Prevalence, T2 Biomarkers, and Cost of Severe Asthma in the Era of Biologics: The BRAVO-1 Study

Background: The last decade has seen new classifications of the pathophysiology of asthma that have changed the treatment options available. Objectives: To update data on the prevalence of T2 asthma, comorbidities, biomarker characterization, and costs of severe asthma in patients aged ≥12 years, taking into account new classifications and treatment options. Methods: Retrospective, observational, nationwide study using a top-down approach. Data were obtained from BIG-PAC®, an electronic medical record database of 1.7 million patients in Spain. The study population comprised patients aged ≥12 years who had received medical care during the period 2016-2017 and been diagnosed with asthma at least 1 year prior to the index date. Patients were followed for 1 year. Results: The prevalence of asthma was 5.5%. Asthma was severe in 3031 of these patients (7.7%), 81.2% of whom presented T2 asthma. Among patients with severe asthma, 64.1% had uncontrolled disease, 31.2% were oral corticosteroid–dependent (37% in the uncontrolled severe asthma group), and only 3.8% were receiving biologics. The most common T2 comorbidities were allergic rhinitis (66.1%), atopic dermatitis (29.1%), and chronic rhinosinusitis with nasal polyps (14.6%). Mortality rates in the total population and uncontrolled severe asthma groups were 4.2% and 5.5%, respectively. The total annual costs per patient with severe asthma were €5890 (uncontrolled) and €2841 (controlled). Conclusions: In the era of biologics, most severe asthma patients present T2 asthma. Despite the availability of new treatments, rates of oral corticosteroid–dependent patients with uncontrolled severe asthma remain high, although biologics continue to be underused. The costs of uncontrolled severe asthma are twice as high as those of controlled severe asthma. (AU)

Introducción: En la última década se han concadenado una serie de clasificaciones de la fisiopatología del asma que han cambiado las opciones de tratamientos disponibles. Objetivos: Actualizar los datos de prevalencia del asma T2, comorbilidades, caracterización de biomarcadores y costes del asma grave en pacientes ≥12 años en esta nueva situación. Métodos: Estudio retrospectivo, observacional y de ámbito nacional con un enfoque descendente. Los datos se obtuvieron de BIG-PAC®, una base de datos de historias clínicas electrónicas de 1,7 millones de pacientes en España. Se incluyeron pacientes ≥12 años que habían recibido atención médica durante el periodo 2016-2017 y que habían sido diagnosticados de asma al menos un año antes de la fecha índice y fueron seguidos durante un año. Resultados: La prevalencia del asma fue del 5,5%. De estos pacientes, 3.031 presentaban asma grave (7,7%), de los cuales el 81,2% presentaba asma T2. Entre los pacientes con asma grave, el 64,1% no estaban controlados, el 31,2% eran dependientes de corticosteroides orales (37% en el grupo de asma grave no controlada) y solo el 3,8% estaban en tratamiento con biológicos. Las comorbilidades T2 más frecuentes fueron la rinitis alérgica (66,1%), la dermatitis atópica (29,1%) y la rinosinusitis crónica con poliposis nasal (14,6%). Las tasas de mortalidad en los grupos de asma grave total y no controlada fueron del 4,2% y del 5,5%, respectivamente. Los costes totales anuales por paciente con asma grave fueron de 5.890 euros (no controlado) y 2.841 euros (controlado). Conclusiones: En la era de los biológicos, la mayoría de los pacientes con asma grave presentan asma T2. A pesar de la disponibilidad de nuevos tratamientos, las tasas de pacientes con asma grave no controlados y dependientes de corticosteroides orales siguen siendo altas, y los biológicos siguen estando infrautilizados. Los costes del asma grave no controlada duplican los del asma grave controlada. (AU)

Respiratory comorbidities in severe asthma: focus on the pediatric age.

INTRODUCTION: Asthma comorbidities are a frequent cause of adverse outcomes, such as poor asthma control, frequent asthma attacks, reduced quality of life, and higher healthcare costs. Comorbidities are well-known treatable traits whose proper management can help achieve optimal asthma control. Although multimorbidity is frequent among asthmatics, comorbidities are still a potential cause of misdiagnosis and under or over treatments, and little is known about their impact on severe pediatric asthma. AREAS COVERED: We provided a comprehensive, 5-year updated review focusing on the main respiratory comorbidities in severe asthma, particularly in epidemiology, pathogenesis, and current and future therapies. EXPERT OPINION: Respiratory comorbidities have unique characteristics in childhood. Their management must be multidisciplinary, age-specific, and integrated. Further longitudinal studies are needed to understand better the mutual interrelation and synergistic effect between asthma and its respiratory comorbidities, the identification of common, treatable risk factors leading to potential asthma prevention, the effectiveness of actual and future target-therapies, and the correlation between long-lasting respiratory comorbidities and poor lung function trajectories.

Prevalence, T2-biomarkers and cost of severe asthma in the era of biologics: The BRAVO-1 study.

