Study protocol: a 52-week, multicentre, observational, prospective study on the use of a smart platform connected to a single-inhaler triple therapy (ICS/LABA/LAMA) to evaluate effectiveness on treatment adherence and inhaler technique in patients with poorly controlled asthma

Abstract

Background

Good adherence to controller medication and correct inhaler technique is essential for effective asthma management. However, many patients struggle with these aspects, leading to poor symptom control and a higher risk of exacerbations. This study (SiASMARTer) aims to evaluate the impact of the SiA®SMARTer platform - a digital smart platform consisting of an app and an add-on module connected to a pressurized metered-dose inhaler delivering triple therapy (ICS/LABA/LAMA) - on improving adherence and inhaler technique in patients with poorly managed inflammation in asthma (defined as fractional exhaled nitric oxide [FeNO] > 25 ppb).

Methods

This observational study will enrol 60 patients from two sites in Denmark. At baseline, participants will begin using the SiA®SMARTer platform, which includes, on the patient side a smart inhaler cap, a patient app and on the physician side a dashboard. The primary endpoint, with follow-up at 12 and 52 weeks, is the platform’s effect on FeNO levels. Secondary endpoints will include changes from baseline in treatment adherence and inhaler technique scores, Asthma Control Test scores, Mini Asthma Quality of Life Questionnaire scores, lung function parameters, FeNO category distribution, exacerbation rates, short-acting β2-agonist use, and patient-reported satisfaction with the SiA®SMARTer platform. Data on adherence and inhaler technique will be continuously collected through the SiA^®SMARTer platform, and adverse events will be monitored.

Discussion

This study may offer valuable insights into whether a digital platform can enhance adherence and inhaler technique, and by that improve asthma control. Additionally, it may help discriminate patients requiring therapy escalation from those with poor control due to non-adherence or incorrect inhaler technique.

Trial registration

ClinicalTrials.gov identifier: NCT06908421, Registration date: 2025-03-26.

Background

Asthma affects approximately 300 million people worldwide, contributing to significant disability and premature mortality [1–4]. It is responsible for an estimated 180,000 to 250,000 potentially preventable deaths annually, with considerable variation across regions, age classes, and economic backgrounds [5, 6]. Beyond its health impact, asthma imposes a substantial burden on patients’ Quality of Life (QoL), society, healthcare systems, and economies worldwide, generating both direct costs - such as hospitalizations, emergency room visits, diagnostic tests, and medications - and indirect costs, including lost productivity, missed workdays, and reduced economic output [1, 2, 5, 6].

As the primary objectives of asthma treatment are to achieve sustained symptom control, prevent exacerbations, and minimize airway damage to avoid loss of lung function, management strategies involve the daily use of a controller medication - most commonly inhaled corticosteroids (ICS) - while short-acting bronchodilators are only used for as-needed relief [1, 2, 7]. Bronchodilators, such as β2-agonists, are classified into short-acting β2-agonists (SABAs), which provide rapid symptom relief during acute episodes, and long-acting β2-agonists (LABAs), which are prescribed for individuals with frequent or persistent symptoms. LABA is used as add-on to ICS to enhance symptom control and reduce the risk of exacerbations [1, 2, 8]. For difficult-to-treat asthma that remains uncontrolled despite moderate dose ICS/LABA therapy, increased ICS dose, additional treatments such as long-acting muscarinic antagonists (LAMAs) or leukotriene receptor antagonists (LTRAs) may be incorporated into the regimen [1, 2, 8–12]. In patients with type 2 biomarker inflammation who continue to experience severe symptoms despite all these treatments, escalation to biologic therapies - including anti-IgE, anti-IL-5, anti-IL-5R, anti-IL-4Rα, and anti-TSLP - is recommended [1, 2, 8–11]. Use of systemic corticosteroids should be minimized and preferably only be used for acute exacerbations due to their potential long-term side effects [1, 2, 8, 10, 11].

