The applications of eHealth technologies in the management of asthma and allergic diseases

Abstract Portable devices, such as smartphones and mobile Internet access have become ubiquitous in the last decades. The term ‘eHealth’ stands for electronic health. The tools included in the eHealth concept utilize phones, computers and the Internet and related applications to improve the health care industry. Implementation of eHealth technologies has been documented for the management of different chronic diseases, including asthma and allergic conditions. Clinicians and patients have gained opportunity to communicate in new ways, which could be used cost‐effectively to improve disease control and quality of life of those affected. Additionally, these innovations bring new opportunities to academic researchers. For example, eHealth has allowed researchers to compile data points that were previously unavailable or difficult to access, and analyse them using novel tools, collectively described as ‘big data’. The role of eHealth become more important since early 2020, due to the physical distancing rules and the restrictions on mobility that have been applied worldwide as a response to the coronavirus disease 2019 pandemic. In this review, we summarize the most recent developments in various eHealth platforms and their relevance to the speciality of allergy and immunology, from the point of view of three major stakeholders: clinicians, patients and researchers.

opened new horizons for patients, clinicians and researchers. 6 The coronavirus disease 2019 (COVID- 19) pandemic has been reported to dramatically increase the adoption rate of communication technologies in a few months' time. 7 The spectrum of allergic diseases comprises a variety of chronic conditions that can severely impair quality of life, including asthma, atopic dermatitis, allergic rhinitis and food allergy. These disorders have been reported to affect up to 20%-40% of the general population in developed countries. In addition, their prevalence is rising up to the point that it has described as an 'allergy epidemic'. 8 Allergic diseases require implementation of self-management plans and patient empowerment. Unfortunately, this laudable goal may not be as easy achieved in real life clinical environments. 9 Implementation of various eHealth technologies has already been documented for the management of different chronic diseases, including asthma and allergic conditions. However, there are many eHealth aspects that still remain uncertain and under investigation.
In most cases, study evidence is still limited, lower quality, based on the current research standards or inconsistent. 10 It is still necessary to identify and define eHealth interventions or combinations of them that may be adequate for different patients and allergic disorders. As with any clinical intervention, some eHealth tools may have a negative impact on certain vulnerable patient subpopulations. 11 In addition, privacy remains an important concern that must always be addressed with the highest standards of protection, as mandated by the specific government regulations. 12 In this review, we summarize the most recent developments in various eHealth platforms and their relevance to the speciality of allergy and immunology, from the point of view of three major stakeholders: clinicians, patients and researchers.

| mHealth
Web applications (apps), wearables and other personal monitoring devices have a potential to improve the management of asthma and allergic conditions. Proposed benefits of asthma apps include the ability to longitudinally collect symptoms and inhaler usage data, thus allowing the detection of changes over time to help patients and caregivers determine whether the symptoms are worsening. Data from external information sources, including weather, allergen load and air quality reports, can be integrated. 13 The collected data from the apps can be shared with the allergy clinicians during clinic visits or via telemedicine portals.
An online health diary platform can be used to assess the effects of personal behaviour and environmental exposure on allergic rhinitis and asthma symptoms. A pilot study of an online asthma diary included 132 patients, who provided 25,016 diary entries. The analysis of this data showed the effects of multiple risk factors for asthma symptoms, including contact with persons with influenza-like illness, perception of cold or hot temperature, high-intensity exercise, dehumidifiers at home, second-hand smoke, poor sleep quality, poor quality of indoor and outdoor air. 14 Adolescents and their caregivers agreed with the acceptability of using smartphones for real-time asthma monitoring. 15 An app-based portable spirometer has recently been found to be comparable to a conventional spirometer. 16 The ability to access high quality lung function measures outside of the clinical setting might potentially aid patients in recognition of changes in asthma status over time. The data points collected from this kind of platforms could lead to a more complete evaluation of the symptoms and their triggers by the allergy clinicians that would extend beyond the time-limited interactions with patients during a clinic or telemedicine visit.
Electronic inhaler sensors can track the time, frequency and location of short-acting β-agonist (SABA) use. A pilot study of a sensor-driven asthma management platform, which included 120 patients, reported a significant reduction in SABA use, increased number of symptom-free day, and improvements in asthma control during a 30-day period 17 (Figure 2).

