Comparison of Long-term Response and Remission to Omalizumab and Anti-IL-5/IL-5R Using Different Criteria in a Real-life Cohort of Severe Asthma Patients.

BACKGROUND: Evaluation of biologic therapy response is vital to monitor its effectiveness. Authors have proposed various response criteria including good responder, super-responder, non-responder, and clinical remission. OBJECTIVES: To ascertain the prevalence of response and clinical remission after long-term treatment (>6 months) of anti-IgE and anti-IL-5/IL-5Rα biologics, compare these results with existing criteria, and identify predictors for non-responders and clinical remission. METHODS: A multicenter, real-life study involving severe asthma patients in Spain. Various outcomes were assessed to gauge response and clinical remission against established criteria. RESULTS: The study included 429 patients, 209 (48.7%) omalizumab, 112 (26.1%) mepolizumab, 19 (4.4%) reslizumab and 89 (20.7%) benralizumab, with a mean treatment duration of 55.3±38.8 months. In the final year of treatment, 218 (50.8%) were super-responders, 173 (40.3%) responders, 38 (8.9%) non-responders, and clinical remission in 116 (27%), without differences among biologics. The short-term non-responders (<6 months) were 25/545 (4.6%). Substantial variations in response and clinical remission were observed when applying different published criteria. Predictors of non-response included higher BMI (OR:1.14; 95% CI:1.06-1.23; p<0.001), admissions at ICU (2.69; 1.30-5.56; p=0.01), high count of SAE (1.21; 1.03-1.42; p=0.02) before biologic treatment. High FEV1% (0.96; 0.95-0.98; p<0.001), a high ACT score (0.93; 0.88-0.99; p=0.01) before biologic treatment or NSAID-ERD (0.52; 0.29-0.91; p=0.02) showed strong associations with achieving clinical remission. CONCLUSION: A substantial proportion of severe asthma patients treated long-term with omalizumab or anti-IL5/IL-5Rα achieved a good response. Differences in response criteria highlight the need for harmonization in defining response and clinical remission in biologic therapy to enable meaningful cross-study comparisons.

Treatment Patterns of Monoclonal Antibodies in Patients With Severe Uncontrolled Asthma Treated by Pulmonologists in Spain.

Introduction and objectives: The use of monoclonal antibody (mAb)-based therapies is becoming the new standard of care for severe uncontrolled asthma (SUA). Even though patients may qualify for one or more of these targeted treatments, based on different clinical criteria, a global vision of mAb prescription management in a large sample of hospitals is not well characterised in Spain.The objective was to give a global vision of mAb prescription management in a large sample of hospitals in Spain. Materials and methods: We used an aggregate data survey method to interview pulmonology specialists in a large sample of Spanish centres (90). The following treatment-related information was obtained on patients treated with mAbs: specific mAbs prescribed, treatment interruption, switch and restart and the reasons for these treatment changes. Results: mAb prescription was more frequent in females (13.3% females vs 7.4% males; p < 0.001). There were no differences in prevalence by hospital complexity level. In contrast, there were differences by geographical area. Omalizumab was the most prescribed mAb (6.2%), followed by mepolizumab (2.9%). Discontinuation of Omalizumab (due to a lack of effectivity) and switches from this mAb to mepolizumab were more frequent. Very few restarts to the first treatment were observed after a switch from ≥2 mAbs. Conclusions: Omalizumab appeared as the most prescribed mAb in SUA but was also the most withdrawn; a specific and objective characterisation of patients with SUA, along with asthma phenotyping, and together with further evaluation of safety and effectiveness profiles, will lead to future progress in the management of SUA with mAbs.