BACKGROUND AND OBJECTIVES: The last decade has seen a new era of classifications of asthma pathophysiology which have changed the treatment options available. To update the figures of prevalence of T2 asthma, comorbidities, biomarker characterization and costs of severe asthma in patients≥12-years-old adapted to this new situation. METHODS: Retroprospective, observational, nationwide study using a top-down approach. Data were obtained from the BIG-PAC®, an electronic medical record database of 1.7 million patients in Spain. Patients≥12-years-old who had received medical care during the period 2016-2017 and diagnosed with asthma at least one year prior to the index date were included and followed for one year. RESULTS: Prevalence of asthma was 5.5%. Of these patients, asthma was severe in 3.031 (7.7%), 81.2% of whom presented T2 asthma. Among severe asthma patients, 64·1% were uncontrolled, 31.2% were Oral corticosteroids-dependent (37% in the uncontrolled severe asthma group) and only 3.8% were on biologics. The most common T2 comorbidities were allergic rhinitis (66·1%), atopic dermatitis (29·1%) and chronic rhinositis with nasal polyps (14.6%). Mortality rates in the total and the uncontrolled severe asthma groups were 4.2% and 5.5% respectively. The total annual costs per patient with severe asthma were 5.890€ (uncontrolled) and 2.841€ (controlled). CONCLUSIONS: In the era of biologics, most severe asthma patients present T2 asthma. Despite the availability of new treatments, the rates of uncontrolled and oral corticosteroids-dependent patients with severe asthma remain high, but biologics still underused. The costs of uncontrolled severe asthma are twice as high as those of controlled severe asthma.

Comorbid allergic rhinitis and asthma: important clinical considerations.

INTRODUCTION: The numerous links between allergic rhinitis and asthma have been extensively explored in the last two decades, gaining great concern within the scientific community. These two conditions frequently coexist in the same patient and share numerous pathogenetic and pathophysiological mechanisms. AREAS COVERED: We reviewed major pathophysiological, epidemiological, and clinical links between allergic rhinitis and asthma. We also provided a comprehensive discussion of allergic rhinitis treatment according to current guidelines, with a particular focus on the relevance of allergic rhinitis therapies in patients with comorbid asthma. EXPERT OPINION: We believe that there are several unmet needs for our patients, however, there are promising advances forecasted for the future. Although allergic rhinitis is a recognized risk factor for asthma, a proper asthma detection and prevention plan in allergic rhinitis patients is not available. Allergen immunotherapy (AIT) represents a promising preventive strategy and may deserve an earlier positioning in allergic rhinitis management. A multidisciplinary approach should characterize the journey of patients with respiratory allergies, with an adequate referral to specialized Allergy/Asthma centers. Molecular Allergy Diagnosis may provide support for optimal AIT use. Finally, a possible evolution of biological treatment can be envisaged, mainly if biosimilars decrease such therapies' costs.

Determinants of severe exercise-induced bronchoconstriction in Nigerian children with asthma.

BACKGROUND/PURPOSE: Asthmatics with severe exercise-induced bronchoconstriction (EIB) are at high risk of exacerbations. The purpose of this study was to determine the prevalence, phenotypic, and laboratory determinants of severe EIB in Nigerian children with asthma. METHODS: Children with controlled asthma (n = 101) underwent characterization and free-running exercise bronchoprovocation at a center in Nigeria. Lung function was measured before, then 5, 10, 15, and 30 minutes after 6 to 8 minutes exercise. Severe EIB was defined as ≥50% decrease in forced expired volume in 1 second (FEV1 ) from preexercise. Serum vitamin D and total antioxidant capacity were measured chromatographically. Factors predicting severe EIB were tested by logistic regression. RESULT: The sample was enriched in children with corticosteroid-naïve, mild intermittent asthma (71%). Thirteen percent had no EIB, 22% had severe and 65% nonsevere EIB. Children with severe EIB had higher preexercise FVC (105% vs 96%; P = .03) and FEV1 (98% vs 90%; P = .07), greater obesity (13.6% vs 1.3%; P = .02), more allergic rhinitis (AR) (63.6% vs 35.4%; P = .03), but less exposure to household pets (31.8% vs 72.2%; P = .003) compared to children with nonsevere EIB. Significant determinants (odds ratios/confidence intervals) for severe EIB were obesity = 12.3 (1.2-125.1), AR = 3.18 (1.19-8.52), blood eosinophilia = 1.005 (1.001-1.009), and hypovitaminosis D = 0.87 (0.81-0.93). CONCLUSION: In Nigerian children with asthma, severe EIB is common and associated with remediable comorbidities including type 2 pattern inflammation and vitamin D deficiency.

Evaluation of asthma control in the pharmacy: an Italian cross-sectional study.

