Phenotype-Guided Asthma Therapy: An Alternative Approach to Guidelines

Abstract

Despite recent advances in therapy, a substantial proportion of asthmatics remain not well controlled. The classical stepwise approach to pharmacological therapy in adult asthma recommends that treatment is progressively stepped up by increasing the inhaled corticosteroid (ICS) dose or by adding another controller medication-to achieve symptom control and reduce the risk of exacerbations, and stepped down after a period of control. In general, asthma guideline recommendations do not reflect that there are significant differences between ICS in terms of potency. Moreover, they do not consider efficacy and safety separately, incorrectly assuming that "low" and "high" dose categories inevitably correspond with low and high risk of systemic effects. Another point of criticism is the fact that guidelines do not take into account the inflammatory profile of the patient, although substantial groups of patients with mild and moderate asthma have little evidence of "T2high" inflammation, and by extension are likely to show a poor response to ICS treatment. On the other hand, the latest version of the Global Initiative for Asthma (GINA) equally recommends regular ICS and ICS/formoterol as needed to prevent exacerbations in step 2 patients, without taking into consideration that the therapeutic objectives (exacerbations, symptoms) may differ between individual patients and that different goals may warrant distinct treatment strategies. In this review, we bring to the table several controversial issues concerning asthma treatment and suggest an alternative proposal that takes into consideration the potential side effects of high ICS doses, the patient's inflammatory profile and the therapeutic goals to be achieved.

"Possibilities of Control of IgE-Associated Respiratory Diseases in Pediatric Practice. Clinical Case"

“…The frequency of adverse events was low. Thus, in the era of personalized medicine and targeted therapy, phenotyping-based management of asthma may be an effective approach to optimize the management of patients with moderate to severe uncontrolled asthma [30][31][32].…”

Recent trends in management of bronchial asthma

“…Many factors should be considered during study design for efficient management of asthma. For example, they need to ensure that their findings have applicability for various settings and patient populations and that they have a patient-centred focus, such as that taken in pragmatic comparative effectiveness studies (de Llano et al, 2021). Nonetheless, although there is an ongoing need for further research in some areas, the evidence base in support of patient-centred and co-management approaches to asthma is strong (Ödling, 2021).…”

Targeting TSLP in Asthma

“… 5 Allergic asthma and asthma with high eosinophil counts are associated with type 2 (T2) inflammation, mediated by the cytokines interleukin (IL)-4, IL-5, and IL-13, as well as by immunoglobulin (Ig)E. These endotypes can account for up to approximately 80% of all patients with asthma. 6–8 The pathophysiology underlying the non-T2 asthma, or T2-low, endotype has not been fully elucidated, and may have biomarker elements that overlap with T2 asthma. Structural changes to the airways involving smooth muscle cell hypertrophy and neutrophil infiltration driven by IL-17 have been reported in the non-T2 endotype.…”

“…Baseline blood eosinophil count, FeNO level, and serum specific IgE status are inflammatory biomarkers used by clinicians to inform treatment decisions. 6 Biomarker assessment can be useful for defining asthma molecular phenotypes, as well as for predicting disease course or response to therapy. In the tezepelumab development program subgroup analyses of patients in clinical trials defined by baseline inflammatory biomarker status demonstrated that tezepelumab treatment responses were comparable across subgroups.…”