The GINA guidelines recommend assessing adherence to therapy and inhaler technique before deciding to escalate treatment at each treatment step, as both are essential for achieving optimal therapeutic outcomes [1, 10]. Nevertheless, a recent global study, based on a questionary asking subjects if specific inhaled medication was used “as needed”, “in short courses”, or “every day” found that approximately 45% to 60% of individuals with severe asthma did not consistently use ICS as controller medications but instead took them “as-needed” [13]. In contrast, SABAs were the most commonly used medications, with usage rates up to 85% [13]. Additionally, many patients struggle with proper inhaler technique, leading to inadequate medication delivery and poor disease control [14–17]. Factors such as misunderstanding and/or lack of education on inhaler handling, dexterity issues and hand-breath coordination difficulties further impair effective inhaler use [14, 17].

To improve treatment adherence and patient education on correct inhaler techniques, various smart inhalers and add-on modules have been developed [15, 18]. However, their widespread adoption is limited by usability challenges and high costs, which many patients are unwilling to incur [18]. To overcome the limitations of existing smart devices, a cost-effective, reusable smart inhaler cap connected to both a mobile application for patients and a dashboard for physicians has recently been developed (SiA^® platform, Briota ApS, Copenhagen, Denmark), referred to as the SiA®SMARTer platform in the present study. This study protocol is thus envisioned to evaluate the effectiveness of the SiA®SMARTer platform in improving adherence to controller medication and inhaler technique in patients with poorly controlled asthma. In addition to supporting treatment adherence and inhaler technique, the SiA®SMARTer platform may enable a more precise identification of patients who require treatment escalation. By differentiating persistently high FeNO levels due to therapy-resistant type 2 inflammation from those caused by non-adherence or incorrect inhaler use, the platform could support more targeted and appropriate treatment decisions, including the timely initiation of biologics where necessary.

Methods

Study design and aim

This observational, single-arm, open-label study will be conducted at two sites in Denmark to assess the effectiveness of the SiA®SMARTer platform implementation over a 52-week period in improving adherence to controller medication and inhaler technique in patients with poorly controlled asthma. Enrolled patients are receiving single-inhaler triple therapy (ICS/LABA/LAMA) through pressurized metered-dose inhalers (pMDI); Trimbow 87/5/9 (BDP/FF/G) at baseline or Trimbow 172/5/9 (BDP/FF/G), as a possible switch after enrolment during the study, as judged by the physicians; Chiesi Farmaceutici, Parma, Italy.

Furthermore, the study seeks to assess if the SiA®SMARTer platform can effectively discriminate between uncontrolled asthma caused by an inadequate therapeutic strategy – therefore, necessitating treatment escalation, possible add-on controllers or biologic treatments – and that resulting from poor adherence and/or incorrect inhaler technique.

Study product

The SiA®SMARTer platform consists of three main components designed to enhance treatment adherence and inhaler technique through real-time feedback, data analysis, and personalized support.

The first component is the Smart Inhaler Cap - RespiPRO™ (hereinafter RespiPRO™), an innovative cap that collects inhalation data for processing and display in a dedicated mobile application. It is reusable and equipped with a replaceable battery to ensure long-term usability.

The second component is the SiA^® Mobile Application (hereinafter app), attached to the pMDI, which includes several key features to support patients in adherence and good inhaler technique. It provides an Adherence Score and an Inhaler Technique Score, accessible through a user-friendly dashboard. The app includes personalized reminders, and smart notifications to promote proper medication use. Additionally, it features an Inhaler Technique Analytics Dashboard, which provides personalized tips to help patients improve their inhaler technique, and easily accessible inhaler technique instructions and videos.

The third component is the SiA^® Dashboard for health care professionals allowing monitoring patient adherence and inhaler technique through the integrated Adherence Analytics Dashboard and an Inhaler Technique Dashboard.

Study population

Patients will be enrolled consecutively during routine visits if they meet the following inclusion criteria: (i) aged 18 years or older, (ii) objectively verified asthma diagnosis according to GINA guidelines [1], (iii) poorly controlled asthma, indicated by FeNO levels > 25 ppb, (iv) receiving single-inhaler triple therapy (SITT) through pMDI with or without a spacer (Trimbow 87/5/9; Chiesi Farmaceutici, Parma, Italy) for more than four weeks prior to enrolment and prescribed with rescue medication (SABA) also as pMDI, (v) literate in Danish, (vi) owning a personal Android or iOS smartphone with an internet connection, (vii) comfortable using a smartphone and Bluetooth-enabled digital devices, (viii) willing to participate in the study, able to understand the written patient information, and providing written informed consent.