SUMMARY: Background. In Western countries a large proportion of asthmatic patients remain uncontrolled, despite the availability of effective drugs. An involvement of pharmacies / pharmacists in asthma management has been suggested in guidelines, since this could provide a relevant support. Objective. The present cross-sectional study aimed at assessing the level of asthma control, by using ACT questionnaire, in the community pharmacies in the County of Verona, North East of Italy. Methods. A call for participation was sent by Verona Pharmacists' Association to all the pharmacies located in the Verona municipality. Patients with a medical prescription and an asthma exemption code were recruited in pharmacies. They were asked to fill the ACT questionnaire and to answer some additional questions on asthma treatment, smoke habits and comorbidities. Results. Thirty-seven community pharmacies recruited 239 patients. According to the ACT score, more than 50% of patients had a controlled asthma but 20% of them were totally uncontrolled and 12% were using oral steroid. Only 2.9% of patients had received an asthma action plan. Asthma was intermittent in 17.6% of patients, mild persistent in 13.8%, moderate persistent in 63.1% and severe in 5.4%. Discordance was observed between the self-perceived asthma control and objective parameters, when available. Of note, in the severe asthma group, most patients had an ACT > 20. Conclusion. This is the first Italian pharmacy-based study on asthma control. A better asthma control was recorded in this study in comparison with other trials, but about 50% of patients were insufficiently controlled. The community pharmacies can play a relevant role in the preliminary assessment of asthma control by using easy and not time consuming tools, such as ACT.

Co-morbidities and cognitive status in a cohort of teenagers with asthma.

BACKGROUND: There is limited data regarding co-morbidities and cognitive status of asthma during childhood and adolescence. The aim of the current study was to explore the presence of co-morbidities and cognitive status in a large cohort of teenagers with asthma. METHODS: The medical records of 314,897 consecutive 17-year-old males, undergoing comprehensive medical and cognitive evaluation prior to recruitment for military service, were reviewed. The prevalence of co-morbidities and a cognitive assessment in subjects with asthma were compared to those without asthma. Both a univariate and multivariate logistic regression analysis were performed. RESULTS: Active asthma was documented in 21,728 (6.9%) subjects: 3.3% were diagnosed with mild intermittent asthma, and 3.6% with persistent asthma. A significant positive correlation between a higher cognitive score and prevalence of asthma was found (P < 0.001), with a 55% increased prevalence of asthma in the subjects with the highest cognitive score compared to those with the lowest score. The following co-morbidities were significantly more prevalent in asthmatics compared to non-asthmatics: chronic rhinitis (35% vs. 5%), atopic dermatitis (2% vs. 0.4%), urticaria (1% vs. 0.3%), anaphylaxis (0.4% vs. 0.1%), chronic sinusitis (0.4% vs. 0.1%), overweight with body mass index (BMI) above 25 kg/m(2) (20% vs. 17%) and underweight with BMI less than 17 kg/m(2) (3.2% vs. 2.8%), irritable bowel syndrome (IBS) (1% vs. 0.5%), and thyroid disorders(0.4% vs. 0.2%). Chronic rhinitis and sinusitis, atopic dermatitis, IBS, and thyroid disorders were all significantly more prevalent in persistent compared to intermittent asthma (P < 0.001). CONCLUSIONS: In adolescence, a higher cognitive status was associated with a higher rate of asthma. Chronic rhinitis was the most prevalent co-morbidity and was found in one third of adolescent asthmatics. Other allergic diseases, chronic sinusitis, over and underweight, IBS, and thyroid disorders were also more prevalent in asthmatics. Pediatr Pulmonol. 2016; 51:901-907. © 2016 Wiley Periodicals, Inc.

Omalizumab management beyond clinical trials: the added value of a network model.

BACKGROUND: Omalizumab is effective and safe in severe allergic asthma. Few data are available about its impact on lung function and on asthma comorbidities, long-term follow-up of treated patients, adherence, non-responders profile, and optimal treatment duration. OBJECTIVE: We aimed at evaluating omalizumab-related clinical outcomes and unmet needs in a real-life setting. METHODS: We created a collaborative network (NEONet - North East Omalizumab Network) involving 9 Allergy and Respiratory referral centres for severe asthma placed in the North-East of Italy. Patients' data were entered into a common study database shared by all the participating physicians. A preliminary retrospective analysis was performed. RESULTS: Patients come from a common well-defined geographical and environmental district providing a homogeneous population sample. A moderate but statistically significant improvement of the FEV1, and an increasing proportion of exacerbations-free patients were observed since the treatment start. These findings were independent of the baseline severity of bronchial obstruction. A positive impact of omalizumab on rhinitis in patients with both asthma and rhinitis was detected. Moreover the efficacy of omalizumab on asthma seemed not to be affected by the baseline severity of rhinitis. CONCLUSION: Our retrospective analysis represents a preliminary report from the NEONet activity. It confirmed omalizumab efficacy and provided some new insights about its impact on lung function and on comorbid rhinitis. The network approach, under a prospective view, allows creating a large uniform database, by means of a standardized shared tool for data collecting, and joining a multidisciplinary expertise.