Asthma Control According to the Community Pharmacists: Evidence and Potential Implications from an Italian Cross-Sectional Study

Background . Asthma control and monitoring still represents a challenge worldwide. Although the international guidelines suggest the interplay with primary care as an effective strategy, the community pharmacies’are rarely involved in asthma management. The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control according to the community pharmacies’ perspective of the health district of Verona (North-Eastern Italy). Methods . A call for participation was launched through the Pharmacists’ Association of Verona.Patients referring to the participating pharmacies with an anti-asthmatic drug medical prescription and an asthma exemption code were asked to completethe Asthma Control Testand a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined the severity level of asthma.A multinomial logistic regression model was fitted to investigate the risk of uncontrolled as well as poorly controlled vs. controlled asthma (base). Results were expressed as relative risk ratios (RRR) with 95% confidence interval (95%CI). Results. 57 community pharmacies accepted to participate and 584 asthmatic patients (54% females; mean-age: 51 ± 19 years) were recruited. According to the ACT score 50.5% patients hada controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion patients with uncontrolled asthma was observed at every level of severity, although more frequently in mild persistent form of disease. Most patients (92%) reported regular compliance with therapy. At multinomial regression analysis, patients under regular asthma treatment course (RRR=0.33; 95%CI: 0.15; 0.77) were less likely to have an ACT<16 compared to those not taking medications regularly. Conclusions. Overall, our findings highlighted an unsatisfactory asthma control from the pharmacists’ perspective, independently of the asthma severity level. The relevance of community pharmacies as a first line interface suggest their involvement inan effective asthma management plan, from disease control and treatment compliance assessment to referral of asthmatic patients to medical consultancies.


Background
Asthma is one of the most common chronic disorders on a global scale, with a prevalence in the general population ranging from 1-18% [1][2][3].
The burden of asthma includes considerable financial impact in terms of direct (health care services, medications) and indirect (sickness absence from work, disability, other) costs [1,2,4].
The most striking contradiction in asthma is a general lack of its control [5][6][7][8], even for milder cases, despite the availability of very effective drugs which have been proven to be effective in most patients, if regularly taken [9].
Several countries have been adopting national plans to manage asthma, with the aim to improve its control and contain its impact, yet with unsatisfactory health outcomes [1,[12][13][14]. Since they frequently represent the first point of contact for patients affected by chronic conditions, the involvement of primary care services in asthma management has been suggested as a successful strategy to improve the control of the disease [1,15]. In particular, in several countries the involvement of community pharmacies has already proven to offer an efficient support for the management of chronic conditions such as diabetes, hypertension and, with more limited evidence, asthma [16]. Nonetheless, community pharmacies are still largely underused to promote health in the general population in high-income countries [17].
Usually patients have good relationships with their local pharmacists, they rely on them and are more comfortable in that health care setting than in a medical environment. Moreover, pharmacists are more easily accessible for patients, also because an appointment is not required. As a result, local pharmacies may be extremely relevant in promoting behavioural changes aimed at improving healthy life-styles and treatment adherence to medications for various conditions, which considerably impacts on health care costs for the national health services (NHS) [17]. Furthermore, pharmacists can contribute to disease control assessment and medical referral if need be. In the case of asthma, easy to use and accurate tools for at a glance disease control evaluation are currently available. For instance, the asthma control test (ACT) is a standardized and validated five-item questionnaire measuring asthma control [10]. Although being easy-to-use, ACT is still underused by general practitioners (GPs) and medical consultants [11].

Aim of the study
In view of the above, the present cross-sectional study aimed at assessing the role of community pharmacists in the assessment and control of asthma within the health district of Verona (North-Eastern Italy).

