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Impact of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region: the EPIC Asia population-based survey

Impact of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region: the EPIC Asia... Background: Chronic obstructive pulmonary disease (COPD) is a clinical syndrome encompassing a group of chronic, progressive, and debilitating respiratory conditions, that are characterized by incompletely reversible airflow limitation. Within the Asia-Pacific region, prevalence estimates have been derived using various protocols and study methods, and there is little data on the impact of COPD exacerbations. This study aimed to provide a comprehensive picture of the current prevalence and burden of COPD in this region. Methods: A population-based survey was conducted in nine Asia-Pacific territories between 01 February 2012 and 16 May 2012. Overall, 112,330 households were screened to identify eligible subjects (aged ≥40 years, with a physician diagnosis of COPD, chronic bronchitis or emphysema, or with identifiable symptoms of chronic bronchitis). Out of a sample of 69,279 individuals aged ≥40 years, 4,289 subjects with COPD were identified. Data were collected via face-to- face interviews or by fixed-line telephone, using a structured questionnaire. A total of 1,841 completed questionnaires were analyzed. Results: The overall estimated COPD prevalence was 6.2%, with 19.1% of subjects having severe COPD. In the 12 months prior to the survey, nearly half of all subjects (46%) had experienced exacerbations, and 19% had been hospitalized as a result of their condition. When subjects were asked about the impact of their condition on employment, 23% said their condition kept them from working, and 42% felt that their condition limited their ability to work or their activities. Of those who reported taking prescription drugs, 20% did not know the name of the drugs they were taking. Prescription of oral corticosteroids was common, with 44% of subjects having used these during the previous year to manage their respiratory symptoms; in contrast, inhaler use was low (25%). Only 37% of subjects had taken a lung function test, and the majority (89%) of those tested did not know their test results. Conclusions: Across the Asia-Pacific territories surveyed, the prevalence of COPD is high, indicating a substantial socioeconomic burden. Our findings suggest that there is considerable room for improvement in the management of COPD, and highlight a need to enhance patient and physician education in the region. Keywords: Chronic obstructive pulmonary disease (COPD), Asia-Pacific, Population-based, Survey, Prevalence, Exacerbations, Impact, Quality of life (QoL) * Correspondence: sam.lim@duke-nus.edu.sg Duke-NUS Graduate School of Medicine, Singapore, Singapore Full list of author information is available at the end of the article © 2015 Lim et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 2 of 11 Background and Vietnam (Southeast Asia). Household screening and Chronic obstructive pulmonary disease (COPD) is a clin- subject selection were carried out by telephone or face-to- ical syndrome that encompasses a group of chronic, face interviews (Figure 1; Additional file 1: Table S1). A progressive, and debilitating respiratory conditions, in- structured questionnaire was then administered to eligible cluding emphysema and chronic bronchitis. COPD is subjects. the fourth leading cause of global mortality [1], and its Households were screened by random sampling to re- prevalence is predicted to rise [2,3]. Despite the wealth duce selection bias. Fixed-line random digit dialing of information regarding its causes, pathophysiology, (RDD) sampling was conducted in regions with a high and treatment options, the disease has historically been coverage of fixed telephone lines. Numbers were chosen under-diagnosed and under-reported, especially within based on randomly selected blocks of numbers. In the the Asia-Pacific region [1,4]. remaining regions, area probability (cluster) sampling was COPD is characterized by persistent, progressive air- conducted face-to-face (FF) in subjects’ homes. Areas flow limitation, and is often accompanied by cough and were divided into primary sampling units, which were increased sputum production [4]. Airflow limitation is then randomly selected, and a block or building was associated with chronic inflammation in the lungs and is chosen as a starting point. principally caused by long-term exposure to airborne ir- Individuals who met the following criteria were eligible ritants such as cigarette smoke. In the Asia-Pacific re- for inclusion in the survey: individuals aged ≥40 years, gion, smoke from biomass fuels and industrial toxins are who reported either a physician diagnosis of the follow- also known to be problematic risk factors [5-7]. The ing: emphysema, chronic bronchitis, COPD, chronic ob- symptoms of COPD cause significant impairment of structive airways disease, or chronic obstructive lung quality of life (QoL), including breathlessness, anxiety, disease; or who met the following symptomatic defin- and physical limitations, resulting in days of missed ition of chronic bronchitis: production of phlegm or work [8]. mucus from the lungs on all or most days for three con- COPD exacerbations, consisting of an acute worsening secutive months. As this was a community survey which of the usual symptoms beyond normal day-to-day vari- did not include any research intervention, no ethical ap- ation, can be particularly debilitating [4]. While some ex- proval was required. Verbal consent was obtained from all acerbations may be relatively mild and go unreported subjects prior to participation in the survey. Participation [9], in severe cases they can be particularly debilitating, was voluntary. Subjects were informed that their results requiring weeks for full recovery [10]. Recent studies may be published in scientific articles and their responses have indicated that there may be exacerbation-specific would be kept both anonymous and confidential. phenotypes [11,12], and that cough and sputum (chronic The structured questionnaire used for data collection bronchitis) are associated with a greater exacerbation was based on those used in previous studies [21,22], with frequency [13,14]. additional questions to capture information on exacerba- Previous studies of the prevalence of COPD and its ex- tions. This questionnaire was developed and implemented acerbations in the Asia-Pacific have focused on individ- by Abt SRBI, Inc., on behalf of Takeda Pharmaceuticals. ual countries or cities [15-19], or relied on mathematical The same questionnaire and study design were utilized modeling [20]. The Epidemiology and Impact of COPD across all territories. Where necessary, the English lan- (EPIC) Asia survey is the first population-based COPD guage questionnaire was translated by a local translator to survey to cover nine Asia-Pacific regions using the same the local language and then reviewed by an independent study design and questionnaire. We collected data on translator with health research experience, as well as by COPD exacerbation and its indicators, such as cough local medical experts. During data collection, potential and sputum, as these aspects of the disease have not bias was mitigated by random sampling within households been well documented in this region. We also consid- containing more than one eligible individual, multiple ered measures of disease reporting, disease severity, and contact attempts to reduce contact failure, and quality socioeconomic factors, along with treatment and man- control during interviews. The fieldwork teams received agement practices. The aim was to gain further insight extensive training in all aspects of administering the ques- regarding the current prevalence and burden of COPD tionnaire. Mock and pre-test interviews were used to con- in the Asia-Pacific region. firm training standards and identify areas for modification. Only eligible subjects who completed the study ques- Methods tionnaire were included in the analyses, which involved The EPIC survey was conducted between 01 February standard descriptive statistics. Disease prevalence was 2012 and 16 May 2012 in nine Asia-Pacific territories: calculated as (100 × number of eligible subjects ÷ num- China, Hong Kong, and Taiwan (North Asia), and ber of individuals aged ≥40 years), and expressed as a Indonesia, Malaysia, the Philippines, Singapore, Thailand, percentage. Severe COPD was defined based on subjects’ Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 3 of 11 Figure 1 Sampling strategy and response rate for the EPIC Asia survey. ‘Study subjects’ refers to the subset of individuals aged ≥40 years who were identified as having COPD, based on the definitions used in this study (see Methods), and who completed the questionnaire. recall of COPD classification by their physicians, accord- For country-specific figures, please refer to Additional file 1: ing to the Global Initiative for Chronic Obstructive Lung Table S1. The mean interview duration was 41 minutes. Disease (GOLD) criteria (GOLD grade III or IV), or using the following symptomatic definition: presence of Estimated prevalence of COPD and related conditions the symptoms of chronic bronchitis, together with two Based on the above criteria, the overall estimated preva- or more exacerbations in the previous 12 months. lence of COPD was 6.2%, ranging from 4.5% in Indonesia to 9.5% in Taiwan (Table 1). The proportion of subjects Results with a physician diagnosis of COPD was 59%, with the re- Subject demographics mainder having the symptomatic definition. Physician In the nine territories surveyed, a total of 112,330 house- diagnosis was higher in North Asia (72–93%) than in holds were screened, identifying 69,279 households with Southeast Asia (19–60%), with the exception of Vietnam one or more individuals aged ≥40 years. Of the 69,279 (92%). Overall, 19.1% of the subjects met the definition of individuals aged ≥40 years, 4,289 either had a physician’s the severe phenotype used in this study, ranging from diagnosis of COPD or met the symptomatic definition 12.5% in Malaysia to 37.5% in Vietnam (Table 1). The ma- used in this survey. Of these 4,289 subjects with identified jority of subjects reported their COPD classification as COPD, a total of 1,841 subjects completed the question- GOLD stage I or II (34.1% and 37.9%, respectively), with naire (Figure 1). Almost half of the study population (44%) only a minority reporting it as stage III (9.3%) or IV (2.1%) was between 45 and 60 years of age, and 56% were female. (Table 1). However, Southeast Asian countries had higher Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 4 of 11 Table 1 Subject demographics Overall North Asia Southeast Asia Self-reported EPIC Asia China Hong Kong Taiwan Indonesia Malaysia Philippines Singapore Thailand Vietnam characteristic n = 1,841 n = 215 n = 205 n = 207 n = 200 n = 200 n = 200 n = 200 n = 214 n = 200 Age (years), % 40–44 26 45 50 46 18 12 16 18 18 10 45–49 19 28 28 30 14 14 15 10 14 18 50–54 14 9 10 8 18 19 13 9 15 22 55–59 11 4 4 3 13 16 14 13 15 15 60–64 11 6 2 4 16 15 19 18 11 12 65+ 20 7 5 9 22 26 23 34 28 25 Gender, % Female 56 40 47 60 49 67 63 59 64 60 Work status, % Employed 47 66 75 68 36 31 37 30 40 40 Smoking, % Never smoked on a 58 45 53 60 53 69 56 68 55 64 regular basis COPD prevalence, % EPIC Asia 6.2 8.1 7.7 9.5 4.5 5.1 4.2 5.9 5.3 9.4 Prevalence estimation 6.3 6.5 3.5 5.4 5.6 4.7 3.5 6.3 5.0 6.7 models [20] Severe symptomatic 19.1 13.0 16.1 24.2 20.5 12.5 13.0 20.0 15.9 37.5 phenotype Diagnosed vs symptomatic 59 vs 41 72 vs 28 90 vs 10 93 vs 7 60 vs 40 33 vs 67 40 vs 60 19 vs 81 33 vs 67 92 vs 8 (Mean age of diagnosis/yrs) (44 vs 40) (43 vs 41) (42 vs 42) (43 vs 46) (42 vs 35) (44 vs 40) (46 vs 38) (46 vs 38) (45 vs 41) (50 vs 50) MRC dyspnea score 2.3 1.8 2.2 2.2 2.6 2.4 2.6 2.4 2.1 2.5 (mean) [23] GOLD stage of severity [4], % Stage I – Mild 34.1 44.7 52.2 44.0 28.0 26.5 30.5 27.0 20.6 32.5 Stage II – Moderate 37.9 32.1 32.2 34.8 44.0 34.0 35.5 48.5 36.0 44.5 Stage III – Severe 9.3 5.6 2.9 4.8 16.5 9.5 5.0 13.5 9.3 17.5 Stage IV – Very severe 2.1 0.9 1.0 0.5 <0.5 2.5 4.0 4.0 4.2 2.0 Not diagnosed/not told 11.2 14.4 10.2 13.5 6.5 14.5 6.5 4.5 28.0 1.5 Don’t know 5.3 2.3 1.0 2.4 5.0 13.0 18.5 2.5 1.9 2.0 Other frequent health conditions, % None 45 61 61 63 47 47 29 39 18 40 Nasal allergies 13 18 20 15 2 3 11 2 32 14 Arthritis 11 7 11 6 5 6 19 4 13 24 Asthma 19 1 5 2 17 21 40 33 48 7 Diabetes 10 5 4 4 8 18 10 24 17 4 Hypertension 21 9 8 5 13 23 23 36 42 28 Heart disease 5 <1 2 1 7 11 6 5 8 5 General health status, % Excellent 2 2 <1 1 9 <1 <1 <1 <1 <1 Very good 3 9 2 5 2 6 3 2 <1 <1 Good 17 17 14 12 13 25 20 19 26 6 Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 5 of 11 Table 1 Subject demographics (Continued) Fair 48 61 70 69 33 22 58 33 53 37 Poor 23 9 13 10 35 40 19 15 19 54 Very poor 6 2 1 4 8 7 <1 32 2 5 Subjects from each of the nine territories were sampled either by telephone, using random digit dialing (RDD), or face-to-face (FF) interviews in their local language, to identify individuals who had either received a physician diagnosis of COPD or met the symptomatic criteria used (see Methods). A total of 1,841 subjects completed the study questionnaire for the EPIC Asia survey. All figures are percentages of subjects from the respective territory, with the exception of mean age of COPD diagnosis and mean MRC dyspnea score. percentages of subjects with severe or very severe disease. Asia being higher (66–75%) than in Southeast Asia (30– The mean MRC dyspnea score [23] was 2.3. 