Asthma is a chronic and heterogeneous disease1 that affects people from all ages and ethnicities worldwide.2 There is an estimated a global prevalence of 315 million people with asthma,3 contributing with more than 23 million of Disability-Adjusted Life Years (DALYs).4 Asthma prevalence has been increasing in many countries, in parallel with the development of urbanization and the adoption of modern lifestyles.5 It is estimated that by 2025 100 million of people more will have asthma worldwide.5

Despite the existence of treatment guidelines, many individuals with asthma remain undertreated and uncontrolled, resulting in a significant burden, not only in terms of quality of life, but also in terms of health costs.2 Health cost associated with asthma could be direct costs, like treatments and hospitalizations, as well as indirect costs, due to work absences and premature death.2 In 2010, the yearly cost per asthmatic adult patient in Europe, according to estimates from Accordini et al.,6 ranged from 509.é¼ for a controlled asthma patient to 2281.é¼ for an uncontrolled asthma patient.

The Global Initiative for Asthma (GINA) was created in 1993 with the objective of disseminating accurate information about asthma and improving the quality of asthma patient care worldwide.1 At present, according to GINA guidelines, achieving and maintaining asthma control represents one of the main goals for the management of the disease and consists of the evaluation of the control of symptoms and future risk of unfavourable outcomes.1

Numerous factors such as age, gender,7 comorbidities7,8 psychological aspects9 and socioeconomic determinants10 have been studied and reported as associated with asthma control. Behavioural reasons such as smoking habits7 or therapeutic compliance have also been related to poor asthma control levels.11

A multiway and a complex causal relationship between health, education level, work and income has been reported. Having a chronic disease can be considered a risk factor for employment. In Portugal, 66,294 of potential productive life years were lost due to non-communicable diseases (cardiovascular disease, diabetes, cancer and respiratory diseases) in 2013, according Organization for Economic Co-operation and Development (OECD).12

The Portuguese National Asthma Survey reported a proportion of 43.1% uncontrolled disease in asthmatic Portuguese population.13 In a national population study non-modifiable factors such as age and gender were associated with uncontrolled asthma.14 Self-evaluation of uncontrolled asthma, participation in decisions related to treatment and the presence of comorbidities have also been considered as important contributions to asthma control.14

The purpose of this study was to investigate the distribution of asthma control level in Portuguese adult population, using different approaches of control level evaluation, and to examine the determinants associated with uncontrolled asthma.

This study showed that 64.8% subjects had their asthma controlled, and 35.2% of them had uncontrolled asthma, according to the evaluation of a questionnaire for asthma control purpose, the ACT.

Evaluation of asthma control has been assessed in diverse countries worldwide and despite the different measurement tools used, a sub-optimal level of control has been revealed.

Results from a multinational study involving twelve countries of Europe (n=3.123), indicate a similar overall percentage (38.5) for uncontrolled asthma, with the lowest levels of asthma control found in Hungary, The Netherlands and France.7 Higher levels of uncontrolled asthma (71.3%) were found in surveyed African countries (Algeria, Morocco, and Tunisia),19 USA (71%),20 Asia-Pacific countries (92.4%)21 and Latin America (93%).22

From a national perspective, the Portuguese National Asthma Survey using Control of Allergic Rhinitis and Asthma Test (CARAT), reported 43.1% of uncontrolled asthma in Portuguese population.13 In 2007, a study in a central hospital in Lisbon using the ACT questionnaire in the context of allergology consultation found that 23.3% of the respondents presented ACT values .ëñ1911 and a study carried out in Portuguese pharmacies, with the application of the same questionnaire to evaluate the control, revealed even higher scores for poor asthma control (61.2%).23

In this study it was possible to observe that the level of control assessed can differ with the asthma control tool utilized. The different methodologies that can be used in epidemiological studies such as in clinical practice for control assessment [e.g., GINA based symptom control tool1; CARAT24; Asthma Control Questionnaire (ACQ)25; ACT16] can make it more difficult to compare results between studies. Additionally, there are different approaches used to gather information (e.g. telephone interview, online questionnaire, face-to-face interview), several methods used to assess asthma control level and different situations in different health systems, literacy and social barriers among the different countries; all of which should be taken into consideration when comparing results from different studies.

Most of the adult patients interviewed overestimated their disease control revealing a discrepancy between patient perception of asthma control and the objective measurement, since 93.9% of the individuals perceived their asthma with some level of control. It has been shown that most of these patients can tolerate their symptoms and lifestyle limitations as inevitable consequences of the disease.26 The self-perception and expectations about asthma disease may result in misinterpretations of control level.26

In terms of demographic factors, our results indicate that uncontrolled asthma was more frequently associated with older age and with female sex.

Asthma disease in the elderly population is of special concern since most of patients are polypathological and polymedicated, which can have a negative impact on disease management.27 Besides, there are often more difficulties in the execution of proper inhaler techniques.27,28 K.ñmpe et al.29 stated that uncontrolled asthma was more common in older groups (.ëÑ65years); Mendes et al.,23 using a Portuguese population, found that 69% of elderly (>70 years) had uncontrolled asthma.

Our results observing the association between sex and poor asthma control, are in agreement with other studies,23,29,30 with females associated with poor scores in asthma control. Usually women perceive asthma differently from men, reporting higher levels of symptoms and more limitations in day-to-day life.31,32 In addition, women have been associated with a higher incidence of later asthma onset and a higher prevalence of non-allergic asthma phenotype, favouring a less effective response to corticosteroid treatments.1,33,34

In this study, socioeconomic determinants, especially occupation have a considerable association with poor control score of asthma as well as greater influence on other important determinants. The PAR% for being looking for a first job or being unemployed was 26.8%, suggesting a very significant contribution for poor asthma control. Moreover studies identified that the severity of asthma,35 the frequency of asthma symptoms and night awakenings because of asthma can contribute to work disability and unemployment.36

The inverse association between income37 and education29 with poor controlled asthma outcomes has been documented. The PAR% register for having at least post-secondary education was 38.7% suggesting a contribution for preventing worse levels of control in asthma. The same positive contribution was verified for higher levels of income.