The exclusion criteria will include: (i) participation in a clinical trial within four weeks prior to enrolment or planned participation in another clinical trial during the observational period, (ii) use of systemic corticosteroids as maintenance (controller) medication or biologic treatments (such as monoclonal antibodies), (iii) concomitant diagnosis of chronic obstructive pulmonary disease (COPD), (iv) current or previous history of lung cancer, (v) respiratory tract infection or asthma exacerbation within four weeks prior to enrolment, (vi) administration of systemic corticosteroids within four weeks before enrolment.

Visits and data collection

Patients will be consecutively enrolled during a 12-month period at routine visits if deemed eligible by the physician, after receiving detailed study information and providing signed informed consent. Following enrolment, patients will attend a baseline visit (V1), initiating the use of SiA®SMARTer platform. This will be followed by two scheduled follow-up visits: the first at 12 weeks (V2) and the second at 52 weeks (V3), which marks the study’s conclusion. Patients flow is illustrated in Fig. 1.

Fig. 1.

Patient flow chart

At the baseline visit (V1), demographic and anthropometric characteristics, as well as the presence of concomitant diseases - such as rhinitis, chronic rhinosinusitis (with or without nasal polyps), and allergies – will be documented. Data on current treatments will also be collected, including the initiation date of SITT with pMDI and any other prescribed asthma medications. Additionally, information on asthma history, including the date and method of diagnosis, will be recorded. Retrospective data from the past 12 months will also be gathered on the number of moderate and severe exacerbations (as defined by the American Thoracic Society/European Respiratory Society statement [4]), the use of systemic corticosteroids, and asthma-related healthcare utilization, including emergency room visits and hospitalizations. The use of a spacer (yes/no) and adherence to spacer in the seven days prior to enrolment will be gathered through a questionnaire, along with details on the use of rescue medication during the same period. Smoking status will also be documented, and number of pack-years for ever smokers.

Baseline clinical assessments will include spirometry measurements, including FEV1 (forced expiratory volume in one second), FEV1%-predicted, PEF (peak expiratory flow), FVC (forced vital capacity), and FEF25-75 (forced expiratory flow at 25–75% of FVC). Biological tests will include FeNO and, optionally, blood eosinophil counts. The highest recorded FeNO and eosinophil levels in the past 12 months will also be recorded.

To evaluate asthma control and QoL, patients will complete two validated questionnaires: the Asthma Control Test (ACT) [19, 20], which helps identify poorly controlled asthma, and the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) [21], a 15-item self-administered questionnaire assessing asthma-specific QoL.

Patients will receive two RespiPRO™ caps, one attached to their SITT pMDI and the other to their rescue medication inhaler (SABA pMDI). They will also be guided through the process of downloading the app onto their mobile device. Within one to five days after the baseline visit, patients will be required to record a video through the app demonstrating all steps of an inhalation before receiving any inhaler technique training through the app. They will then be able to receive inhaler technique training through written instructions and videos available in the app.

Some data will be reassessed at both follow-up visits (V2 and V3), including current treatments, spacer use and adherence in the seven days prior to the visit, rescue medication use during the same period, FeNO levels, optionally blood eosinophils count, spirometry, and the ACT and Mini-AQLQ questionnaires.

At V3 only, further information from the past 12 months will be collected, including the number of moderate and severe asthma exacerbations, asthma-related healthcare visits, and the use of systemic corticosteroids. Furthermore, patient satisfaction with the SiA®SMARTer platform will be evaluated using a dedicated questionnaire developed by Briota in collaboration with the principal investigators. One to five days before V3, patients will be asked to record another inhalation video using the app, demonstrating all steps of an inhalation.

Throughout the 52-week observational period, data on treatment adherence and inhaler technique will continuously be collected via the SiA®SMARTer platform (further details are provided in subsection 2.4.1). Adverse events will be recorded throughout the entire duration of the study. Data collections and clinicals assessments performed at each visit are summarized in Fig. 2.

Fig. 2.

