We undertook a modified Delphi mixed-method consensus-building process, to gain clinician insights on real-world clinical decision-making around SABA use in asthma, with the objective of providing guidance on identification of SABA overuse and appropriate clinical action. US clinicians reported their opinions and experiences concerning real-world SABA use in asthma. Subsequently, a two-step process involving key experts produced 70 consensus statements providing valuable insight into asthma management in the USA relating to SABA use. Importantly, asthma specialists and PCPs participated in this study, thereby ensuring that multiple clinical practice settings treating a variety of patient types were represented.

The Scale of the Challenge: Defining SABA Overuse and Its Link to Poor Outcomes

It is by now well established that SABA overuse is widespread and is linked to poor asthma outcomes [10••, 12, 32•]. The SABINA study investigators reported that the greater the number of SABA canisters prescribed per year, the greater the odds of patients having uncontrolled asthma [10••].

Several asthma guidelines and expert reports define SABA overuse based on a specified numeric threshold of canisters/year or on rates of usage. GINA state that refill rates of ≥3 SABA canisters/year are associated with an increased risk of severe exacerbations, and rates of ≥12 canisters/year are associated with substantially increased risk of death [11]. They advise that SABA overuse necessitates intervention to improve overall control [11]. Baylor University Rules of Two® guidance states that using SABA for ≥2 days/week or for ≥2 episodes/week signals uncontrolled asthma [16, 19], and NIH/NAEPP guidelines comment that using >1 SABA canister for as-needed symptom relief during 1 month (potentially ≥12 canisters/year) indicates SABA overuse [21].

Phase 1 participants and Phase 3 experts had differing opinions on asthma guidelines’ clarity on SABA use. In Phase 1, the NIH/NAEPP guidelines were the most commonly followed overall and the guidelines of choice for allergists, whereas most pulmonologists preferred GINA recommendations. However, many PCPs surveyed did not consult asthma guidelines or expert reports for SABA guidance. Thus, it is not surprising that adherence to asthma guidelines is often poor, particularly in the primary care setting [33•, 34, 35••].

Consistent with the guidelines, however, our experts agreed that use of ≥3 SABA canisters/year was associated with an increased risk of exacerbations and asthma-related death and recommended that refill rates be monitored closely. In the real world, these thresholds are routinely exceeded. In the multinational SABINA III study, 38% of patients were prescribed ≥3 canisters/year, and some were prescribed ≥13 canisters/year [10••]. To et al. reported that in Canada, 5.3% of patients with asthma (≥65 years) were prescribed ≥6 SABA canisters/year [12]. Worth et al. reported that in Germany, 36 to 38% of patients with asthma were prescribed ≥3 canisters/year, with overuse increasing with increasing asthma severity [32•]. One-fifth of the PCPs in our Phase 1 reported routinely providing ≥4 SABA refills in a year. It was noted in Phase 3 of our study that changing practice around SABA prescribing will be important in addressing the problem of overuse, and a key goal will be the provision of additional guidance around the recommended number of SABA refills.

Since a change to the GINA guidelines in 2019, SABA monotherapy is no longer recommended [11, 36]. Instead, to reduce the risk of serious exacerbation, adults and adolescents with moderate to severe asthma should receive daily inhaled corticosteroid (ICS)-containing treatment. Evidence shows, however, that real-world adherence with ICS is poor [37] and most patients are still receiving SABA monotherapy [38].

Perception Versus Reality: Self-Reported SABA Use and Asthma Control

The rate of SABA use tends to be underestimated by both patients and physicians, and the ready availability of SABA over the counter as well as the possibility of obtaining prescription refills for up to 12 inhalers at a time likely exacerbates the problem. An Australian study of electronic medical records and questionnaires from 720 people with asthma found potential SABA overuse in >50% of patients, yet only 28% self-reported overuse [39•].

Furthermore, many patients are unaware of the risks of SABA overuse. In a real-world cross-sectional observational study in Australian community pharmacies, surveying 375 patients, 23% of SABA overusers (≥3 occasions per week) considered SABAs to be “safe to use,” compared with 8% of non-high SABA users [40•]. Evidence also suggests that high SABA users are less likely to self-report good or excellent health [40•, 41]. Indeed, it was found that a higher proportion (43%) of SABA overusers experienced side effects of dry mouth, palpitations, tremors, chest tightness, muscle cramps, or headache compared with 31% of non-high SABA users [3].

