Asthma is a syndrome characterized by airway inflammation, reversible airway obstruction,
and airway hyper-responsiveness. As a result, patients present clinically with recurrent
wheezing, shortness of breath, cough, and chest tightness. Asthma is a leading cause of
morbidity, with a global prevalence of approximately 300 million; it is estimated that
the number of people with asthma may increase to 400 to 450 million people worldwide by
2025.
Despite the availability of multiple therapeutic options, 5-10% of asthmatic patients
present with severe disease that is associated with substantial morbidity. Severe asthma
patient, as defined by the Global Initiative for Asthma (GINA) 2022 guidelines, is the
asthmatic patient that is uncontrolled despite adherence with maximal optimized therapy
and treatment of contributing factors, or worsens with high dose treatment is stepped
down. They stated that severe asthmatic patient requires therapeutic options for steps
4-5 to prevent them from becoming "uncontrolled" or remaining "uncontrolled" despite
therapy Severe asthma is recognized as a major unmet need that poses a great burden on
the healthcare system. While accounting for only a small proportion of the total
asthmatic population, severe asthma-related costs are 1.7 to 4-fold higher than those
observed in the mild-persistent asthma population and may represent up to 50% of the
total asthma-associated healthcare costs. Severe asthma also has a high personal and
social impact as patients with severe asthma typically present with greater levels of
anxiety and depression, with measures of quality of life (QoL) being far worse in severe
asthma than in mild or moderate asthma.
Most of asthma patients experiencing frequent exacerbations and significant limitations
on their lung function and quality of life. Oral corticosteroid (OCS) has been a mainstay
of severe asthma management for almost 60 years, helping patients manage their
exacerbations. Clinical guidelines, including the Australian Asthma Handbook and the GINA
guidelines, recommend adding low-dose maintenance OCS when all other conventional
treatments have failed to control asthma, when adequate inhaler technique and adherence
have been attained, and when other contributing factors have been ruled out.
Additionally, short bursts of OCS (i.e. 5-10 days) are recommended to manage severe
asthma exacerbations. OCS is currently used by more than 13.5 million people with severe
asthma worldwide to manage exacerbations and avoid hospitalization. For patients, this
cumulative, prolonged use of OCS is linked to disabling adverse effects that might
further impair their quality of life. Serious health hazards, such as diabetes,
osteoporosis, and heart disease, can result from long-term OCS usage. Limited published
studies suggest OCS usage varies across countries. Also, recent registry data show that
at least 25-60% of patients with severe asthma in affluent nations may at some point be
prescribed OCS.
Severe asthma is not considered a single disease; instead, it is divided into several
phenotypes, owing to the variety of inflammatory, clinical, and functional
characteristics that can manifest on the patients. One of these proposed and most studied
phenotypes is severe eosinophilic asthma. Eosinophils have long been recognized as a key
element in asthmatic inflammation. This persistent airway inflammation is partly
responsible for the high frequency of exacerbations seen in severe asthma. Patients with
severe asthma accompanied by a high concentration of eosinophils require greater
healthcare resource utilization, greater disease management costs, and a much more
impaired QoL than those who do not present with raised eosinophilia.
Despite its impact, severe eosinophilic asthma is yet to be clearly defined. Peripheral
blood eosinophil counts as high as 400 cells/mm3 have been linked to increased asthma
exacerbations. Nevertheless, adult-onset asthma patients with blood eosinophil counts
above a lower threshold (≥300 cells/mm3) already present with a distinct phenotype of
severe asthma with frequent exacerbations and poor prognosis. Additionally, studies of
anti-eosinophilic therapies indicate patients with blood eosinophil levels ≥300 cells/mm3
already benefit from the targeted treatment.
Although eosinophilic inflammation of the airways has been classically associated with
allergic asthma (i.e., asthma that is triggered by an allergen), there is evidence that
eosinophilia is present in the airways of severe asthmatic patients without the allergic
disease. Contrary to early-onset eosinophilic asthma, adult-onset eosinophilic asthma
frequently develops in the absence of allergen-dependent activation of Th2 lymphocytes,
which suggests a mechanism of eosinophilic inflammation other than allergy. Late-onset
asthmatics have also been found to present a lower rate of skin prick sensitization,
indicating that eosinophilic airway inflammation and atopy are not fully concordant. Of
note, asthma patients may present with atopy (i.e., elevated immunoglobulin E [IgE]
levels), but no sensitization to common inhaled allergens and asthma without allergic
etiology.
The number of targeted treatments for asthma management has been growing in recent years.
Still, the heterogeneity of clinical presentations, treatment responses, and inflammatory
processes involved represent an added challenge for health care professionals.