Data collection and clinical assessment according to visits. Abbreviations: FeNO, fractional exhaled nitric oxide; ACT, Asthma Control Test; Mini-AQLQ, Mini Asthma Quality of Life Questionnaire

Data on treatment adherence and inhaler technique via the SiA®SMARTer platform

Inhaler adherence will be continuously monitored through the RespiPRO™ smart cap. A total daily adherence score, defined based on the criteria outlined in Table 1, is calculated according to the prescribed dosage of two puffs in the morning and two puffs in the evening.

Table 1.

Inhaler adherence score calculation

Participant action	Morning score	Evening score	Total daily adherence score*
Takes 2 puffs (as prescribed)	1.0	1.0	2.0
Takes 1 puff	0.5	0.5	1.0
Takes 0 puffs	0.0	0.0	< 1.0
Takes 3 puffs	0.5	0.5	1.0
Takes 4 or more puffs	0.0	0.0	< 1.0

*Total daily adherence score classification: 2.0 = Optimal adherence; 1.0–1.5 = Suboptimal adherence; <1.0 = Poor adherence

Similarly, inhaler technique will be assessed using the video recordings conducted 1–5 days after V1 and 1–5 days before V3 or via automated analysis performed by RespiPRO™. The scoring system used to evaluate the accuracy of each step in the inhalation process is outlined in Table 2 and is based on the “Essential Inhalation Maneuver Steps” elsewhere [16].

Table 2.

Inhaler technique score calculation

Step of inhalation	Correct execution (video analysis)	Correct execution (RespiPRO™)	Incorrect execution
1. Remove the protective cap	1	(1)	0
2. Breathe out slowly and deeply	1	(1)	0
3. Hold the inhaler upright, place the mouthpiece between front teeth	1	1	0
4. Whilst breathing in slowly and deeply through the mouth, press down firmly on the pressurised container to release one puff	1	1	0
5. Hold breath for 5–10 s or as long as it is comfortable, remove the inhaler, and breathe out slowly	1	1	0
Inhaler technique score*	5	5	0

*Total inhaler technique score classification: 5 = Optimal technique; 4 = Poor technique with one critical error; 3 = Poor technique with two critical errors; ≤2 = Poor technique with three or more critical errors. The RespiPRO™ cannot monitor step 1 and 2, thus are these by default set to 1, hence the minimum inhaler technique scores achievable from RespiPRO™ is 2

Objectives and endpoints

The primary objective of the study is to evaluate the impact of the SiA®SMARTer platform on reducing the type 2 inflammation biomarker FeNO. Accordingly, the primary endpoint is the change in FeNO levels from baseline at weeks 12 and 52, with a clinically significant reduction defined as at least 20% from baseline.

Regarding the secondary objectives, these include evaluating the impact of SiA®SMARTer platform use on: (i) adherence to controller medication and inhaler technique, (ii) asthma control, (iii) health-related QoL, (iv) lung function, (v) changes in FeNO category (normal, intermediate, or high) [22], (vi) annualized exacerbation rates, (vii) use of rescue medication (SABA), and (viii) patient satisfaction with the use of the SiA®SMARTer platform in combination with a pMDI. Therefore, the secondary endpoints will include changes from baseline at weeks 12 and 52 of: (i) inhaler adherence and technique scores, (ii) ACT scores, (iii) mini-AQLQ scores, (iv) lung function parameters (FEV1, FEV1%-predicted, FEV1/FVC ratio, FEF25-75), (v) FeNO category distribution, (vi) annualized exacerbation rates (week 52 only), (vii) SABA use, and (viii) patient satisfaction score. Study’s objectives and endpoints are outlined in Table 3.

Table 3.

Study objectives and endpoints

Objectives	Endpoints
Primary
To evaluate the impact of the SiA®SMARTer platform on the type 2 inflammation biomarker FeNO	Change in FeNO levels from baseline at weeks 12 and 52
Secondary
To evaluate the impact of the SiA®SMARTer platform on adherence to SITT and inhaler technique	Change in inhaler adherence and technique scores from baseline at weeks 12 and 52
To evaluate the impact of the SiA®SMARTer platform on asthma control	Change in ACT scores from baseline at weeks 12 and 52
To evaluate the impact of the SiA®SMARTer platform on health-related quality of life	Change in mini-AQLQ scores from baseline at weeks 12 and 52
To evaluate the impact of the SiA®SMARTer platform on lung function	Change in lung function parameters (change in mean FEV1, FEV1%-predicted, FEV1/FVC ratio, FEF25-75) from baseline at weeks 12 and 52
To evaluate the impact of the SiA®SMARTer platform on shifts in FeNO category	Change in FeNO category (normal, intermediate, high) from baseline at weeks 12 and 52
To evaluate the impact of the SiA®SMARTer platform on annualized exacerbations rates	Change in annualized exacerbation rates from baseline at week 52
To evaluate the impact of the SiA®SMARTer platform on the use of rescue medication (SABA)	Change in SABA use from baseline (first 7 days) at weeks 12 and 52
To evaluate patient satisfaction with the of the SiA®SMARTer platform	Satisfaction score at week 52 assessed using a customized questionnaire