| Electronic health records
Electronic health record systems have been widely adopted in health care, thus generating large amounts of real-world data. Natural language processing techniques is an artificial intelligence (AI) approach that extracts information from clinical narratives in electronic health records. 18 In addition, electronic health records allow temporal condition pattern mining that may reveal previously unknown associations between diagnoses, thus informing future research into causation. 19 Applications of these technologies to the allergy practice are still in early developmental stages. There are studies that have calculated food allergy or drug allergy prevalence in different populations mining electronic health records. [20][21][22] A natural language processing algorithm has demonstrated to be able to ascertain asthma analysing such records. 23 Potential future uses of AI might include detection patients who need allergy care before their diseases deteriorate. This could be particularly relevant to address the case of patients that missed their consultations or interrupted their treatments due to the COVID-19 pandemic.

| Telemedicine
Telemedicine is rapidly gaining acceptance as a convenient way of accessing medical services worldwide. In 2019 alone, the Cleveland Clinic, a large health system in the United States, completed 41,000 virtual visits, including all medical specialities. Six months into 2020, the volume of virtual visits jumped to more than 500,000. 24 There are studies that support that telemedicine is as effective as in-person visits for outpatient treatment of asthma. 25 A study including 169 children with asthma compared disease control and patients satisfaction after 6 months of in-person visits or telemedicine care and found them to be similar. 26 There are also surveys that have found ALVAREZ-PEREA ET AL.
-3 of 13 that both patients and allergists tend to be as satisfied with telemedicine, or even prefer it over in-person visits. 25,27 As a result of the COVID-19 pandemic, telemedicine has become an integral part of allergy and immunology clinics daily practice all over the world. 28 Telemedicine could be especially useful for providing proper speciality care for allergic conditions in rural communities, where inperson visits are problematic, due to shortage of resources. 29 In countries, such as the USA, where the private practice is common, there are still significant policy barriers, including a fragmented reimbursement system, that challenge more widespread implementation. 30 In the near future, when combined with device sensor input, electronic health records and big data AI, telemedicine is expected to deliver transformational changes in the way allergy care is delivered.

| Social media
An online social network is defined as an app or website that enables users to communicate with each other. The professional organizations in the field of allergy and immunology use social networks for member relations, public advocacy and education and Twitter and Facebook are actively utilized to stay up-to-date with the latest news. 31 Twitter use by individual allergy practitioners often peaks during the annual meetings of the major professional organizations, such as the European Academy of Allergy and Clinical Immunology (EAACI), the American College of Allergy, Asthma, and Immunology (ACAAI), the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the World Allergy Organization (WAO). 32,33 Table 2 provides a list of social network pages of the most relevant professional organizations in the field of allergy and clinical immunology.
Tweets are tagged with a meeting-specific searchable hashtag. YouTube. eHealth has a great potential for professional education, for example, Conferences On-Line Allergy (COLA) is a lecture programme by ACAAI (childrensmercy.org/cola_online). Its YouTube channel with more than 400 videos and 3200 subscribers has received over 490,000 views as of 2021.
The risks to social media use by the allergy clinicians are related to breaches of patient confidentiality, professionalism, privacy, F I G U R E 2 Some electronic inhaler sensors can be applied to a regular inhaler. Others are already built into the device. They collect adherence data and can submit it wirelessly to a portable device, usually a smartphone or tablet, which can upload it to a cloud-based service, so it can be processed from a desktop computer, either by patients or healthcare providers malpractice and liability. 43 Personal attacks and harassment of physicians have also been reported. 44 Table 3 provides recommendations for allergists considering having a presence on social media.

| eHEALTH FOR PATIENTS AND PATIENT REPRESENTATIVES
eHealth interventions are recognized as an effective way to promote patient engagement and health care access in chronic diseases, such as diabetes. 45,46 However, eHealth utilization has been described to be low among patients with asthma 47 and evidence supporting clinical benefit is still preliminary. Research protocols have found specific benefits of eHealth application in patients with allergic conditions. 4

