Asthma is a heterogeneous entity that is the result of complex interactions between environmental and genetic factors. The expression of the disease can vary with age, sex, airway inflammation patterns or severity, association with atopy or other triggering factors.1 In recent years, various clinical subtypes of asthma have been described and to date it is still unknown whether they are variations of a same disease or whether, contrarily, they are different diseases that run their course with similar symptoms.2

World-wide, asthma affects approximately 300 million people and, despite the notable therapeutic advances, it currently causes around 250,000 deaths per year. In Spain, according to the results of the European Community Respiratory Health Survey, the prevalence is high, although there is a clear geographical variation, ranging from 5% in Galdácano to 14.5% in Huelva.3

Given the high prevalence and the incidence of said affectation in the western world and its socioeconomic consequences, there is a need to identify risk factors in order to define possible primary prevention strategies.1,4 Currently, there are a very limited number of recommendations to prevent the development of asthma with sufficient scientific evidence.5

The current understanding about risk factors for developing asthma is mostly based on studies carried out in children; meanwhile, those involved in the development of the process in adults are less defined.4 In adults, atopy has been associated with the development of asthma as have the exposure to possible allergens present in the home and environment, such as pollen and grasses.6

A close relationship has also been reported between rhinitis and asthma. Both entities coexist in a large majority of patients and they share common risk factors, as is the case of atopy.7 Allergic rhinitis tends to precede asthma, and some authors propose it as an independent risk factor for the development of asthma, even in persons over the age of 50.8 Furthermore, if smoking and chronic sinusitis are excluded, the risk factors for the development of asthma in adults have not been clarified.

The objective of this study is to describe the clinical profile of asthma patients and identify possible risk factors for the development of asthma in subjects over the age of 12.

A total of 369 researchers recruited 1475 subjects. Out of these, 552 (37.6%) were excluded for not meeting the selection criteria. In the final sample, 918 subjects were included (62.6%), out of which 247 were cases (26.9%) and 671 controls (73.1%). In total, 490 cases and 62 controls were excluded.

The reasons for exclusion were: the diagnosis of asthma more than 12 months before (467); the onset of symptoms indicating asthma before the age of 12 (69); being younger than 12 or older than 40 years of age (59); having a spirometry compatible with a restrictive or mixed pattern (4); incomplete data (1) and/or lack of informed consent (1). The control subjects were excluded for being under the age of 12 or older than 40 (56); presenting some type of chronic respiratory disease (6); incomplete data (1) and/or lack of informed consent (1).

The characteristics of the patients are reflected in Table 1, 54.9% were women. Mean age was 30.1±7.5. In the case group, the mean age was 28.3±8.2 (P<.0001), 43.7% of the subjects had secondary school education, 35.6% university studies and 19.1% primary studies.

The mean body mass index (BMI) was 25±4.7. According to the classification of the WHO, 54.2% of the patients had a normal body weight, while the rest presented obesity at varying degrees.13 No statistically significant differences were observed between the different groups.

22.2% of the subjects evaluated were active smokers, with no significant differences between the groups. The average number of daily cigarettes in the sample was 12.9±8, which was less in the case group at 11.4±7.8, while in the control group the amount was 13.4±8.1 (P=.047). The average number of years smoking was 11.3±6.2, with no differences observed. The pack-years index of the cases was 6.1±5.6 and that of the controls was 8.4±7.4 (P=.004).

12.5% of the individuals studied had an occupation at risk or were exposed to environmental irritants, which was more frequent in the case group (P=.004). Among the irritating agents which the patients reported being exposed to in the work setting were cleaning products (26.1%), smoke/fumes (26.2%) and chemical agents (15.3%).

The allergens due to which the cases were sensitized were mainly inhalants: pollens 61.5%, dust mites in el 59.8% and animal epithelial cells in 25.5%, respectively. Only the allergy to dust mites (P=.026) and animals (P<.001) showed significant differences between the cases and controls.

As for their personal medical histories (Table 2), the mean age at onset was 24.1±11.2 in the case of atopic dermatitis, rhinitis at 18.9±8, hypersensitivity or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) at 24.8±10.7 and anxiety disorders at 25.6±7.6. Statistically significant differences were found in atopic dermatitis, rhinitis, hypersensitivity or intolerance to (NSAIDs), hypersensitivity to other allergen and gastroesophageal reflux disease.

