Introduction
Asthma is a chronic and heterogeneous airway disease that has traditionally been managed with a reactive, stepwise approach, in which controller medications are added incrementally to achieve control of symptoms and prevent exacerbations [1]. This stepwise treatment strategy often delayed the introduction of advanced therapy until after significant disease progression, resulting in prolonged exposure to high-dose steroid therapies and increased the risk of adverse events [2,3]. With the advent of biologic therapies, the paradigm of asthma management has shifted, and has provoked interest in the concept of asthma remission as a novel and aspirational therapeutic goal [4].
However, the definition of asthma remission remains controversial and inconsistent across studies. An expert international framework first proposed clinical remission (absence of significant symptoms, absence of systemic corticosteroid use, stabilization/optimization of lung function, and agreement between clinician and patient regarding remission) versus complete remission (clinical remission plus normalization of type 2 inflammation markers and the absence of bronchial hyperresponsiveness) either on- or off-treatment [5]. Since then, several international expert groups have suggested modified definitions, incorporating various domains such as exacerbation history, lung function threshold, patient-reported outcomes, reliever use, absenteeism, inhaled corticosteroid (ICS) dose, partial remission, and treatment-related adverse events [6-11]. This lack of consistency poses major challenges for both research and clinical implementation, as the prevalence of remission in real-world registries has varied significantly depending on the components of definitions, the thresholds applied, and even the number of assessment time points [12-14].
Most existing works have been developed in Western settings and may not directly apply to other regions with different health care systems and asthma characteristics. In South Korea, where the use of biologics is rapidly increasing [15], the lack of a standardized definition of remission poses a significant barrier to establish detailed treatment goals and evaluate patient outcomes properly. To address this gap, we conducted a Delphi survey among expert pulmonologists in South Korea under the auspices of the Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) to establish a regionally relevant definition of remission in severe asthma.
Materials and Methods
1. Study design and panel selection
A two-round modified Delphi study [16,17] was conducted to achieve expert consensus on the definition of clinical remission in severe asthma (Figure 1). Twenty-eight expert pulmonologists, all of whom were board-certified specialists in pulmonary medicine, were invited from the KATRD study groups, including asthma study group (n=22), chronic obstructive pulmonary disease study group (n=3), bronchiectasis study group (n=2), and practice guideline committee (n=1). Panelists had extensive clinical experience in managing patients with asthma: 14 had 10-19 years, nine had ≥20 years, and five had <10 years of experience. The study protocol was approved by the Institutional Review Board of Samsung Medical Center (No. SMC 2025-01-109-001) and all 28 panelists agreed to participate and provided informed consent.
2. Development of survey questions
Four core panelists (Shin SH, Choi JY, Oh YM, and Lim SY) prepared the initial draft of the survey questions through a series of discussions and by reviewing previous publications, including consensus statements on clinical remission published by several international expert groups [5-11]. Based on feedback from the Delphi panelists, obtained via email circulation and an online meeting held on January 27, 2025, the first-round questionnaire was finalized with six domains and 27 items (Table 1).
3. Survey rounds 1 and 2
The first two rounds were conducted via online Google Forms (https://docs.google.com/forms), distributed through personalized links by email. Demographic information about the participants was collected, including their age group, gender, and years in the profession. All panelists completed the surveys and the responses were collected anonymously.
The results of the first-round survey were reviewed by the core panelists and subsequently circulated via email to all panelists prior to the second round. Based on the round 1 responses, questionnaire was revised (three questions were added and two were removed) in round 2.
Following the completion of the second round, the results from both rounds were formally discussed during a symposium of the asthma study group held on March 17, 2025. As consensus was not reached regarding the lung function component, the core panelists held several additional discussions, including an online meeting. Subsequently, a focused third-round survey consisting of two revised questions related to lung function was conducted.
4. Statistical analysis
Panelists were asked to respond using a 5-point Likert scale: 1=strongly disagree, 2=disagree, 3=neutral, 4=agree, 5=strongly agree. For each item, we calculated the mean, standard deviation, interquartile range (IQR), level of agreement, and content validity ratio (CVR) [18-20]. Agreement was defined as the proportion of participants who selected either ‘agree’ or ‘strongly agree.’ The CVR was calculated according to Lawshe’s method, based on the ‘strongly agree’ responses from 28 expert panelists [21]. At a significance level of 0.05, the minimum acceptable CVR for 28 panelists is 0.31.