Abbreviations: FeNO fractional exhaled nitric oxide, SITT single-inhaler triple therapy, ACT Asthma Control Test, Mini-AQLQ Mini Asthma Quality of Life Questionnaire, FEV1 forced expiratory volume in one second, FVC forced vital capacity, FEF25-75 forced expiratory flow at 25–75% of FVC, SABA Short-acting beta-agonist

As an exploratory objective, the study will evaluate the impact of the SiA®SMARTer platform on morbidity status. The dedicated endpoint will analyse changes in healthcare utilization costs, including emergency room visits, hospital visits, and hospitalizations, comparing the 52 weeks prior to enrolment with the 52-week study period.

Study timeline

Planned milestones include the first patient first visit (FPFV) in the second quarter 2025 and the last patient last visit (LPLV) in the first quarter 2027. Patient recruitment will take place during the first 12 months, followed by the monitoring of enrolled patients and data collection. Patients will be followed for 12 months and data collection will continue until the LPLV. The final phase, after LPLV (months 24–28), will focus on data analysis, report and manuscript writing, and submissions to peer-reviewed scientific journals.

Termination criteria

Termination criteria include treatment discontinuation due to adverse events requiring a switch to another inhaler therapy (except Trimbow 172/5/9), participants withdrawal of informed consent or enrolment in an interventional study. Patients who discontinue or withdraw will receive routine follow-up care in accordance with local guidelines to ensure best possible asthma management.

Sample size

The sample size is determined based on the study’s primary objective. Previous literature indicates that the percentage of patients demonstrating error-free inhaler technique ranges from 0% to 23%. For this study, approximately 15% of patients are expected to exhibit correct inhaler technique, defined as performing all required steps for optimal inhalation (Table 2). For logistical considerations, the sample size has been set at 60 patients. Based on this sample size, a paired t-test with a two-sided significance level of 0.05 and assuming a within-subject standard deviation of 25 ppb will have 80% power to detect a mean difference of approximately 9 ppb in FeNO levels between time points. Differences smaller than 9 ppb, which corresponds to a 20% reduction when baseline FeNO is 45 ppb, are considered clinically insignificant. The calculation was performed using R version 4.3.2.

Patients who discontinue participation and are subsequently excluded from the study within the recruitment period will be replaced by enrolling additional participants to ensure that approximately 60 patients complete the study.

Statistical analyses

All statistical analyses will be conducted by a Contract Research Organization (CRO) using Statistical Analysis System (SAS) or equivalent software. A detailed Statistical Analysis Plan will be finalized before the completion of data collection, specifying the statistical database, population definitions, and procedures.

Briefly, descriptive statistics will be used to summarize quantitative data, reporting parameters such as mean, standard deviation, median, minimum, and maximum values. Where appropriate, two-sided 95% confidence intervals will be reported. Quantitative variables will be compared between follow up and baseline visits, with statistical significance defined as p ≤ 0.05. When applicable, a two-sided paired t-test will be used. Categorical variables will be presented as absolute and relative frequencies. The kappa index will be used to assess the concordance between improved inhaler technique and adherence scores.

Data management and study oversight

Each patient will be assigned a unique identification code for tracking throughout the study and data analysis. The data will be pseudonymized, with the subject identification list securely maintained at each study site. Patient data from medical records and biological analyses will be manually entered into the electronic case report form (eCRF), while data from the SiA®SMARTer platform and online questionnaires will be automatically collected. All data will be recorded using a validated, internet-based electronic data capture system, with site personnel granted access through unique usernames and secure passwords.