40%) (Figure 4A). A substantial proportion of subjects (23%) reported that their condition kept them from work- Health status and disease symptoms ing (Figure 4B), particularly in Indonesia (44%) and in the There was a clear North/Southeast division in reported Philippines (51%). In addition, 42% felt that their condi- health status (Table 1). The proportion of subjects who re- tion limited the kind or amount of work they could do, or port that their health was ‘poor’ or worse ranged from 11– limited their activities (Figure 4B). Subjects were also 14% in North Asia to 19–59% in Southeast Asia. Similarly, asked to estimate their levels of productivity on a typical the proportion who considered their general health to be day, and on a day when symptoms were at their worst. ‘fair’ varied from 22% in Malaysia to 70% in Hong Kong. Overall, average estimated productivity was 72% on a typ- Overall, a substantial proportion of subjects (33–53%) ical day, falling to 45% when the condition was at its worst reported symptoms typical of COPD at least twice a week (Figure 4C). during their worst month in the previous 12 months The impact of disease symptoms on daily activities (Additional file 2: Figure S1). Overall, 34% of the subjects was also explored (Additional file 2: Figure S3). Notably, reported that physical exertion instigated their COPD 39% reported that their condition limited normal phys- symptoms (Additional file 2: Figure S1D). ical activities, such as walking. A substantial proportion of subjects (27–49%) said that their respiratory symp- Exacerbations and unplanned healthcare utilization toms placed restrictions on a range of daily activities, in- Almost half (46%) of all subjects reported experiencing cluding sleep, household chores, social or recreational exacerbations in the 12 months prior to the survey activities, or affected their sex life (Additional file 2: (Figure 2A). The frequency and seasonal variation of re- Figure S3, A–C). ported exacerbations is shown in Figure 2B and C. The median number of exacerbations reported was 3, with Disease management all territories falling within the range of 2–4 (Figure 2B). Most subjects reported seeing either a specialist (44%) Exacerbations occurred more frequently between October or general practitioner (34%) for their condition. How- and January (Figure 2C). For the North Asian territories ever, only 37% of study subjects reported that they had and the Philippines, an increase in exacerbations was also been given a lung function test. Of those tested, 89% did seen in the months from February to April. Subjects not know their test results (either forced expiratory vol- reported worsening of their disease symptoms during ex- ume in the first second [FEV ] value, or percent pre- acerbations, with over half of the subjects reporting dicted FEV ). Of those who reported taking prescription coughing up phlegm or sputum, or coughing during the drugs, 20% did not know the name of the drugs they day (Additional file 2: Figure S2). were taking. When subjects were asked to describe the Overall, a sizable proportion of study subjects reported delivery format of their medication, 57% stated pill/cap- visiting a hospital emergency room (26%), or making sule, 13% stated inhaler with spacer, and 12% stated in- other unscheduled visits to a doctor or clinic (32%) in haler without spacer (Figure 5). In addition, 44% of the the previous 12 months, as a result of their condition subjects reported the use of oral corticosteroids to man- (Figure 3A). China (46%), Hong Kong (59%), and Taiwan age their symptoms during the previous 12 months (59%) recorded the highest percentages of unscheduled (Figure 6). Overall, 35% of the subjects had taken anti- doctor or clinic visits (Figure 3A). Overall, 19% of study biotics for respiratory infections during the previous subjects reported being hospitalized in the previous 12 months, and 13% had received an influenza vaccination. 12 months as a result of their condition (Figure 3B). Perceptions of disease and attitudes toward physician Impact of disease on employment and daily activities advice Less than half (47%) of all subjects were employed (either Subjects were asked questions related to their perception full- or part-time), with the employment rate in North of their condition. More than one-third (35%) felt that Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 6 of 11 Figure 2 Prevalence, frequency, and seasonal variation of exacerbations. (A) Proportion of study subjects who reported experiencing one or more exacerbations within the 12 months prior to the survey. (B) Median number of exacerbations reported by subjects over this period. (C) Proportion of subjects who reported exacerbations within each month over this period. there were no truly effective treatments for COPD habits helped, a similar percentage of subjects (39%) said (Additional file 2: Figure S4A). The majority of subjects ‘a lot’ (Additional file 2: Figure S5B). (76%) believed that smoking was the cause of their con- dition, and 70% felt that their condition worsened with Discussion increasing age, regardless of treatment (Additional file 2: The EPIC Asia survey was a multi-country, cross-sectional, Figure S4B). However, most subjects felt that with ap- population-based study that examined the prevalence and propriate treatments, progressive increase in breathless- burden of COPD in the participating Asian territories, ness could be slowed (86%) or they could lead a full and from the perspective of individuals who were diagnosed active life (84%) (Additional file 2: Figure S4C). with the disease or who reported symptoms of the disease. When asked about the extent to which their doctor’s This approach contrasts with previous studies in Asia, advice regarding treatment and management helped im- which have tended to focus on individual countries or prove their condition, 43% said ‘a lot’ (Additional file 2: areas within countries [15-19]. Figure S5A). When subjects were asked about the extent Using data obtained from the nine Asian territories in to which their doctor’s advice regarding lifestyle and this population-based survey, the average prevalence of Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 7 of 11 Figure 3 Unplanned healthcare utilization. (A) Proportion of subjects who either visited a hospital emergency room or made unscheduled visit(s) to a doctor or clinic as a result of their condition, in the 12 months prior to the survey. (B) Subjects who had ever been hospitalized because of their condition (n; %) were asked how many times they had been hospitalized in the previous 12 months. The proportions of subjects who had been hospitalized 0, 1, 2, or 3 or more times are indicated by the shading within each bar. Results are shown only for subjects who were able to report the number of times they had been hospitalized. COPD was estimated at 6.2%. Almost one-fifth of the The results of this survey may not be directly com- identified subjects were categorized as having severe or parable to those of other COPD studies, due to differ- very severe COPD, based on recalled disease classification ences in measurement methodology or study population. by a physician, or on their reported symptoms of chronic Nevertheless, our findings and those of other studies in bronchitis and frequent exacerbations. The prevalence of Asia and elsewhere [15,16,22,24-26] indicate that COPD COPD estimated in this study is similar to that reported represents a substantial socioeconomic burden in this by Tan et al. who used a mathematical model to estimate region and worldwide. In this study, a large proportion the prevalence of COPD in this region (6.3%) [20]. Simi- of subjects reported that their condition restricted their larly, it is consistent with the pooled global prevalence work or activities (42%), or kept them from working (7.6%) obtained from a meta-analysis of 37 population- altogether (23%). Another noteworthy finding is the high based COPD studies using different definitions of COPD rate of hospitalization reported; almost a fifth (19%) of including spirometric criteria, patient-reported diagnoses, subjects said they had been hospitalized as a result of physician diagnoses, etc. [24]. However, a population- their condition in the previous year. Unplanned health- based study which employed spirometric measurements care utilization was also common, with a substantial to estimate the prevalence of COPD in 12 countries (the proportion of subjects visiting a hospital emergency BOLD study), revealed higher COPD estimates (world- room (26%), or making unscheduled doctor or clinic wide 10.1%; participating Asian countries 11.4–13.9%) visits (32%) in the year prior to the survey. In the BOLD compared with our study. The BOLD study also showed study, patients with COPD reported poorer health status higher levels of severe COPD in the participating Asian than those without COPD; the degree of impairment countries (1.7–5.0%) [25]. Given that identification of was greater with increasing COPD severity. Further- COPD in our study was based on subject-reported phys- more, patients regarded severe COPD to have a greater ician diagnoses and subjects’ perception of their condition negative impact on their health status than diabetes and and symptoms, it is likely that the actual prevalence of cardiovascular [26]. COPD in the participating Asian territories is higher than Other findings from our study suggest an urgent need was estimated. for improved clinical management in this region, as well Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 8 of 11 Figure 4 Impact of disease on employment and work productivity. (A) Employment status of study subjects. (B) Proportion of subjects who reported that their condition kept them from working, limited the kind or amount of work they could do, or limited their activities. (C) Subjects’ estimated level of productivity on a typical day, and on a day when symptoms are at their worst. Upper row of n values: subjects who answered the question regarding productivity on a typical day; lower row of n values: subjects who answered the question regarding their worst day. as for better patient education. For instance, a relatively such as industrial toxins and smoke from biomass fuels, low proportion of subjects had undergone lung function are also highly relevant risk factors, particularly in the tests (37%), and the majority of those tested did not Asia-Pacific region [5-7]. Further, smoking status tends to know their test results (either FEV value or percent pre- be under-reported [27]. Inclusion of both self-reported dicted FEV ). A fifth of those who reported taking pre- smokers and non-smokers in this survey allows the capture scription drugs did not know the name of the drugs they of important information on subjects who are smokers but were taking. From the perspective of recommended clin- do not accurately report their smoking status, or those ical practice, oral corticosteroids appear to be over- whose COPD may be caused by environmental pollutants. prescribed, whereas the use of inhalers is low. Our findings need to be interpreted within the limita- Most studies on COPD are conducted on a selected tions of the study. Firstly, identification of COPD in sub- population who are smokers. Although smoking history is jects was based on subject-reported physician diagnoses, important for COPD diagnosis, environmental pollutants, where available, or on the presence of self-reported Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 9 of 11 Figure 5 Delivery format of prescribed medication. Subjects who reported taking a prescription drug were asked about the delivery format of their medication. Numbers below the bars indicate the total number of valid answers for this question, for the corresponding territory. Results are shown only for subjects who were able to report the delivery format of their medication. Figure 6 Use of oral corticosteroids. All study subjects (upper row of n values) were asked if they had been told to use oral steroids to manage their respiratory symptoms in the past 12 months. Those who had been prescribed steroids (lower row of n values) were asked if they had been told to take the steroids for three days or longer. Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 10 of 11 respiratory symptoms. Similarly, classification of disease to-face (FF) interviews in their local language, to identify individuals who severity was based either on subjects’ recall of GOLD had either received a physician diagnosis of COPD or who met the symptomatic criteria used (see Methods). classification by a physician, where available, or on their Additional file 2: Figure S1. Frequency of COPD symptoms recall of symptomatic criteria. As this was a community experienced over the previous 12 months. Proportion of subjects who survey, subjects were screened based on their reported experienced the following COPD symptoms at least twice per week in information; there was no confirmation of diagnoses via their worst month over this period: (A) being awakened at night either by coughing or shortness of breath, (B) coughing or shortness of breath subject diaries or spirometric measurements. Conse- during the day, (C) coughing up phlegm or wheezing, or (D) tightness of quently, there is potential underdiagnosis, as well as mis- the chest or coughing, wheezing, shortness of breath, or chest tightness classification of COPD and disease severity due to recall due to physical exertion. Figure S2. Exacerbation symptoms. The types of symptoms reported to be elevated during exacerbation episodes, as bias and subjects’ misperception of their disease condition reported by subjects who experienced exacerbations in the 12 months or symptoms. This may lead to less reliable prevalence es- prior to the survey. Figure S3. Restriction of daily activities by COPD timates. Secondly, subjects who were interviewed via the symptoms. The proportion of subjects who reported that their symptoms impose ‘some’ limitation or limit their activities ‘a lot’ with respect to: telephone were likely to have higher social economic sta- (A) sports and recreation and normal activities such as walking, (B) social tus than those who had face-to-face interview. This could activities or sleeping, and (C) housekeeping chores or their sex life. result in a selection bias. Potential bias was minimized by Figure S4. Subjects’ attitudes to COPD. The proportion of subjects who ‘agreed’ or ‘agreed strongly’ that: (A) there are no truly effective conducting random sampling both in regions with high treatments for their condition; (B) smoking is the cause of their condition, coverage of fixed telephone lines, as well as in those areas and that their condition tends to get worse as they get older; (C) with without telephone access. proper treatment, a progressive increase in breathlessness can be slowed, and that most people with the condition can live a full and active life. Another limitation of this study is the low response Figure S5. Subjects’ attitudes to their physician’s advice. The proportion rate which could have introduced the potential for re- of subjects who reported that their physician’s advice on (A) management sponse bias. Subjects were unable to participate in the and treatment, or (B) modification of lifestyle and habits, improved their ability to manage their respiratory symptoms to the following degrees: ‘Not survey due to various reasons which included ineligible at all’, ‘Only a little’, ‘Some’,or ‘Alot’. Results are shown only for subjects or refusal to participate, contact failure, and inability to who provided valid answers to the questions. complete survey. Hence, it was not possible to collect demographics information from the non-respondents to Competing interests assess if response bias exists. Nonetheless, steps were SL, DCLL, SW, LTTL, JPZ, and TG have received consulting fees from Takeda Pharmaceuticals GmbH. SL has received speaker fees from GlaxoSmithKline taken to mitigate potential bias. Households were ran- (GSK) and AstraZeneca. TG has received research grants, lecture fees or travel domly selected by RDD or area probability sampling. In grants from GSK, United Laboratories (UNILAB), AstraZeneca, Boehringer households where more than 1 subject was eligible, ran- Ingelheim, Sanofi-Aventis, Getz Pharma, Nycomed-Takeda, Pfizer, and Novartis, and has served on Advisory Boards for GSK, Novartis, Nycomed-Takeda, dom sampling was performed to select only 1 subject. In Boehringer Ingelheim, and UNILAB. LTTL has served on Advisory Boards for GSK, addition, multiple contact attempts were made to reduce AstraZeneca, Novartis, and Boehringer Ingelheim, and has received research contact failure. Another limitation of this study is that grants from Astra Zeneca, MSD, and GSK. She has received speaker fees and travel grants from GSK, Astra Zeneca, Novartis, and Boehringer Ingelheim. JPZ the sample size of each country may not be large enough has received lecture fees from GSK, AstraZeneca, Boehringer Ingelheim, to allow meaningful conclusions to be drawn about each Nycomed-Takeda, and Novartis, and has served on Advisory Boards for country. Nevertheless, the study enrolled a near uniform AstraZeneca, GSK, Novartis, Nycomed-Takeda, and Boehringer Ingelheim. VS and RC are both an ex-employees of Takeda Pharmaceuticals. They were number of subjects in each country that minimized the employees of Takeda Pharmaceuticals during the conduct of this study. All likelihood that the overall prevalence would be affected other authors declare that they have no competing financial interests. by unbalanced sample size in any country. Authors’ contributions All authors contributed equally to the analysis of the data and the Conclusions development of the manuscript. All authors have read and approved the The results of the EPIC Asia population-based survey sug- final manuscript. gest a high prevalence of COPD in the participating Asia- Acknowledgements Pacific territories, and indicate a substantial socioeconomic The study was funded by Takeda Pharmaceuticals International GmbH. burden of the disease in this region. Individuals with the Additional medical writing support was provided by Caroline Loder and Michael Kirwan at Synergy Vision (London), and by Research2Trials Clinical disease reported substantial limitations in their daily activ- Solutions Pte. Ltd (Singapore); this support was funded by Takeda. ities and loss in work productivity. These findings highlight the need to enhance patient and physician education, and Author details 1 2 Duke-NUS Graduate School of Medicine, Singapore, Singapore. Department improve the management of COPD in this region. of Medicine, University of Hong Kong, Pokfulam, Hong Kong. Institute of Respiratory Medicine, Kuala Lumpur, Malaysia. Department of Pulmonology Additional files and Respiratory Medicine, Universitas Indonesia (FMUI), Jakarta, Indonesia. Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand. Respiratory Care Center, University Medical Center, Ho Chi Minh Additional file 1: Table S1. Sampling frame for the EPIC Asia survey, by City, Vietnam. Takeda Pharmaceuticals (Asia-Pacific) Pte. Ltd, Singapore, country. Subjects from each of the nine participating territories were Singapore. State Key Lab of Respiratory Disease, National Clinical Research sampled either by telephone, using random digit dialing (RDD), or face- Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 11 of 11 First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 22. 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J Med Assoc Thai. and take full advantage of: 2002;85:1147–55. 18. Yoo KH, Kim YS, Sheen SS, Park JH, Hwang YI, Kim SH, et al. Prevalence of • Convenient online submission chronic obstructive pulmonary disease in Korea: the fourth Korean National • Thorough peer review Health and Nutrition Examination Survey, 2008. Respirology. 2011;16:659–65. 19. Zhong N, Wang C, Yao W, Chen P, Kang J, Huang S, et al. Prevalence of • No space constraints or color figure charges chronic obstructive pulmonary disease in China: a large, population-based • Immediate publication on acceptance survey. Am J Respir Crit Care Med. 2007;176:753–60. 20. Tan WC, Seale JP, Charoenratanakul S, de Guia T, Ip M, Mahayiddin A, et al. • Inclusion in PubMed, CAS, Scopus and Google Scholar COPD prevalence in 12 Asia-Pacific countries and regions: projections based • Research which is freely available for redistribution on the COPD prevalence estimation model. Respirology. 2003;8:192–8. 21. Halpern MT, Stanford RH, Borker R. The burden of COPD in the U.S.A.: results Submit your manuscript at from the Confronting COPD survey. Respir Med. 2003;97(Suppl C):S81–9. www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Asia Pacific Family Medicine Springer Journals

Impact of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region: the EPIC Asia population-based survey

Impact of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region: the EPIC Asia population-based survey

Background: Chronic obstructive pulmonary disease (COPD) is a clinical syndrome encompassing a group of chronic, progressive, and debilitating respiratory conditions, that are characterized by incompletely reversible airflow limitation. Within the Asia-Pacific region, prevalence estimates have been derived using various protocols and study methods, and there is little data on the impact of COPD exacerbations. This study aimed to provide a comprehensive picture of the current prevalence and burden of COPD in this region. Methods: A population-based survey was conducted in nine Asia-Pacific territories between 01 February 2012 and 16 May 2012. Overall, 112,330 households were screened to identify eligible subjects (aged ≥40 years, with a physician diagnosis of COPD, chronic bronchitis or emphysema, or with identifiable symptoms of chronic bronchitis). Out of a sample of 69,279 individuals aged ≥40 years, 4,289 subjects with COPD were identified. Data were collected via face-to- face interviews or by fixed-line telephone, using a structured questionnaire. A total of 1,841 completed questionnaires were analyzed. Results: The overall estimated COPD prevalence was 6.2%, with 19.1% of subjects having severe COPD. In the 12 months prior to the survey, nearly half of all subjects (46%) had experienced exacerbations, and 19% had been hospitalized as a result of their condition. When subjects were asked about the impact of their condition on employment, 23% said their condition kept them from working, and 42% felt that their condition limited their ability to work or their activities. Of those who reported taking prescription drugs, 20% did not know the name of the drugs they were taking. Prescription of oral corticosteroids was common, with 44% of subjects having used these during the previous year to manage their respiratory symptoms; in contrast, inhaler use was low (25%). Only 37% of subjects had taken a lung function test, and the majority (89%) of those tested did not know their test results. Conclusions: Across the Asia-Pacific territories surveyed, the prevalence of COPD is high, indicating a substantial socioeconomic burden. Our findings suggest that there is considerable room for improvement in the management of COPD, and highlight a need to enhance patient and physician education in the region. Keywords: Chronic obstructive pulmonary disease (COPD), Asia-Pacific, Population-based, Survey, Prevalence, Exacerbations, Impact, Quality of life (QoL) * Correspondence: sam.lim@duke-nus.edu.sg Duke-NUS Graduate School of Medicine, Singapore, Singapore Full list of author information is available at the end of the article © 2015 Lim et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 2 of 11 Background and Vietnam (Southeast Asia). Household screening and Chronic obstructive pulmonary disease (COPD) is a clin- subject selection were carried out by telephone or face-to- ical syndrome that encompasses a group of chronic, face interviews (Figure 1; Additional file 1: Table S1). A progressive, and debilitating respiratory conditions, in- structured questionnaire was then administered to eligible cluding emphysema and chronic bronchitis. COPD is subjects. the fourth leading cause of global mortality [1], and its Households were screened by random sampling to re- prevalence is predicted to rise [2,3]. Despite the wealth duce selection bias. Fixed-line random digit dialing of information regarding its causes, pathophysiology, (RDD) sampling was conducted in regions with a high and treatment options, the disease has historically been coverage of fixed telephone lines. Numbers were chosen under-diagnosed and under-reported, especially within based on randomly selected blocks of numbers. In