Introducción y objetivos: El uso de terapias basadas en anticuerpos monoclonales (mAb) se está convirtiendo en el nuevo estándar de atención para el asma grave no controlada (AGNC). A pesar de que los pacientes pueden optar a uno o varios de estos tratamientos dirigidos, con base en diferentes criterios clínicos, en España no se ha caracterizado bien una visión global de la gestión de la prescripción de mAb en una gran muestra de hospitales.El objetivo fue dar una visión global de la gestión de la prescripción de mAB en una amplia muestra de hospitales en España. Materiales y métodos: Se utilizó un método basado en una encuesta de datos agregados para entrevistar a especialistas en Neumología en una amplia muestra de centros españoles (90). Se obtuvo la siguiente información relacionada con el tratamiento de los casos tratados con mAbs: mAbs específicos prescritos, interrupción del tratamiento, cambio y reinicio, y las razones de estos cambios de tratamiento en consultas de Neumología. Resultados: La prescripción de mAB fue más frecuente en mujeres (13,3% mujeres vs. 7,4% hombres; p < 0,001). No hubo diferencias de prevalencia por nivel hospitalario. En cambio, hubo diferencias por área geográfica. Omalizumab fue el mAb más prescrito (6,2%), seguido de mepolizumab (2,9%). La interrupción y los cambios (debido a la falta de efectividad) también fueron más frecuentes para omalizumab. Conclusiones: Omalizumab fue el mAb más prescrito en el manejo de AGNC, pero también fue el mAB que presentó más retiradas; una caracterización específica y objetiva de los pacientes con AGNC, mediante fenotipificación de asma, junto con una evaluación adicional de los perfiles de seguridad y efectividad, conducirá a nuevos avances en el manejo del AGNC con mABs.

Prognostic Usefulness of Basic Analytical Data in Chronic Obstructive Pulmonary Disease Exacerbation.

Introduction: COPD causes high morbidity and mortality and high health costs. Thus, identifying and analyzing the distinctive and treatable traits seems useful to optimize the management of AEPOC patients. While various biomarkers have been researched, no solid data for systematic use have been made available. Aim: Assessing the short-term prognostic usefulness of clinical and analytical parameters available in routine clinical practice in COPD exacerbations. Material and methods: Multicenter prospective observational study conducted between 2016 and 2018. Patients admitted for COPD exacerbation who agreed to participate and signed an informed consent form were included. Prolonged stay, in-hospital mortality or early readmission was considered an unfavorable progression. 30-Day mortality was also analyzed. Results: 615 patients were included. Mean age was 73.9 years (SD 10.6); 86.2% were male. Progression of 357 patients (58%) was considered unfavorable. Mortality at 1 month from discharge was 6.7%. The multivariate analysis shows a relationship between the CRP/Albumin ratio and unfavorable progression (OR 1.008, 95% CI 1.00; 1.01), as well as increased risk of death at 1 month from discharge with elevated urea (OR 1.01, 95% CI 1.005; 1.02) and troponin T (OR 2.21, 95% CI 1.06; 4.62). Conclusion: Elevated CRP/Albumin, urea and TnT are prognostic indicators of poor short-term outcome in patients admitted for COPD exacerbation. Cardiovascular comorbidity and systemic inflammation could explain these findings.

Introducción: : La EPOC provoca una elevada morbimortalidad y elevados costes sanitarios. Identificar y analizar los rasgos distintivos y tratables parece útil para optimizar el tratamiento de los pacientes con AEPOC. Se han investigado varios biomarcadores sin que de momento se disponga de datos sólidos para su uso sistemático. Objetivo: Evaluar la utilidad pronóstica a corto plazo de los parámetros clínicos y analíticos disponibles en la práctica clínica habitual en las exacerbaciones de la EPOC. Material y métodos: Estudio observacional prospectivo multicéntrico realizado entre 2016 y 2018. Se incluyeron pacientes ingresados por exacerbación de EPOC que aceptaron participar y que firmaron consentimiento informado. Se consideró evolución desfavorable la estancia prolongada, la mortalidad hospitalaria o el reingreso precoz. También se analizó la mortalidad a 30 días. Resultados: Se incluyeron 615 pacientes. La edad media fue 73,9 años (DE 10,6); El 86,2% eran varones. Se consideró desfavorable la evolución de 357 pacientes (58%). La mortalidad al mes del alta fue del 6,7%. El análisis multivariante muestra una relación entre el ratio PCR/Albúmina y la progresión desfavorable (OR 1,008, IC 95% 1,00; 1,01), así como un mayor riesgo de muerte al mes del alta con urea elevada (OR 1,01, IC 95% 1,005; 1,02) y troponina T (OR 2,21; IC del 95%: 1,06; 4,62). Conclusión: La elevación de PCR/albúmina, la urea y la TnT son indicadores de mal pronóstico a corto plazo en pacientes ingresados por exacerbación de la EPOC. La comorbilidad cardiovascular y la inflamación sistémica podrían explicar estos hallazgos.