Data collection and storage will comply with General Data Protection Regulation (GDPR) and Danish data protection laws. Personal data will be stored locally at study sites, while only pseudonymized data will be transferred to the eCRF and securely stored in a cloud environment for data handling and analysis, with a backup maintained in a separate cloud instance.

A CRO will oversee data management, and a study monitor will be appointed by the Sponsor to ensure compliance with International Council for Harmonisation - Good Clinical Practice guidelines (ICH-GCP), relevant regulations, and the study protocol.

Discussion

Achieving good adherence to controller medication is a cornerstone of asthma management, as good adherence has been associated with reduced airway inflammation, improved lung function, lower use of SABA and systemic corticosteroids, fewer hospitalizations, and lower mortality rates [23, 24]. While optimal asthma control is generally reached when adherence to treatment is ≥ 80% [25], global adherence rates range between 45% and 60% [13, 26]. Poor adherence is often due to unintentional factors like forgetfulness, financial constraints, or misunderstanding of the purpose of treatment, as well as intentional reasons such as beliefs that medication is unnecessary, fear of side effects, cultural influences, or cost concerns [1].

Furthermore, incorrect inhaler technique remains widespread despite advancements in inhaler design. Among pMDI users, at least one inhaler technique error has been reported in up to 90% of cases [27]. Most frequent pMDI errors including poor hand-breath coordination, incorrect inhalation speed or depth, and failure to perform a post-inhalation breath-hold [16, 17]. A review on inhaler use found that only 30% of users demonstrated correct technique, while around 40% had an acceptable technique and 30% a poor technique, with no improvement reported over the past 40 years [16, 28].

This body of evidence underscores the urgent need for improved patient education to enhance adherence to controller medication and inhaler technique. To this end, smart, interactive, and cost-effective systems could help address these challenges by providing continuous education and actively engaging patients in disease management.

The SiA®SMARTer platform, which will be used in this study, is designed to assist asthma patients to adhere correctly to their prescribed pMDI regimen and optimize their inhaler technique. Accordingly, the study aims to determine whether the use of this platform promotes the reduction of FeNO levels in patients with poorly controlled asthma, a population typically characterized by type 2 inflammation with FeNO levels above 25 ppb [1, 22, 29]. Beyond assessing the platform’s impact on FeNO reduction, this objective serves a crucial clinical purpose: distinguishing patients whose persistently elevated inflammatory biomarkers truly indicate therapy-resistant asthma - necessitating treatment escalation with targeted biologic therapies - from those whose high FeNO levels are instead attributable to poor adherence or incorrect inhaler technique. Given that current GINA recommendations emphasize optimizing adherence and inhaler technique before considering biologic therapy [1, 10], the ability to differentiate between these patient subgroups is essential for ensuring appropriate and individualized treatment decisions. Ultimately, the findings of this study may help inform clinical decision-making, preventing unnecessary treatment escalation while ensuring that truly therapy-resistant patients receive timely and targeted interventions.

To achieve this more comprehensively, in addition to continuously collecting data on adherence and inhaler technique through the SiA®SMARTer platform, patients will be required to record videos at baseline and at week 52 of platform use, demonstrating the essential inhalation steps [16]. The inclusion of video evaluation allows for the collection of crucial information that cannot be captured by the RespiPRO™ cap, such as the initial steps of removing the protective cap and exhaling slowly and deeply. A cross-sectional study conducted in Sweden with 364 COPD patients revealed that failure to perform one of these steps is among the most common errors. Indeed, 66% of participants made at least one critical error while using inhaler devices, with the failure to exhale before inhalation contributing to 65% of all recorded errors [28]. Additionally, the use of multiple inhaler devices increases the risk of inhalation technique errors [28].

Another key strength of this study is the vast and detailed amount of data on rescue medication (SABA) use that will be collected through the RespiPRO™ cap connected to the rescue treatment. Altogether, the simultaneous monitoring of controller medication and rescue treatment, will allow for precise tracking of medication consumption, offering valuable insights into patterns of asthma exacerbations, such as seasonal variations (e.g., winter vs. summer) and diurnal fluctuations (e.g., morning vs. evening). By capturing these detailed usage trends, the study could contribute to refining the assessment of uncontrolled asthma and treatment response. Given the potential clinical relevance of these findings, a dedicated publication on this aspect will be considered.