the the Asia-Pacific region [1,4]. remaining regions, area probability (cluster) sampling was COPD is characterized by persistent, progressive air- conducted face-to-face (FF) in subjects’ homes. Areas flow limitation, and is often accompanied by cough and were divided into primary sampling units, which were increased sputum production [4]. Airflow limitation is then randomly selected, and a block or building was associated with chronic inflammation in the lungs and is chosen as a starting point. principally caused by long-term exposure to airborne ir- Individuals who met the following criteria were eligible ritants such as cigarette smoke. In the Asia-Pacific re- for inclusion in the survey: individuals aged ≥40 years, gion, smoke from biomass fuels and industrial toxins are who reported either a physician diagnosis of the follow- also known to be problematic risk factors [5-7]. The ing: emphysema, chronic bronchitis, COPD, chronic ob- symptoms of COPD cause significant impairment of structive airways disease, or chronic obstructive lung quality of life (QoL), including breathlessness, anxiety, disease; or who met the following symptomatic defin- and physical limitations, resulting in days of missed ition of chronic bronchitis: production of phlegm or work [8]. mucus from the lungs on all or most days for three con- COPD exacerbations, consisting of an acute worsening secutive months. As this was a community survey which of the usual symptoms beyond normal day-to-day vari- did not include any research intervention, no ethical ap- ation, can be particularly debilitating [4]. While some ex- proval was required. Verbal consent was obtained from all acerbations may be relatively mild and go unreported subjects prior to participation in the survey. Participation [9], in severe cases they can be particularly debilitating, was voluntary. Subjects were informed that their results requiring weeks for full recovery [10]. Recent studies may be published in scientific articles and their responses have indicated that there may be exacerbation-specific would be kept both anonymous and confidential. phenotypes [11,12], and that cough and sputum (chronic The structured questionnaire used for data collection bronchitis) are associated with a greater exacerbation was based on those used in previous studies [21,22], with frequency [13,14]. additional questions to capture information on exacerba- Previous studies of the prevalence of COPD and its ex- tions. This questionnaire was developed and implemented acerbations in the Asia-Pacific have focused on individ- by Abt SRBI, Inc., on behalf of Takeda Pharmaceuticals. ual countries or cities [15-19], or relied on mathematical The same questionnaire and study design were utilized modeling [20]. The Epidemiology and Impact of COPD across all territories. Where necessary, the English lan- (EPIC) Asia survey is the first population-based COPD guage questionnaire was translated by a local translator to survey to cover nine Asia-Pacific regions using the same the local language and then reviewed by an independent study design and questionnaire. We collected data on translator with health research experience, as well as by COPD exacerbation and its indicators, such as cough local medical experts. During data collection, potential and sputum, as these aspects of the disease have not bias was mitigated by random sampling within households been well documented in this region. We also consid- containing more than one eligible individual, multiple ered measures of disease reporting, disease severity, and contact attempts to reduce contact failure, and quality socioeconomic factors, along with treatment and man- control during interviews. The fieldwork teams received agement practices. The aim was to gain further insight extensive training in all aspects of administering the ques- regarding the current prevalence and burden of COPD tionnaire. Mock and pre-test interviews were used to con- in the Asia-Pacific region. firm training standards and identify areas for modification. Only eligible subjects who completed the study ques- Methods tionnaire were included in the analyses, which involved The EPIC survey was conducted between 01 February standard descriptive statistics. Disease prevalence was 2012 and 16 May 2012 in nine Asia-Pacific territories: calculated as (100 × number of eligible subjects ÷ num- China, Hong Kong, and Taiwan (North Asia), and ber of individuals aged ≥40 years), and expressed as a Indonesia, Malaysia, the Philippines, Singapore, Thailand, percentage. Severe COPD was defined based on subjects’ Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 3 of 11 Figure 1 Sampling strategy and response rate for the EPIC Asia survey. ‘Study subjects’ refers to the subset of individuals aged ≥40 years who were identified as having COPD, based on the definitions used in this study (see Methods), and who completed the questionnaire. recall of COPD classification by their physicians, accord- For country-specific figures, please refer to Additional file 1: ing to the Global Initiative for Chronic Obstructive Lung Table S1. The mean interview duration was 41 minutes. Disease (GOLD) criteria (GOLD grade III or IV), or using the following symptomatic definition: presence of Estimated prevalence of COPD and related conditions the symptoms of chronic bronchitis, together with two Based on the above criteria, the overall estimated preva- or more exacerbations in the previous 12 months. lence of COPD was 6.2%, ranging from 4.5% in Indonesia to 9.5% in Taiwan (Table 1). The proportion of subjects Results with a physician diagnosis of COPD was 59%, with the re- Subject demographics mainder having the symptomatic definition. Physician In the nine territories surveyed, a total of 112,330 house- diagnosis was higher in North Asia (72–93%) than in holds were screened, identifying 69,279 households with Southeast Asia (19–60%), with the exception of Vietnam one or more individuals aged ≥40 years. Of the 69,279 (92%). Overall, 19.1% of the subjects met the definition of individuals aged ≥40 years, 4,289 either had a physician’s the severe phenotype used in this study, ranging from diagnosis of COPD or met the symptomatic definition 12.5% in Malaysia to 37.5% in Vietnam (Table 1). The ma- used in this survey. Of these 4,289 subjects with identified jority of subjects reported their COPD classification as COPD, a total of 1,841 subjects completed the question- GOLD stage I or II (34.1% and 37.9%, respectively), with naire (Figure 1). Almost half of the study population (44%) only a minority reporting it as stage III (9.3%) or IV (2.1%) was between 45 and 60 years of age, and 56% were female. (Table 1). However, Southeast Asian countries had higher Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 4 of 11 Table 1 Subject demographics Overall North Asia Southeast Asia Self-reported EPIC Asia China Hong Kong Taiwan Indonesia Malaysia Philippines Singapore Thailand Vietnam characteristic n = 1,841 n = 215 n = 205 n = 207 n = 200 n = 200 n = 200 n = 200 n = 214 n = 200 Age (years), % 40–44 26 45 50 46 18 12 16 18 18 10 45–49 19 28 28 30 14 14 15 10 14 18 50–54 14 9 10 8 18 19 13 9 15 22 55–59 11 4 4 3 13 16 14 13 15 15 60–64 11 6 2 4 16 15 19 18 11 12 65+ 20 7 5 9 22 26 23 34 28 25 Gender, % Female 56 40 47 60 49 67 63 59 64 60 Work status, % Employed 47 66 75 68 36 31 37 30 40 40 Smoking, % Never smoked on a 58 45 53 60 53 69 56 68 55 64 regular basis COPD prevalence, % EPIC Asia 6.2 8.1 7.7 9.5 4.5 5.1 4.2 5.9 5.3 9.4 Prevalence estimation 6.3 6.5 3.5 5.4 5.6 4.7 3.5 6.3 5.0 6.7 models [20] Severe symptomatic 19.1 13.0 16.1 24.2 20.5 12.5 13.0 20.0 15.9 37.5 phenotype Diagnosed vs symptomatic 59 vs 41 72 vs 28 90 vs 10 93 vs 7 60 vs 40 33 vs 67 40 vs 60 19 vs 81 33 vs 67 92 vs 8 (Mean age of diagnosis/yrs) (44 vs 40) (43 vs 41) (42 vs 42) (43 vs 46) (42 vs 35) (44 vs 40) (46 vs 38) (46 vs 38) (45 vs 41) (50 vs 50) MRC dyspnea score 2.3 1.8 2.2 2.2 2.6 2.4 2.6 2.4 2.1 2.5 (mean) [23] GOLD stage of severity [4], % Stage I – Mild 34.1 44.7 52.2 44.0 28.0 26.5 30.5 27.0 20.6 32.5 Stage II – Moderate 37.9 32.1 32.2 34.8 44.0 34.0 35.5 48.5 36.0 44.5 Stage III – Severe 9.3 5.6 2.9 4.8 16.5 9.5 5.0 13.5 9.3 17.5 Stage IV – Very severe 2.1 0.9 1.0 0.5 <0.5 2.5 4.0 4.0 4.2 2.0 Not diagnosed/not told 11.2 14.4 10.2 13.5 6.5 14.5 6.5 4.5 28.0 1.5 Don’t know 5.3 2.3 1.0 2.4 5.0 13.0 18.5 2.5 1.9 2.0 Other frequent health conditions, % None 45 61 61 63 47 47 29 39 18 40 Nasal allergies 13 18 20 15 2 3 11 2 32 14 Arthritis 11 7 11 6 5 6 19 4 13 24 Asthma 19 1 5 2 17 21 40 33 48 7 Diabetes 10 5 4 4 8 18 10 24 17 4 Hypertension 21 9 8 5 13 23 23 36 42 28 Heart disease 5 <1 2 1 7 11 6 5 8 5 General health status, % Excellent 2 2 <1 1 9 <1 <1 <1 <1 <1 Very good 3 9 2 5 2 6 3 2 <1 <1 Good 17 17 14 12 13 25 20 19 26 6 Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 5 of 11 Table 1 Subject demographics (Continued) Fair 48 61 70 69 33 22 58 33 53 37 Poor 23 9 13 10 35 40 19 15 19 54 Very poor 6 2 1 4 8 7 <1 32 2 5 Subjects from each of the nine territories were sampled either by telephone, using random digit dialing (RDD), or face-to-face (FF) interviews in their local language, to identify individuals who had either received a physician diagnosis of COPD or met the symptomatic criteria used (see Methods). A total of 1,841 subjects completed the study questionnaire for the EPIC Asia survey. All figures are percentages of subjects from the respective territory, with the exception of mean age of COPD diagnosis and mean MRC dyspnea score. percentages of subjects with severe or very severe disease. Asia being higher (66–75%) than in Southeast Asia (30– The mean MRC dyspnea score [23] was 2.3. 40%) (Figure 4A). A substantial proportion of subjects (23%) reported that their condition kept them from work- Health status and disease symptoms ing (Figure 4B), particularly in Indonesia (44%) and in the There was a clear North/Southeast division in reported Philippines (51%). In addition, 42% felt that their condi- health status (Table 1). The proportion of subjects who re- tion limited the kind or amount of work they could do, or port that their health was ‘poor’ or worse ranged from 11– limited their activities (Figure 4B). Subjects were also 14% in North Asia to 19–59% in Southeast Asia. Similarly, asked to estimate their levels of productivity on a typical the proportion who considered their general health to be day, and on a day when symptoms were at their worst. ‘fair’ varied from 22% in Malaysia to 70% in Hong Kong. Overall, average estimated productivity was 72% on a typ- Overall, a substantial proportion of subjects (33–53%) ical day, falling to 45% when the condition was at its worst reported symptoms typical of COPD at least twice a week (Figure 4C). during their worst month in the previous 12 months The impact of disease symptoms on daily activities (Additional file 2: Figure S1). Overall, 34% of the subjects was also explored (Additional file 2: Figure S3). Notably, reported that physical exertion instigated their COPD 39% reported that their condition limited normal phys- symptoms (Additional file 2: Figure S1D). ical activities, such as walking. A substantial proportion of subjects (27–49%) said that their respiratory symp- Exacerbations and unplanned healthcare utilization toms placed restrictions on a range of daily activities, in- Almost half (46%) of all subjects reported experiencing cluding sleep, household chores, social or recreational exacerbations in the 12 months prior to the survey activities, or affected their sex life (Additional file 2: (Figure 2A). The frequency and seasonal variation of re- Figure S3, A–C). ported exacerbations is shown in Figure 2B and C. The median number of exacerbations reported was 3, with Disease management all territories falling within the range of 2–4 (Figure 2B). Most subjects reported seeing either a specialist (44%) Exacerbations occurred more frequently between October or general practitioner (34%) for their condition. How- and January (Figure 2C). For the North Asian territories ever, only 37% of study subjects reported that they had and the Philippines, an increase in exacerbations was also been given a lung function test. Of those tested, 89% did seen in the months from February to April. Subjects not know their test results (either forced expiratory vol- reported worsening of their disease symptoms during ex- ume in the first second [FEV ] value, or percent pre- acerbations, with over half of the subjects reporting dicted FEV ). Of those who reported taking prescription coughing up phlegm or sputum, or coughing during the drugs, 20% did not know the name of the drugs they day (Additional file 2: Figure S2). were taking. When subjects were asked to describe the Overall, a sizable proportion of study subjects reported delivery format of their medication, 57% stated pill/cap- visiting a hospital emergency room (26%), or making sule, 13% stated inhaler with spacer, and 12% stated in- other unscheduled visits to a doctor or clinic (32%) in haler without spacer (Figure 5). In addition, 44% of the the previous 12 months, as a result of their condition subjects reported the use of oral corticosteroids to man- (Figure 3A). China (46%), Hong Kong (59%), and Taiwan age their symptoms during the previous 12 months (59%) recorded the highest percentages of unscheduled (Figure 6). Overall, 35% of the subjects had taken anti- doctor or clinic visits (Figure 3A). Overall, 19% of study biotics for respiratory infections during the previous subjects reported being hospitalized in the previous 12 months, and 13% had received an influenza vaccination. 