Consensus was based on the second round responses for all survey items. The level of consensus was categorized into three groups: ‘high consensus’ was defined as an IQR ≤1, agreement ≥75%, and CVR ≥0.7; ‘moderate consensus’ as an IQR ≤1, agreement between 50% and 74%, and CVR between 0.5 and 0.69; and ‘low consensus’ as an IQR >1, agreement <50%, and CVR <0.5. These criteria for consensus categorization have been widely adopted in previous Delphi studies for guideline development and were therefore applied in the present study to ensure methodological consistency and comparability [18,19]. These criteria were applied using an ‘AND’ rule, indicating that all predefined thresholds needed to be satisfied for classification. However, as borderline cases are not uncommon in Delphi processes, items that narrowly missed one of the predefined criteria but demonstrated strong agreement across the remaining metrics were reviewed and finalized by the investigators.
All analyses were performed using R statistical software version 3.6.2 (R Foundation for Statistical Computing, Vienna, Austria).
Results
A detailed summary of two rounds of survey response is provided in Table 1 and the Korean consensus on clinical remission in severe asthma is proposed in Table 2.
1. Framework of the clinical remission
Three statements of the framework of the clinical remission in severe asthma reached high consensus among panelists across both rounds of the Delphi survey. Clinical remission in severe asthma should be defined as a composite of symptoms, exacerbations, systemic corticosteroid use, and pulmonary function, assessed while on maintenance treatment. Evaluation requires at least 12 months of treatment and follow-up.
2. Acute exacerbation and maintenance systemic corticosteroids
Both criteria regarding acute exacerbations and maintenance systemic corticosteroid use achieved high consensus among panelists across the two Delphi rounds. Notably, the requirement for no exacerbations, defined as no unplanned outpatient visits, emergency department visits, hospitalizations, or use of systemic corticosteroids (oral or intravenous) due to asthma, received near-unanimous agreement. Additionally, systemic corticosteroids used for maintenance therapy must be completely discontinued.
3. Symptom control
For the symptom domain, both items Q6 and Q7 received high levels of agreement in the first round. To distinguish between the two, an additional item was included in the second round, asking participants to select their preferred approach. A majority (71.4%) indicated that a structured measurement tool should be used. High consensus was reached on defining symptom control using the Asthma Control Test (ACT) score of ≥20. It was also agreed that symptom assessment should be conducted at every visit and measured at least three times over a 12-month period. However, the criterion requiring reliever use of no more than once per month failed to reach consensus.
4. Pulmonary function
In the first round of the survey, none of the seven survey items related to pulmonary function achieved high consensus, including the one asking whether pulmonary function criteria should be included in the definition of clinical remission, and all failed to reach the agreement threshold of 75%. In the second round, panelists reached moderate agreement on two statements: (1) that absolute values or changes in pulmonary function (in mL or %) should be used to define clinical remission, and (2) that clinical remission should be defined as forced expiratory volume in 1 second (FEV1) ≥90% of the patient’s personal best value. However, due to the persistently low agreement rate and consensus level regarding whether pulmonary function should be included in the definition of remission at all, a third-round survey was conducted focusing solely on this point. In this round, 82% of panelists agreed that pulmonary function should be included in the definition of clinical remission. When asked to choose between two options for defining pulmonary function criteria in the third round, the majority (61%) favored clinical judgment based on ‘stabilization and optimization’ over a quantitative threshold, while 39% supported defining remission as achieving ≥90% of the individual's historical best FEV1 value.
5. Maintenance therapy
In both rounds, the item stating that the dose of maintenance ICSs should be reduced to medium or lower levels to define clinical remission failed to reach the 75% agreement threshold and showed a low CVR. Additionally, the item regarding the tapering of background asthma controller medications beside ICS (such as leukotriene receptor antagonists, xanthines, and macrolides) demonstrated particularly low agreement and low consensus, and was therefore excluded from the second-round survey.
6. Complete remission
A high level of consensus was reached on the concept of complete remission, including that normalization of previously elevated type 2 inflammatory markers is essential. Specifically, the agreed thresholds were fractional exhaled nitric oxide (FeNO) <25 ppb and blood eosinophils <300/μL. However, consensus was not reached regarding the inclusion of sputum eosinophil counts or bronchial hyperresponsiveness. The use of chest imaging findings—such as airway remodeling or small airway disease—was excluded from the second round due to very low agreement and consensus in the first round. Finally, when panelists discussed whether treatment intensity should be escalated in patients with clinically controlled asthma but persistently elevated inflammatory markers to achieve complete remission, low consensus was observed.
