Eosinophilic Phenotype Research Articles

Quality improvement project to increase screening and referral for biologic therapy for patients with uncontrolled asthma

Background Asthma is a treatable chronic disease of airway inflammation with varying levels of control and severity. Biological therapy is an effective evidence-based treatment for patients with allergic and eosinophilic phenotypes of asthma who are classified as poorly controlled moderate to severe asthma. Yet, evidence-based treatments are infrequently used to support effective care of poorly controlled moderate and severe asthma. This quality improvement (QI) project aimed to increase the number of patients with uncontrolled moderate to severe asthma at an outpatient asthma center who are screened and referred for biologic therapy when appropriate. Methods A guideline-based biologic screening protocol was implemented using plan-do-study-act (PDSA) methodology allowing for a systematic approach for implementation, monitoring and making adjustments. A pre- and post-independent groups comparative design was utilized to evaluate screening and referral data. Results Screening improved significantly from pre- (n = 30, 23.8%) to post-implementation (n = 17, 70.8%), p < 0.001; phi = .372. Referrals to biologics also improved from 42.4% (n = 28) to 93.3% (n = 14), p < 0.001; phi = .396. Providers reported increased knowledge, confidence, and satisfaction with the asthma screening protocol at post-implementation. Conclusions The implementation of an asthma screening protocol for asthma patients in an ambulatory center is an effective way of increasing screening for eligibility for biologic therapy. Adhering to the standard of care based on evidence-based guidelines increased access to biologic therapy with a higher percentage of patients being referred for therapy.

Cost-utility analysis of dupilumab add on therapy versus standard therapy in adolescents and adults for severe asthma in Colombia

ABSTRACT Introduction Dupilumab is a recombinant human IgG4 monoclonal antibody that inhibits IL-4 and IL-13 signaling. This drug raises concerns about the economic impact in scenarios with constrained resources. This study aimed to estimate the cost-utility of dupilumab plus standard care (SoC) vs SoC alone in adolescents and adults with severe asthma and eosinophilic phenotype. Methods A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with uncontrolled allergic asthma in Colombia. Total costs and QALYs of standard therapy (ICS + LABA), add-on therapy with dupilumab, were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of $19,000. Results The base-case analysis showed dupilumab was associated with higher annual annual per-patient costs (US$5,719 for dupilumab and US$1,214 for standard therapy) and higher QALYs than standard therapy (fe 4.06 QALYs vs 3.97 QALYs, respectively). . The incremental cost–effectiveness ratio estimated was US$50,160 per QALY gained Conclusion Dupilumab is not cost-effective using a WTP of US$19000 per QALY threshold in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy.

Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

Особливості відповіді на базисну протизапальну терапію школярів з альтернативними запальними фенотипами бронхіальної астми

