Pulmonary function in adults with recent and former asthma and the role of sex and atopy

Asthma is an inflammatory airway disease and airway function may not be completely reversible in those with asthma. Studies have revealed reduced pulmonary function in individuals with clinically stable asthma [1] or a history of asthma [2, 3] in children and young adults. Chronic airway inflammation may result in long-term pulmonary function reduction in asthma patients [4, 5] including thickening of the airway wall and the development of incompletely reversible airway narrowing, airway hyperresponsiveness, and reduced airway distensibility [6]. The anomalies may occur early in disease pathogenesis [7, 8], and continues into adult life [9], however data from adult populations are scarce. Atopy may [10] or may not [1, 11] influence the association between asthma and pulmonary function. In this study we examined the association between asthma and pulmonary function and the effect modification of sex and atopy in a general population of adults to clarify these issues.

Of 2057 participants, 1492 (72.5%) provided all related questionnaire information, had pulmonary function testing and skin prick testing results and height, weight and WC measures. Table 1 describes the distribution of anthropometric measures, pulmonary function testing variables and pack-years of smoking according to the status of ever asthma stratified by sex and atopic status.

In multivariate analysis, we first examined the independent associations of FVC and FEV₁ and FEV₁/FVC ratio with ever asthma, sex and atopy. Age, height, weight, WC and pack-years of smoking were important predictors for FVC and FEV₁ and/or FEV₁/FVC ratio and were included in the regression models (Table 2). Body mass index was no longer significant predictor and was excluded from the models. Interactions for these variables with asthma status were not statistically significant at the alpha level of 0.05. Ever asthma was significantly associated with reduced FEV₁ and FEV₁/FVC ratio, while atopy showed no impact on the pulmonary function testing variables. Women had lower mean values of FVC and FEV₁ compared with men, but average FEV₁/FVC ratio was almost the same.

Similar results were revealed when former asthma and recent asthma were considered separately. Significantly lower values of FEV₁ and FEV₁/FVC ratio were observed in those with former asthma than those with no asthma and in those with recent asthma than those without recent asthma (Figure 1).

The association between asthma and reduced FEV₁ was more pronounced in men than in women and in non-atopic than atopic individuals. Table 3 shows that on average people with ever asthma had a reduction of 0.33 L of FEV₁ compared to non-asthmatic persons in men (p<0.05), and the corresponding reduction was only 0.09 L for women (p > 0.05). The interaction between asthma and sex was statistically significant. Ever asthma was associated with a reduction of 0.20 L of FEV₁ in people with no atopy (p<0.05) and with only 0.10 L in atopic people (p > 0.05), but the interaction between ever asthma and atopy was not statistically significant. Similarly, the association between ever asthma and FEV₁/FVC ratio was statistically significant in men and non-atopic people, but not in women and atopic people, while the interaction between asthma and atopy did not reach statistical significance. We did not detect other important effect modifiers for the association between asthma status and pulmonary function testing variables.

Our data demonstrated that adults with asthma had reduced airway function indicated by FEV₁ and FEV₁/FVC ratio in adults. This reduced airway function was observed not only in adults with recent asthma but also in those with only former asthma. Our results are consistent with earlier observations among children and young adults. Nakadate and Kagawa [3] investigated 441 primary school children and found reduced lung function with a history of asthma even if they had been in remission for several years. Yang et al. [1] found reduced lung function in 242 children with clinically stable asthma compared with 100 non-asthmatic controls. Mosfeldt Laursen et al. [2] studied 77 children or young adults aged 12–24 years with former asthma, current asthma or no asthma and demonstrated that former asthmatics with no current respiratory symptoms had obstructive airflow limitation and increased bronchial responsiveness.

Our data suggest that in adults with recent or former asthma, pulmonary function was not fully reversible. The damage to airway function is likely due to pathological modification of the bronchial airway structures or airway remodeling. Although the mechanisms are not fully understood, there is an expansion of the airway wall vascular compartment involving both enlargement of existing vascular structures and the formation of new vessels [6], and an increased smooth muscle mass and airway narrowing [18]. Damage to the epithelium may play an important role in the process, which can be caused by exposures to pathogens, allergens, environmental pollutants, cigarette smoke, and mechanical injuries [19]. Irreversible loss of pulmonary function in asthma can begin in childhood and continue into adult life [9]. In a cohort from birth to the age of 26 years Rasmussen et al. [9] found that asthma in childhood was associated with a low postbronchodilator ratio of FEV₁ to vital capacity at the age of 18 and 26 years, and with an accelerated decline in pulmonary function and decreased reversibility. Thus, asthma may cause some permanent airway function damage. Irreversible airway obstruction is related to poor prognosis in asthma [20].

In the present study, we found that sex was a significant effect modifier for the association between asthma and pulmonary function. The reduction in pulmonary function due to recent or former asthma was more marked in men than in women. A previous study showed that asthma and male sex were independently associated with low postbronchodilator ratio of FEV₁ to vital capacity [9]. In animal studies, sex influences the remodeling process in asthma [21, 22], and possible reasons need to be further explored. Reporting bias should not be ignored for the observed sex difference if men tended to under-report and/or women to over-report asthma. In our study, women were more likely to have asthma than men, and this has been observed in previous surveys in the same region and in Canada. A recent report demonstrated that female sex was an independent risk factor for the incidence of non-allergic asthma [23]. Non-allergic asthma was more likely to be under-diagnosed but the diagnoses bias was similar for men and women [23] The differences in asthma prevalence and incidence need to be further explored.

Our data demonstrated that atopy had no notable impact on pulmonary function. Some previous cross-sectional and longitudinal studies have shown no significant associations between atopy and FEV₁ in adults [24, 25]. One study found that atopy alone was not related to the FEV₁, but in atopic patients the relationship between bronchial hyperresponsiveness and FEV₁ was stronger compared with nonatopic patients [26]. Other studies demonstrated that atopy was related to lower lung function in young adults with asthma [27] or independently of asthma [28]. Atopy seems not an independent risk factor for pulmonary function in children [1, 29], although atopy was found to be associated with low pulmonary function in children with asthma or wheeze [30]. Our study showed that atopy did not significantly modify the association between asthma and pulmonary function and was not an important risk factor for pulmonary function in adults.

Among the study subjects, 27 reported using asthma medication during the past 12 months. Self-reported asthma medication use during the past 12 months did not significantly predict pulmonary function or modified the association between asthma and pulmonary function testing variables. One limitation of the study is that asthma diagnosis is solely based on self-reporting. The current study did not have information on bronchial hyperreactivity. If pulmonary function was fully reversible in asthma and chronic obstructive pulmonary disease (COPD) was misdiagnosed as asthma, we would have observed reduced pulmonary function in “asthma” patients. Since COPD is common in elderly people but rare in young adults, we analyzed the data stratified by age. The association between self-reported asthma and pulmonary function was similar in younger and older age groups. In addition, self-reported former asthma, which is not likely to be COPD, was significantly related to low pulmonary function, suggesting possible information bias is not an explanation for our findings. In this study we used four most important allergens for our skin prick test and 28% were positive. A larger panel of allergens would increase the likelihood of atopy detected, and there was a potential under-diagnosis of atopy in our study.

There was reduced pulmonary function in adults with ever, recent or former asthma and the association tended to be stronger in men than in women, but similar in those with and without atopy. There is a possibility that airway remodeling in asthma results in reduced pulmonary function and risk factors for irreversible airway obstruction need further investigation.