In addition, evidence suggests that patients overestimate the degree of control of their asthma, and both patients and clinicians have low expectations for effective asthma management [42,43,44]. Findings from an online survey of ~2500 people in Asia indicated that, of 2198 patients who perceived their asthma to be controlled, 80% had not in fact achieved GINA-defined asthma control. Furthermore, of the 1225 patients with GINA-defined uncontrolled asthma, only 18% correctly perceived that their asthma is not controlled [45]. Similarly, in a cross-sectional observational study of Australian adults, 11.5% of participants had controlled asthma according to GINA guidelines, but a much larger proportion (66.5%) believed their asthma was well controlled [46].

Together, these observations clearly highlight the present unmet need and the importance of addressing SABA overuse and accurately assessing asthma control.

Getting Personal: Individualizing Asthma Management

Data on SABA use has potential to contribute invaluable insights for risk stratification [47].

GINA indicates that a short-term increase in use of as-needed SABA is associated with increased likelihood of severe exacerbation in the subsequent days or weeks [11]. However, no indicative number of SABA episodes/week likely constituting an impending or ongoing asthma exacerbation is provided. Nor is it made clear how a patient’s baseline level of usage (from which the increase should be observed) should be determined. Clarity on these points is needed to support individualized asthma management.

In Phase 1 of our process, over half of the participants agreed that increased SABA usage indicated loss of asthma control. Our expert consensus reflects current SABA medication guidance and literature suggesting that patients using SABA on ≥2 days/week or for ≥2 SABA episodes/week have inadequately controlled asthma [16, 19]. Importantly, our Delphi consensus indicates that 2 to 3 (and, more strongly, ≥5) SABA episodes/week may be a more appropriate signal for an impending or ongoing exacerbation. It is important to note that the experts concurred that patients who exceeded their normal SABA use by 50 to 100% from their baseline level of usage are at a higher risk of an impending or ongoing exacerbation.

Weekly SABA use thresholds—both absolute and dynamic (changes from baseline behavior)—could help signal a patient’s increased risk of an impending or ongoing exacerbation, which requires prompt medical attention. Inclusion of such thresholds should be considered in future asthma guidelines.

While understanding weekly SABA use is important, SABA use history is also a useful indicator for clinicians to monitor reliever treatment. Most Phase 1 clinicians indicated that they obtain information about prior reliever use at every patient visit; almost all allergists and pulmonologists agreed with collecting SABA history in this way, whereas just over half of PCPs followed this practice. It was noted in Phase 3 that the need for prescription refills can present opportunity for discussions around a patient’s current level of asthma control. Improving guideline adherence in this setting, and so providing patients with access to best-practice management regardless of clinical setting and disease severity, is a key unmet need.

The Unvarnished Truth: Accurately Monitoring SABA Use

A key question naturally arising from recognition of the value of individualized insights on SABA use regards the most effective way to accurately monitor actual use. Phase 3 participants acknowledged that patients need access to SABA, but questioned how this should be monitored. Most asthma guidelines consulted by Phase 1 participants cover general management [11, 16, 18,19,20,21]. While current asthma treatment guidelines emphasize monitoring SABA overuse, most lack detailed guidance on how to do this effectively and do not include specific recommendations for clinical action when a patient has already intensified maintenance therapy [11, 16, 18,19,20,21].

In Phase 1 of our process, patient history/recall was the most common way to assess SABA use (89% of clinicians). However, patient recall is subjective and can be inaccurate [22•]. Indeed, clinicians recognized the need to use other information, as they recognize that patient recall is only generally accurate (28% of clinicians) or is variable (49% of clinicians). Pharmacy refills were the second most common method to monitor SABA use (58% of clinicians), but refill data are inaccurate as they do not capture actual SABA use [48] and also do not lend themselves to acute intervention. Obtaining refill histories can also be difficult and time-consuming, particularly if multiple pharmacies need to be contacted. Moreover, availability of over-the-counter SABAs [3, 10••, 25] could be deleterious as accurate purchasing information would not be available.

The present expert panel favored using digital health tools where possible, as they provide objective, accurate, and reliable reliever usage and maintenance adherence data [22•, 48,49,50, 51•]. Such devices have the potential to support improvements in adherence and asthma control [51•, 52••], though other factors such as poor technique leading to unintentional nonadherence [53] and cost-related underuse [54] may also need to be addressed. In particular, as we aspire achievement of control/remission on therapy [55], the availability of objective insights on SABA use has potential to be of considerable clinical benefit. Phase 3 participants acknowledged the value of information about how SABA is used and its effect on patient’s level of asthma control.

