponsiveness at a range of doses without evidence of significant pathology relative to vehicle control.NEW & NOTEWORTHY For decades, coffee has been shown to improve symptoms in patients with asthma. One component, theophylline, is conventionally used to treat asthma, whereas the dosage required for orally administered caffeine has yielded modest improvement. We sought to determine whether aerosolization of caffeine directly to the lungs of susceptible A/J mice challenged with methacholine would alter pulmonary function via forced oscillation technique. We found nebulized caffeine yielded a consistent improvement on murine AHR.

Risk factors of NSAID-exacerbated respiratory disease: Apopulation-based study.

Asthma with NSAID-exacerbated respiratory disease (NERD) is associated with uncontrolled or severe asthma. NERD patients are more prone to severe allergic reactions and their asthma exacerbations lead to hospitalisations twice as often compared to patients with non-NERD-asthma. NERD patients are prone to recurrent nasal polyposis requiring frequent endoscopic sinus surgeries. However, the early risk factors of NERD are not fully understood. The aim was to identify risk factors of NERD among patients with adult-onset asthma. We used data from 1350 population-based adult asthmatics with adult-onset asthma from Finnish national registers. NERD was defined as self-reported wheeze or other typical respiratory symptoms after ingestion of NSAIDs. Thirty-six covariates covering several domains (personal characteristics, life-style, early life factors, asthma characteristics and multimorbidities) were selected based on literature and were studied in association with NERD using logistic regressions. The study population included 153 (11.3%) asthmatics with NERD. Thirty-six covariates were entered in univariate logistic regression analysis, in which 23 were associated with NERD (p<0.05). These variables were entered in a multivariable logistic regression model in which allergic respiratory symptoms, female sex, osteoarthritis, difficult asthma, nasal polyps, second-hand smoke exposure at home, having 3 or more older siblings and being overweight were significantly associated with asthma with NERD (p<0.05). Overweight decreased the risk of NERD, other factors increased it. According to our study, risk factors of NERD in part are associated with female sex, BMI, exposure to tobacco smoke, allergy, orthopaedic disorders and infection history, and their early recognition might thus be important to manage the burden of NERD.

Enabling Adults With Severe Asthma to Exercise: A Qualitative Examination of the Challenges for Patients and Health Care Professionals

Adults living with severe asthma have lower physical activity levels, particularly high intensity physical activity, compared to their healthy peers. Physical inactivity is associated with increased morbidity and mortality. We aimed to understand patient and healthcare professional attitudes to exercise to inform future strategies for the improvement of healthy lifestyle behaviours, including exercise. Participants recruited from a specialist Difficult Asthma Service were interviewed individually, and healthcare professionals (HCPs) from primary care, secondary care and a tertiary centre were invited to attend focus groups. Interviews and focus groups were transcribed verbatim. Thematic analysis was performed on interviews and focus groups separately, followed by an adapted framework analysis to analyse datasets together. Twenty-nine people with severe asthma participated in a semi-structured interview. 51 HCPs took part in 8 focus groups across the East Midlands, UK. Final analysis resulted in 3 major themes: Barriers to exercise and exercise counselling whereby patients and HCPs identified disease and non-disease factors impacting on those living with severe asthma; Attitudes towards HCPsupportfor exercise highlighting education needs for HCPs and preference for supervised exercise programmes; Areas for system improvement insupportingHCPs describing the challenges existing across services that limit patient support. The important role of HCPs in supporting and advising on lifestyle change was identified by patients. Despite a preference for supervised exercise programmes, both patient and HCP barriers existed. To meet patients' varied support needs, improved integration of services is required and HCP skills need extending.

Characteristics of patients with asthma overprescribed short-acting beta-agonist (SABA) reliever inhalers stratified by blood eosinophil count in North East London: a cross-sectional observational study.