Purpose — to evaluate the effectiveness of long-term anti-inflammatory therapy with inhaled glucocorticosteroids in children with alternative inflammatory phenotypes of bronchial asthma (BA) for the development of individualized control treatment. Materials and methods. A comprehensive survey of 94 school-age children with BA was conducted. According to the results of cytological examination of sputum, 2 clinical observation groups were formed. The first group of patients was formed by 38 patients with non3eosinophilic (neutrophilic) nature of the inflammatory process of the bronchi (mean age — 11.1±2.9 years, the proportion of boys — 52.6±8.1%), and the second group — 56 children with eosinophilic type of airway inflammation (3% or more of eosinophilic granulocytes in sputum), ie eosinophilic asthma phenotype (mean age — 12.2±3.2 (P&gt;0.05) years, the proportion of boys — 67.9±6.2%, P&gt;0.05). According to the main characteristics of the observation group could be compared. All patients underwent a comprehensive clinical and paraclinical (spirographic) examination. Scoring control of BA symptoms was performed using a questionnaire at the beginning and at the end of the course of anti-inflammatory basic therapy. The questionnaire included the clinical signs of BA reflected in the scores, which were evaluated by patients and their parents, as well as the scale of instrumental studies according to the spirographic examination of patients. Results. The paper shows that the best effect of long-term courses of basic therapy with inhaled glucocorticosteroids (ICS) was observed in patients with eosinophilic airway inflammation. Thus, the share of patients with a relatively satisfactory level of clinical control of the disease and with close to normal spirographic indicators was in group II: before the course of treatment with inhaled corticosteroids 25.0% and 31.9%, and after treatment — 81.3% (P&lt;0,01) and 69.0% (P&lt;0.01), respectively. Thus, an increase of 69.3% in relative risk (IRR) and 56.3% in absolute risk (IAR) of BA control reflected a pronounced control effect of inhaled corticosteroids in the eosinophilic nature of airway inflammation. The minimum number of patients needed to treat (NNT) in order to obtain at least one positive result was 2. At the same time, in patients with neutrophilic inflammatory process, the proportion of patients with a relatively satisfactory level of clinical and paraclinical (according to spirography) disease control was: before the appointment of ICS — 30.8% and 30.8%, and after treatment — 50% (PFisher's exact test&gt;0.05) and 76.9% (PFisher's exact test&lt;0.01), respectively. This persistence of clinical manifestations of the disease indicated an insufficient level of control of non3eosinophilic BA in the treatment of inhaled corticosteroids and questioned the feasibility of monotherapy with this group of neutrophilic bronchitis. The insufficient effect of anti3inflammatory therapy with inhaled corticosteroids was evidenced by the fact that IRR of satisfactory level of clinical control was 38.4%, IAR — 19.2%, and NNT — 6 patients. Conclusions. In patients with the eosinophilic phenotype of BA, the use of long courses of inhaled glucocorticosteroids led to an increased chance of achieving disease control, while the chances of improving of the pulmonary function tests were also observed in the neutrophilic phenotype of the disease. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: bronchial asthma, children, basic anti-inflammatory therapy.

Association of Differential Mast Cell Activation with Granulocytic Inflammation in Severe Asthma.

Rationale: Mast cells (MCs) play a role in inflammation and both innate and adaptive immunity, but their involvement in severe asthma (SA) remains undefined. Objectives: We investigated the phenotypic characteristics of the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) asthma cohort by applying published MC activation signatures to the sputum cell transcriptome. Methods: Eighty-four participants with SA, 20 with mild/moderate asthma (MMA), and 16 healthy participants without asthma were studied. We calculated enrichment scores (ESs) for nine MC activation signatures by asthma severity, sputum granulocyte status, and three previously defined sputum molecular phenotypes or transcriptome-associated clusters (TACs) 1, 2, and 3 using gene set variation analysis. Measurements and Main Results: MC signatures except unstimulated, repeated FcεR1-stimulated and IFN-γ-stimulated signatures were enriched in SA. A FcεR1-IgE-stimulated and a single-cell signature from asthmatic bronchial biopsies were highly enriched in eosinophilic asthma and in the TAC1 molecular phenotype. Subjects with a high ES for these signatures had elevated sputum amounts of similar genes and pathways. IL-33- and LPS-stimulated MC signatures had greater ES in neutrophilic and mixed granulocytic asthma and in the TAC2 molecular phenotype. These subjects exhibited neutrophil, NF-κB (nuclear factor-κB), and IL-1β/TNF-α (tumor necrosis factor-α) pathway activation. The IFN-γ-stimulated signature had the greatest ES in TAC2 and TAC3 that was associated with responses to viral infection. Similar results were obtained in an independent ADEPT (Airway Disease Endotyping for Personalized Therapeutics) asthma cohort. Conclusions: Gene signatures of MC activation allow the detection of SA phenotypes and indicate that MCs can be induced to take on distinct transcriptional phenotypes associated with specific clinical phenotypes. IL-33-stimulated MC signature was associated with severe neutrophilic asthma, whereas IgE-activated MC was associated with an eosinophilic phenotype.

Characterizing Inflammatory Cell Asthma Associated Phenotypes in Dental Health Workers Using Cytokine Profiling.

