Treatment of Asthma in the Elderly : Questionnaire Survey in Japan

Introduction: The prevalence of asthma in the elderly has been increasing due to the aging of the global population. Appropriate treatment for asthma in the elderly is now a major issue, as the disease is often fatal and incurs high medical costs in the elderly population. There have been few recent reports on asthma treatment for the elderly in the real-world clinical settings. Objectives: This study was performed to assess how respiratory physicians manage asthma in elderly patients in clinical settings in Japan. Methods: Respiratory physicians in 16 Japanese hospitals responded to a questionnaire survey on asthma and COPD treatment between December 2014 and February 2015. The analysis was performed using data collected from medical records on 2041 asthma patients. Results: The mean patient age was 61.2 years, and 36.6% of the patients were men. In the breakdown by age, 1018 (49.9%) of the patients were elderly (≥ 65 years). Compared to the non-elderly, the elderly patients How to cite this paper: Chiba, S., Tsuchiya, K., Ogata, T., Imase, R., Yagi, T., Mishima, Y., Jinta, T., Saito, K., Taki, R., Isogai, S., Jinn, Y., Kawasaki, T., Natsume, I., Miyashita, Y., Takagiwa, J., Ishiwata, N., Chiaki, T., Kishi, M., Tsukada, Y., Yamasaki, M. and Inase, N. (2017) Treatment of Asthma in the Elderly: Questionnaire Survey in Japan. International Journal of Clinical Medicine, 8, 236-247. https://doi.org/10.4236/ijcm.2017.84023 Received: March 19, 2017 Accepted: April 27, 2017 Published: April 30, 2017 DOI: 10.4236/ijcm.2017.84023 April 30, 2017


Introduction
The prevalence of asthma among older adults has been reported to range from 2.5% to 7.0% in Europe and the United states [1] [2] [3] and is predicted to continue increasing in the future as the global population ages [4].Asthma in the elderly requires urgent attention in view of the higher mortality rates, higher costs for hospitalization and medication, and poorer quality of life elderly asthmatics endure compared to younger adults with the disease [5] [6].
Elderly patients with asthma are more likely to be under diagnosed and undertreated [7], partly because the pathophysiology of asthma in the elderly becomes more complex with age-related changes such as loss of lung function [8], alterations in immune function such as elevated basal levels of inflammation and reduced innate and adaptive responses [9], and increasing comorbidities [10].Long-term cigarette smoking might modify the pathophysiology of asthma in the elderly.Tobacco smoking exposure and aging have been identified as risk factors for the development of asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), a condition characterized by partly irreversible airflow limitation, neutrophilic airway inflammation, and airway remodeling [11].
Japan currently has the world's oldest population.The elderly (65 years or older) accounted for 26.6% of the Japanese population in 2015 and are forecasted to account for about 40% by 2050 [12].Accordingly, the proportion of adult asthma patients aged 65 and over has increased from 36.7% in 1996 to 41.7% in 2014 [13].While the total mortality from asthma has gradually decreased, the elderly (65 years or older) account for a growing percentage of asthma deaths in Japan.As of 2013, almost 90% of the patients who died from asthma were elderly [14].While the appropriate treatment to reduce asthma mortality in the elderly is crucially needed, the treatments for the elderly some-times diverge from the current guidelines because of conditions such as inspiratory flow limitation, poor inhaler technique, cognitive impairment, and comorbidities [15] [16].Drug-drug interactions are another particular concern in the elderly, as well as adverse drug effects induced by dysfunctions of the liver and kidney [17].Elderly patients have also been excluded from many of the clinical trials [4], which limits the available data on asthma treatment strategies for them.
In this study, we aimed to assess how respiratory physicians manage asthma in the elderly in real-world clinical settings in Japan.less than 0.05 was regarded as statistically significant.Data are given as the mean ± SD unless otherwise indicated.For smoking status, percentages were calculated based on the number of known patients.BMI, body mass index; VC, vital capacity; FVC, forced vital capacity; FEV1, forced expiratory volume in one second.