Overprescription of short-acting beta-agonist (SABA) inhalers and blood eosinophil count have strong associations with exacerbation risk in asthma. However, in the authors' recent publication only a minority of patients overprescribed SABA (≥6 inhalers in 12 months) were eosinophilic (≥0.3 x 109 cells/l). To compare the characteristics of eosinophilic and non-eosinophilic patients with asthma overprescribed SABA inhalers, and identify latent classes using clinical variables available in primary care. Cross-sectional analysis of patients with asthma in North East London, England, using primary care electronic health record data. Unadjusted and adjusted multi-variate regression models and latent class analysis. Eosinophilia was significantly less likely in female patients (P = 0.004), those with multiple mental health comorbidities (P<0.001), and those with SABA on repeat prescription (P<0.001). Latent class analysis identified the following three classes of patients overprescribed SABA: class 1, which represents classical uncontrolled asthma (oral steroids required for exacerbations, step 2-3 asthma medications, high probability of being eosinophilic); class 2, which represents mild asthma (low exacerbation frequency, low asthma medication step, low probability of being eosinophilic); and class 3, which represents difficult asthma (high exacerbation frequency despite high-strength preventer inhalers, low probability of being eosinophilic). The mild asthma class was the largest. Many patients being overprescribed SABA were non-eosinophilic with a low exacerbation frequency, suggesting disproportionately high SABA prescription compared with other asthma control markers. Potential reasons for high SABA prescription in these patients included repeat prescription (being dispensed but not taken) and use of SABA for non-asthma breathlessness (for example, breathing pattern disorders with anxiety). Further research is needed into management of SABA overuse in patients without other markers of uncontrolled asthma.

Letter from Norway

Letter from Norway

Subtypes of Adult-Onset Asthma at the Time of Diagnosis: A Latent Class Analysis.

Only a few previous studies have investigated the subtypes of adult-onset asthma. No previous study has assessed whether these subtypes are different between men and women, or whether these subtypes have different risk factors. We applied latent class analyses to the Finnish Environment and Asthma Study population, including 520 new cases of adult-onset asthma. We formed subtypes separately between women and men and analyzed the following determinants as potential predictors for these subtypes: age, body mass index, smoking, and parental asthma. Among women, the subtypes identified were: 1. Moderate asthma, 2. Cough-variant asthma, 3. Eosinophilic asthma, 4. Allergic asthma, and 5. Difficult asthma. Among men, the subtypes were: 1. Mild asthma, 2. Moderate asthma, 3. Allergic asthma, and 4. Difficult asthma. Three of the subtypes were similar among women and men: Moderate, Allergic, and Difficult asthma. In addition, women had two distinct subtypes: Cough-variant asthma, and Eosinophilic asthma. These subtypes had different risk factor profiles, e.g., heredity was important for Eosinophilic and Allergic asthma (RR for Both parents having asthma in Eosinophilic 3.55 (1.09 to 11.62)). Furthermore, smoking increased the risk of Moderate asthma among women (RR for former smoking 2.21 (1.19 to 4.11)) and Difficult asthma among men but had little influence on Allergic or Cough-variant asthma. Conclusion: This is an original investigation of the subtypes of adult-onset asthma identified at the time of diagnosis. These subtypes differ between women and men, and these subtypes have different risk factor profiles. These findings have both clinical and public health importance for the etiology, prognosis, and treatment of adult-onset asthma.

Updates on the management of difficult asthma in school-aged children

Updates on the management of difficult asthma in school-aged children

Multimorbidity in Difficult Asthma: The Need for Personalised and Non-Pharmacological Approaches to Address a Difficult Breathing Syndrome.

Three to ten percent of people living with asthma have difficult-to-treat asthma that remains poorly controlled despite maximum levels of guideline-based pharmacotherapy. This may result from a combination of multiple adverse health issues including aggravating comorbidities, inadequate treatment, suboptimal inhaler technique and/or poor adherence that may individually or collectively contribute to poor asthma control. Many of these are potentially “treatable traits” that can be pulmonary, extrapulmonary, behavioural or environmental factors. Whilst evidence-based guidelines lead clinicians in pharmacological treatment of pulmonary and many extrapulmonary traits, multiple comorbidities increase the burden of polypharmacy for the patient with asthma. Many of the treatable traits can be addressed with non-pharmacological approaches. In the current healthcare model, these are delivered by separate and often disjointed specialist services. This leaves the patients feeling lost in a fragmented healthcare system where clinical outcomes remain suboptimal even with the best current practice applied in each discipline. Our review aims to address this challenge calling for a paradigm change to conceptualise difficult-to-treat asthma as a multimorbid condition of a “Difficult Breathing Syndrome” that consequently needs a holistic personalised care attitude by combining pharmacotherapy with the non-pharmacological approaches. Therefore, we propose a roadmap for an evidence-based multi-disciplinary stepped care model to deliver this.