Discussion
In this modified Delphi survey, Korean asthma specialists reached consensus on a definition of clinical remission in severe asthma (Table 2). The agreed criteria—no acute exacerbations, no systemic steroid use, sustained absence of significant symptoms, and stabilization and optimization of pulmonary function while on maintenance therapy for ≥12 months—generally align with definitions proposed by international expert societies [6-11].
While spontaneous remission has long been described in some children and adults [22,23], the concept of asthma remission as a ‘treat-to-target (TTT) goal’ was proposed in 2020, emphasizing near-total symptom control, optimized or stabilized lung function, shared understanding between patients and physicians, and no systemic steroid use for exacerbation or disease control for at least 1 year [5]. Based on this framework, the Korean panel adopted concept of clinical remission, whereas complete remission requires normalization of physiology and biomarkers, and defined it as remission on treatment. This pragmatic approach reflects the view that remission can be achieved with ongoing controller therapy, even if not permanent cure.
Among proposed definitions of asthma remission [6-11], absence of exacerbation and systemic steroid use are the universally consistent components, also commonly used in the definition of asthma remission in post hoc analyses of biologics trials [24]. Our Delphi panel similarly showed a high level of consensus on these two domains.
Regarding the symptom control, the criteria varied among the proposed consensus. Some definitions require the apparent absence of symptoms [7,9], whereas others recommend structured tools such as ACT [6,8,10], asthma control questionnaire (ACQ) [6,8], or Asthma Impairment and Risk Questionnaire [8]. Through multiple discussions, our panel reached moderate consensus on using an ACT ≥20, which represents partly and well-controlled symptom [25]. ACT is also simple to use and is endorsed tool by the Korean Asthma Guideline [1]. It is worth noting that, based on the panelists’ clinical experience, an ACT score ≥23 is often not achievable even in patients who are doing very well and have had no exacerbations. Consistent with this, adding a symptom criterion reduced remission prevalence from 50.2% to 33.5% in International Severe Asthma Registry (ISAR) data [12], and symptom control showed the lowest achievement rate among remission domains in dupilumab trials [26]. Applying stricter thresholds (e.g., ACQ-6 ≤0.75) also halved remission rates compared with less strict cutoffs (≤1.5) [27]. Therefore, to establish clinical remission as an attainable goal, our society reached a consensus on using an ACT score ≥20 as the criterion for symptom control.
While the United States consensus suggested ICS dose should be low-to-medium or less [8], Korean experts were reluctant to mandate ICS tapering. There have been attempts to reduce background controller medication with biologics therapy [28,29]. Although reducing ICS was feasible in most patients, it led to worsened lung function and increased airway inflammation [29]. Thus, our panel believes ICS reduction is not sufficient or safe for defining remission, which is consistent with most other consensuses. Furthermore, stepping down to as-needed ICS regimen is challenging in the Korean setting, where the proportion of patients prescribed ICS is monitored by the national Asthma Quality Assessment Program [30]. This highlights the need for further research on safely reducing controller therapy during sustained remission.
Pulmonary function was the most debated domain in this study process. Surprisingly, all seven survey items in the first round failed to reach an agreement threshold. As seen in the result of item 12, the agreement rate and CVR regarding whether to include pulmonary function in the definition of clinical remission were notably low. This aligns with the heterogeneous definitions proposed by other societies. While some (e.g., the Spanish Society of Pulmonology and Thoracic Surgery and the Japan Asthma Society) have suggested absolute thresholds, such as FEV1 ≥80% predicted [7,10] or >90% of individual’s historical best [7], other expert groups including the Severe Asthma Network Italy and the joint American College of Allergy, Asthma, and Immunology, American Academy of Allergy, Asthma, and Immunology, and American Thoracic Society workgroup, reported low agreement on the use of absolute values and instead recommended only ‘stabilization and optimization’ [6,8]—a position consistent with our final consensus. This variability may be due to the fact that some patients with asthma exhibit abnormal lung growth, airway remodeling, or comorbid conditions such as chronic obstructive pulmonary disease and other structural lung diseases, which prevent their lung function from reaching normal values [5]. The Japanese society proposed criteria for stable lung function, including FEV1 fluctuation <10%, FEV1 decrease <30 mL/year, peak expiratory flow diurnal fluctuation <10% for these patients [10]. Reflecting this lack of consensus, real-world studies and post hoc analyses of clinical trials adopted various lung function criteria in defining remission, including FEV1 ≥80% predicted or lower limit of normal, FEV1 increase ≥100 mL or decline by no more than 5% or 100 mL [12,13,24,26,27].
