Anxiety and depression in COPD patients of a regional hospital in HongKong: the relationship with disease severityand dyspnoea.

Transcription

1 Title Anxiety and depression in COPD patients of a regional hospital in HongKong: the relationship with disease severityand dyspnoea Author(s) Kwok, Hau-chung.; 郭 孝 聰. Citation Issued Date 2012 URL Rights The author retains all proprietary rights, (such as patent rights) and the right to use in future works.

2 Abstract of the thesis entitled Anxiety and Depression in COPD patients of a regional hospital in Hong Kong: The relationship with disease severity and dyspnoea Submitted by Kwok Hau Chung for the degree of Master of Public Health at the University of Hong Kong in August 2012

3 Introduction: COPD is a worldwide public health issue, while anxiety and depression are highly prevalent comorbidities in COPD, some reviews in overseas reported prevalence rates of up to 75% for anxiety and up to 80% for depression among COPD patients The situation in Hong Kong is largely unclear and information is lacking. Objective: To assess the prevalence of anxiety and depression in a regional hospital in Hong Kong and to evaluate the odds ratio of different stages of severity in COPD. Method: COPD patients before hospital discharge from E3 ward in Princess Margaret Hospital (in-patient) and COPD patients who attend out-patient clinic in block K7 in PMH (out-patient) will be asked for consent to participate in the study. Baseline demographic and clinical information includes staging of COPD, questionnaires of HADS, MMRC, CAT score will be collected by research nurses after consent is obtained. Result: A total of 260 patients have been approached, with a response rate of 58.08%. 75 in-patients and 76 out-patients were eligible for the study. Our study showed the overall prevalence of depression and anxiety among COPD population are 61.6% and 23.2% respectively. Odds Ratio of depression and anxiety were increased when severity of COPD increased from stage I to IV. Compared with stage I COPD patients, the respective crude

4 odds ratio of depression for stage II is 1.25 (95% CI: ), stage III is 1.44 (95% CI: ), while stage IV is 2.09 (95% CI: ); But in anxiety, the value is insignificant as the odds ratio is less than 1. Conclusion: This is the first study in Hong Kong which is targeted on estimating the prevalence of depression and anxiety among COPD population and to correlate the finding with the COPD severity. Depression and anxiety are prevalent among the COPD patients as suggested in the study. The possibility of depression increased when severity of COPD stage increases, but the result in anxiety cannot be confirmed. No specific risk factors were found to have statistical significant association with the presence of depression and anxiety, but the current study still warrant attention. Further large scale study may be needed to reveal the situation. A more comprehensive and holistic approach to the COPD patients should be employed to tackle their special need during disease progress, in order to reduce the whole health care system burden.

5 Anxiety and Depression in COPD patients of a regional hospital in Hong Kong: The relationship with disease severity and dyspnoea by Kwok Hau Chung MBBS (HKU), MRCP (UK), FHKAM (Medicine) A thesis submitted in partial fulfillment of the requirements for the Degree of Master of Public Health at the University of Hong Kong August 2012

6 Declaration I declare that the thesis and the research work thereof represents my own work, except where due acknowledgement is made, and that it has not been previously included in a thesis, dissertation or report submitted to this University or to any other institution for a degree, diploma or other qualifications. Current research work has been funded by the Hong Kong Lung Foundation Signed: Kwok Hau Chung I

7 Acknowledgements I would like to show my gratitude to those who made this dissertation success. Firstly, I would like to express my sincere thanks to my supervisor, Dr. LM Ho, for his suggestion, guidance and support for the whole study. May I also take this opportunity to express my great thanks to my workplace supervisors, Dr. Yu WC, Dr. Yeung YC, Dr. Kwong KC for their utmost support and advice on the topic and other insight suggestion. Special thanks should also be given to our team research nurses, Ms. Polly Pang, and Ms. Maggie Wong for their great support and assistance in interacting with patients to facilitate the smooth progress of the study and Mr. Kong for his statistical advice. Another Special thanks should be given to the committees of the Hong Kong Lung Foundation, for their advice and financial support towards this study. Finally, I wish to thank all my patients who have participate into this study and contribute their valuable information into the current study. Their efforts would be greatly appreciated and would benefit the other patients in the future. My heartfelt appreciation to all your contribution. II

8 Contents Declaration... I Acknowledgements. II Table of Content III-VI List of Figure/Tables VII-IX Abbreviations.. X-XI Chapter 1: Introduction and literature reviews 1.1 Pathogenesis and pathophysiology of COPD Smoking and air-pollution as factors for COPD Diagnosis of COPD Scope of problem of COPD worldwide COPD prevalence worldwide Mortality of COPD worldwide Service utilization arising from COPD worldwide Economic Burden and Disability-adjusted Life Years 9 worldwide 1.4 Scope of problem in Hong Kong and Asia-Pacific regions COPD prevalence in Hong Kong Mortality of COPD in Hong Kong Disability and Health related Quality of Life of COPD in Hong 13 Kong III

