There is a sharp increase in asthma prevalence since the 1960s, especially in developed countries[4]. It was proposed that decreased exposure to house dust, mites, fungi, and other unhygienic environments in the developed country contributes to the increasing number of asthma patients[19]. As expected, our study highlights the increase in total prescription counts per year and the number of patients with asthma exacerbations. However, the rise in physician-identified patients and the implementation of electronic medical records can also contribute to the increase in our findings.
In this retrospective, real-world analysis, we demonstrated the prevalence of different medications used for asthma management in China. ICS is part of the first-line therapy in asthma, regardless of disease severity. It is delivered directly into the lungs, thus, limiting the systemic adverse effects of corticosteroids[20]. The underuse of ICS may be due to poor adherence, intolerable side effects, contraindications, and concerns for increased risk of pneumonia, especially in patients with mild or moderate asthma. Over half of the cohort uses ICS for stable asthma. ICS-containing medications were prescribed to 44.66% of patients with stable asthma, similar to ICS uses in the U.K. and the U.S, both over 40%[21, 22], and much higher than those in Japan and Korea, which were around 10% [23]. This proportion is also higher than 10.2% reported by Huang, et al in patients with physician-diagnosed asthma[6]. The conflicting results of ICS use may be due to the changes in the guidelines, the perceptions of long-term steroid use, and the transformation of hand-written medical records to electronic data.
According to the GINA report, ICS/LABA is recommended in almost all adult asthma patients. Regular use of ICS and LABA allows a lower dose of ICS, improves symptom management, and reduces the risk of exacerbations[24]. In addition, the combination is more effective than ICS+LTRA[25]. In our study, ICS/LABA was the most frequently prescribed medication (33.67%) to patients with stable asthma, much lower than 90.2% of patients in the INITIAL study[26]. There was a significantly decreased risk of exacerbations (P < 0.05) in patients using ICS+LTRA. Our finding is consistent with earlier studies regarding the benefits of ICS/LABA[24, 27-29].
LTRA improves asthma control and reduces the frequency of asthma exacerbations, but is less effective than ICS[30]. Therefore, LTRA is listed by the guidelines as an alternative add-on in patients with moderate or severe asthma. LTRA is the second most prescribed medication in our cohort (22.97%). However, LTRA did not show significant benefit in preventing exacerbations in this study.
In our cohort, over 60% of patients received TCM management. Though the exact mechanisms of TCM are still unclear, it has shown some effects in anti-inflammation, airway relaxation, and reducing airway hypersensitivity[31]. TCM, used as adjuvant therapy, can reduce asthma symptoms, enhance patients’ lung function, and improve the quality of life, but the treatment effects were limited and may not reduce the risk of exacerbations[31, 32]. Our study showed a continuous decrease in TCM use over the years while increasing use of western medicine, which may be explained by the implementation of the guidelines or the limited efficacy of TCM in patients with moderate to severe asthma.
The GINA report recommends using SABA, oxygen, intravenous corticosteroids, and ICS for managing exacerbations. Other studies showed that 87% to 92.24% of patients with asthma exacerbation received ICS or ICS/LABA or ICS/LABA[33, 34]. In the current study, systemic antibiotics (57.91%), systemic corticosteroids (46.1%), and theophylline (51.45%) were frequently prescribed to patients with asthma exacerbations. The rate (51.45%) of theophylline use during acute exacerbations of asthma, which is comparable to theophylline application in the UK[35]. Theophylline reduces days of hospitalizations but is not as effective as SABA in improving lung functions in acute settings[36]. In addition, theophylline requires frequent blood concentration monitoring to avoid toxicity. It is no longer recommended due to its poor efficacy and safety profile.
Strengths and Limitations
To our knowledge, this is the largest retrospective observational cohort study evaluating real-world prescribing patterns of asthma medications in China. It is also the first one that includes both western medicine and TCM for asthma management, and changes in asthma medication use over time. The study has several limitations. First, the data extraction was based on the medical encounters recorded in the data platform. Office visits and prescriptions that were in paper-based records were not included which might account for the lower proportion of patients receiving each medication. Changes in medications in patients did not experience exacerbations, and medication adherence was also not analyzed in the study. Due to the nature of retrospective observational design, the strength and frequency of medication were decided by physicians. In addition, it is unclear why each medication was prescribed. Lastly, the specific TCM prescribed was not included in the study, thus the effect of TCM in addition to western medicine on asthma management cannot be determined.