Details of Treatment
In the questionnaire survey, the respiratory physicians provided details on the treatments the patients received.Figure 1 compares the medications received by the elderly and non-elderly.The treatments administered in the elderly and non-elderly patients were as follows: inhaled corticosteroids (ICS) in 96.0% and 97.0%, long-acting beta-agonists (LABA, inhaler or transdermal patch) in 71.9% and 75.5%, long-acting muscarinic antagonists (LAMA) in 3.9% and 4.9%, and leukotriene receptor antagonists (LTRA) in 46.4% and 50.3%, respectively.There were no significant differences between the two groups in the prescription rates of ICS, LABA, LAMA, LTRA, theophylline, oral corticosteroids, or omalizumab.

Drug Delivery Devices
The types of preferred drug delivery devices prescribed for the elderly were also analyzed.Patients using both types of device were doubly counted.Table 2 shows the results.Among patients receiving LABA, the proportion receiving  transdermal LABA was significantly higher in the elderly than in the non-elderly (4.7% vs. 2.4%, P = 0.02).Among patients receiving ICS or ICS/LABA combinations, the proportion of patients using pressurized metered-dose inhalers (pMDIs) did not differ between the elderly and non-elderly (14.9% vs. 15.5%).
Among patients receiving both ICS and LABA, the proportion of patients receiving ICS/LABA combinations did not significantly differ between the elderly and non-elderly (96.0% vs. 97.4%).

Asthma Symptoms and the mMRC Scale
We analyzed the survey data on the patients' asthma symptoms and the mMRC scale.Figure 2

Hospitalizations for Exacerbation in the Previous Year
We analyzed the survey data on hospitalizations due to asthma exacerbation.
The proportion of patients who had been hospitalized in the previous year did not differ between the elderly and non-elderly (54/974 [5.5%] vs. 56/992 [5.6%]).
When we performed a further analysis disregarding age, however, a significantly higher proportion of patients receiving mucoactive drugs or macrolides had been hospitalized in the previous year compared to patients not receiving them (10.1% vs. 4.8%, P < 0.01; 19.8% vs. 4.8%, P < 0.01; respectively).