Update on Long-Acting Anticholinergics in Children and Adolescents With Difficult and Severe Asthma.

Tiotropium bromide is the only long-acting muscarinic antagonist (LAMA) approved for treatment of patients aged ≥6 years old who have symptoms of uncontrolled asthma. Results from several clinical trials have found that once-daily inhaled tiotropium bromide is safe and efficacious in 6- to 17-year-olds with symptomatic asthma despite treatment with inhaled corticosteroids, with or without other medications. There are still few available studies investigating the impact of tiotropium bromide treatment in preschool children with suboptimal control. In this narrative review, we summarize the pharmacological effects of the LAMA tiotropium bromide, provide an overview about current asthma studies at different pediatric ages, and describe future research needs.

How to Choose the Correct Drug in Severe Pediatric Asthma.

When a child with severe asthma (asthma defined clinically for the purposes of this review as wheeze, breathlessness, and chest tightness sometimes with cough) does not respond to treatment, it is important to be sure that an alternative or additional diagnosis is not being missed. In school age children, the next step is a detailed protocolized assessment to determine the nature of the problem, whether within the airway or related to co-morbidities or social/environmental factors, in order to personalize the treatment. For example, those with refractory difficult asthma due to persistent non-adherence may benefit from using budesonide and formoterol combined in a single inhaler [single maintenance and reliever treatment (SMART)] as both a reliever and preventer. For those with steroid-resistant Type 2 airway inflammation, the use of biologicals such as omalizumab and mepolizumab should be considered, but for mepolizumab at least, there is a paucity of pediatric data. Protocols are less well developed in preschool asthma, where steroid insensitive disease is much more common, but the use of two simple measurements, aeroallergen sensitization, and peripheral blood eosinophil count, allows the targeted use of inhaled corticosteroids (ICSs). There is also increasing evidence that chronic airway infection may be important in preschool wheeze, increasing the possibility that targeted antibiotics may be beneficial. Asthma in the first year of life is not driven by Type 2 inflammation, so beyond avoiding prescribing ICSs, no evidence based recommendations can be made. In the future, we urgently need to develop objective biomarkers, especially of risk, so that treatment can be targeted effectively; we need to address the scandal of the lack of data in children compared with adults, precluding making evidence-based therapeutic decisions and move from guiding treatment by phenotypes, which will change as the environment changes, to endotype based therapy.

The Detrimental Clinical Associations of Anxiety and Depression with Difficult Asthma Outcomes.

Difficult asthma describes asthma in which comorbidities, inadequate treatment, suboptimal inhaler technique and/or poor adherence impede good asthma control. The association of anxiety and depression with difficult asthma outcomes (exacerbations, hospital admissions, asthma control, etc.) is unclear. This study assessed the clinical associations of anxiety and depression with difficult asthma outcomes in patients with a specialist diagnosis of difficult asthma. Using real-world data, we retrospectively phenotyped patients from the Wessex Asthma Cohort of Difficult Asthma (N = 441) using clinical diagnoses of anxiety and depression against those without anxiety or depression (controls). Additionally, we stratified patients by severity of psychological distress using the Hospital Anxiety and Depression Scale (HADS). We found that depression and/or anxiety were reported in 43.1% of subjects and were associated with worse disease-related questionnaire scores. Each psychological comorbidity group showed differential associations with difficult asthma outcomes. Anxiety alone (7.9%) was associated with dysfunctional breathing and more hospitalisations [anxiety, median (IQR): 0 (2) vs. controls: 0 (0)], while depression alone (11.6%) was associated with obesity and obstructive sleep apnoea. The dual anxiety and depression group (23.6%) displayed multimorbidity, worse asthma outcomes, female predominance and earlier asthma onset. Worse HADS-A scores in patients with anxiety were associated with worse subjective outcomes (questionnaire scores), while worse HADS-D scores in patients with depression were associated with worse objective (ICU admissions and maintenance oral corticosteroid requirements) and subjective outcomes. In conclusion, anxiety and depression are common in difficult asthma but exert differential detrimental effects. Difficult asthma patients with dual anxiety and depression experience worse asthma outcomes alongside worse measures of psychological distress. There is a severity-gradient association of HADS scores with worse difficult asthma outcomes. Collectively, our findings highlight the need for holistic, multidisciplinary approaches that promote early identification and management of anxiety and depression in difficult asthma patients.