| mHealth
In the field of mHealth, studies conducted in patients with asthma have demonstrated an improvement in symptoms and a reduction in the number of visits to the emergency room, by using home spirometers and a SMS alert service. 48,49 A randomized trial in children with asthma using a monitoring mobile app showed a decrease in urgent care visits, although it failed to prove any difference in emergency room visits or hospitalizations. 50 Regarding the use of mHealth for remote monitoring, a recent pilot study demonstrated that a smartphone built-in microphone, used in combination with a cloud-based platform could approximate pulmonary function tests. 51  Therapy adherence remains a challenge in the management of patients with chronic conditions. 52 Specifically, patients with asthma frequently fail to use their controller medications. 53 In many cases, patients with anaphylaxis, despite their life-threatening disease, are reluctant to carry their epinephrine auto-injectors or to use them. 54 mHealth has been proposed as a possible solution to these challenging clinical situations. 55 Reminder systems and gamification of the management, including digital and real-life rewards, may seem like obvious choices. 56 However, a recent meta-analysis found T A B L E 2 Social network pages of the most relevant professional organizations in the field of allergy and clinical immunology American Academy of Allergy, Asthma, and Immunology (AAAAI): important limitations regarding the evidence supporting the potential effects of mHealth in asthma control. They found that these interventions have only reported modestly improvement of inhaler adherence and reduction of rescue inhaler use, without an actual impact on asthma control. 57 In addition, their long-term effects remain to be evaluated. 48 Uncontrolled asthma is associated with extensive use of healthcare resources. In a significant number of cases, this lack of control is related to inadequate inhalation technique and adherence to treatment. 58 In recent years, the interest in the field of inhaler adherence has increased steadily, supported by mHealth apps and wearables. Most of the currently available studies have addressed electronic reminders and inhaler tracker interventions 59 ( Figure 2). A recent observational study described a 14.5% increase in inhalers adherence by using digital trackers among patients with asthma and COPD during the COVID-19 pandemic. 60 An electronic monitoring sensor attached to inhalers has proven to increase asthma control in paediatric patients, as well as caregivers quality of life. 61 A multicentre observational study concluded that a gamification strategy using a mobile app could be useful to monitor adherence to asthma medication. 62 Additionally, patients' feedback on these devices has also been described to be positive. 63 MASK-Air is a mobile app that has been designed for patients with allergic rhinitis, allergic conjunctivitis and asthma. It is part of Allergic Rhinitis and its Impact on Asthma (ARIA) and it has been translated into multiple languages. 64 Through this app, patients are able to record their daily symptoms using analogue visual scales.
Subsequently, they can download reports and share them with their healthcare providers in order to optimize the management of their diseases. Its utility has been thoroughly validated for multiple purposes, both for patients and professionals. 65 In addition, global data is available to researchers, which is leading to a better understanding of respiratory allergic diseases. 66 mHealth has also been used to provide allergic patients with pollen counts in order to predict symptoms 67 and improve selfcontrol. 68 A pilot study led in Australia found that most participants found this service useful. 69  There are several devices under development that aim to detect traces of food allergens in prepared meals. There is a patent for a device using molecularly imprinted polymers, 72 which would detect peanuts, tree nuts, fish, shellfish, wheat, eggs, milk and soy. 73 At the time of this writing, there is no published evidence supporting such claims.
Heterogeneity in the quality of the studies endorsing the use of mHealth in allergic diseases is high and the number of robust randomized controlled trials is still low. 10 Information contained in most of the apps about asthma available for iOS and Android-based smartphones do not contain evidence-based recommendations.
Thus, their actual clinical efficacy is doubtful. 74

| Telemedicine
Telemedicine has several potential benefits for allergic patients, including better access to health care and cost reduction. 75  Telemedicine received a tremendous boost in acceptance and utilization during the COVID-19 pandemic. 78 The most heavily affected countries saw their allergy practices rapidly being T A B L E 3 Recommendations aimed at maintaining a professional social media presence • Social media is a method of building relationships and a professional reputation. Content posted may have a positive or negative effect among patients and colleagues.
• Identify yourself and be cautious of your online image. Adhere to institutional rules and recommendations.
• Distinguish private from professional online presence by using different accounts and adjusting privacy settings. Redirect patients' requests to professional accounts. Avoid providing specific medical advice.
• Maintain patients' confidentiality. Avoid disclosing specific information. It can still be linked to the particular patient, even after anonymization. Do not acknowledge a physician-patient relationship online.
• Once content is online, it is almost impossible to remove and can quickly spread beyond one's control.
• Social media abusers can be blocked and reported to the platform where the issue was raised.
converted to telemedicine within days. 79 In many cases, the radical change in practice had to happen without much of the needed preparation or advanced planning. 80  Moreover, patients show a significant level of engagement during the annual meetings of the major professional organizations. It has been described that, during the period from 2013 to 2016, up to 12.3% of the users of the official hashtags of the SEAIC annual congresses were patients. 33 The main limitation for the use of social media for patients is reliability. There is no standardized method to measure the characteristics of information available in social networks. 86 Quality of the information contained in videos posted on YouTube has been found to be low for asthma, rhinitis, immunodeficiencies 35  There is a multitude of mHealth apps for smartphones and tablets, with information on risk factors for allergic rhinitis and asthma, including pollen and air pollution data. However, there is evidence that the quality and reliability of the information contained on most of these apps is low. Consequently, the number of apps providing adequate scientific information is small. 91

| Electronic health records
In the field of health informatics, electronic health records are used in a wide range of clinical trials, including for improvements of the patient-clinician interface and data analysis. The low adoption rate of standardized procedures and protocols for electronic health records platforms may lead to difficulties in coordinating research activities. 97 Electronic health records analysis use for drug hypersensitivity warrants further investigation. 98 Computerized physician order entry and mHealth facilitate real-time identification of potential study subjects for clinical research. 99 ALVAREZ-PEREA ET AL.