Cytokines elicit a pro-inflammatory response by modifying the airway microenvironment in patients with acute or chronic asthma. The expression pattern of several distinct cytokines could be a useful discriminator in asthma. This study aimed to identify asthma subject groupings based on common inflammatory patterns and to determine the relationship between these identified patterns and asthma-associated clinical indices. A sub-group of 76 dental healthcare workers (HCWs) identified from a larger cross-sectional study of 454 dental HCWs in five dental institutions were evaluated further. A self-administered questionnaire elicited the health and employment history of subjects. Sera were analyzed for atopic status, latex sensitization, and 12 cytokines (IL-1β, 3, 4, 5, 6, 7, 8, 10, 12p70, eotaxin, GM-CSF, TNF-α). Pre and post-bronchodilator spirometry was performed on all HCWs. Data clustering and factor analysis were used to identify inflammatory cluster patterns of cytokines. Associations between the cytokine cluster groupings and relevant asthma-associated clinical indices were determined using multivariate logistic regression. The classification of asthma subtype based on cytokine patterns demonstrated both eosinophilic and neutrophilic inflammatory responses. Four phenotypically distinct subgroups relating to the severity of inflammation (acute or chronic) of the cell types were identified. Cytokine determinants for the neutrophilic subtype included IL-1β, 6, 8, 10, 12p70, and TNF-α whereas for the eosinophilic subtype these included IL-3, 4, 5, 7, eotaxin, and GM-CSF. The multivariate models showed a significant association between work-related chest symptoms and all four inflammatory patterns. However, stronger associations were observed for the acute neutrophilic (OR = 6.00, p < 0.05) compared to acute and chronic eosinophilic responses (OR = 4.30, p < 0.05; OR = 4.93, p < 0.05), respectively. Subjects with airway obstruction were more likely to have a mixed cellular infiltrate. The odds of work-exacerbated asthma were increased in acute or chronic eosinophilia (OR = 7.75 and 8.12; p < 0.05), respectively as well as with acute neutrophilia (OR = 6) sub-type. This study demonstrated that neutrophilic inflammatory cell asthma phenotypes coexist with eosinophilic inflammatory phenotypes suggesting a possible dual pathway for asthma in dental health workers, probably due to mixed exposures to high molecular weight (e.g., latex) and low molecular weight (e.g., acrylates) agents.

P070 EFFICACY OF BIOLOGIC THERAPIES IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA STRATIFIED BY BLOOD EOSINOPHIL COUNT

Patients with severe, uncontrolled asthma may be prescribed biologic therapies to achieve better control. Randomized controlled trials (RCTs) of biologic therapies have shown differential results by baseline blood eosinophil count (BEC), and approvals of several biologics are specific to patients with an eosinophilic phenotype. In the absence of head-to-head trials, we describe annual asthma exacerbation rate (AAER) reductions by baseline BEC in RCTs.

Long-term oxygen treatment need is less frequent in eosinophilic COPD patients.

IntroductionEosinophilic airway inflammation is a recognized inflammatory pattern in subgroups of patients with chronic obstructive pulmonary disease (COPD). However, there are still conflicting results between various studies concerning the effect of eosinophils in COPD patients. Our aim with this study was to evaluate eosinophilic inflammation and its relation to the clinical characteristics in a group of COPD patients.MethodsStable COPD patients with FEV1% predicted < 50 or with ≥ 1 exacerbation leading to hospital admission or ≥2 moderate or severe exacerbation history were consecutively enrolled from outpatient clinics.ResultsWe included 90 male COPD patients, with a mean age of 63.3 ± 9.2. Mean FEV1% predicted was 35.9 ± 11.3. Eosinophilic inflammation (eosinophil percentage ≥2%) was evident in 54 (60%) of the patients. Participants with eosinophilic inflammation were significantly older and had better FEV1 predicted % values. Eosinophilic COPD patients were characterized with better quality of life and fewer symptoms. COPD patients with noneosinophilic inflammation used supplemental long‐term oxygen therapy (LTOT) more frequently compared to patients with eosinophilic inflammation (36.1% vs. 14.8%, p = 0.01). Eosinophilic inflammation is associated with less dyspnea severity measured by mMRC (OR: 0.542 95% CI: 0.342–0.859, p = 0.009) and less LTOT use (OR: 0.334 95% CI: 0.115–0.968, p = 0.04) regardless of age, severity of airflow limitation, and having frequent exacerbation phenotype.ConclusionOur study supports the growing evidence for a potential role of eosinophilic inflammation phenotype in COPD with distinctive clinical characteristics. Eosinophilic inflammation is inversely associated with dyspnea severity measured by mMRC and LTOT use independently from age, total number of exacerbations, St. George Respiratory Questionnaire (SGRQ) total score and FEV1% predicted.