Ethical approval
The Ethic Committee of the Pharmacists' Association of Verona Health District approved the study protocol. Written informed consent was obtained from all study participants.

a. Community pharmacies
By expanding a previous pilot study [18], a call for participation was launched through the local Pharmacists' Association, which includes all the community pharmacies in the Verona health district.
Before the study start, pharmacists attended a two-sessions seminar on bronchial asthma, its management, study design and study tools.The study lasted six months, from the 1st of January 2018 to 30th of June 2018.

b. Patients
Within the study time frame,consenting patients referring to the participating pharmacies with an anti-asthmatic drug medical prescription and an asthma exemption code were consecutively recruited. The asthma exemption code (007-493) enables patients to access free health care and medications related to their asthma condition and is released by the Italian NHS to individuals with a confirmed diagnosis of bronchial asthma, based on clinical history and lung function tests. The asthma exemption code therefore allows to accurately identify asthmatic patients.
Participating study subjects were asked to complete the Asthma Control Test (ACT, see below) and a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise andhabitual asthma therapy, which also defines the severity of asthma according to Global Initiative for Asthma (GINA)recommendations [20].

c. Asthma Control assessment
Asthma control was assessed through ACT, a validated 5 item questionnaire which provides a snapshot on the degree of asthma control achieved over the past four weeks [19].Theoverall ACT scoreattained by answering each of the five questions classifies asthma control as follows: In the presence of a score < 16 the patient was recommended to refer to his GP/medical consultantas soon as possible.

d. Statistical analysis
Numbers and percentages of each variable (age, sex, smoking status, aerobic physical exercise, ACT, asthma level, habitual asthma therapy) were estimated. Furthermore, the mean, standard deviation, median and range were calculated for age and ACT.A multinomial logistic regression model was fitted to investigate the risk of uncontrolled (ACT [16][17][18][19] as well as poorly controlled (ACT<16) asthma compared to controlled asthma (Base=ACT 20+), adjusting for sex, age, asthma treatment regimen (regular vs. non-regular) and asthma level (coded from 1 to 5). Results were expressed as relative risk ratios (RRR) with 95% confidence interval (95%CI).
Asthma coded as "unclassified" was classified as missing.All missing data were excluded, and complete case analysis was performed.
Analysis was carried out with Stata 14 (Stata Corporation, College Station, Texas, USA).