12 months as a result of their condition (Figure 3B). Perceptions of disease and attitudes toward physician Impact of disease on employment and daily activities advice Less than half (47%) of all subjects were employed (either Subjects were asked questions related to their perception full- or part-time), with the employment rate in North of their condition. More than one-third (35%) felt that Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 6 of 11 Figure 2 Prevalence, frequency, and seasonal variation of exacerbations. (A) Proportion of study subjects who reported experiencing one or more exacerbations within the 12 months prior to the survey. (B) Median number of exacerbations reported by subjects over this period. (C) Proportion of subjects who reported exacerbations within each month over this period. there were no truly effective treatments for COPD habits helped, a similar percentage of subjects (39%) said (Additional file 2: Figure S4A). The majority of subjects ‘a lot’ (Additional file 2: Figure S5B). (76%) believed that smoking was the cause of their con- dition, and 70% felt that their condition worsened with Discussion increasing age, regardless of treatment (Additional file 2: The EPIC Asia survey was a multi-country, cross-sectional, Figure S4B). However, most subjects felt that with ap- population-based study that examined the prevalence and propriate treatments, progressive increase in breathless- burden of COPD in the participating Asian territories, ness could be slowed (86%) or they could lead a full and from the perspective of individuals who were diagnosed active life (84%) (Additional file 2: Figure S4C). with the disease or who reported symptoms of the disease. When asked about the extent to which their doctor’s This approach contrasts with previous studies in Asia, advice regarding treatment and management helped im- which have tended to focus on individual countries or prove their condition, 43% said ‘a lot’ (Additional file 2: areas within countries [15-19]. Figure S5A). When subjects were asked about the extent Using data obtained from the nine Asian territories in to which their doctor’s advice regarding lifestyle and this population-based survey, the average prevalence of Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 7 of 11 Figure 3 Unplanned healthcare utilization. (A) Proportion of subjects who either visited a hospital emergency room or made unscheduled visit(s) to a doctor or clinic as a result of their condition, in the 12 months prior to the survey. (B) Subjects who had ever been hospitalized because of their condition (n; %) were asked how many times they had been hospitalized in the previous 12 months. The proportions of subjects who had been hospitalized 0, 1, 2, or 3 or more times are indicated by the shading within each bar. Results are shown only for subjects who were able to report the number of times they had been hospitalized. COPD was estimated at 6.2%. Almost one-fifth of the The results of this survey may not be directly com- identified subjects were categorized as having severe or parable to those of other COPD studies, due to differ- very severe COPD, based on recalled disease classification ences in measurement methodology or study population. by a physician, or on their reported symptoms of chronic Nevertheless, our findings and those of other studies in bronchitis and frequent exacerbations. The prevalence of Asia and elsewhere [15,16,22,24-26] indicate that COPD COPD estimated in this study is similar to that reported represents a substantial socioeconomic burden in this by Tan et al. who used a mathematical model to estimate region and worldwide. In this study, a large proportion the prevalence of COPD in this region (6.3%) [20]. Simi- of subjects reported that their condition restricted their larly, it is consistent with the pooled global prevalence work or activities (42%), or kept them from working (7.6%) obtained from a meta-analysis of 37 population- altogether (23%). Another noteworthy finding is the high based COPD studies using different definitions of COPD rate of hospitalization reported; almost a fifth (19%) of including spirometric criteria, patient-reported diagnoses, subjects said they had been hospitalized as a result of physician diagnoses, etc. [24]. However, a population- their condition in the previous year. Unplanned health- based study which employed spirometric measurements care utilization was also common, with a substantial to estimate the prevalence of COPD in 12 countries (the proportion of subjects visiting a hospital emergency BOLD study), revealed higher COPD estimates (world- room (26%), or making unscheduled doctor or clinic wide 10.1%; participating Asian countries 11.4–13.9%) visits (32%) in the year prior to the survey. In the BOLD compared with our study. The BOLD study also showed study, patients with COPD reported poorer health status higher levels of severe COPD in the participating Asian than those without COPD; the degree of impairment countries (1.7–5.0%) [25]. Given that identification of was greater with increasing COPD severity. Further- COPD in our study was based on subject-reported phys- more, patients regarded severe COPD to have a greater ician diagnoses and subjects’ perception of their condition negative impact on their health status than diabetes and and symptoms, it is likely that the actual prevalence of cardiovascular [26]. COPD in the participating Asian territories is higher than Other findings from our study suggest an urgent need was estimated. for improved clinical management in this region, as well Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 8 of 11 Figure 4 Impact of disease on employment and work productivity. (A) Employment status of study subjects. (B) Proportion of subjects who reported that their condition kept them from working, limited the kind or amount of work they could do, or limited their activities. (C) Subjects’ estimated level of productivity on a typical day, and on a day when symptoms are at their worst. Upper row of n values: subjects who answered the question regarding productivity on a typical day; lower row of n values: subjects who answered the question regarding their worst day. as for better patient education. For instance, a relatively such as industrial toxins and smoke from biomass fuels, low proportion of subjects had undergone lung function are also highly relevant risk factors, particularly in the tests (37%), and the majority of those tested did not Asia-Pacific region [5-7]. Further, smoking status tends to know their test results (either FEV value or percent pre- be under-reported [27]. Inclusion of both self-reported dicted FEV ). A fifth of those who reported taking pre- smokers and non-smokers in this survey allows the capture scription drugs did not know the name of the drugs they of important information on subjects who are smokers but were taking. From the perspective of recommended clin- do not accurately report their smoking status, or those ical practice, oral corticosteroids appear to be over- whose COPD may be caused by environmental pollutants. prescribed, whereas the use of inhalers is low. Our findings need to be interpreted within the limita- Most studies on COPD are conducted on a selected tions of the study. Firstly, identification of COPD in sub- population who are smokers. Although smoking history is jects was based on subject-reported physician diagnoses, important for COPD diagnosis, environmental pollutants, where available, or on the presence of self-reported Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 9 of 11 Figure 5 Delivery format of prescribed medication. Subjects who reported taking a prescription drug were asked about the delivery format of their medication. Numbers below the bars indicate the total number of valid answers for this question, for the corresponding territory. Results are shown only for subjects who were able to report the delivery format of their medication. Figure 6 Use of oral corticosteroids. All study subjects (upper row of n values) were asked if they had been told to use oral steroids to manage their respiratory symptoms in the past 12 months. Those who had been prescribed steroids (lower row of n values) were asked if they had been told to take the steroids for three days or longer. Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 10 of 11 respiratory symptoms. Similarly, classification of disease to-face (FF) interviews in their local language, to identify individuals who severity was based either on subjects’ recall of GOLD had either received a physician diagnosis of COPD or who met the symptomatic criteria used (see Methods). classification by a physician, where available, or on their Additional file 2: Figure S1. Frequency of COPD symptoms recall of symptomatic criteria. As this was a community experienced over the previous 12 months. Proportion of subjects who survey, subjects were screened based on their reported experienced the following COPD symptoms at least twice per week in information; there was no confirmation of diagnoses via their worst month over this period: (A) being awakened at night either by coughing or shortness of breath, (B) coughing or shortness of breath subject diaries or spirometric measurements. Conse- during the day, (C) coughing up phlegm or wheezing, or (D) tightness of quently, there is potential underdiagnosis, as well as mis- the chest or coughing, wheezing, shortness of breath, or chest tightness classification of COPD and disease severity due to recall due to physical exertion. Figure S2. Exacerbation symptoms. The types of symptoms reported to be elevated during exacerbation episodes, as bias and subjects’ misperception of their disease condition reported by subjects who experienced exacerbations in the 12 months or symptoms. This may lead to less reliable prevalence es- prior to the survey. Figure S3. Restriction of daily activities by COPD timates. Secondly, subjects who were interviewed via the symptoms. The proportion of subjects who reported that their symptoms impose ‘some’ limitation or limit their activities ‘a lot’ with respect to: telephone were likely to have higher social economic sta- (A) sports and recreation and normal activities such as walking, (B) social tus than those who had face-to-face interview. This could activities or sleeping, and (C) housekeeping chores or their sex life. result in a selection bias. Potential bias was minimized by Figure S4. Subjects’ attitudes to COPD. The proportion of subjects who ‘agreed’ or ‘agreed strongly’ that: (A) there are no truly effective conducting random sampling both in regions with high treatments for their condition; (B) smoking is the cause of their condition, coverage of fixed telephone lines, as well as in those areas and that their condition tends to get worse as they get older; (C) with without telephone access. proper treatment, a progressive increase in breathlessness can be slowed, and that most people with the condition can live a full and active life. Another limitation of this study is the low response Figure S5. Subjects’ attitudes to their physician’s advice. The proportion rate which could have introduced the potential for re- of subjects who reported that their physician’s advice on (A) management sponse bias. Subjects were unable to participate in the and treatment, or (B) modification of lifestyle and habits, improved their ability to manage their respiratory symptoms to the following degrees: ‘Not survey due to various reasons which included ineligible at all’, ‘Only a little’, ‘Some’,or ‘Alot’. Results are shown only for subjects or refusal to participate, contact failure, and inability to who provided valid answers to the questions. complete survey. Hence, it was not possible to collect demographics information from the non-respondents to Competing interests assess if response bias exists. Nonetheless, steps were SL, DCLL, SW, LTTL, JPZ, and TG have received consulting fees from