| Social media and infodemiology
Social media services are increasingly used to obtain or share scientific content, including curated information from clinical trials, and to utilize the available communities for crowdfunding and crowdsourcing. 32,33,107,108 Interested allergists may use social media to discuss research ideas, future and ongoing research projects. 31,35 The term 'infodemiology' has been used to define the use of content publicly available in electronic mediums, most frequently the Internet, to inform public health. Tools, such as Google Trends may reflect a real-life epidemiological approach to allergic rhinitis. A study found that searching Google Trends for a certain set of keywords ('hay fever', 'allergy' and 'pollen') could detect seasonality of allergic rhinitis in different European countries. 109 Twitter microblogging platform has been used in health research in multiple trials. 110 Geolocation techniques and the networks of users allow gathering spatial information. 111 In a Japanese study, data on pollen counts and the number of tweets during an allergic rhinitis season were analysed using Granger causality. 112 A UK research of social sensing for allergic rhinoconjunctivitis evaluated Twitter data and generated a dynamic spatial map of pollen levels based on user reports of symptoms with great similarity to measurements from the pollen monitoring stations. 113 An Australian study validated the practical application of state-of-art Deep Learning in the context of pollen allergy surveillance on Twitter. 114 Natural language processing (NLP) 115 was used in a US study which explored large public textbased social media data from Twitter, Facebook and Reddit. The data were analysed using a patented algorithm that applied NLP to online free-text discussions in order to detect adverse events related to allergen immunotherapy. 116 Reddit, with its application programming interface, has become a widely studied social media platform for understanding opinions on health issues, especially among young people. 117 Image-based social media platforms, especially Instagram and Pinterest, deserve further research assessment, 118 while at the same time posing additional ethical issues. 119,120 Pinterest, with its image searching lens, may be analysed for visual and textual medicalrelated information. 121 Furthermore, social media research on allergy information-seeking behaviour is also needed. 122

| Big data
The application of big data to allergy and immunology research generates complex, multidimensional and massive quantities of information. 68,123,124 A prediction model using big data to assess asthma emergency department visits had a good accuracy. 125 Big data can be obtained from genome, transcriptome, epigenome, microbiome and metabolome studies. Recently it was published a study protocol to estimate the prevalence of severe asthma using big data methods. 126 Integration of big data from large cohorts, using machine learning approaches, is also needed to identify disease biomarkers and define molecular phenotypes/endotypes required for precision medicine approaches. 127 (Table 4).

Feature Application
Clinicians mHealth Mobile apps used as electronic diaries in asthma and rhinitis, leading to more detailed symptom monitoring.

Adherence monitors
Provide reliable information on the use of prescribed treatments, creating an opportunity to support patient education.
Electronic health records Increased opportunities to mine clinical data in order to get a more realistic analysis of activity. Clinical decision support systems might be an opportunity to provide better care to patients, reinforcing evidence-based recommendations.

Telemedicine
Extend the reach of the practitioner beyond the limitations of a physical clinic.
Social media Real-time information-sharing with colleagues, engaging the general public, enabling novel methods of patient education, accessing professional education.
Patients mHealth Electronic diaries and gamification may increase awareness of symptoms and improve control. Reminder systems may improve treatment adherence.
Adherence monitors Reinforce medication use, leading to better control of the diseases and improvements in the quality of life of patients and caregivers.
Wearables Provide real-time information to improve the perception of the disease and early detection of triggers.

Telemedicine
Give better access to health care resources regardless of geographical location and cost reduction.
Social media Source of medical information and education. Engagement with healthcare professionals and other patients.

Researchers mHealth
Mobile apps and sensors may be cost-effective methods of rapid and valid collection of data.
Adherence monitors Increase adherence to clinical trials interventions, giving information about the causes of non-adherence.

Wearables
Automatic collection of data about subjects and activities.
Electronic health records Data mining can be used to identify potential research participants.
Social media Source of easy to collect, real-time data. Increase visibility and impact of publications.
Big data Process huge datasets, including subjects profiling, phenotyping, exposome analysis, etc.

ACKNOWLEDGEMENT
The authors declare that no funding was received for the present manuscript.

CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interests regarding this article.

AUTHOR CONTRIBUTIONS
Alberto Alvarez-Perea participated in the design of the review and