9 1.4.4 Service utilization arising from COPD in Hong Kong Economic Burden from COPD in Hong Kong Comorbidities of COPD Management of COPD Pharmacological Treatment Smoking Cessation program Bronchodilator therapy Inhaled corticosteroid Combination therapy Oral corticosteroid Non-Pharmacological Treatment Pulmonary Rehabilitation Oxygen Therapy Ventilatory Support Scope of problem of Anxiety and Depression among COPD Prevalence of Anxiety and Depression Screening problem for Anxiety and Depression Impact of Anxiety and Depression to COPD patient Management modalities of Anxiety and Depression patients 27 in COPD Pharmacological Treatment Cognitive Behavior Therapy Pulmonary rehabilitation Situation in Hong Kong Knowledge Gaps of Anxiety and Depression 32 IV

10 Chapter 2: Study Rationale, aim and objective 2.1 Study Rationale Aim and Objective 35 Chapter 3: Study Methodology 3.1 Study Design Study Population Sampling Procedure Outcome measures Questionnaires Statistical Method Ethics Approval 44 Chapter 4: Result 4.1 Total Number of Collectible Data Demographic of the recruited patients Characteristics of Depression Characteristics of Anxiety Prevalence and Odds of Anxiety and Depression to COPD stages 68 and other variables Chapter 5: Discussion 5.1 Prevalence of Anxiety and Depression Challenges in making a diagnosis of COPD Challenges in diagnosing and managing Anxiety and Depression Diagnostic Tool Patients Barrier Physicians Barrier System-level Barrier Odds ratio of COPD stages to depression and anxiety 82 V

11 5.2 Association of Anxiety and Depression to Demographic data Association between inpatient and outpatient setting Management of Anxiety and Depression Limitation of Current Study Future research direction 89 Chapter 6: Public Health Impact and Suggestion 90 Chapter 7: Conclusion 93 Appendices 95 Reference 105 VI

12 Illustration List of Figures Figure 1: Flow chart of eligible subjects Figure 2: Diagrammatic presentation of the 95% CI Error bar for mean CAT score by stage of COPD Figure 3: Diagrammatic presentation of the 95% CI Error bar for mean MMRC score by stage of COPD Figure 4: Diagrammatic presentation of the 95% CI Error bar for mean HADS-D score by in-patient and out-patient Figure 5: Diagrammatic presentation of 95% CI Error bar of mean HADS-A score by in-patient and out-patient Figure 6: Diagrammatic presentation of the 95% CI of the mean HADS-D score among different COPD stages Figure 7: Diagrammatic presentation of the 95% CI Error bar of the mean HADS-A score among different COPD stages VII

13 List of Tables Table 1: COPD GOLD Stages Table 2: Descriptive statistics of the recruited patients in out-patient setting and in-patient setting Table 3: Descriptive statistics of the variables Table 4: Values of Mean of CAT score of different COPD stages Table 5: Values of Mean of MMRC score of different COPD stages Table6: Values of mean HADS-D among in-patient and out-patient Table 7: Demographics and health related variables of the depression and anxiety patients in both in-patients and out-patients Table 8: Life style features of depression and anxiety patients in both in-patients and VIII

14 out-patients Table 9: Values of mean HADS-A among in-patient and out-patient Table 10: Summary of calculated prevalence of depression and anxiety of different stages in COPD Table 11: Values of Mean of HADS-D score of different COPD stages Table 12: Values of the mean of HADS-A score of different COPD stages Table 13: Summary of the calculated crude odd ratio IX

15 Abbreviations CAT COPD Assessment Test CBT Cognitive Behavior Therapy CI Confidence Interval COPD Chronic Obstructive Pulmonary Disease DALY Disability-Adjusted Life Years DSM-IV Diagnostic and Statistical Manual of Mental Disorders (fourth edition) epr electronic Patient Record FEV 1 Forced Expiratory volume in 1 second FVC Forced Vital Capacity GDS Geriatrics Depression Scale GOLD Global Initiative for chronic Obstructive Lung Disease HADS Hospital Anxiety and Depression Scale HADS-A Hospital Anxiety and Depression Scale-Anxiety HADS-D Hospital Anxiety and Depression Scale-Depression ICD International statistical Classification of Diseases and related health problem IP In-patient X