Takeda Pharmaceuticals GmbH. SL has received speaker fees from GlaxoSmithKline taken to mitigate potential bias. Households were ran- (GSK) and AstraZeneca. TG has received research grants, lecture fees or travel domly selected by RDD or area probability sampling. In grants from GSK, United Laboratories (UNILAB), AstraZeneca, Boehringer households where more than 1 subject was eligible, ran- Ingelheim, Sanofi-Aventis, Getz Pharma, Nycomed-Takeda, Pfizer, and Novartis, and has served on Advisory Boards for GSK, Novartis, Nycomed-Takeda, dom sampling was performed to select only 1 subject. In Boehringer Ingelheim, and UNILAB. LTTL has served on Advisory Boards for GSK, addition, multiple contact attempts were made to reduce AstraZeneca, Novartis, and Boehringer Ingelheim, and has received research contact failure. Another limitation of this study is that grants from Astra Zeneca, MSD, and GSK. She has received speaker fees and travel grants from GSK, Astra Zeneca, Novartis, and Boehringer Ingelheim. JPZ the sample size of each country may not be large enough has received lecture fees from GSK, AstraZeneca, Boehringer Ingelheim, to allow meaningful conclusions to be drawn about each Nycomed-Takeda, and Novartis, and has served on Advisory Boards for country. Nevertheless, the study enrolled a near uniform AstraZeneca, GSK, Novartis, Nycomed-Takeda, and Boehringer Ingelheim. VS and RC are both an ex-employees of Takeda Pharmaceuticals. They were number of subjects in each country that minimized the employees of Takeda Pharmaceuticals during the conduct of this study. All likelihood that the overall prevalence would be affected other authors declare that they have no competing financial interests. by unbalanced sample size in any country. Authors’ contributions All authors contributed equally to the analysis of the data and the Conclusions development of the manuscript. All authors have read and approved the The results of the EPIC Asia population-based survey sug- final manuscript. gest a high prevalence of COPD in the participating Asia- Acknowledgements Pacific territories, and indicate a substantial socioeconomic The study was funded by Takeda Pharmaceuticals International GmbH. burden of the disease in this region. Individuals with the Additional medical writing support was provided by Caroline Loder and Michael Kirwan at Synergy Vision (London), and by Research2Trials Clinical disease reported substantial limitations in their daily activ- Solutions Pte. Ltd (Singapore); this support was funded by Takeda. ities and loss in work productivity. These findings highlight the need to enhance patient and physician education, and Author details 1 2 Duke-NUS Graduate School of Medicine, Singapore, Singapore. Department improve the management of COPD in this region. of Medicine, University of Hong Kong, Pokfulam, Hong Kong. Institute of Respiratory Medicine, Kuala Lumpur, Malaysia. Department of Pulmonology Additional files and Respiratory Medicine, Universitas Indonesia (FMUI), Jakarta, Indonesia. Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand. Respiratory Care Center, University Medical Center, Ho Chi Minh Additional file 1: Table S1. Sampling frame for the EPIC Asia survey, by City, Vietnam. Takeda Pharmaceuticals (Asia-Pacific) Pte. Ltd, Singapore, country. Subjects from each of the nine participating territories were Singapore. State Key Lab of Respiratory Disease, National Clinical Research sampled either by telephone, using random digit dialing (RDD), or face- Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 11 of 11 First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 22. 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The Global Initiative for Chronic Obstructive Lung Disease (GOLD): The accuracy of self-reported smoking: a systematic review of the relationship Global Initiative for Chronic Obstructive Lung Disease (GOLD) Global between self-reported and cotinine-assessed smoking status. Nicotine Tob Res. Strategy for the Diagnosis, Management, and Prevention of Chronic 2009;11:12–24. Obstructive Pulmonary Disease, Revised 2013. Available from: http://www. goldcopd.org. 5. Boschetto P, Quintavalle S, Miotto D, Lo Cascio N, Zeni E, Mapp CE. Chronic obstructive pulmonary disease (COPD) and occupational exposures. J Occup Med Toxicol. 2006;1:11. 6. Hu G, Zhou Y, Tian J, Yao W, Li J, Li B, et al. Risk of COPD from exposure to biomass smoke: a metaanalysis. Chest. 2010;138:20–31. 7. Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009;374:733–43. 8. Kessler R, Stahl E, Vogelmeier C, Haughney J, Trudeau E, Lofdahl CG, et al. 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J Med Assoc Thai. and take full advantage of: 2002;85:1147–55. 18. Yoo KH, Kim YS, Sheen SS, Park JH, Hwang YI, Kim SH, et al. Prevalence of • Convenient online submission chronic obstructive pulmonary disease in Korea: the fourth Korean National • Thorough peer review Health and Nutrition Examination Survey, 2008. Respirology. 2011;16:659–65. 19. Zhong N, Wang C, Yao W, Chen P, Kang J, Huang S, et al. Prevalence of • No space constraints or color figure charges chronic obstructive pulmonary disease in China: a large, population-based • Immediate publication on acceptance survey. Am J Respir Crit Care Med. 2007;176:753–60. 20. Tan WC, Seale JP, Charoenratanakul S, de Guia T, Ip M, Mahayiddin A, et al. • Inclusion in PubMed, CAS, Scopus and Google Scholar COPD prevalence in 12 Asia-Pacific countries and regions: projections based • Research which is freely available for redistribution on the COPD prevalence estimation model. Respirology. 2003;8:192–8. 21. Halpern MT, Stanford RH, Borker R. The burden of COPD in the U.S.A.: results Submit your manuscript at from the Confronting COPD survey. Respir Med. 2003;97(Suppl C):S81–9. www.biomedcentral.com/submit
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Copyright © 2015 by Lim et al.; licensee BioMed Central.
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Medicine & Public Health; General Practice / Family Medicine; Primary Care Medicine
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Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a clinical syndrome encompassing a group of chronic, progressive, and debilitating respiratory conditions, that are characterized by incompletely reversible airflow limitation. Within the Asia-Pacific region, prevalence estimates have been derived using various protocols and study methods, and there is little data on the impact of COPD exacerbations. This study aimed to provide a comprehensive picture of the current prevalence and burden of COPD in this region. Methods: A population-based survey was conducted in nine Asia-Pacific territories between 01 February 2012 and 16 May 2012. Overall, 112,330 households were screened to identify eligible subjects (aged ≥40 years, with a physician diagnosis of COPD, chronic bronchitis or emphysema, or with identifiable symptoms of chronic bronchitis). Out of a sample of 69,279 individuals aged ≥40 years, 4,289 subjects with COPD were identified. Data were collected via face-to- face interviews or by fixed-line telephone, using a structured questionnaire. A total of 1,841 completed questionnaires were analyzed. Results: The overall estimated COPD prevalence was 6.2%, with 19.1% of subjects having severe COPD. In the 12 months prior to the survey, nearly half of all subjects (46%) had experienced exacerbations, and 19% had been hospitalized as a result of their condition. When subjects were asked about the impact of their condition on employment, 23% said their condition kept them from working, and 42% felt that their condition limited their ability to work or their activities. Of those who reported taking prescription drugs, 20% did not know the name of the drugs they were taking. Prescription of oral corticosteroids was common, with 44% of subjects having used these during the previous year to manage their respiratory symptoms; in contrast, inhaler use was low (25%). Only 37% of subjects had taken a lung function test, and the majority (89%) of those tested did not know their test results. Conclusions: Across the Asia-Pacific territories surveyed, the prevalence of COPD is high, indicating a substantial socioeconomic burden. Our findings suggest that there is considerable room for improvement in the management of COPD, and highlight a need to enhance patient and physician education in the region. Keywords: Chronic obstructive pulmonary disease (COPD), Asia-Pacific, Population-based, Survey, Prevalence, Exacerbations, Impact, Quality of life (QoL) * Correspondence: sam.lim@duke-nus.edu.sg Duke-NUS Graduate School of Medicine, Singapore, Singapore Full list of author information is available at the end of the article © 2015 Lim et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 2 of 11 Background and Vietnam (Southeast Asia). Household screening and Chronic obstructive pulmonary disease (COPD) is a clin- subject selection were carried out by telephone or face-to- ical syndrome that encompasses a group of chronic, face interviews (Figure 1; Additional file 1: Table S1). A progressive, and debilitating respiratory conditions, in- structured questionnaire was then administered to eligible cluding emphysema and chronic bronchitis. COPD is subjects. the fourth leading cause of global mortality [1], and its Households were screened by random sampling to re- prevalence is predicted to rise [2,3]. Despite the wealth duce selection bias. Fixed-line random digit dialing of information regarding its causes, pathophysiology, (RDD) sampling was conducted in regions with a high and treatment options, the disease has historically been coverage of fixed telephone lines. Numbers were chosen under-diagnosed and under-reported, especially within based on randomly selected blocks of numbers. In the the Asia-Pacific region [1,4]. remaining regions, area probability (cluster) sampling was COPD is characterized by persistent, progressive air- conducted face-to-face (FF) in subjects’ homes. Areas flow limitation, and is often accompanied by cough and were divided into primary sampling units, which were increased sputum production [4]. Airflow limitation is then randomly selected, and a block or building was associated with chronic inflammation in the lungs and is chosen as a starting point. principally caused by long-term exposure to airborne ir- Individuals who met the following criteria were eligible ritants such as cigarette smoke. In the Asia-Pacific re- for inclusion in the survey: individuals aged ≥40 years, gion, smoke from biomass fuels and industrial toxins are who reported either a physician diagnosis of the follow- also known to be problematic risk factors [5-7]. The ing: emphysema, chronic bronchitis, COPD, chronic ob- symptoms of COPD cause significant impairment of structive airways disease, or chronic obstructive lung quality of life (QoL), including breathlessness, anxiety, disease; or who met the following symptomatic defin- and physical limitations, resulting in days of missed ition of chronic bronchitis: production of phlegm or work [8]. mucus from the lungs on all or most days for three con- COPD exacerbations, consisting of an acute worsening secutive months. As this was a community survey which of the usual symptoms beyond normal day-to-day vari- did not include any research intervention, no ethical ap- ation, can be particularly debilitating [4]. While some ex- proval was required. Verbal consent was obtained from all acerbations may be relatively mild and go unreported subjects prior to participation in the survey. Participation [9], in severe cases they can be particularly debilitating, was voluntary. Subjects were informed that their results requiring weeks for full recovery [10]. Recent studies may be published in scientific articles and their responses have indicated that there may be exacerbation-specific would be kept both anonymous and confidential. phenotypes [11,12], and that cough and sputum (chronic The structured questionnaire used for data collection bronchitis) are associated with a greater exacerbation was based on those used in previous studies [21,22], with frequency [13,14]. additional questions to capture information on exacerba- Previous studies of the prevalence of COPD and its ex- tions. This questionnaire was developed and implemented acerbations in the Asia-Pacific have focused on individ- by Abt SRBI, Inc., on behalf of Takeda Pharmaceuticals. ual countries or cities [15-19], or relied on mathematical The same questionnaire and study design were utilized modeling [20]. The Epidemiology and Impact of COPD across all territories. Where necessary, the English lan- (EPIC) Asia survey is the first population-based COPD guage questionnaire was translated by a local translator to survey to cover nine Asia-Pacific