Alpine altitude climate treatment for severe and uncontrolled asthma: An EAACI position paper.

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro-immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways.

Poor outcome of SARS-CoV-2 infection in patients with severe asthma on biologic therapy.

BACKGROUND: It is unclear whether asthma and asthma medications increase or decrease the risk of severe COVID-19, and this is particularly true for patients with severe asthma receiving biologics. OBJECTIVES: The aim of this study was to assess incidence and disease course of COVID-19 in patients with severe asthma on biologic therapy (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab), as compared with COVID-19 data from the general Dutch population. METHODS: COVID-19 cases were identified through a prospective ongoing survey between March 17 and April 30, 2020 among all severe asthma specialists from 15 hospitals of the Dutch Severe Asthma Registry RAPSODI. From these cases, data was collected on patient characteristics, including co-morbidities, COVID-19 disease progression and asthma exacerbations. Findings were then compared with COVID-19 data from the general Dutch population. RESULTS: Of 634 severe asthma patients who received biologic therapy in RAPSODI, 9 (1.4%) were diagnosed with COVID-19. Seven patients (1.1%) required hospitalization for oxygen therapy, of which 5 were admitted to the intensive care for intubation and mechanical ventilation. One patient died (0.16%). All intubated patients had ≥1 co-morbidities. Odds (95%CI) for COVID-19 related hospitalization and intubations were 14 (6.6-29.5) and 41 (16.9-98.5) times higher, respectively, compared to the Dutch population. One patient presented with an asthma exacerbation. CONCLUSION: Patients with severe asthma using biologic therapy showed to have a more severe course of COVID-19 compared to the general population. This may be due to co-morbidities, the severity of asthmatic airway inflammation, the use of biologics, or a combination of these.

Treatment Eligibility of Real-Life Mepolizumab-Treated Severe Asthma Patients.

BACKGROUND: Patients with severe asthma not meeting the strict trial eligibility criteria for mepolizumab are now routinely treated with this biological in clinical practice, but it remains unclear whether these ineligible patients respond differently to mepolizumab treatment. OBJECTIVE: This study investigated the extent and reasons for trial ineligibility of real-life, mepolizumab-treated patients with severe asthma and compared the characteristics of these patients with trial populations. Subsequently, therapeutic response in ineligible patients was assessed on the basis of oral corticosteroid (OCS) reduction. METHODS: Trial eligibility, population differences, and therapeutic response were assessed using the baseline characteristics of mepolizumab-receiving patients with severe asthma treated in the Amsterdam University Medical Centres and OCS dose at 6 months for OCS-dependent patients extracted from patients' electronic health records. Eligibility criteria and population characteristics from trials investigating mepolizumab were extracted from their original publications. RESULTS: A total of 82.4% of 119 mepolizumab-receiving, real-life patients with severe asthma were ineligible for trial inclusion, wherein 42.9% and 39.5% were excluded on the basis of inclusion and exclusion criteria, respectively. The clinical care population was older, more often male and demonstrating a better lung function under lower OCS maintenance dosages in comparison with trial populations. A total of 50% of 66 ineligible, OCS-dependent mepolizumab-treated patients were able to reduce their maintenance OCS dosage to ≤5 mg prednisone/day. CONCLUSIONS: A large proportion of the real-life, mepolizumab-treated population with severe asthma would be excluded from trial participation, and significant differences in population characteristics exist. Regardless, a large fraction of ineligible patients in clinical care can reduce maintenance OCS dosage under mepolizumab therapy.

Systematic Assessment of Difficult-to-Treat Asthma: Principles and Perspectives.

Difficult-to-treat asthma affects a minority of adults and children with asthma but represents a challenging mix of misdiagnosis, multimorbidity, inadequate self-management, severe airway pathobiology, and treatment complications. Management of these patients extends beyond asthma pharmacotherapy, because multiple other patient-related domains need to be addressed as well. Such complexity can hinder adequate clinical assessment even when performed in specialist practice. Systematic assessment undertaken by specialized multidisciplinary teams brings a broad range of resources to bear on patients with difficult-to-treat asthma. Although the concept of systematic assessment is not new, practices vary considerably and implementation is not universal. Nevertheless, assessment protocols are already in place in several institutions worldwide, and outcomes after such assessments have been highly encouraging. This review discusses the rationale, components, and benefits of systematic assessment, outlining its clinical utility and the available evidence for improved outcomes. It describes a range of service configurations and assessment approaches, drawing examples from severe asthma centers around the world to highlight common essential elements. It also provides a framework for establishing such services and discusses practical considerations for implementation.

Internet-based tapering of oral corticosteroids in severe asthma: a pragmatic randomised controlled trial.

BACKGROUND: In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects. However, the optimal strategy for tapering oral corticosteroids is unknown. OBJECTIVE: To investigate whether an internet-based management tool including home monitoring of symptoms, lung function and fraction of exhaled nitric oxide (FE(NO)) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life. METHODS: In a 6-month pragmatic randomised prospective multicentre study, 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies: according to conventional treatment (n=43) or guided by a novel internet-based monitoring system (internet strategy) (n=52). Primary outcomes were cumulative sparing of prednisone, asthma control and asthma-related quality of life. Secondary outcomes were forced expiratory volume in 1 s (FEV1), exacerbations, hospitalisations and patient's satisfaction with the tapering strategy. RESULTS: Median cumulative sparing of prednisone was 205 (25-75th percentile -221 to 777) mg in the internet strategy group compared with 0 (-497 to 282) mg in the conventional treatment group (p = 0.02). Changes in prednisone dose (mixed effect regression model) from baseline were -4.79 mg/day and +1.59 mg/day, respectively (p < 0.001). Asthma control, asthma-related quality of life, FEV1, exacerbations, hospitalisations and satisfaction with the strategy were not different between groups. CONCLUSIONS: An internet-based management tool including home monitoring of symptoms, lung function and FE(NO) in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life. Clinical trial registration number Clinical trial registered with http://www.trialregister.nl (Netherlands Trial Register number 1146).