The effectiveness of benralizumab in the treatment of the eosinophilic phenotype of severe asthma in real clinical practice

To evaluate the effectiveness of benralizumab in patients with the eosinophilic phenotype of severe asthma in real clinical practice after a year of therapy.Methods. During Benralizumab therapy, 13 patients with severe eosinophilic asthma (average age – 55.44 ± 7.18 years old) were examined twice: before the treatment and after 1 year of benralizumab therapy. The assessment included collection of complaints, medical history, current therapy, Asthma Control Questionnaire (ACQ-5) test, absolute blood count of eosinophils, spirometry.Results. All patients initially had pronounced eosinophilia of 577.5 ± 356.4 cells/μl. After 1 year of using benralizumab, the eosinophil count decreased by 96.15%. During therapy, the ACQ-5 index decreased from 1.63 ± 0.62 to 0.73 ± 0.41 in the study patients, which corresponded to the achievement of asthma control. The forced expiratory volume in 1 second (FEV1) increased by 23 %. The number of exacerbations decreased by 58.09%. 12 (92.31%) patients were on oral corticosteroids (OCS) (10 ± 2.17 mg of prednisolone daily) before benralizumab therapy. All subjects noted a decrease in night and day symptoms over time and were able to reduce the use of OCS. 5 (38.46%) patients achieved complete elimination of daily OCS use, 7 (53.84%) patients were able to reduce their daily OCS dose.Conclusion. Benralizumab therapy as an add-on maintenance treatment in patients with eosinophilic phenotype of severe asthma contributes to a significant decrease in peripheral blood eosinophils, which mediates an improvement in asthma control, an increase in FEV1, a reduction in the number of exacerbations, and a decrease in the need for the OCS usage. Careful monitoring of long-term adverse events is necessary during treatment with benralizumab.

LONG-TERM EFFICACY OF DUPILUMAB IN ORAL CORTICOSTEROID-DEPENDENT PATIENTS WITH ASTHMA: LIBERTY ASTHMA TRAVERSE

LONG-TERM EFFICACY OF DUPILUMAB IN ORAL CORTICOSTEROID-DEPENDENT PATIENTS WITH ASTHMA: LIBERTY ASTHMA TRAVERSE

The effect of chronic hepatitis-C virus infection on asthma control, severity, and induced sputum analysis in bronchial asthma patients

Background Bronchial asthma is a heterogeneous disease, manifested by chronic airway-inflammatory changes. Viral hepatitis-C infection is a major worldwide illness with about 130–150 million that are chronically infected. Hepatitis-C virus (HCV) is associated with liver pathology and extrahepatic manifestations, which can lead to many indirect and direct pulmonary complications. Alteration of airway inflammation may be the underlying mechanism predisposing asthmatics with chronic HCV to more severe asthma. Discrete inflammatory types have been recognized in the sputum of asthmatics. This study aims to assess the effect of HCV infection on asthma control, asthma severity, and airway inflammation and to analyze sputum in bronchial asthma patients graded according to Global Initiative for Asthma Classification. Patients and methods This study included 60 adult nonsmoking asthmatic patients who were enrolled from the outpatient clinic of Chest and Tropical Departments, Mansoura University Hospital from February 2016 to September 2017. They were classified into two groups. Group A: patients without HCV infection and group B: patients with chronic HCV infection. Analysis of induced sputum to evaluate airway-inflammatory cell type in relation to asthma control, severity, and treatment step. Results Regarding asthma severity and treatment step, there is a significant difference between the two studied groups, while no significant differences in asthma control between the two groups were found. Successfully induced samples illustrated that airway-inflammatory cells varied in both groups; although an eosinophilic phenotype predominates in both groups, a higher percentage was present in group A (50%) than patients in group B (35%), also, paucigranulocytic phenotype was higher in group A than group B. On the other hand, the percentage of neutrophilic and mixed granulocytic phenotypes was more in group B in comparison with group A. Conclusion Patients with asthma and chronic HCV infection had a significant later onset of bronchial asthma, eosinophilic phenotype predominated in all asthmatic patients, especially in patients without HCV. High percentage of neutrophils was present in asthmatics with HCV infection and this suggested more severe airway inflammation.