Individuals with higher levels of education can have a better understanding of the prescribed therapeutics and may have a greater tendency to adhere to treatment regime.29 Furthermore, there are work environments associated with trigger agents exposure (e.g., diisocyanates, acrylates or cleaning agents)38 to which individuals with higher educational levels are less likely to be exposed.29

Although only 8.8% of the individuals considered that the price of asthma treatments influenced taking medication according medical indications, asthma expenses related to medical treatments are usually high which can be a significant burden for low-income families,39,40 and in turn can compromise treatment adherence.

Higher BMI was shown to be associated with uncontrolled levels in asthma, as stated above: Lessard et al.41 found that regardless of a similar perception of symptoms, obese individuals had poorer asthma control than non-obese asthmatics; Lavoie et al.42 in a 382 adults study found that patients with higher BMI had poor asthma control (scored higher in ACQuestionnaire) independent of their age, sex and asthma severity; with an odds ratio of 2.99 (95% CI 1.14.Çô7.08) Ferreira et al.11 reported that obesity is a factor associated with non-control of asthma.

Obesity has a negative impact on overall breathing mechanisms,43 has been reported as a risk factor for the development of asthma and for increasing exacerbations and hospitalizations.44 The pro-inflammatory characteristics of obesity can induce more difficulties in asthma control, secondary to a reduction in the response to corticosteroids.45

Weight loss has been shown to improve lung function parameters in individuals with obesity and better scores of disease control in asthma patients.44,46 In this way, nutritional education promoting diet modification and weight loss in obese asthmatic patients must be encouraged.47 According to our results a considerable number of individuals (PAR%=23.5%) with uncontrolled asthma could be spared if obesity was not present.

Findings from studies11,48.Çô50 conclude that rhinitis is an important contributor to a non-optimal asthma control level, as also was supported by our results. Bousquet et al.51 in a multivariate analysis found that patients with simultaneous asthma and allergic rhinitis are associated with higher levels of acute exacerbations (OR 1.35, 95% CI: 1.03.Çô1.77) with more emergency visits (OR 2.35, 95% CI: 1.12.Çô4.80).

The PAR% register for having rhinitis symptoms in our study (65.9%) suggests that controlling nasal symptoms could contribute positively to preventing worse levels of control in asthma disease. Consequently, it is important to optimize the treatment of both diseases in patients with a concomitant diagnosis.52

The presence of smoking habits was not observed to be a determinant associated with poor asthma control in our study, as already stated.30,53 In this regard, other studies also did not identify smoking as an independent risk factor for uncontrolled asthma11 or for decline in lung function in asthmatic patients54 which could be related to a healthy smoker effect,55 underestimating the effect of tobacco at pulmonary level.

Nor was an association found with determinants of poor asthma control that have been reported in other studies, such as patients having a written asthma action plan56 and therapeutic compliance. Although a higher number of individuals have reported allergies as a trigger for asthma crises (78%), a significant association with uncontrolled asthma was not detected, which is similar to that reported by other research.11,53

Lung function assessment with peak flow metre or lung function tests were not significant determinants for asthma control in our study. However minimizing airflow limitation is one of the main goals for these patients and the importance of these exams in diagnosis and follow-up of asthma has been stressed.1

The use of inhaled corticosteroid plays an important role in an asthma treatment plan.1 Rabe et al.15 reported that the use of inhaled corticosteroids was low even among patients with severe persistent symptoms. In our study, the use of these medications was associated with lower ACT scores, which represents worse control outcomes. This association with the level of control could be explained by the relation of treatment plan with disease severity. For example, patients with mild asthma degree and well controlled symptoms might only be at step 1 of treatment plan and only using a reliever inhaler as needed, as was defined before 2019 GINA guidelines.1 However, severe asthma patients may present corticosteroid resistance,57 of which the molecular pathophysiology is beginning to be understood,58 leading to the possibility of development of new treatments for these patients.

In this study uncontrolled asthma was associated with several factors: age, sex, educational level, occupation, income, BMI, having rhinitis symptoms and use of inhaled corticosteroids as part of a treatment plan. Some of these factors remain associated after full adjustment, notably occupation, BMI and having rhinitis symptoms, which are important modifiable factors.

The values of PAR% for unemployment, obesity and rhinitis symptoms were relatively high (respectively 26.8%, 23.5% and 65.9%). Since these are modifiable factors from the point of view of public health and health planning, intervention strategies more directed to these concerns can promote benefits for asthmatic patients and consequently for other health problems. Similarly, their identification by physicians could contribute to a better clinical approach to asthma disease.

In future research there should longitudinal studies to confirm these associations and other comorbidities, such as COPD or GERD and enquiries made about physiological factors. It is also important to standardize a tool for asthma control evaluation that can be used in epidemiological studies and that can provide reliable comparison between studies.

This study was supported by a grant from the General Directorate of Health (DGS) of the Portuguese Health Ministry and by a scientific grant from AstraZeneca Foundation. The supporters did not have any role in the design and conduct of the study, nor in the collection, management, analysis, and interpretation of the data, or in the preparation, review or approval of the article.

The authors have no conflicts of interest to declare.