While digital platforms for asthma management may not be needed by all patients (e.g., those with optimally controlled asthma), certain subpopulations with inadequately controlled asthma could benefit from their use; further research is needed to aid in guiding optimal use/patient selection. Asthma guidelines have yet to recommend digital tools in asthma, although this is a likely topic for future GINA updates [11].

Digital health tools would enable collection of SABA usage data at the granularity needed to enable clinicians to manage patients acutely in a more proactive and personalized way. Indeed, a recent study in adults with poorly controlled asthma, treated with an electronic multidose dry powder inhaler with integrated sensors, demonstrated that data collected by the digital inhaler could be used to develop a machine learning model capable of predicting impending exacerbations [56••].

Patients are increasingly embracing digital technology, many now having access to their own health information via apps and smart watches, for example [57]. Furthermore, they are starting to engage with these data and adjusting their own behavior as a result. There may come a time, in the not-too-distant future, where digital technology could be used to alert patients to changes in their asthma or patterns of inhaler use and enable them, and their physicians, to take the most appropriate action.

Knowledge Is Power: Optimizing Clinical Decision-Making

The combination of objective data on patients’ real SABA use and expert guidance, such as that provided by our panel, has potential to substantially enhance clinical decision-making and so reduce exacerbations and improve patient outcomes.

We explored how clinicians currently respond to observed high SABA use. In Phase 1 of our process, the most frequently mentioned actions were medication change (76% of clinicians), inhaler technique training (60%), additional information gathering (60%), and asthma education refreshers (56%), whereas specialty referral was only mentioned by 22% of clinicians. The expert panel agreed that multiple interrelated clinical actions, including inhaler technique training, medication change, additional information gathering via phone or portal (specifically exploring triggers and comorbidities), and an asthma education refresher, should be considered in response to concerning patterns or levels of SABA use. Importantly, the experts emphasized that—while absolute thresholds might be used to identify patients at immediate risk of worsening—clinical asthma management should ideally be based on individual SABA use data (i.e., increase from baseline, usage patterns over time). This necessitates accurate determination of each patient’s typical usage. Information on patients’ day-to-day SABA usage patterns could contribute to more individualized treatment plans. However, this cannot be gleaned simply from claims data stating the number of refills per year. Some patients may have “spikes” of exacerbation-associated SABA use, interspersed between periods of no SABA use. Others with chronically poor asthma control may be consistently overusing SABA on almost a daily basis.

Thus, individual clinical judgment becomes essential, which is more-or-less reliant on the clinician’s experience and confidence in the specific scenario. The quality of objective information available to clinicians also strongly affects their ability to make rational decisions regarding treatment. The 70 consensus statements agreed upon in Phase 3 provide actionable thresholds for asthma clinical practice that could be adopted by clinicians to better monitor SABA usage and prescriptions on a patient-by-patient basis. Figure 3 provides a putative framework for clinical application of these thresholds. Together with more granular data from digital health tools, these consensus statements may support future updates to guidelines or clarify existing opinions around asthma management for SABA use.

Fig. 3

Putative framework for clinical application of consensus statements agreed in Phase 3. *ACT/ACQ/patient history are reliant on patient recall and may give inaccurate data. Pharmacy refill data provides a quantitative insight but does not provide information on usage pattern. Digital heath tools can provide an objective real-time dynamic insight into true SABA use. ACQ, Asthma Control Questionnaire; ACT, Asthma Control Test; HCRU, healthcare resource utilization; ICU, intensive care unit; QoL, quality of life; SABA, short-acting beta2 agonist

Limitations

The Delphi method is widely used in healthcare settings [58, 59] including asthma [60••, 61•]. However, this method has several well-recognized limitations. The present results are qualitative and should be considered as informative guidance only, which requires further objective evidence.

The Delphi process that we undertook was, by design, limited in its scope and sharply focused on SABA usage data and the information that these can provide about a patient’s disease status and treatment needs. Of note, exploration of individual patient factors underlying symptomatic disease was outside of the scope of this process.

Patterns of utilization of multiple inhalers by patients remain poorly understood. Although possessing several SABA inhalers may demonstrate overuse in some patients, others may prefer having several devices to ensure ready access at home, office, car, etc. Such usage should be understood to differentiate problematic versus cautious inhaler ownership.