Клінічно-патофізіологічне фенотипування хронічного обструктивного захворювання легень

The purpose of the study was to determine the clinical and laboratory features of inflammatory phenotypes among patients with chronic obstructive pulmonary disease, moderate respiratory failure and anemia of chronic disease. Materials and methods. The study included 150 patients with exacerbation of chronic obstructive pulmonary disease and chronic anemia, in which inflammatory phenotypes were identified, among which the largest share was neutrophilic (66/44.0±4.0%), less lymphocytic (35/23.3±3.4%) and eosinophilic (16/10.7±2.5%). In 33/22.0% of patients, the inflammatory phenotype was mixed and patients were excluded from the study. Among 117 patients included in the study, 67.5% were men and 32.5% were middle-aged (25.6%), elderly (42.7%) and senile (24.8%). The results were processed by the methods of variation statistics, the materiality threshold p &lt;0.05. Results and discussion. It was established, that peripheral blood analysis and biochemical parameters, regardless of the pathophysiological nature of inflammation in all groups showed moderate dysfunction of external respiration, normochromic normocytic nature of mild chronic anemia with activation of all components of the external coagulation mechanism and increased prothrombin time and inflammation activation (by C-reactive protein and seromucoids). The neutrophilic phenotype of inflammation, in comparison with lymphocytic and eosinophilic, was the most common and was accompanied by the most pronounced anemic syndrome, the highest activity of systemic inflammation and the most pronounced syndrome of endogenous intoxication with deterioration of liver function. The lymphocytic phenotype of inflammation was the second widespread and was characterized by the most pronounced normochromic anemic syndrome with the most pronounced predisposition to hypercoagulation (the highest prothrombin index) with high activity of the inflammatory syndrome. The eosinophilic phenotype of inflammation was significantly less common than the neutrophilic and lymphocytic with the favorable characteristics of the anemic syndrome and with low inflammatory activity and the small activity of endogenous intoxication but the highest fasting blood glucose level as normo-hyperglycemia. Conclusion. Clinical and pathophysiological phenotyping of chronic obstructive pulmonary disease makes it possible to determine not only the activity of inflammation, but also the severity of anemic syndrome, endogenous intoxication, liver status and carbohydrate metabolism, which is of practical importance for both physicians and scientists

From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases.

Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil‐reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin‐5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add‐on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real‐world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI‐A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases.

A lesson from the wild: The natural state of eosinophils is Ly6Ghi.

With a long history of promoting pathological inflammation, eosinophils are now emerging as important regulatory cells. Yet, findings from controlled laboratory experiments so far lack translation to animals, including humans, in their natural environment. In order to appreciate the breadth of eosinophil phenotype under non‐laboratory, uncontrolled conditions, we exploit a free‐living population of the model organism Mus musculus domesticus. Eosinophils were present at significantly higher proportions in the spleen and bone marrow of wild mice compared with laboratory mice. Strikingly, the majority of eosinophils of wild mice exhibited a unique Ly6Ghi phenotype seldom described in laboratory literature. Ly6G expression correlated with activation status in spleen and bone marrow, but not peritoneal exudate cells, and is therefore likely not an activation marker per se. Intermediate Ly6G expression was transiently induced in a small proportion of eosinophils from C57BL/6 laboratory mice during acute infection with the whipworm Trichuris muris, but not during low‐dose chronic infection, which better represents parasite exposure in the wild. We conclude that the natural state of the eosinophil is not adequately reflected in the standard laboratory mouse, which compromises our attempts to dissect their functional relevance. Our findings emphasize the importance of studying the immune system in its natural context – alongside more mechanistic laboratory experiments – in order to capture the entirety of immune phenotypes and functions.

Comparing hospital admissions, comorbidities, and biomarkers between severe asthma and Gold III-IV chronic obstructive pulmonary disease.