Our panel finally endorsed inclusion of pulmonary function but favored pragmatic, clinician-led definition of ‘stabilization and optimization’ rather than a fixed numeric cutoff, although a sizable minority preferred ≥90% historical best FEV1. These results likely stem from the recognition that absolute value may not be attainable in some patients, and that optimal longitudinal stability may better reflect disease control status.
Our survey demonstrated substantial agreement among experts regarding both clinical remission and the more stringent concept of ‘complete remission,’ which requires clinical symptom control accompanied by normalization of underlying type 2 inflammation. The Korean expert panel established specific criteria for this state, including FeNO levels below 25 ppb and blood eosinophil counts below 300/μL. These criteria are central to the ongoing international debate on the TTT strategy, specifically whether therapy should be intensified in clinically stable patients solely to normalize inflammatory biomarkers [27,31]. Some experts argue that targeting subclinical inflammation may prevent long-term airway remodeling; however, critics express concerns regarding biomarker variability, poorly defined target thresholds, and potential overtreatment risks [32]. The TTT approach in asthma faces a critical limitation that differentiates it from other chronic inflammatory conditions: the absence of reliable and consistent biomarkers comparable to glycated hemoglobin in diabetes or blood pressure in hypertension. This creates a clinical challenge where advanced biologic therapies are available for precise treatment but reliable biomarkers to guide their appropriate use remain limited. Future research should focus on developing more stable and clinically practical biomarkers to fully realize the potential of personalized asthma management.
The introduction of biologicof biologic therapies has markedly transformed the prognosis for patients with severe asthma, transforming complete remission from an uncommon, spontaneous phenomenon to an attainable treatment goal. In response to this paradigm shift, clinical remission is increasingly being used as a composite endpoint in major clinical trials and post hoc analyses, generating comprehensive data on the feasibility of achieving this goal. This evidence is essential for establishing realistic expectations for both clinicians and patients. Post hoc analysis of the QUEST and TRAVERSE trials for dupilumab revealed that 35% of patients achieved a 4-component clinical remission (defined as absence of exacerbations, no oral corticosteroid use, ACQ score <1.5, and FEV1 improvement ≥100 mL) after 1 year of treatment [26]. This response was maintained in 70% of these patients at the 2-year follow-up. Similarly, post hoc analysis of the NAVIGATOR and DESTINATION studies of tezepelumab employed a modified definition for ‘on-treatment clinical remission’ (ACQ-6 ≤1.5, stable FEV1 >95% of baseline, no exacerbations, no oral corticosteroids) [33]. Results showed that 33.5% of patients receiving tezepelumab achieved this state during the second year of treatment, compared to 26.7% on placebo. Data from the real-world ISAR registry, which included patients receiving various biologics, demonstrated that 18.7% of patients achieved a strict 4-endpoint remission (no exacerbations, no long-term oral corticosteroids, well-controlled asthma, and FEV1 ≥80% predicted) [12].
The Korean expert panel consensus concerning whether complete remission should constitute a formal treatment objective for patients receiving biologics requires consideration within the context of this robust international evidence. The data consistently show that while the majority of patients experience substantial benefits from biologic therapy, only a subset, ranging from approximately 20% to 40% [34], achieves the stringent criteria of multi-domain complete remission.
This study has several limitations. First, a fundamental limitation of the Delphi methodology is its susceptibility to consensus bias, whereby minority perspectives may be overshadowed by the prevailing views of the majority, potentially narrowing the scope of the final consensus. Second, most of the expert panelists were affiliated with university hospitals located in urban or metropolitan areas in Korea, which may limit the generalizability of the findings to other healthcare settings. Nevertheless, this may be less concerning given that most patients with severe asthma are managed in such tertiary care settings. Third, unlike previous Delphi surveys conducted in other countries [6-11], our panel was predominantly composed of pulmonologists, and experts from other relevant disciplines (such as allergists and pediatricians) were not included. Finally, the perspectives of patients were not incorporated in this study.
This modified Delphi study established a consensus definition of clinical remission in severe asthma among Korean experts. Clinical remission was defined as the composite achievement of no exacerbations, no systemic corticosteroid use, sustained symptom control (ACT ≥20 on at least three occasions over 12 months), and stabilization and optimization of pulmonary function while on maintenance treatment. Complete remission was additionally defined as fulfilling all clinical remission criteria with normalization of type 2 inflammation (blood eosinophils <300/μL and FeNO <25 ppb). These consensus statements provide a pragmatic framework to guide clinical practice and future research on remission as a treatment goal in severe asthma.
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