When we correlated the odds ratio and 95% CI according to analysis groups, it was found that the patients with a history of non-infectious rhinitis had 3.4 times more risk for developing asthma. Those with hypersensitivity or intolerance to NSAIDs showed 3.3 times more risk, and those with hypersensitivity to other allergens (pollen, dust mites, fungi, animals) had 4 times more (Table 3). Among the variables analyzed, age (OR=0.969; 95% CI 0.948–0.991) and level of studies (OR=0.684; 95% CI 0.546–0.856) were demonstrated to be protective factors. Out of the comorbidities researched, only hives, chronic sinusitis and anxiety disorders showed no relationship with the diagnosis of bronchial asthma.

Table 4 shows the data for the family histories, 29.2% of the patients with asthma had a family history of atopy. Of these, 80.6% were immediate family members, with no differences between the groups. The most frequent history finding was bronchial asthma, present in 27.9% of the subjects. A family history of asthma was present in 40.2% of the cases, compared with 23.4% of the controls (P<.001). This factor was detected more frequently in the immediate family members of the cases (77.6%) compared with the controls (64.9%) (P=.0333).

The mean age at the onset of asthma symptoms was 24±8 and the mean age at diagnosis was 27.4±8.2. Intermittent asthma was presented by 31.9% of the patients, mild persistent asthma by 41.5% and moderate persistent asthma by 25.8%. Only 0.9% presented severe persistent asthma.

The agents most frequently reported as precipitants of asthma exacerbations were respiratory infections (40.9%), followed by physical exercise (37.7%) and emotional stress (11.3%) (Fig. 1).

Fig. 1.

Main triggers for asthma symptoms.

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In Tables 5 and 6, spirometry levels are given both before and after bronchodilation, respectively. The ratio between forced expiratory volume in one second and forced vital capacity (FEV1/FVC) presented statistically significant differences (P<.001). The FEV1/FVC ratio in the spirometry after bronchodilation did not show differences that were statistically significant. When correlating the odds ratio and the 95% CI by analysis groups, it was observed that the patients with a lower pre-bronchodilator FEV1/FVC ratio had 1.04 times more risk for developing asthma and those with lower post-bronchodilator FEV1 had 1.02 times more risk for having asthma.

Bronchial challenge tests with methacholine or histamine were done in 15.7% of the patients in the case group and 5.5% of the subjects of the control group at the age of 26.8±7.5 and 28.9±8.3, respectively. The result was positive in 43 of the 68 patients who underwent the bronchial challenge (63.2%), more frequently in the case group (94.4%) than in the control group (P<.001). The patients who underwent a provocation test with methacholine or histamine were 3.2 times more likely to develop asthma, and those in whom the result was positive had 43.5 times more risk.

All the patients who underwent the bronchial provocation test had a previous bronchodilator test, therefore the number of subjects who underwent all the studies was 38 cases and 35 controls.

Another of the aspects evaluated in this study were the asthma control and quality of life scales. The mean score of the ACT scale in the group of patients with this disease was 20.5±3.8. Insufficient asthma control was presented by 30.9%. As for the SGRQ, the mean score for the “symptoms” domain was 41.2±17.4, for the “activity” domain it was 26.7±21.7, for “impact” 34.4±12.1 and the total mean score was 33.1±13.7. Last of all, the mean total score on the AQ20 scale was 6±3.9.

This study shows that the variables associated with the presence of asthma in the population between the ages of 12 and 40 are hypersensitivity to animals, level of studies, hypersensitivity to other allergens, rhinitis, age, family history of asthma, occupational exposure to irritants and hypersensitivity or intolerance to NSAIDs. While older age and the higher level of studies behave as protective factors for the appearance of bronchial asthma, hypersensitivity to animal epithelia and other allergens, rhinitis, family history of asthma, work exposure to irritants and hypersensitivity or intolerance to NSAIDs behave like independent risk factors.

One of the most interesting findings among the subjects of our sample is the fact that the risk for presenting asthma diminishes with the age of the patients. This finding agrees with the data from previous studies, such as those carried out in the United Kingdom and Australia, which performed follow-ups until the ages of 33 and 35, respectively, with children who had started to have asthma at early ages.14,15

According to the results of our study, the lower the cultural level of the patient, the greater the risk for presenting asthma. With regards to this fact, some authors have argued that the lower socioeconomic status and cultural level could explain the greater prevalence of asthma in certain ethnic groups, such as Puerto Ricans who reside in the United States.16 However, there are currently no consistent data that establish a clear connection between the risk for having asthma and socioeconomic level.17