In spite of difficulties in differentiating asthma from chronic obstructive pulmonary disease (COPD), physicians should strive for accurate diagnosis because outcomes may be different. Our aims were to compare the frequency of hospital admissions (HA) between severe asthmatic (SA) and Gold III-IV COPD subjects receiving disease-specific guideline recommended therapy and to depict the frequency of prevalent chronic disorders and the laboratorial profile suggesting allergic and eosinophilic phenotypes. This cross-sectional study comprises one group of SA subjects and another group of Gold III-IV COPD subjects. Subjects answered standard questionnaires, underwent spirometry, and provided a peripheral blood sample. We validated the HA that have occurred during the preceding year by review of the report emitted by the hospital. We detected comorbidities by review of current pharmacological therapies. We enrolled 160 SA and 41 Gold III-IV COPD subjects. As compared with Gold III-IV COPD subjects, SA subjects had lower odds of HA (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.05-0.74) and higher odds of obesity (OR 9.17, 95%CI 2.68-31.37), hypertension (OR 2.54, 95%CI 1.16-5.57), and diabetes mellitus (OR 5.71, 95%CI 1.56-20.85). The frequency of atopic and eosinophilic phenotypes was similar between study groups. Our results demonstrated that Gold III-IV COPD subjects had worse outcomes as compared with SA subjects. We also observed that the frequency of atopy and high peripheral blood eosinophil count were similar between study groups. Finally, we exposed aspects of comorbidities related to asthma and COPD that indicate the need of close monitoring the cardiovascular risk in SA subjects above 40 years of age.

Asthma Phenotyping in Primary Care: Applying the International Severe Asthma Registry Eosinophil Phenotype Algorithm Across All Asthma Severities

We developed an eosinophil phenotype gradient algorithm and applied it to a large severe asthma cohort (International Severe Asthma Registry). We sought to reapply this algorithm in a UK primary care asthma cohort, quantify the eosinophilic phenotype, and assess the relationship between the likelihood of an eosinophilic phenotype and asthma severity/health care resource use (HCRU). Patients age 13 years and older with active asthmaand blood eosinophil count or 1 or greater, who were included from the Optimum Patient Care Research Databaseand the Clinical Practice Research Datalink, were categorized according to the likelihood of eosinophilic phenotype using the International Severe Asthma Registry gradient eosinophilic algorithm. Patient demographic, clinicaland HCRU characteristics were described for each phenotype. Of 241,006 patients, 50.3%, 22.2%, and 21.9% most likely (grade 3), likely (grade 2), and least likely (grade 1), respectively, had an eosinophilic phenotype, and 5.6% had a noneosinophilic phenotype (grade 0). Compared with patients with noneosinophilic asthma, those most likely to have an eosinophilic phenotype tended to have more comorbidities (percentage with Charlson comorbidity index of ≥2: 28.2% vs 6.9%) and experienced more asthma attacks (percentage with one or more attack: 24.8% vs 15.3%). These patients were also more likely to have asthma that was difficult to treat (31.1% vs 18.3%), to receive more intensive treatment (percentage on Global Initiative for Asthma 2020 step 4 or 5: 44.2% vs 27.5%), and greater HCRU (eg, 10.8 vs 7.9 general practitioner all-cause consultations per year). The eosinophilic asthma phenotype predominates in primary care and is associated with greater asthma severity and HCRU. These patients may benefit from earlier and targeted asthma therapy.

Metabolic Phenotypes in Asthmatic Adults: Relationship with Inflammatory and Clinical Phenotypes and Prognostic Implications.

Bronchial asthma is a chronic disease that affects individuals of all ages. It has a high prevalence and is associated with high morbidity and considerable levels of mortality. However, asthma is not a single disease, and multiple subtypes or phenotypes (clinical, inflammatory or combinations thereof) can be detected, namely in aggregated clusters. Most studies have characterised asthma phenotypes and clusters of phenotypes using mainly clinical and inflammatory parameters. These studies are important because they may have clinical and prognostic implications and may also help to tailor personalised treatment approaches. In addition, various metabolomics studies have helped to further define the metabolic features of asthma, using electronic noses or targeted and untargeted approaches. Besides discriminating between asthma and a healthy state, metabolomics can detect the metabolic signatures associated with some asthma subtypes, namely eosinophilic and non-eosinophilic phenotypes or the obese asthma phenotype, and this may prove very useful in point-of-care application. Furthermore, metabolomics also discriminates between asthma and other “phenotypes” of chronic obstructive airway diseases, such as chronic obstructive pulmonary disease (COPD) or Asthma–COPD Overlap (ACO). However, there are still various aspects that need to be more thoroughly investigated in the context of asthma phenotypes in adequately designed, homogeneous, multicentre studies, using adequate tools and integrating metabolomics into a multiple-level approach.