In conclusion, the SiA®SMARTer platform has the potential to improve asthma management and disease control by supporting patient adherence to controller medication and ensuring correct inhaler technique. Bridging these well-documented gaps could lead to better long-term health outcomes, a higher Quality of Life for patients, and a reduced economic burden on healthcare systems. Technology-driven solutions can be seamlessly integrated into healthcare systems and clinical practice, particularly when traditional approaches fail to achieve optimal outcomes. Importantly, by continuously monitoring adherence and inhaler technique alongside inflammatory markers, this study aims to generate robust evidence on whether digital interventions can enhance disease control, patient outcomes, and support educated treatment decisions, especially regarding the timely and appropriate escalation to higher ICS dose or biologic therapies. In doing so, the SiA®SMARTer platform may help prevent unnecessary treatment escalation while ensuring that patients with true therapy-resistant asthma receive the targeted interventions they need. Thus, this study is highlighting the potential of digital intervention as a valuable tool in asthma management.

Abbreviations

ACT

Asthma Control Test

BDP

Beclometasone dipropionate

COPD

Chronic obstructive pulmonary disease

CRO

Contract Research Organization

eCFR

electronic case report form

FeNO

Fractional exhaled nitric oxide

FEF25-75

Forced expiratory flow at 25–75% of FVC

FEV1

Forced expiratory volume in one second

FF

Formoterol fumarate dihydrate

FPFV

First patient first visit

FVC

Forced vital capacity

G

Glycopyrronium

GDPR

General Data Protection Regulation

GINA

Global Initiative for Asthma

ICH-GCP

International Council for Harmonisation - Good Clinical Practice guidelines

ICS

Inhaled corticosteroids

LABA

Long-acting β2-agonist

LAMA

Long-acting muscarinic antagonists

LPLV

Last patient last visit

LTRA

Leukotriene receptor agonists

Mini-AQLQ

Mini Asthma Quality of Life Questionnaire

pMDI

Pressurized metered-dose inhaler

SABA

Short-acting β2-agonist

SAS

Statistical Analysis System

SiA

Systematic intervention Agent

SITT

Single-inhaler triple therapy

Authors’ contributions

N.K. and G.S. contributed to the conception of the study and all authors contributed to the design of the study. J.A.B., G.S., E.B., C.S.U., and J.M.S. will take part of data acquisition. All authors will take part of data interpretation and analyses. All authors gave input to the manuscript, approved the submitted version and agree on accountability for their contributions.

Funding

This study is funded by Chiesi Pharma AB, Nordics. Briota ApS (Copenhagen, Denmark) supports the study by providing the SiA®SMARTer platform, including the RespiPRO™ inhaler caps and related technical support.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

A pre-assessment was conducted to determine whether the SiA®SMARTer platform was classified as a medical or non-medical device by the Danish Medicines Agency (DMA). As it was classified as a non-medical device, ethical approval for the present observational study was obtained from The Regional Committees on Health Research Ethics for Central Denmark Region (approval number: 1-10-72-193-23). Individual written informed consent will be obtained from each study participant before enrolment. The study will be conducted in accordance with Good Clinical Practice (GCP) guidelines, the Declaration of Helsinki, and the regulatory requirements of Denmark. Permission to use the ACT (Asthma Control Test) was granted by IQVIA Inc., and all licensing and permission requests should be directed to IQVIA Inc. at COAsolutions@iqvia.com.

Consent for publication

Not applicable.

Competing interests

JAB has received fees for lectures from Novo Nordisk and travel/conference grant from Chiesi Pharma outside the submitted work. NK is employed by Chiesi Pharma AB Nordics, the sponsor of the study. GS is cofounder of Briota ApS, providing the SiA®SMARTer platform for the study. EB declare no competing interest regarding this project. CSU has received fees for lectures, participation in advisory boards etc. from Chiesi, AstraZeneca, GSK, TEVA, Pfizer, Sanofi, IQVIA, Takeda, Roche, Novo Nordisk, Hikma Pharmaceuticals, Berlin Chemie, Boehringer Ingelheim, TFF Pharmaceuticals and Novartis outside the submitted work. JMS has no conflicts of interest regarding this project.