regions using the same the local language and then reviewed by an independent study design and questionnaire. We collected data on translator with health research experience, as well as by COPD exacerbation and its indicators, such as cough local medical experts. During data collection, potential and sputum, as these aspects of the disease have not bias was mitigated by random sampling within households been well documented in this region. We also consid- containing more than one eligible individual, multiple ered measures of disease reporting, disease severity, and contact attempts to reduce contact failure, and quality socioeconomic factors, along with treatment and man- control during interviews. The fieldwork teams received agement practices. The aim was to gain further insight extensive training in all aspects of administering the ques- regarding the current prevalence and burden of COPD tionnaire. Mock and pre-test interviews were used to con- in the Asia-Pacific region. firm training standards and identify areas for modification. Only eligible subjects who completed the study ques- Methods tionnaire were included in the analyses, which involved The EPIC survey was conducted between 01 February standard descriptive statistics. Disease prevalence was 2012 and 16 May 2012 in nine Asia-Pacific territories: calculated as (100 × number of eligible subjects ÷ num- China, Hong Kong, and Taiwan (North Asia), and ber of individuals aged ≥40 years), and expressed as a Indonesia, Malaysia, the Philippines, Singapore, Thailand, percentage. Severe COPD was defined based on subjects’ Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 3 of 11 Figure 1 Sampling strategy and response rate for the EPIC Asia survey. ‘Study subjects’ refers to the subset of individuals aged ≥40 years who were identified as having COPD, based on the definitions used in this study (see Methods), and who completed the questionnaire. recall of COPD classification by their physicians, accord- For country-specific figures, please refer to Additional file 1: ing to the Global Initiative for Chronic Obstructive Lung Table S1. The mean interview duration was 41 minutes. Disease (GOLD) criteria (GOLD grade III or IV), or using the following symptomatic definition: presence of Estimated prevalence of COPD and related conditions the symptoms of chronic bronchitis, together with two Based on the above criteria, the overall estimated preva- or more exacerbations in the previous 12 months. lence of COPD was 6.2%, ranging from 4.5% in Indonesia to 9.5% in Taiwan (Table 1). The proportion of subjects Results with a physician diagnosis of COPD was 59%, with the re- Subject demographics mainder having the symptomatic definition. Physician In the nine territories surveyed, a total of 112,330 house- diagnosis was higher in North Asia (72–93%) than in holds were screened, identifying 69,279 households with Southeast Asia (19–60%), with the exception of Vietnam one or more individuals aged ≥40 years. Of the 69,279 (92%). Overall, 19.1% of the subjects met the definition of individuals aged ≥40 years, 4,289 either had a physician’s the severe phenotype used in this study, ranging from diagnosis of COPD or met the symptomatic definition 12.5% in Malaysia to 37.5% in Vietnam (Table 1). The ma- used in this survey. Of these 4,289 subjects with identified jority of subjects reported their COPD classification as COPD, a total of 1,841 subjects completed the question- GOLD stage I or II (34.1% and 37.9%, respectively), with naire (Figure 1). Almost half of the study population (44%) only a minority reporting it as stage III (9.3%) or IV (2.1%) was between 45 and 60 years of age, and 56% were female. (Table 1). However, Southeast Asian countries had higher Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 4 of 11 Table 1 Subject demographics Overall North Asia Southeast Asia Self-reported EPIC Asia China Hong Kong Taiwan Indonesia Malaysia Philippines Singapore Thailand Vietnam characteristic n = 1,841 n = 215 n = 205 n = 207 n = 200 n = 200 n = 200 n = 200 n = 214 n = 200 Age (years), % 40–44 26 45 50 46 18 12 16 18 18 10 45–49 19 28 28 30 14 14 15 10 14 18 50–54 14 9 10 8 18 19 13 9 15 22 55–59 11 4 4 3 13 16 14 13 15 15 60–64 11 6 2 4 16 15 19 18 11 12 65+ 20 7 5 9 22 26 23 34 28 25 Gender, % Female 56 40 47 60 49 67 63 59 64 60 Work status, % Employed 47 66 75 68 36 31 37 30 40 40 Smoking, % Never smoked on a 58 45 53 60 53 69 56 68 55 64 regular basis COPD prevalence, % EPIC Asia 6.2 8.1 7.7 9.5 4.5 5.1 4.2 5.9 5.3 9.4 Prevalence estimation 6.3 6.5 3.5 5.4 5.6 4.7 3.5 6.3 5.0 6.7 models [20] Severe symptomatic 19.1 13.0 16.1 24.2 20.5 12.5 13.0 20.0 15.9 37.5 phenotype Diagnosed vs symptomatic 59 vs 41 72 vs 28 90 vs 10 93 vs 7 60 vs 40 33 vs 67 40 vs 60 19 vs 81 33 vs 67 92 vs 8 (Mean age of diagnosis/yrs) (44 vs 40) (43 vs 41) (42 vs 42) (43 vs 46) (42 vs 35) (44 vs 40) (46 vs 38) (46 vs 38) (45 vs 41) (50 vs 50) MRC dyspnea score 2.3 1.8 2.2 2.2 2.6 2.4 2.6 2.4 2.1 2.5 (mean) [23] GOLD stage of severity [4], % Stage I – Mild 34.1 44.7 52.2 44.0 28.0 26.5 30.5 27.0 20.6 32.5 Stage II – Moderate 37.9 32.1 32.2 34.8 44.0 34.0 35.5 48.5 36.0 44.5 Stage III – Severe 9.3 5.6 2.9 4.8 16.5 9.5 5.0 13.5 9.3 17.5 Stage IV – Very severe 2.1 0.9 1.0 0.5 <0.5 2.5 4.0 4.0 4.2 2.0 Not diagnosed/not told 11.2 14.4 10.2 13.5 6.5 14.5 6.5 4.5 28.0 1.5 Don’t know 5.3 2.3 1.0 2.4 5.0 13.0 18.5 2.5 1.9 2.0 Other frequent health conditions, % None 45 61 61 63 47 47 29 39 18 40 Nasal allergies 13 18 20 15 2 3 11 2 32 14 Arthritis 11 7 11 6 5 6 19 4 13 24 Asthma 19 1 5 2 17 21 40 33 48 7 Diabetes 10 5 4 4 8 18 10 24 17 4 Hypertension 21 9 8 5 13 23 23 36 42 28 Heart disease 5 <1 2 1 7 11 6 5 8 5 General health status, % Excellent 2 2 <1 1 9 <1 <1 <1 <1 <1 Very good 3 9 2 5 2 6 3 2 <1 <1 Good 17 17 14 12 13 25 20 19 26 6 Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 5 of 11 Table 1 Subject demographics (Continued) Fair 48 61 70 69 33 22 58 33 53 37 Poor 23 9 13 10 35 40 19 15 19 54 Very poor 6 2 1 4 8 7 <1 32 2 5 Subjects from each of the nine territories were sampled either by telephone, using random digit dialing (RDD), or face-to-face (FF) interviews in their local language, to identify individuals who had either received a physician diagnosis of COPD or met the symptomatic criteria used (see Methods). A total of 1,841 subjects completed the study questionnaire for the EPIC Asia survey. All figures are percentages of subjects from the respective territory, with the exception of mean age of COPD diagnosis and mean MRC dyspnea score. percentages of subjects with severe or very severe disease. Asia being higher (66–75%) than in Southeast Asia (30– The mean MRC dyspnea score [23] was 2.3. 40%) (Figure 4A). A substantial proportion of subjects (23%) reported that their condition kept them from work- Health status and disease symptoms ing (Figure 4B), particularly in Indonesia (44%) and in the There was a clear North/Southeast division in reported Philippines (51%). In addition, 42% felt that their condi- health status (Table 1). The proportion of subjects who re- tion limited the kind or amount of work they could do, or port that their health was ‘poor’ or worse ranged from 11– limited their activities (Figure 4B). Subjects were also 14% in North Asia to 19–59% in Southeast Asia. Similarly, asked to estimate their levels of productivity on a typical the proportion who considered their general health to be day, and on a day when symptoms were at their worst. ‘fair’ varied from 22% in Malaysia to 70% in Hong Kong. Overall, average estimated productivity was 72% on a typ- Overall, a substantial proportion of subjects (33–53%) ical day, falling to 45% when the condition was at its worst reported symptoms typical of COPD at least twice a week (Figure 4C). during their worst month in the previous 12 months The impact of disease symptoms on daily activities (Additional file 2: Figure S1). Overall, 34% of the subjects was also explored (Additional file 2: Figure S3). Notably, reported that physical exertion instigated their COPD 39% reported that their condition limited normal phys- symptoms (Additional file 2: Figure S1D). ical activities, such as walking. A substantial proportion of subjects (27–49%) said that their respiratory symp- Exacerbations and unplanned healthcare utilization toms placed restrictions on a range of daily activities, in- Almost half (46%) of all subjects reported experiencing cluding sleep, household chores, social or recreational exacerbations in the 12 months prior to the survey activities, or affected their sex life (Additional file 2: (Figure 2A). The frequency and seasonal variation of re- Figure S3, A–C). ported exacerbations is shown in Figure 2B and C. The median number of exacerbations reported was 3, with Disease management all territories falling within the range of 2–4 (Figure 2B). Most subjects reported seeing either a specialist (44%) Exacerbations occurred more frequently between October or general practitioner (34%) for their condition. How- and January (Figure 2C). For the North Asian territories ever, only 37% of study subjects reported that they had and the Philippines, an increase in exacerbations was also been given a lung function test. Of those tested, 89% did seen in the months from February to April. Subjects not know their test results (either forced expiratory vol- reported worsening of their disease symptoms during ex- ume in the first second [FEV ] value, or percent pre- acerbations, with over half of the subjects reporting dicted FEV ). Of those who reported taking prescription coughing up phlegm or sputum, or coughing during the drugs, 20% did not know the name of the drugs they day (Additional file 2: Figure S2). were taking. When subjects were asked to describe the Overall, a sizable proportion of study subjects reported delivery format of their medication, 57% stated pill/cap- visiting a hospital emergency room (26%), or making sule, 13% stated inhaler with spacer, and 12% stated in- other unscheduled visits to a doctor or clinic (32%) in haler without spacer (Figure 5). In addition, 44% of the the previous 12 months, as a result of their condition subjects reported the use of oral corticosteroids to man- (Figure 3A). China (46%), Hong Kong (59%), and Taiwan age their symptoms during the previous 12 months (59%) recorded the highest percentages of unscheduled (Figure 6). Overall, 35% of the subjects had taken anti- doctor or clinic visits (Figure 3A). Overall, 19% of study biotics for respiratory infections during the previous subjects reported being hospitalized in the previous 12 months, and 13% had received an influenza vaccination. 12 months as a result of their condition (Figure 3B). Perceptions of disease and attitudes toward physician Impact of disease on employment and daily activities advice Less than half (47%) of all subjects were employed (either Subjects were asked questions related to their perception full- or part-time), with the employment rate in North of their condition. More than one-third (35%) felt that Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 6 of 11 Figure 2 Prevalence, frequency, and seasonal variation of exacerbations. (A) Proportion of study subjects who reported experiencing one or more exacerbations within the 12 months prior to the survey. (B) Median number of exacerbations reported by subjects over this period. (C) Proportion of subjects who reported exacerbations within each month over this period. there were no truly effective treatments for COPD habits helped, a similar percentage of subjects (39%) said (Additional file 2: Figure S4A). The majority of subjects ‘a lot’ (Additional file 2: Figure S5B). (76%) believed that smoking was the cause of their con- dition, and 70% felt that their condition worsened with Discussion increasing age, regardless of treatment (Additional file 2: The EPIC Asia survey was a multi-country, cross-sectional, Figure S4B). However, most subjects felt that with ap- population-based study that examined the prevalence and propriate treatments, progressive increase in breathless- burden of COPD in the participating Asian territories, ness could be slowed (86%) or they could lead a full and from the perspective of individuals who were diagnosed active life (84%) (Additional file 2: Figure S4C). with the disease or who reported symptoms of the disease. When asked about the extent to which their doctor’s This approach contrasts with previous studies in Asia, advice regarding treatment and management helped im- which have tended to focus on individual countries or prove their condition, 43% said ‘a lot’ (Additional file 2: areas within countries [15-19]. Figure S5A). When subjects were asked about the extent Using data obtained from the nine Asian territories in to which their doctor’s advice regarding