Regulatory T cell deficiency in patients with eosinophilic asthma

Background: There is a lack of information about regulatory T cells (Tregs) and inflammatory phenotypes in patients with asthma. In this study, we aimed to compare the characteristics of Tregs in patients with eosinophilic asthma.Methods: Forty healthy and 120 stable asthmatic patients were recruited. Sputum and airway inflammatory phenotypes were assessed, and all patients were followed for one year. Human peripheral blood mononuclear cells (PBMCs) were collected and stimulated with phytohemagglutinin (PHA) and Dermatophagoides farina (Derp) to detect CD4+CD25+FOXP3+T cells and Foxp3 levels. Interleukin (IL)-13, IL-5, IL-17, IL-9, and interferon (IFN)-γ levels were measured.Results: 38.33% of patients had eosinophilic asthma, 13.33% had neutrophilic asthma, 6.67% had mixed granulocytic asthma, and 41.67% had pauci-granulocytic asthma. The eosinophilic asthma patients had a relatively high Asthma Control Test (ACT) score, an increased prediction and improvement FEV1 (%) rate, and elevated total IgE serum levels (P < 0.05). T helper cell 2 (Th2) cytokines IL-13 and IL-5 were predominantly expressed in the eosinophilic phenotype, while the Th1 cytokine IFN-γ and Th17 cytokine were found in the neutrophilic phenotype. IL-10 was significantly lower in eosinophilic asthmatic patients compared to the controls (P < 0.05). CD4+CD25+FOXP3+T cells (%Tregs) and Foxp3 gene expression in the PHA stimulated eosinophilic asthma samples were significantly lower compared to the control samples (P < 0.05). The airway inflammation phenotypes remained stable after one-year of therapy.Conclusion: Asthmatic patients with the eosinophilic phenotype in this study were deficient in Tregs, as characterized by a Th2 cell-biased pattern.

Cost-utility analysis and budget impact of benralizumab as add-on therapy to standard care for severe eosinophilic asthma in Colombia

ABSTRACT Introduction:Benralizumab, amonoclonal antibody for human interleukin-5, has been associated with adecrease in asthma exacerbations. The introduction of this drug raises concerns about the economic impact in scenarios with constraints. This study aimed to estimate the cost-utility of benralizumab plus standard care (SoC) vs. SoC alone in adults with severe uncontrolled asthma with evidence of eosinophilic phenotype. Methods:We constructed aMarkov model with three health states (asthma on benralizumab and SOC, asthma on SOC alone, and death) from ahealthcare system perspective over alifetime horizon. The model was populated using local costs while utilities were derived from international literature. Cost and transition probabilities were obtained from amixture of Colombian-specific and internationally published data. Results:The incremental cost-effectiveness ratio (ICER) per patient peryear was $US 42,746per QALY gained. Benralizumab treatment would be cost-effective at the recommended societal US 18,000 WTP threshold if the cost of benralizumab is reduced by 41% more than the base case value. Conclusion:Benralizumab is not cost-effective using WTP of US$18,000per QALY threshold in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Tutto quello che il pediatra dovrebbe sapere sul mepolizumab

Mepolizumab, a monoclonal antibody blocking IL-5, is efficacious in the treatment of severe lung diseases sharing eosinophilic inflammation pattern. The paper describes two cases in which the drug was used with excellent results. The first involved a 14-year-old boy with obliterative bronchiolitis, the other an 11-year-old girl with non-atopic asthma. Both cases shared the eosinophilic phenotype of the disease, defined by an eosinophilic count in the peripheral blood equal to or greater than 2% (i.e. a baseline value of 150-200 cells/µl or 300 cells/µl during the previous year). Its use demonstrates clinical improvement in severe refractory asthma with eosinophilic phenotype and as off-label drug in obliterative bronchiolitis, leading to a decrease in the rate of exacerbations and enabling the reduction of corticosteroids as well as the resolution of structural anomalies, respectively.