Discussion
According to the questionnaire survey on treatments administered to adult patients with asthma in Japan, the prescription rates of mucoactive drugs, macrolides, and transdermal LABA were significantly higher in the elderly than in the non-elderly.There were no significant differences in the prescription rates of ICS, LABA (inhaler or transdermal patch), LAMA, or LTRA between the same two groups.
Although asthma in the elderly has been commonly recognized as undertreated [7], one recent study has shown that the elderly are often prescribed ICS and receive relatively aggressive care compared to younger patients [18].Similarly, the present study found no significant differences between the elderly and non-elderly in the prescription rates of major controller medications such as ICS, LABA, LAMA, or LTRA.Neither the Global Initiative for Asthma (GINA) any recommendations on the use of mucoactive drugs or macrolides for asthmatic patients [14] [19].Some of the patients in this study, however, received these medications in clinical settings in Japan.The proportion of patients who had been hospitalized in the previous year was significantly higher among the patients receiving mucoactive drugs or macrolides than among those not receiving them.We assumed, therefore, that the respiratory physicians in our study considered these medications as treatment options for asthma.Indeed, a real-world investigation in Italy recently reported that macrolides influenced the reduction of severe asthma exacerbations [20].Several clinical trials and animal experiments have demonstrated that mucoactive drugs can prevent airway hyperresponsiveness [21] [22] [23].Another possible reason for the higher prescription rates of mucoactive drugs or macrolides for the elderly in our study was the convenience of administering these medications regardless of low inspiratory flow rates or poor inhaler technique.
On the question of drug delivery, previous studies reported that transdermal LABA was effective in improving asthma control and health status [24] [25], and that elderly patients adhere to transdermal LABA more faithfully than to inhaled LABA [26].The physicians surveyed in our study prescribed transdermal LABA more frequently for the elderly than for the non-elderly, possibly because they recognized these benefits.
Underreporting of subjective symptoms is considered an important issue in elderly asthmatics, given the portended risk of treatment delay [27].The elderly have been shown to be less aware of their own symptoms of bronchoconstriction [28].Similarly, our study identified a significantly higher proportion of asymptomatic patients among the elderly.Several possible explanations for this finding are available: the elderly might be less aware of their symptoms or less likely to report them; physicians might be less reliable in recognizing asthma symptoms in the elderly; asthma in the elderly might actually be well controlled.In either case, physicians should carefully monitor their patients and use objective measures of asthma control, especially for asthma in the elderly.
Dyspnea, a common symptom in the elderly, is mainly caused by respiratory disease, cardiovascular disease, deconditioning, and respiratory muscle weakness [29].While the proportion of patients complaining of dyspnea in our study was significantly higher in the elderly than in the non-elderly, we could not tell whether any comorbidities were affecting their symptoms.Further surveys will be required to accurately identify the causes of their dyspnea.
Hospitalizations for asthma are reported to be more common in older adults than in younger adults [27] [30].On the contrary, there was no significant difference in the proportion of hospitalizations due to asthma exacerbation between the elderly and non-elderly in our study.This might be explained by the exclusion of ACOS patients, a population significantly older and at greater risk of hospitalizations than patients with asthma alone [31] [32], from our analysis.
When we included 404 patients with ACOS in the analysis, the proportion of Statistical analyses were performed using GraphPad Prism 5 software (GraphPad, California, USA).Continuous variables were summarized as means and standard deviations.Categorical data were summarized as numbers and percentages.Denominators varied according to missing responses.The Student's t-test and Chi-square test were applied for comparisons between two groups.A P value of S. Chiba et al.
(a)  shows the existence and frequency of asthma symptoms in the elderly and non-elderly.The proportion of asymptomatic patients was significantly higher in the elderly than in the non-elderly (635/974 [65.2%] vs 544/ 1000 [54.4%],P < 0.01).As Figure2(b)shows, the proportion of patients scoring 0 on the mMRC scale was significantly lower in the elderly than in the non-elderly (439/704 [62.4%] vs. 472/605 [78.0%],P < 0.01).

Figure 2 .
Figure 2. (a) The frequency of asthma symptoms.The respective columns show the proportions of patients with no symptoms (gray), symptoms less than once a week (green), symptoms more than once a week (yellow), daily symptoms with no disturbance of daily life (red), daily symptoms with disturbance of daily life (purple); n = 974 in the elderly, n = 1000 in the non-elderly.(b) The modified Medical Research Council (mMRC) scale.The respective columns show the proportions of patients with mMRC scale 0 (gray), 1 (green), 2 (yellow), 3 (red), and 4 (purple); n = 704 in the elderly, n = 605 in the non-elderly.*P < 0.01 compared to the non-elderly.

Table 1 .
Data on 3426 patients from 16 institutes were collected and the 76 respiratory physicians practicing at the institutes answered the questionnaire.Out of 2466 patients with identified asthma, 21 patients with incomplete demographic information (sex, age) and 404 ACOS patients diagnosed with both asthma and COPD were excluded.The remaining 2,041 patients were used for the study.The Patient characteristics.
and over (elderly) and less than 65 (non-elderly).The mean ages of the elderly and non-elderly were 74.4 and 47.8 years, respectively.The elderly group had a significantly lower BMI, lower percentage of current smokers, and poorer pulmonary function than the non-elderly group.FEV1/FVC (%) 69.1 ± 11.9 75.5 ± 11.8 <0.01

Table 2 .
Drug delivery devices prescribed for the elderly and the non-elderly.