First report on MASK

J Bousquet, D Caimmi, A Bedbrook, M Bewick, P Hellings, S Acaster, S Arnavielhe, C Bachert, KC Bergmann, GW Canonica, N Chavannes, AA Cruz, R Dahl, P Demoly, P Devillier, G De Vries, E Dupas, A Finkwagner, J Fonseca, N Guldemont, T Haahtela, B Hellqvist-Dahl, T Keil, ML Kowalski, M Kuitunen, P Kuna, V Kvedariene, D Laune, A Margarida-Pereira, P Martins, E Melén, M Morais Almeida, J Mullol, A Muraro, R Murray, L Nogueira-Silva, N Papadopoulos, G Passalacqua, F Portejoie, D Price, D Ryan, B Samolinski, J Sanchez, A Sheikh, O Spanger, A Todo Bom, E Valovirta, A Valiulis, O VandenPlas, M van Eerd, M Wickman, T Zuberbier

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Summary

BackgroundThe use of Apps running on consumer smart devices (i.e., smartphones and tablets) profoundly affects medicine. The MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App uses a mobile phone-based daily visual analogue scale (VAS) assessment of disease control. It is freely available in 15 European countries (Apple stores and Android).

AimsTo assess whether (i) participants using the MASK App were able to correctly fill in the baseline characteristics and the VAS, (ii) simple phenotypic characteristics based on the App could be identified and (iii) information gathered by this pilot study may suggest novel research questions.

MethodsParticipants filled in baseline characteristics and VAS levels for global symptoms, rhinitis, ocular symptoms and asthma. Participants were classified into asymptomatic (no response for any nasal or ocular symptom) and symptomatic. Then, rhinorrhea was taken as the first criterion (no rhinorrhea, rhinorrhea). Those with rhinorrhea were classified into 4 groups depending on the number of other nasal or ocular symptoms.

Results730 participants registered to the App. 540 filled in the baseline questionnaire and 2,230 days were available for VAS analyses. Over 50% of the participants with rhinorrhea and ocular symptoms had an impairment at work. None of the participants without ocular symptoms had work impairment. Troublesome symptoms were found mainly in the participants with the most symptoms.

ConclusionsMASK tools are easy to use and enable the proposal of novel concepts and research questions.

AbbreviationsAR: allergic rhinitisARIA: Allergic Rhinitis and its Impact on AsthmaICT: information and communications technologyMACVIA: Contre les MAladies Chroniques pour un VIellissement Actif MASK: MACVIA-ARIA Sentinel NetworKNAR: non allergic rhinitisSIT: specific immunotherapyVAS: visual analogue scale

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Introduction

Survey questionnaires are important tools in clinical practice and epidemiology. The use of apps running on consumer smart devices (i.e., smartphones and tablets) is increasingly popular and profoundly affects medicine (1). Novel app-based collaborative systems can have an important role in gathering information quickly and improving coverage and accessibility (2). Classical tools are being replaced by newer smartphone technologies and are providing individual measures across larger populations. However, variation in the mode of delivering a survey questionnaire may affect the quality of the responses collected, and data equivalence between survey questionnaires and apps is lacking (3). There are potential biases when using apps since the information is usually simple and less complete than when using lengthy questionnaires. Furthermore, the interpretation of studies on health effects is hindered by uncertainties in the exposure assessment (4). Implementing ICT innovations may also result in disruptive consequences and it is important to test applicability in each individual situation. Thus, the information provided by questionnaires and apps is not identical but may be complementary for understanding unmet needs of diseases. Moreover, ICT tools may allow the proposal of novel concepts and research questions.

Several unmet needs have been identified in allergic rhinitis (AR) including time of the pollen season, optimal control of rhinitis and multimorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and patient empowerment (5, 6).

Non-allergic rhinitis (NAR) is a chronic nasal inflammation that is not caused by systemic IgE-dependent mechanisms (7, 8). It also differs from chronic rhinosinusitis (9). It is common and probably affects more than 200 million children and adults worldwide. However, its endotypes and phenotypes (10) need to be evaluated to better understand its pathophysiology, diagnosis and management (7). Many studies have failed to find any effective treatment in NAR (7), possibly because the phenotypes are poorly understood. Studies should compare AR and NAR, and consider gender and different age group populations including old age adults.

Smart devices and internet-based applications are already used in rhinitis and may be of help to fill some unmet needs (11-16). MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis), an ICT system centred around the patient (5), is one of the implementation tools of the B3 Action Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) (17, 18). In particular, the App that uses a mobile phone-based daily visual analogue scale (VAS) assessment of disease control is freely available in 15 European countries (5, 19) (Apple stores and Android Michiel???). Participants using the MASK App are asked to complete a short demographic questionnaire to give baseline characteristics of their disease.

