Discussion
This study described the characteristics of inhaler concordance and PIFR in Chinese patients with chronic airway diseases. Furthermore, this study demonstrated that suboptimal PIFR was an important determinant of poor inhaler concordance among patients with chronic airway diseases. Therefore, not only lung function but also inhaler concordance and PIFR should be assessed during the management of chronic airway diseases.
In accordance with Spanish studies,30 our study revealed that Chinese patients with COPD did not show an optimal proportion of good inhaler concordance, and Chinese patients with asthma were even non-concordant. Our results showed that patients with COPD were older and had worse lung function than patients with asthma, which might make patients with COPD more symptomatic and more likely to experience frequent exacerbations, thus leading them to perceive the necessity of inhalers and adhere to treatment.31 Some similar characteristics may explain why the concordance level between the ACO group and the COPD group was not significantly different. Given these results, we recommend assessing inhaler concordance and strengthening disease education for Chinese patients with chronic airway diseases to avoid worsening outcomes induced by treatment interruption.
Although some studies have described the characteristics of inhaler concordance and PIFR,29–32 the association between them has not been discussed in previous studies. Our study revealed that a suboptimal PIFR is a significant determinant of poor concordance among Chinese patients with chronic airway diseases, especially patients with COPD. To obtain the optimal efficacy of inhalers, inhalation must be able to generate an optimal PIFR to guarantee adequate penetration of the medication into the airways.28 Conversely, patients might lose confidence and eventually give up long-term inhaled therapy due to suboptimal PIFR, resulting in a compromised treatment effect. In addition, patients with COPD receiving triple therapy had a decreased risk of poor concordance. Many studies have confirmed the potential advantages of single-inhaler triple therapy (SITT) in improving inhaler concordance and persistence compared with the use of multiple inhalers.33–36 Combined with the findings of previous studies, our results may be explained by the high percentage of patients who developed better outcomes with SITT than with mono-/dual combination therapy.37 Accordingly, healthcare professionals should pay more attention to follow-up and concordance assessment among patients with COPD with suboptimal PIFR and mono/dual combination therapy.
Overall, 54.9% of patients exhibited suboptimal PIFR, suggesting that many patients cannot generate appropriate PIFR, which might lead to treatment failure. Multivariate regression analysis revealed that four independent variables including older age, lower educational level, use of DPIs and lower FEV1% predicted were associated with insufficient PIFR in all patients. The PIFR is inversely correlated with the internal resistance of inhalation devices.15 20 DPIs have greater resistance than pMDIs (no resistance) and are prone to result in lower and even insufficient PIFR. Although there was no linear relationship between the PIFR and FEV1,18 29 our study observed a greater proportion of insufficient PIFR in patients with lower FEV1% predicted. These results suggested that healthcare professionals should assess PIFR in Chinese patients with chronic airway diseases, especially in older patients with lower educational levels, worse lung function and use of DPIs.
Not only educational level, inhalation devices and FEV1% predicted but also the history of severe exacerbations in the past year was an important predictor of insufficient PIFR in patients with COPD. This may be because inspiratory muscle strength has difficulty completely recovering to a normal degree after serious exacerbations of COPD, leading to insufficient PIFR.38 39 In addition, our study indicated that patients with COPD presented a greater proportion of insufficient PIFR than did patients with asthma and patients with ACO, which might be attributed to older age, worse lung function and severe air trapping among patients with COPD.28 40 41 These results demonstrated that it might be more difficult for patients with COPD to overcome internal resistance to inhalation devices and thus obtain unsatisfactory and ineffective treatment outcomes.
One previous study assessed the difference in PIFR between patients with AECOPD and patients with COPD with stable status and indicated no significant difference between the two groups.29 However, our study revealed that the PIFRs of patients with COPD were lower during acute exacerbation than during a stable status. This contradiction may be due to the different study populations and the heterogeneity of people. The former is a comparison of two groups of people with different states, while the latter is a comparison of different states in a group of people. In addition, there was a larger sample size and a higher proportion of patients in GOLD stages 3 and 4 (58.8%) in our study. Due to hyperinflation and hypoxaemia, respiratory muscles are more fatigued and muscle function is often more compromised in patients with AECOPD than in patients with COPD with a stable status,19 resulting in a lower PIFR in patients with AECOPD. Deteriorative PIFR due to AECOPD might not satisfy the requirements of current inhalation devices and lead to ineffective inhaled therapy. In addition, multivariate regression analysis revealed that the use of DPIs and a lower FEV1% predicted were independent predictors of insufficient PIFR in patients with AECOPD. Therefore, we suggest that patients with AECOPD, especially those with worse lung function and those in groups C and D, should receive a PIFR assessment to determine the optimal inhalation device during exacerbation. On the other hand, nebulisation may rapidly and effectively alleviate symptoms in patients who are unable to measure PIFR for various reasons during exacerbation and therefore cannot determine their optimal inhalation device.23 42
Similar to previous studies,43 our results showed that the PIFR was negatively associated with age and years since diagnosis among patients with asthma. For patients with ACO, a lower FEV1% predicted was the only and strongest determinant of insufficient PIFR. Accordingly, caution should be taken among older patients with asthma with a longer course of disease and patients with ACO with GOLD stages 3 and 4 because they may benefit more from PIFR-optimisation of inhaler choice. It should be noted that the sample sizes in the exacerbation group and GOLD stages 3 and 4 groups of patients with asthma were too small to compare the difference in the PIFR between each asthma subgroup. Similarly, despite a higher percentage of insufficient PIFR in the exacerbation group than in the stable group among patients with ACO, the difference was not statistically significant, which might be due to the small sample size.
There were some limitations in this study. First, the main limitation was utilisation of self-reported questionnaire to assess inhaler concordance. The authors considered that using a self-reported questionnaire was the better option for study design and aim since it is simple and flexible for clinicians, although it can under-report non-concordance. In the corresponding literature, there is an abundance of concordance questionnaires, however, in our study, the chosen questionnaire was TAI because of its specialisation in chronic airway diseases. Further studies should combine self-reports with objective measurements of concordance (eg, prescription refills) to determine inhaler concordance. Furthermore, a larger sample size is needed to observe the characteristics in subgroups of patients with asthma and patients with ACO. In addition, we will determine whether PIFR-optimisation of inhaler choice can improve clinical outcomes in a future prospective study.