In this study, we investigated the correlation between comorbidities and hospitalisation for asthma exacerbation (H-AX) based on CARN 2015, a multi-centre cross-sectional survey participated by 3875 asthma patients in China. As shown, 75.9% of our study population suffered a wide range of comorbidities involving the lungs, heart, vessels, immunity and metabolism. Over a quarter (26.4%) experienced at least one hospitalisation for asthma exacerbation during the previous year, of whom, 12.3% experienced three or more hospitalisations. We showed that comorbidities in asthma patients played an important role in H-AX events. Specifically, comorbidities such as structural lung disease (COPD, bronchiectasis), cardiovascular disease (hypertension, coronary heart disease) and metabolic disorders (diabetes) were associated with the likelihood of any H-AX, whereas H-AX ≥ 2 or ≥ 3, was linked to comorbidities like allergic rhinitis, COPD, diabetes, GERD, and cerebrovascular disease.
Of allergic comorbidities, nasosinusitis and rhinopolypus are common in asthma patients, and were found in 75–80% of severe asthma cases [17, 18]. Nasosinusitis and confirmed food allergy are independent risk factors of asthma exacerbation [6, 19]. Several previous study indicated poorer asthma outcome with comorbidity of allergic rhinitis [20–22]. In this study, we failed to determine a correlation between nasosinusitis, rhinopolypus, food allergy, and asthma exacerbation or frequent H-AX. Surprisingly, asthma patients who experienced H-AX presented lower prevalence of allergic rhinitis; we speculated that this puzzling observation may be associated the higher rate of co-treatment in patients with mild allergic rhinitis, although we did not perform a subgroup analysis for demonstration. However, in terms of H-AX frequency, allergic rhinitis was associated with two or more hospitalisation related to asthma in the previous year.
Cardiovascular disease can influence asthma outcomes, and vice versa. Schanen et al.  reported that asthma patients were more likely to have cardiovascular disease. In a previous survey among adults aged ≥ 65 years, asthma patients with coronary artery disorders showed fairly higher adjusted odd ratios for one or more asthma-related hospitalisations . In the present study, cardiovascular comorbidities were linked to H-AX. We indicated that coronary heart disease was associated with significantly higher likelihood, but not frequeny, of H-AX.
Metabolic disorders are also common in asthma. Obesity has been reported to relates with increased asthma severity and exacerbations . In this setting, data about diabetes remain limited. Song et al. found that women who had ever reported asthma or COPD were at a higher risk for diabetes [26, 27]. Diabetes and insulin resistance are associated with decline in lung function [28–30]. In our study, having diabetes was associated with significantly higher likelihood and frequency of H-AX in univariate analyses, but the statistical differences were not reached in subsequent multivariate logistic analyses. In either univariate or multivariate analysis, cormorbidity with obesity did not correlate with H-AX in likelihood or frequency. Therefore, the role of metabolic disorders in H-AX warrants future studies.
The interplay between asthma and respiratory comorbidities, structural lung diseases in particular, should be noteworthy to mention. Compared to asthma or COPD alone, asthma-COPD overlap leads to heavier burden of symptoms , incurs more frequent exacerbations [31–33] and accounts for greater use of healthcare resources [32, 34]. Mao et al.  noted that concomitant asthma was associated independently with an increase in risk of bronchiectasis exacerbation. In contrast, few studies assessed the impact of bronchiectasis on asthma exacerbation. Kang et al. showed higher annual incidence of asthma exacerbation and frequency of emergency room visits in patients with asthma and bronchiectasis than in those with asthma alone . In the present study, we demonstrated that comorbidity with structural lung diseases, such as COPD, was associated with both higher annual incidence and frequency of H-AX. We believe that our findings add to the evidence supporting the adverse impacts of structural lung disease on asthma outcome.
Concomitant GERD is estimated to affect 34–89% of asthma patients ., and has been linked to the severity of asthma [38, 39]. However, our results indicated neither a higher prevalence of GERD in the asthma patients, nor a statistical correlation of GERD with the likelihood of H-AX. We speculated the self-reporting of comorbidities in CARN 2015 study might undercut the GERD prevalence. Notwithstanding this, in our study, GERD was associated with more frequent H-AX in the univariate analysis albeit with no statistical significance in the multivariate logistic regression.
Finally, we need to elaborate on several special considerations pertaining to the strength and weakness of our study. Firstly, to the best of our knowledge and data availability, CARN 2015 study is so far the largest nationwide survey on H-AX and comorbidities among Chinese asthmatics over the recent years. Using relevant information from full dataset of CARN, our findings regarding the relationship between certain comorbidities and the likelihood and/or frequency of H-AX in asthma patients could therefore be a close reflection of the real world in China. Secondly, comorbidities associated to the risk and/or frequency of H-AX in this study chiefly involved structural lung diseases and chronic, systemic disorders. Given that this was merely an observational rather than a mechanistic study, our findings should be interpreted with prudence and do not mean to propose a causative relationship. Nevertheless, comorbid abnormality in pulmonary architecture, systemic inflammation and immune function, could impose unfavorable impacts on the natural history and treatment outcomes of asthma which is an immune, inflammatory disorder per se. In this context, the goal of asthma control can be achieved not only depending on efforts of respiratory physicians, but also involving a multi-disciplinary treatment protocol. Either other systemic conditions as comorbidity in asthma, or asthma as comorbidity in other systemic conditions, need to be ideally taken together in decision-making for treatments. Thirdly, according to GOLD , annual exacerbations ≥ 2 or hospitalisation due to COPD exacerbation ≥ 1 was defined as frequent COPD exacerbation. However, similar criteria have not been widely recognised for “frequent” asthma exacerbations or “frequent” H-AX. As an attempt for description in this study, we tentatively stratified the asthma patients according to one, two, three or more H-AX in the previous year and also by taking into consideration the comorbidities. The times of H-AX statistically differed with such stratification. Our statistics showed that using annual sessions ≥ 2 or ≥ 3 in a patient was comparably acceptable to define exacerbations as “frequent” in asthma, as like in COPD. In this regard, our work may add to determination of the definition of frequent asthma exacerbation, rendering more discussions needed in the future.
The study has several limitations. Self-reported comorbidities may underestimate the real prevalence and be influenced by interviewees compliance. More confounding factors, such as medications and treatment adherence, should have been included in analyses. Future investigations with follow-up study or comorbidity intervention study would help to validate our findings and clarify more on the relationship between comorbidities and hospitalisation due to exacerbation in asthma patients.