Results
Overall 57 community pharmacies (41% out of all pharmacies within the catchment area of Verona health district) participated to the study, with671 asthma patients consecutively recruited.Complete data were available for 584 out of 671 patients enrolled. Patients' demographic informationcan be seen in Table 1.Study subjects were predominantly females (54%) and had a mean age of 51±19 years, with 53% of them being older than 50. The mean age of female patients(52.1 years) was slightly higher than males' (48.6 years). Most study subjects were non-smokers (54.4%),19.2% were current smokers, and 26.4%ex-smokers. Although the majority of female patients were neversmokers (60.0 % females vs. 48.3% males), the proportion of ex-smokers was higher among males (30.8% males vs. 22.8% females). 10.8%) was higher among males.  Figure 1 report the level of asthma control by severity of the disease. The mean ACT score was rather consistent across the various categories of disease severity, being lower only for severe asthma (level 5). By contrast, whilst the pattern of mean ACT was homogeneous among females,it increased by disease severity in males ( Table 2).   Asthma control still represents a challenge worldwide [7,8] and the community pharmacies have been identified as a relevant partner in sharing this challenge with physicians [16]. Pharmacists canoffer a first point of contact with the health care services to patients,easy to access for disease counselling and symptom relief. In his way,community pharmacies somehow compensate the difficult access of patients to hospitalcare as well asthe limited time for consultationsdedicated inGPs [16,18].
Although the involvement of primary care (particularly pharmacists) in asthma control is recommended by current international guidelines [20], only a few studies have been conducted on this topic and none has been carried out in Italy [21][22][23][24] According to our results the level of asthma control assessed by ACTwas overall higher in comparison withstudies using the same tool but conducted in a medical setting in Italy [5][6][7][8]orin community pharmacies of other European countries [21][22][23][24]. Some reasons may account for this discrepancy. The mean age of our study population is >50 years, whilst in previous studies reporting a worse asthma control, a higher proportion of younger patients wererecruited. It has been previously reported that the prevalence of uncontrolled asthma is higher among young adults and adolescents [25].The older age of our patients raises issues ofdifferential diagnosis with other chronic respiratory conditions, particularlychronic obstructive pulmonary disease (COPD); in which casethe ACT may provide an unreliable score as it is not a validated instrument for obstructive syndromes other than asthma.However, the inclusion of the exemption code (007-493) among patients' selection criteria allowed us to overcome this confounding factor. On the other side,it is well known that patients' reported outcomes do not always tally withobjective measurable indicators [26,27].
Overall, our findings highlight an unsatisfactory asthma control from the pharmacists' perspective, independently of the asthma severity level. The main determinant of asthma control was treatment adherence and not the disease severity or other patient-related features.
The present study addressed two relevant points: the assessment of asthma control in the general population; and the potential role of community pharmacies in managing the disease.
Regarding the first issue, our main finding wasthat a low treatment adherence was the only determinant of poor asthma control (ACT<16). Although this result may be intuitive, it highlights the importance of the local pharmacies in monitoring treatment compliance for asthma, a critical aspect to control the disease.
Patients recruited in the present study showed a surprisingly high treatment adherence (92%), which seems unreliable, as typicallypatients tend to overvalue their compliance to therapy [26]. Further, this finding is in contrast with actual data from the Italian regulatory agency [27]. Nonetheless, the prevalence of patients with moderate and severe persistent asthma in our population may account for higher treatment adherence due to the severity of their disease. Moreover, since adult or elderly patients are more familiar and comfortable with the local pharmacists,they receive more frequent adviceon the need of regular asthma therapy.
On the other hand, in the present study the lack of asthma control was more common among patients with mild persistent asthma. This finding is not surprising, as in our previous pilot study we reported a 31% prevalence of uncontrolled asthma in a GP setting [8]. It is plausible that the presence of intermittent symptoms led these patients to a treatment on demand, with a consequent overuse of beta-2 short agonists and underuse of inhaled steroids. Moreover, these patients prefer selfmedication than regular follow-up by their GPs or by medical consultants. However, the risk of fatal asthma is still possiblewith mild persistentdisease, as recently reported [28].
Our study confirmed the potential role of local pharmacies in the management of asthma, giving patients the opportunity to be counselled ondisease control outside medical settings. However, whilst the positive results of this study suggest feasibility of asthma control at a local pharmacy level in real life, an overall inclusion of community pharmacist is a challenging target, as not allof themmay be interested in be involved in a similar health plan, ratingit demanding and time consuming, particularly in periods of the year of high morbidity withintense access to pharmacies [29]. Therefore, in addition tocareful selection of well trained, motivated community pharmacists, within a structured health plan, value-based incentives (VBI) programs may also be considered. Similar to other health care settings (e.g. GP practices), financial incentives could be granted to pharmacies to accomplish quality health outcomes in patients [17]. Beside assessment of asthma control, trained pharmacists have also the opportunity to teach patients about the disease and the proper use of medical devices,thus facilitatingpatients' engagement [30]. Moreover, the local pharmacy could also be an optimal setting to deliver spirometry tests for a fee. However, despitecharging patients for spirometry could motivate the participation of pharmacists in asthma control plans, similarmeasuresare still open to debate, sincethe interpretation of spirometry entailsspecific competences that should be limited to trained and certified pharmacies [31]. Finally, community pharmacies should be encouraged to provide counselling on smoking cessation, as in our study population one out of five asthmatic patients was a smoker.

Conclusions
The community pharmacy is an underuse yet widely accessible primary care setting potentially useful to promote the health of the general population [17].Due to the high prevalence of asthma, the inclusion of other allied healthcare professionals, such as the community pharmacists may represent a step forward to be considered with the view of improving the control of the disease. The main determinant for asthma control would appear to be compliance with therapy. Patients with chronic conditions may face barriers to access burdenedhealth care services in high income countries. Allied health professionals as local pharmacies may provide critical cost-effective support to screen patients for theirrisk of asthma, increase their knowledge of the disease, assess asthma control, improve inhalation techniques and follow up their treatment compliance. Distribution of patients by asthma control test (ACT) and severity of asthma.