lifestyle and this population-based survey, the average prevalence of Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 7 of 11 Figure 3 Unplanned healthcare utilization. (A) Proportion of subjects who either visited a hospital emergency room or made unscheduled visit(s) to a doctor or clinic as a result of their condition, in the 12 months prior to the survey. (B) Subjects who had ever been hospitalized because of their condition (n; %) were asked how many times they had been hospitalized in the previous 12 months. The proportions of subjects who had been hospitalized 0, 1, 2, or 3 or more times are indicated by the shading within each bar. Results are shown only for subjects who were able to report the number of times they had been hospitalized. COPD was estimated at 6.2%. Almost one-fifth of the The results of this survey may not be directly com- identified subjects were categorized as having severe or parable to those of other COPD studies, due to differ- very severe COPD, based on recalled disease classification ences in measurement methodology or study population. by a physician, or on their reported symptoms of chronic Nevertheless, our findings and those of other studies in bronchitis and frequent exacerbations. The prevalence of Asia and elsewhere [15,16,22,24-26] indicate that COPD COPD estimated in this study is similar to that reported represents a substantial socioeconomic burden in this by Tan et al. who used a mathematical model to estimate region and worldwide. In this study, a large proportion the prevalence of COPD in this region (6.3%) [20]. Simi- of subjects reported that their condition restricted their larly, it is consistent with the pooled global prevalence work or activities (42%), or kept them from working (7.6%) obtained from a meta-analysis of 37 population- altogether (23%). Another noteworthy finding is the high based COPD studies using different definitions of COPD rate of hospitalization reported; almost a fifth (19%) of including spirometric criteria, patient-reported diagnoses, subjects said they had been hospitalized as a result of physician diagnoses, etc. [24]. However, a population- their condition in the previous year. Unplanned health- based study which employed spirometric measurements care utilization was also common, with a substantial to estimate the prevalence of COPD in 12 countries (the proportion of subjects visiting a hospital emergency BOLD study), revealed higher COPD estimates (world- room (26%), or making unscheduled doctor or clinic wide 10.1%; participating Asian countries 11.4–13.9%) visits (32%) in the year prior to the survey. In the BOLD compared with our study. The BOLD study also showed study, patients with COPD reported poorer health status higher levels of severe COPD in the participating Asian than those without COPD; the degree of impairment countries (1.7–5.0%) [25]. Given that identification of was greater with increasing COPD severity. Further- COPD in our study was based on subject-reported phys- more, patients regarded severe COPD to have a greater ician diagnoses and subjects’ perception of their condition negative impact on their health status than diabetes and and symptoms, it is likely that the actual prevalence of cardiovascular [26]. COPD in the participating Asian territories is higher than Other findings from our study suggest an urgent need was estimated. for improved clinical management in this region, as well Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 8 of 11 Figure 4 Impact of disease on employment and work productivity. (A) Employment status of study subjects. (B) Proportion of subjects who reported that their condition kept them from working, limited the kind or amount of work they could do, or limited their activities. (C) Subjects’ estimated level of productivity on a typical day, and on a day when symptoms are at their worst. Upper row of n values: subjects who answered the question regarding productivity on a typical day; lower row of n values: subjects who answered the question regarding their worst day. as for better patient education. For instance, a relatively such as industrial toxins and smoke from biomass fuels, low proportion of subjects had undergone lung function are also highly relevant risk factors, particularly in the tests (37%), and the majority of those tested did not Asia-Pacific region [5-7]. Further, smoking status tends to know their test results (either FEV value or percent pre- be under-reported [27]. Inclusion of both self-reported dicted FEV ). A fifth of those who reported taking pre- smokers and non-smokers in this survey allows the capture scription drugs did not know the name of the drugs they of important information on subjects who are smokers but were taking. From the perspective of recommended clin- do not accurately report their smoking status, or those ical practice, oral corticosteroids appear to be over- whose COPD may be caused by environmental pollutants. prescribed, whereas the use of inhalers is low. Our findings need to be interpreted within the limita- Most studies on COPD are conducted on a selected tions of the study. Firstly, identification of COPD in sub- population who are smokers. Although smoking history is jects was based on subject-reported physician diagnoses, important for COPD diagnosis, environmental pollutants, where available, or on the presence of self-reported Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 9 of 11 Figure 5 Delivery format of prescribed medication. Subjects who reported taking a prescription drug were asked about the delivery format of their medication. Numbers below the bars indicate the total number of valid answers for this question, for the corresponding territory. Results are shown only for subjects who were able to report the delivery format of their medication. Figure 6 Use of oral corticosteroids. All study subjects (upper row of n values) were asked if they had been told to use oral steroids to manage their respiratory symptoms in the past 12 months. Those who had been prescribed steroids (lower row of n values) were asked if they had been told to take the steroids for three days or longer. Lim et al. Asia Pacific Family Medicine (2015) 14:4 Page 10 of 11 respiratory symptoms. Similarly, classification of disease to-face (FF) interviews in their local language, to identify individuals who severity was based either on subjects’ recall of GOLD had either received a physician diagnosis of COPD or who met the symptomatic criteria used (see Methods). classification by a physician, where available, or on their Additional file 2: Figure S1. Frequency of COPD symptoms recall of symptomatic criteria. As this was a community experienced over the previous 12 months. Proportion of subjects who survey, subjects were screened based on their reported experienced the following COPD symptoms at least twice per week in information; there was no confirmation of diagnoses via their worst month over this period: (A) being awakened at night either by coughing or shortness of breath, (B) coughing or shortness of breath subject diaries or spirometric measurements. Conse- during the day, (C) coughing up phlegm or wheezing, or (D) tightness of quently, there is potential underdiagnosis, as well as mis- the chest or coughing, wheezing, shortness of breath, or chest tightness classification of COPD and disease severity due to recall due to physical exertion. Figure S2. Exacerbation symptoms. The types of symptoms reported to be elevated during exacerbation episodes, as bias and subjects’ misperception of their disease condition reported by subjects who experienced exacerbations in the 12 months or symptoms. This may lead to less reliable prevalence es- prior to the survey. Figure S3. Restriction of daily activities by COPD timates. Secondly, subjects who were interviewed via the symptoms. The proportion of subjects who reported that their symptoms impose ‘some’ limitation or limit their activities ‘a lot’ with respect to: telephone were likely to have higher social economic sta- (A) sports and recreation and normal activities such as walking, (B) social tus than those who had face-to-face interview. This could activities or sleeping, and (C) housekeeping chores or their sex life. result in a selection bias. Potential bias was minimized by Figure S4. Subjects’ attitudes to COPD. The proportion of subjects who ‘agreed’ or ‘agreed strongly’ that: (A) there are no truly effective conducting random sampling both in regions with high treatments for their condition; (B) smoking is the cause of their condition, coverage of fixed telephone lines, as well as in those areas and that their condition tends to get worse as they get older; (C) with without telephone access. proper treatment, a progressive increase in breathlessness can be slowed, and that most people with the condition can live a full and active life. Another limitation of this study is the low response Figure S5. Subjects’ attitudes to their physician’s advice. The proportion rate which could have introduced the potential for re- of subjects who reported that their physician’s advice on (A) management sponse bias. Subjects were unable to participate in the and treatment, or (B) modification of lifestyle and habits, improved their ability to manage their respiratory symptoms to the following degrees: ‘Not survey due to various reasons which included ineligible at all’, ‘Only a little’, ‘Some’,or ‘Alot’. Results are shown only for subjects or refusal to participate, contact failure, and inability to who provided valid answers to the questions. complete survey. Hence, it was not possible to collect demographics information from the non-respondents to Competing interests assess if response bias exists. Nonetheless, steps were SL, DCLL, SW, LTTL, JPZ, and TG have received consulting fees from Takeda Pharmaceuticals GmbH. SL has received speaker fees from GlaxoSmithKline taken to mitigate potential bias. Households were ran- (GSK) and AstraZeneca. TG has received research grants, lecture fees or travel domly selected by RDD or area probability sampling. In grants from GSK, United Laboratories (UNILAB), AstraZeneca, Boehringer households where more than 1 subject was eligible, ran- Ingelheim, Sanofi-Aventis, Getz Pharma, Nycomed-Takeda, Pfizer, and Novartis, and has served on Advisory Boards for GSK, Novartis, Nycomed-Takeda, dom sampling was performed to select only 1 subject. In Boehringer Ingelheim, and UNILAB. LTTL has served on Advisory Boards for GSK, addition, multiple contact attempts were made to reduce AstraZeneca, Novartis, and Boehringer Ingelheim, and has received research contact failure. Another limitation of this study is that grants from Astra Zeneca, MSD, and GSK. She has received speaker fees and travel grants from GSK, Astra Zeneca, Novartis, and Boehringer Ingelheim. JPZ the sample size of each country may not be large enough has received lecture fees from GSK, AstraZeneca, Boehringer Ingelheim, to allow meaningful conclusions to be drawn about each Nycomed-Takeda, and Novartis, and has served on Advisory Boards for country. Nevertheless, the study enrolled a near uniform AstraZeneca, GSK, Novartis, Nycomed-Takeda, and Boehringer Ingelheim. VS and RC are both an ex-employees of Takeda Pharmaceuticals. They were number of subjects in each country that minimized the employees of Takeda Pharmaceuticals during the conduct of this study. All likelihood that the overall prevalence would be affected other authors declare that they have no competing financial interests. by unbalanced sample size in any country. Authors’ contributions All authors contributed equally to the analysis of the data and the Conclusions development of the manuscript. All authors have read and approved the The results of the EPIC Asia population-based survey sug- final manuscript. gest a high prevalence of COPD in the participating Asia- Acknowledgements Pacific territories, and indicate a substantial socioeconomic The study was funded by Takeda Pharmaceuticals International GmbH. burden of the disease in this region. Individuals with the Additional medical writing support was provided by Caroline Loder and Michael Kirwan at Synergy Vision (London), and by Research2Trials Clinical disease reported substantial limitations in their daily activ- Solutions Pte. Ltd (Singapore); this support was funded by Takeda. ities and loss in work productivity. These findings highlight the need to enhance patient and physician education, and Author details 1 2 Duke-NUS Graduate School of Medicine, Singapore, Singapore. Department improve the management of COPD in this region. of Medicine, University of Hong Kong, Pokfulam, Hong Kong. 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Journal

Asia Pacific Family MedicineSpringer Journals

Published: Apr 23, 2015

References