Burden of refractory and unexplained chronic cough on patients' lives: a cohort study.

Background: Chronic cough (cough lasting for ≥8 weeks) can lead to significant impairment in quality of life (QoL). Using patient-reported outcomes, this cohort study assessed the perceived impact of chronic cough on QoL and everyday life in patients from outpatient hospital clinics with refractory chronic cough (RCC) or unexplained chronic cough (UCC). Methods: This was a multicentre, non-interventional survey study. Cough severity was assessed on a 0-100 mm Visual Analogue Scale (VAS). Frequency, intensity and disruptiveness of cough were assessed using an adaptation of the Cough Severity Diary. The impact of cough on QoL was assessed using the Leicester Cough Questionnaire (LCQ). The physical impact of cough and associated impact on everyday life activities were explored using purpose-designed questions. Results: 191 patients responded to the survey; 121 (63.4%) had RCC and 149 were women (78.0%). Mean score on the cough severity VAS was 62.9 mm. Mean LCQ total score of 11.9 indicated reduced QoL. Cough impaired patients' everyday life, including the inability to speak fluently (58.0% of patients) and feeling tired/drained (46.6%). Women perceived poorer chronic cough-related QoL than men, as reflected by lower LCQ scores, and greater impairment of physical health, including cough-related stress urinary incontinence, and psychological health. Conclusions: Patients with RCC/UCC experience a significant burden in their everyday life, including impaired QoL, and perceive a negative impact on physical and psychological health and everyday activities, affecting work, relationships and leisure activities. The impact appears to be greater in women than men for several of the aspects studied.

Impact of Air Pollution on Asthma: A Scoping Review.

Asthma is the most common chronic respiratory disease and a major public health problem. Although the causal relationship between air pollution and asthma remains controversial, a large number of studies have provided increasingly consistent evidence of the involvement of air pollutants in asthma onset and exacerbations. We conducted a keyword search-based literature review using PubMed, Scopus and Web of Science databases for studies with titles or abstracts containing predefined terms. This narrative review discusses the current evidence on the pathological effects of pollution throughout life and the mechanisms involved in the onset, development, and exacerbation of asthma, and presents current measures and interventions for pollution damage control. Further global efforts are still needed to improve air quality.

El asma es la enfermedad respiratoria crónica más común, y un importante problema de salud pública. Aunque la relación causal entre la contaminación del aire y el asma sigue siendo controvertida, una gran cantidad de estudios han proporcionado evidencia cada vez más consistente de la participación de los contaminantes del aire en el inicio y las exacerbaciones del asma. Realizamos una revisión de la literatura basada en búsqueda de palabras clave utilizando las bases de datos PubMed, Scopus y Web of Science para estudios con títulos o resúmenes que contienen términos predefinidos. Esta revisión narrativa analiza la evidencia actual sobre los efectos patológicos de la contaminación a lo largo de la vida y los mecanismos involucrados en el inicio, desarrollo y exacerbación del asma, y presenta las medidas e intervenciones actuales para el control de daños por contaminación. Todavía se necesitan más esfuerzos globales para mejorar la calidad del aire.

[A Study of the Prevalence of Asthma in the General Population in Spain]. / Estudio de prevalencia de asma en población general en España.

Introduction: Asthma is a disease with high prevalence, which affects all age groups and generates high health and social care costs. Studies carried out in a number of populations show great variability in its prevalence, even in geographically close populations, with data suggesting a relevant influence of socio-economic factors. At present, we do not have reliable data on the prevalence of this disease in the adult population of Spain. The objectives of this study are to estimate the prevalence of asthma in the Spanish population for those aged 18-79, to describe the variability between autonomous communities, to estimate the prevalence of under and overdiagnosis, to analyse the prevalence of uncontrolled asthma and steroid-dependent asthma, to evaluate the health care cost, to identify the most frequent phenotypes and to establish a starting point to evaluate the temporal trend with subsequent studies. Methods: A cross-sectional, two-stage study will be carried out, including patients from 50 catchment areas. The study will be carried out in 3 phases: 1) screening and confirmation in the clinical history, in which patients with a previously correctly established diagnosis of asthma will be identified; 2) diagnosis of asthma to evaluate patients without a confirmed or excluded diagnosis; 3) characterization of asthma, where the characteristics of the asthmatic patients will be analysed, identifying the most frequent phenotypes. Discussion: It seems necessary and feasible to carry out an epidemiological study of asthma in Spain to identify the prevalence of asthma, to optimize healthcare planning, to characterize the most frequent phenotypes of the disease, and to evaluate inaccurate diagnoses.