AimsOn February 29, 2016, information on baseline characteristics was made available for the first 730 participants of the MASK survey in Europe. The aims of this cross-sectional pilot study were to assess whether (i) participants using the MASK App were able to correctly complete the baseline characteristics and the VAS, (ii) simple phenotypic characteristics based on the App could be identified and (iii) information gathered by this pilot study may suggest novel concepts and research questions.

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Methods

Participants

All consecutive participants from December 1, 2015 to February 29, 2016 were included in the study. Some demographic characteristics (age, sex, country and language) were recorded.

The App

MASK rhinitis is based on a simple baseline questionnaire (Table 1 and Annex) and daily measurement of rhinitis control using visual analogue scales (VAS) (5, 19). VAS integrates symptoms and quality-of-life and is a highly reliable measure of rhinitis control (5). Mobile phone messaging facilitates the management of AR. MASK rhinitis uses cell phones (Apple and Android) with a touch screen. Geolocalized patients can evaluate daily their symptoms daily by VAS. Daily, 4 VAS (global evaluation, nasal, ocular and bronchial symptoms) are completed by the patient. Moreover, medications and immunotherapy are integrated in the application. The system is initially being deployed in 15 countries with 15 languages (translation and back-translation, cultural adaptation and legal issues).

Outcomes

Only the type and number of nasal/ocular symptoms were assessed to classify the participants (Table 1 and online supplement 1).

Table 1: Questions on symptoms and impact of symptoms

Q1: I have rhinitis: Yes/No

Q2: I have asthma: Yes/No

Q3: My symptoms (tick) Runny nose Itchy nose Sneezing Congestion (blocked nose) Red eyes Itchy eyes Watery eyes

Q4: How they affect me: My symptoms (tick) Affect my sleep Restrict my daily activities Restrict my participation in school or work Are troublesomeQ5: MedicationsQ6: Are you currently receiving immunotherapy (a small dose of the thing you are allergic to, usually taken as

an injection or placed under your tongue)? Yes/No

If YES to Q6

Q7: (if Q1 YES): What allergy is this Grass pollen Parietaria pollen Birch pollen Other pollen

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Dust mite Animal Cypress tree pollen Don’t know Add allergy

Q8: How do you receive your treatment Tablet under the tongue Drops under the tongue Spray under the tongue Other

The severity of the disease was assessed by VAS but was not used in this study.

Classification of participants

The clinical differentiation between AR and NAR may be difficult. Symptoms may differ depending on allergen sensitivity and exposure as well as ethnicity, age, sex and other environmental risk factors. In ARIA, the major symptom differentiating AR and NAR was proposed to be rhinorrhea (20) although it may exist in NAR (7, 8). Broadly, “sneezers” and “runners” are ascribed to AR whereas “blockers” are ascribed to NAR (21, 22). Patients suffering from AR usually present all four cardinal nasal symptoms (nasal obstruction, rhinorrhea, sneezing and pruritus) (23-26) and often suffer from conjunctivitis (27, 28).

As a working hypothesis, we used the concepts proposed in ARIA (20). Subjects with rhinorrhea are more likely to have AR (Figure 1 online).

Figure 1 online: ARIA classification of rhinitis symptoms (20)

We then used the MeDALL hypothesis indicating that multimorbity is associated with severe disease (29, 30). We hypothesized that participants with many nasal and ocular symptoms have a severe disease (31). Moreover, ocular symptoms are associated with severe AR (31, 32).

Participants were classified into asymptomatic (no response for any nasal or ocular symptom) and symptomatic. Then, rhinorrhea was taken as the first criterion (no rhinorrhea, rhinorrhea). Those with rhinorrhea were classified into 4 groups depending on the number of other nasal or ocular symptoms) (Figure 1).

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Figure 1: Classification of participants

Biases

There are potential biases when using apps since the information is usually simple and less complete than when using lengthy questionnaires. Furthermore, the interpretation of studies on health effects is hindered by uncertainties in the exposure assessment (4). However, the study design was not aimed to compare questionnaires with apps.

Size of the study

In this pilot study, there was no calculation of the number of participants.

Quantitative variables

Statistical methods.

The effect of specific immunotherapy (SIT) was analysed. Double-blind, placebo-controlled randomized trials have shown that SIT is an effective treatment of AR (33). SIT is the only treatment which affects the natural course of allergy. Participants were classified into 3 groups: Q6 “NO” (no SIT), Q6 + Q7 + Q8 “YES” (SIT), Q6 “YES” and Q7 and/or Q8 “NO” (patients were excluded from the analysis of SIT).