The sensitization to animal epithelia seems to have a clear relationship with asthma in adults. It has been demonstrated that the aeroallergens from dogs and cats are associated with smaller-sized particles than other allergenic sources, which facilitate their penetration into the lower airways and increase their pathogenic potential.18 But, paradoxically, the presence of animals in the home does not seem to be related with the diagnosis of asthma, which concurs with the notifications made regarding the innocuity of dog epithelium, and even its protective role. In the case of cats, the results to date have been more disparate.19

In the subjects evaluated in the present study, there is a notable incidence of rhinitis and nasal polyposis in patients with asthma, which at the same time conditions a greater severity of the latter. Prospective studies with up to 20 years of follow-up affirm that rhinitis is a risk factor for the development and severity of asthma. Numerous studies show that both entities often coexist in the same patient, and that a large part of asthmatics present symptoms of rhinitis. Rhinitis appears in 75% of patients with allergic asthma and in 80% of those with non-allergic asthma.20,21 A multicenter Spanish study about the coexistence of rhinitis and asthma corroborates the high prevalence of the referred to association in allergic patients, affecting 89.5% of a total of 942 included in the study.22

What is evident in our study is the importance of family history as a risk factor for the diagnosis of asthma in adults. Even though to date this tendency towards family aggregation leaves little room for doubt,23–25 the attempts made at establishing a pattern of inheritance have been unfruitful, probably due to the fact that bronchial asthma can be the phenotypic expression of different genotypes.26

With regards to the exposure to certain irritating agents in the environment, this present study has demonstrated that it is a risk factor for the development of asthma in adults. In the case of occupational asthma, it has been confirmed that the continuous exposure to the causal agent is associated with a poorer prognosis and with a more accelerated decrease in lung function.27,28

The relationship between adult asthma and intolerance to NSAIDs is well known. Between 5% and 10% of asthmatic adults present exacerbations after the administration of acetylsalicylic acid,29 associated in the characteristic ASA triad (asthma, intolerance to NSAIDs and nasal polyposis). Our finding corroborates this relationship as other studies have previously done.29–31

In agreement with numerous previous studies, we have also been able to verify that in our patients respiratory infections can exacerbate bronchial asthma as they are known to be capable of increasing the degree of bronchial hyperreactivity32 and to produce various alterations in the airways that compromise their maintained function.33

Even though in our study smoking showed no statistically significant differences between cases and controls, the greater asthma severity in active smokers is well known.34 Likewise, both smoking and rhinitis predict a great risk for developing bronchial asthma in the future.35

Even though it is accepted that low physical activity is closely related to the risk for developing obesity, in our study no statistically significant differences were observed between the cases and controls in this aspect. This fact contrasts with the data of the National Asthma Survey36,37 regarding the level of sedentarism and excess weight or obesity and their influence in asthma, which established a relationship between obesity and severity of asthma in American adults. In this same direction, in a multicenter study recently published in the United States with a population of 368 adolescents between the ages of 12 and 20 with moderate-severe asthma, it was observed that adiposity is associated with poorer asthma control only in women, as there was evidence of a better control of the disease in males due to influx by adiponectin.38 However, in 2002 Phelan et al. published a study on risk factors in adult asthma carried out in monozygotic and dizygotic twins in which a protective effect was found for sedentary lifestyles with regards to developing asthma, indicating that excessive physical activity would be considered a risk factor for a subject to have episodes of bronchospasm.39 This could be related to our finding.

This present study has some limitations that should be kept in mind. As it is a cross-sectional study, we cannot establish causal relationships nor can we give a temporary evaluation in the conclusions. On the other hand, as we have selected patients between the ages of 12 and 40, we have not evaluated a high percentage of asthma patients, and therefore the conclusions obtained may only be extrapolated to this age group.

Likewise, the study is limited by the fact that the recruitment of cases depends upon the fact that the patients assure not having presented symptoms before the age of 12. In this point, there may be an evident memory bias as patients, especially with a history of asthma at early ages, may not be able to properly relate it during the medical interview. This takes on more importance when we consider that 31% of the sample presented intermittent symptoms, among whom memory bias would be more frequent.

In addition, the fact that not all the patients underwent the bronchodilation test and the bronchial provocation test with methacholine or histamine could make the study fall into a selection bias, as patients considered asthmatic may not be, despite having compatible symptoms. This seems not to affect the group of control subjects as they did not have subjective symptoms of bronchial asthma.

In conclusion, there are different variables associated with the development of asthma in adults. Their identification may help prevent the appearance of this disease in said population. Therefore, longitudinal studies are required in order to clarify the role of these factors in the development of asthma in adults.

Pfizer.

Verónica Sanz de Burgoa Gómez-Piñán is an employee of Pfizer. The rest of the authors have no conflict of interests.