Omalizumab in Severe Asthma: Effect on Oral Corticosteroid Exposure and Remodeling. A Randomized Open-Label Parallel Study.

INTRODUCTION: Data on the clinical efficacy and remodeling of omalizumab therapy in patients on oral corticosteroids (OC) are limited. OBJECTIVE: The purpose of the study is to show that in patients with corticosteroid-dependent asthma, omalizumab is a corticosteroid-sparing therapy able to inhibit airway remodeling and to reduce disease burden (lung function impairment, exacerbations). METHODS: This study is a randomised open-label study evaluating the addition of omalizumab to the standard of care in patients with severe asthma receiving oral corticosteroids. The primary endpoint was represented by the change in OC monthly dose by the end of treatment and secondary endpoints included spirometry changes, airway inflammation (FeNO), number of exacerbations and airways remodelling assessed by bronchial biopsies studied by transmission electron microscopy. As a safety variable, adverse effects were recorded. RESULTS: Efficacy was assessed for 16 patients in the omalizumab group and 13 in the control group. The final cumulative mean monthly OC doses were 34.7 mg and 217 mg for the omalizumab and control group, respectively; the mean difference between groups adjusted for baseline was -148.1 [95% confidence interval (CI) -243.6, -52.5; p = 0.004]. OC withdrawal of 75% versus 7.7% (p = 0.001) was observed in the omalizumab and control group, respectively. Omalizumab provided a slowing of forced expiratory volume in one second (FEV1) loss (70 mL versus 260 mL), a significant decrease in FeNO values and a reduction in the annual relative risk of clinically significant exacerbations of 54%. The treatment was well tolerated. The morphological study showed a significant decrease in basement membrane thickness in the omalizumab group (6.7 µm versus 4.6 µm) compared with controls (6.9 µm versus 7 µm) [mean difference between groups adjusted for baseline was -2.4 (95% CI -3.7, -1.2; p < 0.001], as well as a decrease in intercellular spaces (1.18 µm versus 0.62 µm and 1.21 µm versus 1.20 µm, p = 0.011, respectively). A qualitative improvement was also observed in the treated group. CONCLUSIONS: Omalizumab showed a marked OC-sparing capacity and was associated with an improvement in clinical management that correlated with bronchial epithelial repair. In OC-dependent asthma, reversibility of remodelling is possible; the concepts that basement membrane enlargement is detrimental and that chronic airway obstruction is systematically irreversible are outdated (EudraCT: 2009-010914-31).

Outpatient atorvastatin use and severe COVID-19 outcomes: A population-based study.

Evidence of the effect of statins on patients with coronavirus disease (2019) COVID-19 is inconsistent. The aim of this study was to evaluate the association between chronic use of statins-both overall and by active ingredient-and severe outcomes of COVID-19 (risk of hospitalization and mortality), progression to severe outcomes, and susceptibility to the virus. We conducted a population-based case-control study with data from electronic records to assess the risk of (1) hospitalization: cases were patients admitted due to COVID-19 and controls were subjects without COVID-19; (2) mortality: cases were hospitalized patients who died due to COVID-19 and controls were subjects without COVID-19; (3) progression: cases were hospitalized COVID-19 subjects and controls were nonhospitalized COVID-19 patients; and (4) susceptibility: cases were patients with COVID-19 (both hospitalized and nonhospitalized) and controls were subjects without COVID-19. We collected data on 2821 hospitalized cases, 26 996 nonhospitalized cases, and 52 318 controls. Chronic use of atorvastatin was associated with a decreased risk of hospitalization (adjusted odds ratios [aOR] = 0.83; 95% confidence interval [CI]: 0.74-0.92) and mortality (aOR = 0.70; 95% CI: 0.53-0.93), attributable in part to a lower risk of susceptibility to the virus (aOR = 0.91; 95% CI: 0.86-0.96). Simvastatin was associated with a reduced risk of mortality (aOR = 0.59; 95% CI: 0.40-0.87). The wide degree of heterogeneity observed in the estimated odds ratios (ORs) of the different statins suggests that there is no class effect. The results of this real-world study suggest that chronic use of atorvastatin (and to a lesser degree, of simvastatin) is associated with a decrease in risk of severe COVID-19 outcomes.