Drug-repositioning indicates a way to conquest corticosteroid-insensitivity

Recent advance of medications and devices brings more effective treatment intervention to the patients with asthma. As far as obeying guidelines, approximately 90% of patients with asthma acquire good control. However, there are still small number of patients with asthma who resist conventional treatment. Most of them are corticosteroid-insensitive. It would be thought that there are two ways to deal with this problem. The first one is biologics. However, these are very expensive. The second way is a treatment intervention focusing on cancellation of corticosteroid-resistance. In early 2010s, a new-intracellular signaling pathway (phosphatydilinositol-3-kinese: PI3K pathway) is proven to be closely associated with corticosteroid-resistance. PI3K-inhibitor should be one of the promising candidates to attenuate corticosteroid-resistance. But PI3K-inhibitor also has a toxicity when given systemically. Drug-repositioning (DR) is a good option to deal with it. To find out PI3K-inhibitor from numerous medicines gives an answer how to inhibit PI3K pathway. The presenter has found both low-dose theophylline and long-acting beta-2 agonist have a potential to antagonize PI3K. These medicines have been prescribed for decades and their safety has already been proved. It is possible for clinicians to inhibit PI3K activation in patients with asthma associated with corticosteroid-resistance using these medicines without waiting for development of bran-new PI3K inhibitors. DR revealed that nortriptyline acts as a steroid-enhancer via its anti-PI3K activity. Calcium-channel blocker saves lung function in patients with asthma in long-term observation. DR promises us to find cheap and safe options to treat difficult asthma by inhibiting specific intracellular signaling pathways.

Real-world Omalizumab and Mepolizumab Treated Difficult Asthma Phenotypes and Their Clinical Outcomes

To examine the real-world effectiveness of omalizumab and mepolizumab and better understand the clinical characteristics of real-world populations treated with these biologics.In the study, researchers included 478 patients from the Wessex Asthma Cohort recruited from a difficult to control asthma clinic in the United Kingdom. Patients were seen between June 2006 and May 2019. Inclusion criteria included patients on “high dose therapies” and/or “continuous or frequent use of oral corticosteroids.”This was a retrospective study of biological naïve patients with severe asthma. In the study, researchers compared 182 patients who started either omalizumab or mepolizumab and 178 patients who did not start biological therapy. Data concerning asthma control were collected at the baseline visit and each injection visit. The effectiveness of biologics was determined by using biological specific standard criteria.Omalizumab treated subjects were found to be younger and more ethnically diverse and had higher prevalence of rhinitis, allergic bronchopulmonary aspergillosis, and nasal polyps, compared with that of the mepolizumab or no biological treatment groups. Mepolizumab-treated subjects had greater eosinophilia and were diagnosed later in life. They also had more nasal polyps than the control group did. Both biological therapies significantly improved asthma control and reduced asthma exacerbations, acute health care encounters, and maintenance oral steroid dose. Patients in the nonresponder groups were evaluated and found to have worse baseline asthma control and greater prevalence of anxiety, when compared with biological responders.Omalizumab and mepolizumab both showed significant clinical benefit in real-world populations. Omalizumab patients were younger and more atopic. Mepolizumab patients were older with a less atopic phenotype. Nonresponders had more severe asthma at that baseline and more psychological comorbidities.It has been widely discussed that populations in clinical trials of asthma biologics are not representative of the full population that needs these therapies. In this cohort study, the authors evaluate the efficacy of these 2 biologics in real-world populations. There is no information on how the biological was selected, but, with this cohort, the authors still gives valuable information about the population characteristics and potential exacerbating factors in biological nonresponders. The authors also highlight that both omalizumab and mepolizumab were highly efficacious.