The next analyses compared the 6 groups of participants defined in Figure 2 with “bothersome symptoms”, impairment of daily activities and work impairment.

Results

Participants

Of the 730 registered participants, 165 did not reply to the questionnaire (Table 1). 565 files were analysable with reported symptoms and treatments in 15 EU countries (Table 1 online). All participants filled all items.

Table 1 online: Countries of participants

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Country Number of participantsAT 14BE 15DE 54DK 16ES 99FI 13FR 49GB 103GR 2IT 66LT 9NL 60PL 31PT 18SE 16

Total 565

Specific immunotherapy (Q6) was reported by 94 participants. 15 of them did not respond to Q7 and/or Q8 and were excluded from further analyses. The repartition of the 565 participants in the different groups differed is presented in Figure 2 and Figure 2 online. The number of SIT participants was too low to allow further analyses. However, in group 3 (rhinorrhea with no other symptom) there was a greater number of participants with SIT than without SIT (Figure 3).

Figure 2: Distribution of the participants

Figure 2 online: Distribution of the participants according to SIT

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Figure 3: Repartition of symptomatic participants depending on SIT (Q6 + Q7 + Q8)

Main results

The impact of the disease (troublesome symptoms, sleep, daily activities) in different groups assessed by nasal and ocular symptoms was estimated in the full data set (Table 2) and participants who did not reported SIT (Table 2 online). The results are hilghy comparable between the two groups and only analyses using the full data set will be done further.

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The study showed that participants with no reported nasal and ocular symptoms rarely had any impairment. Those with symptoms but without rhinorrhea often had troublesome symptoms (69%) but few impairment, in particular work or school and daily activities. Participants with reported rhinorrhea had an increased impairment depending on the number of symptoms.

Sleep was impaired similarly in all symptom groups (2 to 6) whereas impairment in work, school or daily activities increased with the number of symptoms in participants with rhinorrhea (groups 3 to 6).

Table 2: Impairment in participants of the full data set

Group Symptom N Troublesome symptoms

ImpairmentRhinorrhea Any other

symptomWork or school

Daily activities

Sleep Any

1 NO NO 134 9 (7%) 2 (1%) 3 (2%) 5 (4%) 8 (6%)

2 NO Yes 115 79 (69%) 23 (20%) 25 (22%) 38 (33%) 54 (47%)

3 YES None 66 11 (17%) 7 (11%) 11 (17%) 35 (53%) 49 (74%)

4 YES 1 or 2 81 42 (52%) 14 (17%) 18 (22%) 35 (43%) 48 (59%)

5 YES 3, 4 or 5 105 75 (71%) 43 (41%) 57 (54%) 46 (44%) 79 (75%)

6 YES ALL (6) 64 60 (94%) 31 (48%) 33 (52%) 35 (55%) 44 (69%)

Table 2 online: Impairment in participants who did not report SIT

Group Symptom N Troublesome symptoms

ImpairmentRhinorrhea

Any other symptom

Work or school

Daily activities

Sleep Any

1 NO NO 126 7 (6%) 2 (2%) 3 (2%) 5 (4%) 8 (6%)

2 NO Yes 106 73 (69%) 19 (18%) 22 (21%) 33 (31%) 48 (45%)

3 YES None 27 6 (22%) 3 (11%) 4 (15%) 11 (41%) 14 (52%)

4 YES 1 or 2 67 39 (58%) 11 (16%) 13 (19%) 29 (43%) 37 (55%)

5 YES 3, 4 or 5 91 64 (70%) 37 (41%) 49 (54%) 40 (44%) 67 (74%)

6 YES ALL (6) 55 52 (95%) 23 (42%) 25 (45%) 28 (51%) 36 (65%)

Impact of individual symptoms on impairment

In the 411 participantssubjects with rhinorrheanasal symptoms (groups 2-6), work impairment occurred in 18% of those without ocular symptoms and in 38% of those with ocular symptoms. 71% of work impairment were associated with participants with ocular symptoms. Moreover, there was an increased prevalence of work impairment depending on the number of ocular symptoms (1 symptom: 22%, 2 symptoms: 43%, 3 symptoms: 51%).

In subjects with rhinorrhea, the impact of individual symptoms on impairment is shown in Table 3

Table 3: Impact of individual symptoms on impairment in subjects with rhinorrhea

Impairment

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Work or school

Daily activities Sleep

Bothersome symptoms

Yes N=

No N=

Nasal obstruction Yes N=

No N=

Ocular symptoms No N= 34 (18%)

1 N= 17 (22%)

2 N= 27 (43%)

3 N= 40 (51%)

References

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ANNEX 1: Cell phone screens

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