Severe asthma patients' and physicians' perspectives of disease burden: do they match?

A novel open-ended survey revealed contrasting viewpoints and priorities between patients with severe asthma and clinicians. These divergences must be considered when treating individual patients in multidisciplinary treatment teams. https://bit.ly/40Fsr9o.

Disposition of Work-Related Asthma in a Spanish Asthma Cohort: Comparison of Asthma Severity Between Employed and Retired Workers.

BACKGROUND: Exposure to certain agents in the workplace can trigger occupational asthma or work-exacerbated asthma, both of which come under the heading of work-related asthma (WRA). Understanding the burden that WRA represents can help in the management of these patients. OBJECTIVE: To assess the influence of occupation on asthma in real life and analyze the characteristics of patients with WRA included in an asthma cohort. METHODS: This was a prospective multicenter study of a cohort of consecutive patients with asthma. A standardized clinical history was completed. Patients were classified as having WRA or non-WRA. All patients underwent respiratory function tests, FeNO test, and methacholine challenge (methacholine concentration that causes a 20% drop in FEV1) at the beginning of the study. They were classified into two groups, depending on their employment status: employed (group 1) or unemployed (group 2). RESULTS: Of the 480 patients included in the cohort, 82 (17%) received the diagnosis of WRA. Fifty-seven patients (70%) were still working. Mean age (SD) was 46 (10.69) years in group 1 and 57 (9.91) years in group 2 (P < .0001). Significant differences were observed in adherence to treatment (64.9% in group 1 vs 88% in group 2; P = .0354) and in severe asthma exacerbations (35.7% in group 1 vs 0% in group 2; P = .0172). No significant differences were observed in the rest of the variables analyzed. CONCLUSIONS: The burden of WRA in specialized asthma units is not negligible. The absence of differences in the severity of asthma, the treatment administered, alterations in lung function, and the number of exacerbations in those working versus not working may support the idea that advice regarding changing jobs should be customized for individual patients.

Criteria to evaluate efficacy of biologics in asthma: a Global Asthma Association survey.

BACKGROUND: Currently, there are no universally accepted criteria to measure the response to biologics available as treatment for severe asthma. This survey aims to establish consensus criteria to use for the evaluation of response to biologics after 4 months of treatment. METHOD: Using Delphi methodology, a questionnaire including 10 items was validated by 13 international experts in asthma. The electronic survey circulated within the Interasma Scientific Network platform. For each item, five answers were proposed graduated from 'no importance' to 'very high importance' and by a score (A = 2 points; B = 4 points; C = 6 points; D = 8 points; E = 10 points). The final criteria were selected if the median score for the item was ≥7 and > 60% of responses according 'high importance' and 'very high importance'. All selected criteria were validated by the experts. RESULTS: Four criteria were identified: reduce daily systemic corticosteroids dose by ≥50%; decrease the number of asthma exacerbations requiring systemic corticosteroids by ≥50%; have no/minimal side effects; and obtain asthma control according validated questionnaires. The consensual decision was that ≥3 criteria define a good response to biologics. CONCLUSIONS: Specific criteria were defined by an international panel of experts and could be used as tool in clinical practice.

Does asthma-bronchiectasis overlap syndrome (ABOS) really exist?

