Biologics have been a key component of severe asthma treatment, and there are currently biologics available that target IgE, IL-5, IL-4/IL-13, and TSLP. Randomized controlled trials have established clinical evidence, but a significant portion of patients with severe asthma in real-life settings would have been excluded from those trials. Therefore, real-world research is necessary, and there is a growing body of information about the long-term efficacy and safety of biologics. Multiple clinical phenotypes of severe asthma exist, and it is crucial to choose patients based on their phenotypes. Blood eosinophil count is an important biomarker for anti-IL-5 therapies, and FeNO and eosinophil counts serve as prediction markers for dupilumab. Reliable markers for predicting response, however, have not yet been fully established for omalizumab. Identification of clinical or biological prediction factors is crucial for the path toward clinical remission because the current treatment goal includes clinical remission, which is defined as a realistic goal for remission off treatment. Additionally, since there are now multiple biologic options and overlaps in eligibility for biologics in clinical practice, the evidence regarding the effectiveness of switching the biologics is crucial. Investigations into the clinical trajectory following the cessation of biologics are another important issue. Recent research on omalizumab, mepolizumab, benralizumab and dupilumab's real-world effectiveness, the prediction factor for the efficacy, and the impact of switching or discontinuation will be reviewed and discussed in this review.

Interleukin (IL)-4 and IL-13, signature type 2 cytokines, exert their actions by binding to two types of receptors sharing the IL-4R α chain (IL-4Rα). Since IL-4 and IL-13 play important and redundant roles in the pathogenesis of allergic diseases, blocking both the IL-4 and IL-13 signals would be a powerful and effective strategy for treating allergic diseases. Dupilumab (Dupixent®) is a fully human monoclonal antibody recognizing IL-4Rα and blocking both the IL-4 and IL-13 signals. Dupilumab was first prescribed for atopic dermatitis (AD) patients and has been widely approved for adult patients with moderate to severe AD since 2018. Dupilumab has since been used for asthma, receiving approval for uncontrolled asthma in 2019. A phase 3 study using dupilumab for chronic rhinosinusitis with nasal polyps (CRSwNP) has been just completed, with positive results. Several clinical trials of dupilumab for other diseases in which type 2 inflammation is dominant are now underway. It is hoped that dupilumab will open the door to a new era for treating allergic patients with AD, asthma, and CRSwNP, and for more patients with type 2 inflammations.

Because the pathophysiology of asthma has diverse characteristics, to manage the disease effectively, it is important for clinicians to distinguish among the clinical phenotypes. Among them, adult-onset asthma, that is, late-onset asthma (LOA), is increasing because of the aging of the population. The phenotype of LOA is largely divided into two types according to the presence or absence of eosinophilic inflammation, T-helper (Th)2- and non–Th2-associated LOA. Especially in Th2 LOA related to rhinosinusitis, as pulmonary function at onset is poor and asthma exacerbations occur frequently, it is important to detect this phenotype in the early phase by using a biomarker of Th2-type inflammation such as fractional exhaled nitric oxide (FE_NO). As non–Th2-LOA is often resistant to corticosteroids, this phenotype often requires another treatment strategy such as macrolide, diet, or smoking cessation. We often struggle with the management of LOA patients due to a lack of evidence; therefore, the elucidation of the mechanism of LOA contributes to increased efficiency of diagnosis and treatment of LOA. Age-related immune system and structural changes are thought to be associated with the pathophysiology of LOA. In the former case, changes in inflammatory cell function such as variations in the innate immune response and acquisition of autoimmunity or upregulation of oxidative stress are thought to be involved in the mechanism. Meanwhile, the latter can also become triggers or exacerbating factors of LOA via enhancement of airway hyperresponsiveness, decline in lung function, increased air trapping, and reduction in chest wall compliance. Therefore, appropriate individualized management in LOA may be possible through precisely assessing the pathophysiology based on age-related functional changes, including the immune and structural system.

It remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function. This was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non-high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated. A FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 ± 37.5 mL/yr) than patients with non-high FeNO (16.7 ± 31.5 mL/yr) (p < 0.0005). The changes in BDR from baseline to the end of the study, in patients who had high or non-high levels of FeNO were -0.8% and 0.1%, respectively (p < 0.01). In a multivariate analysis adjusted by age, body mass index, asthma control, blood eosinophil numbers, and FEV1% of predicted, a FeNO level of ≥40 ppb was independently associated with an accelerated decline in FEV1 (p < 0.05). This study suggests that FeNO is potentially valuable tool for identifying individuals who are at risk of a progressive loss of lung function among patients with controlled asthma.