OBJECTIVE: To analyze the relationship between asthma and bronchiectasis, as well as the necessary conditions that this connection must meet for this group of patients to be considered a special phenotype. DATA SOURCES: We performed a PubMed search using the MeSH terms "asthma" and "bronchiectasis." The literature research was limited to clinical trials, meta-analyses, randomized controlled trials, cohort studies, and systematic reviews, involving adult patients, published until November 30th, 2022. STUDY SELECTIONS: Selected papers were initially evaluated by the Authors, to assess their eligibility in contributing to the statements. RESULTS: The prevalence of bronchiectasis is higher than expected in patients with asthma, particularly in those with more severe disease, and in some patients, between 1.4% and 7% of them, asthma alone could be the cause of bronchiectasis. Both diseases share etiopathogenic mechanisms, such as neutrophilic and eosinophilic inflammation, altered airway microbiota, mucus hypersecretion, allergen sensitization, immune dysfunction, altered microRNA, dysfunctional neutrophilic activity, and variants of the HLA system. Besides that, they also share comorbidities, such as gastroesophageal reflux disease and psychiatric illnesses. The clinical presentation of asthma is very similar to patients with bronchiectasis, which could cause mistakes with diagnoses and delays in being prescribed the correct treatment. The coexistence of asthma and bronchiectasis also poses difficulties for the therapeutic focus. CONCLUSIONS: The evidence available seems to support that the asthma-bronchiectasis phenotype really exists although longitudinal studies which consistently demonstrate that asthma is the cause of bronchiectasis are still lacking.

Trends in prevalence and the effects on hospital outcomes of dementia in patients hospitalized with acute COPD exacerbation.

AIMS: To assess changes in prevalence and the effects on hospital outcomes of dementia among patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD); and to evaluate sex-differences, as well as the impact of COVID-19 pandemic in this relationship. METHODS: We used a nationwide discharge database to select patients admitted with AE-COPD in Spain from 2011 to 2020. We identified those with any type of dementia, vascular dementia (VaD) or Alzheimer's disease (AD). RESULTS: We identified 658,429 hospitalizations with AE-COPD (4.45% had any type of dementia, 0.79% VaD and 1.57% AD). The presence of any type of dementia remained stable from 2011 to 2015, and increased significantly between 2016 and 2020. For VaD, the time trend showed no change until 2020, when a significant increment was found. The probability of AD decreased significantly overtime. The in-hospital mortality (IHM) among patients with any type of dementia remained stable overtime until 2020, when it increased significantly. Older age, higher comorbidity, COVID-19, and use of mechanical ventilation were variables associated to IHM. Women had lower risk of dying in the hospital than men in all subgroups. CONCLUSIONS: After a previous period of stability, the prevalence of any type of dementia increased over the last 5 years of the study, although we identified different trends depending on the specific cause of dementia. The IHM remained stable overtime until 2020, when it increased, probably related to the COVID-19 pandemic. It is remarkable the protective effect of female sex for IHM.

Time Trends in Clinical Characteristics and Hospital Outcomes of Hospitalizations for Lung Transplantation in COPD Patients in Spain from 2016 to 2020-Impact of the COVID-19 Pandemic.

(1) Background: To examine the clinical characteristics and hospital outcomes of hospitalization for lung transplantation in COPD patients in Spain from 2016 to 2020; and to assess if the COVID-19 pandemic has affected the number or the outcomes of lung transplantations in these patients. (2) Methods: We used the Spanish National Hospital Discharge Database to select subjects who had a code for COPD (ICD-10: J44) and had undergone a lung transplantation (ICD-10 codes OBYxxxx). (3) Results: During the study period, 704 lung transplants were performed among COPD patients (single 31.68%, bilateral 68.32%). The absolute number of transplants increased with raising rates of 8%, 14% and 19% annually from 2016 to 2019. However, a marked decrease of -18% was observed from 2019 to year 2020. Overall, 47.44% of the patients suffered at least one complication, being the most frequent lung transplant rejection (24.15%), followed by lung transplant infection (13.35%). The median length of hospital stay (LOHS) was 33 days and the in-hospital-mortality (IHM) was 9.94%. Variables associated with increased risk of mortality were a Comorbidity Charlson Index ≥ 1 (OR 1.82; 95%CI 1.08-3.05) and suffering any complication of the lung transplantation (OR 2.14; 95%CI 1.27-3.6). COPD patients in 2020 had a CCI ≥ 1 in a lower proportion than 2019 patients (29.37 vs. 38.51%; p = 0.015) and less frequently suffered any complications after the lung transplantation (41.26 vs. 54.6%; p = 0.013), no changes in the LOHS or the IHM were detected from 2019 to 2020. (4) Conclusions: Our study showed a constant increase in the number of lung transplantations from 2016 to 2019 in COPD patients, with a drop from 2019 to 2020, probably related to the COVID-19 pandemic. However, no changes in LOHS or IHM were detected over time.

Identification of Asthma Phenotypes in the Spanish MEGA Cohort Study Using Cluster Analysis.

INTRODUCTION: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes. METHODS: We performed a multicentre prospective cohort study, including adult patients with asthma (N=512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. RESULTS: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. CONCLUSION: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps.

Real-Life Effectiveness of Benralizumab, Mepolizumab and Omalizumab in Severe Allergic Asthma Associated with Nasal Polyps.

Biological therapies are available for the treatment of the severe allergic asthma (SAA) with blood eosinophil count ≥ 0.3 × 109/L. Several of them also showed benefits on nasal polyps (NP), one of the most frequent comorbidities of the severe asthma, but comparative studies on their effectiveness in the association SAA-NP are currently lacking. The aim of this study is to compare the effectiveness of benralizumab, mepolizumab and omalizumab in patients with SAA-NP in real-life settings. A retrospective, observational, multicenter real-life study was realized including patients with SAA-NP treated by benralizumab, mepolizumab or omalizumab for 6 months. We analysed the nasal and respiratory symptoms, the number of asthma attacks and salbutamol use/week, acute sinusitis and severe exacerbation rates, the asthma control score, the lung function parameters, the NP endoscopic score, the sinus imaging and the blood eosinophil count 6 months before and after treatment. Seventy-two patients with SAA-NP were included: 16 treated by benralizumab, 21 by mepolizumab and 35 by omalizumab. After 6 months of treatment, almost all studied parameters were improved (except sinus imaging) with a greater effect of omalizumab on the nasal pruritus (p = 0.001) and more benefits of benralizumab on exacerbations rate, asthma attacks per week and lung function (all p < 0.05). Benralizumab and mepolizumab were more effective to improve the NP endoscopic score and the blood eosinophil count (both p < 0.001). All three biological therapies showed effectiveness by improving asthma and nasal outcomes in patients with SAA-NP. Several differences have been found that should be confirmed by larger comparative studies.

Serum exosome inflamma-miRs are surrogate biomarkers for asthma phenotype and severity.

BACKGROUND: Asthma is a heterogeneous disease with several phenotypes, endotypes and severity degrees, in which different T-cell subpopulations are involved. These cells express specific miRNAs (i.e. inflamma-miRs) that can be released to serum in exosomes after activation and be used as biomarkers of underlying inflammation. Thus, we aim to evaluate specific T-cell miRNA signatures in serum exosomes from different subgroups of asthmatic patients. METHODS: Samples from healthy donors (N = 30) and patients (N = 119) with different asthma endotypes (T2high -Atopic/T2high -Non-atopic/T2low ) and severity degrees (mild/MA and moderate-severe/MSA) were used. Demographic, clinical, haematological and biochemical characteristics were collected. Twelve miRNAs previously associated with different Th subsets were preselected and their levels in serum exosome samples were measured using RTqPCR. RESULTS: We detected five miRNAs with high confidence in serum exosomes: miR-16-5p, miR-21-5p, miR-126-3p, miR146a-5p and miR-215-5p. All of them, except miR-16-5p were upregulated in MSA patients compared to MA. A logistic regression model including each of these miRNAs was created to discriminate both conditions, rendering a ROC curve AUC of 0.896 (0.830-0.961). miR-21-5p and miR-126-3p, both involved in Th1/Th2 differentiation, were specifically augmented in T2high -Atopic patients. Of note, all these changes were found in samples collected in autumn. On the contrary, IL-6high patients with MSA, which were more obese, older, with higher neutrophil and basophil counts and TNF levels, displayed a decrease of miR-21-5p, miR-126-3p and miR-146a-5p. CONCLUSION: Immune-related miRNAs, including miR-21-5p, miR-126-3p, miR-146a-5p and miR-215-5p, can be used as clinically relevant non-invasive biomarkers of the phenotype/endotype and severity of asthma.