16 LLN Lower Limit of Normal LVRS Lung Volume Reduction Surgery MDI Metered Dose Inhaler MMRC Modified Medical Research Council NIV Non Invasive Ventilation NNT Number Needed to Treat OP Out-patient PHS Population health Survey PR Pulmonary Rehabilitation QoL Quality of Life S.D. Standard Deviation SSRI Selective Serotonin Reuptake Inhibitor TCA Tricyclic Antidepressant UK United Kingdom US United State of America WHO World Health Organization XI

17 Chapter 1 Introduction and Literature Review Chronic Obstructive pulmonary disease (COPD) is a worldwide public health issue and among the hot topic in the field of respiratory medicine for its special presentation and unique management. Management of COPD has even been changing rapidly within decades; management has been evolved from pharmacological centered, to multi-disciplinary approach. Not only is the medical care for COPD patients, but also the psychological health is important too. Psychological disorder namely depression and anxiety will bring both extra cost of medical burden and impact to the whole health care system. This is the ultimate goal for this research thesis, in order to update and enhance the understanding of this ever changing disease, together with the exploration of its impact in the public health perspective, so to help a better formulation of COPD patients care in Hong Kong. 1.1 Pathogenesis and pathophysiology of COPD Chronic Obstructive Pulmonary Disease, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive 1

18 and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. 1 This statement summarized the essential understanding of the COPD. Chronic airway limitation is the essential pathophysiology of COPD; it is a mixture of small airway disease, called obstructive bronchiolitis, and parenchymal destruction, called emphysema. Both situations contribute into the overall airflow limitation of the COPD patients. However, both emphysema and chronic bronchitis are pathological diagnosis only, therefore, it is no longer included inside the definition of COPD. It is the inflammation in the respiratory tracts that cause the disease, but the mechanisms for this amplified inflammation are not yet well understood, with possibility of genetic predisposition. Oxidative stress 2 and excess of proteinases in the lung further modify lung inflammation. The extent of inflammation, induced fibrosis, and luminal exudates in the small airways causing the airflow limitation and air-trapping (defined by reduction in FEV1 and FEV1/FVC ratio, will be further discussed in 1.2) and gradual decline in FEV1. 3 Hyperinflation due to air-trapping is the main mechanism for exertional dyspnoea (shortness of breath). 4 The encountered risk factor for COPD is noxious particles or gases, which 2

19 tobacco smoking is the main contributing factor. Smokers have a higher prevalence of respiratory symptoms and lung function abnormalities, a greater annual rate of decline in FEV1, and a greater COPD mortality rate than non smoker. 5 Passive exposure to tobacco smoke may also contribute to respiratory symptoms and COPD by increasing the lung s total burden of inhaled particles and gases. 6,7 Other particles include mariguana 8, occupational exposure (including organic and inorganic dusts and chemical agents and fumes) 9, indoor pollutant from biomass cooking and heating in poorly ventilated dwellings 10,11 are well known risk factors for COPD. Almost 3 billion people worldwide use biomass and coal as their main energy source in daily living, so the population at risk is very large worldwide. 12 however, the role of outdoor air pollution in causing COPD is unclear, but appears to be small when compared to tobacco smoking because it is difficult to isolate the effect of a single pollutant in long term exposure for causing the COPD. Only, the association with decrements of respiratory function is found in air pollution from fossil fuel combustion, primarily from motor vehicle emissions in cities etc Smoking and air-pollution as factors for COPD In Hong Kong, the prevalence of daily cigarette smokers aged 15 and above decreased generally from 1982 to Male smoking prevalence rate decreased 3

20 from 39.7% in 1982 to 20.5% in 2007/2008, and female smoking prevalence rate decreased from 5.6% to 3.6% in the same period. But if further analyzed by age group and sex, the prevalence rate of daily female smokers aged 20 to 29 were actually increased from 1.5% in 1982 to 6.1% in 2007/2008, also, those aged 30 to 39 increased from 2.6% to 6.4% during the same period. This suggested a potential increased prevalence of COPD among female population in the future. Although there is no direct causal relationship evidence between the second-hand smoke exposures to COPD prevalence, there is sufficient evidence to support a causal relationship between second-hand smoke with asthma induction and exacerbation, as well as eye and nasal irritation. 15 Outdoor air pollution has actually been declining in most developed countries, but it is still increasing in developing countries, especially Asia 17. The cited air pollution levels are based on the four criteria of air pollutant as: nitrogen dioxide, sulphur dioxide, particulates and Ozone. The role of outdoor air pollution in the development of COPD is not yet confirmed by studies, but there is strong evidence to support the relationship between outdoor air pollution and worsening of existing COPD exacerbation rate. 16 Air pollution in china has been increasing due to the use of fossil fuel, Hong Kong also shares the same air as the Pearl River Delta which is a fast developing economic zone in china. 17 Therefore, Hong Kong in recent years has 4

21 been observed to have higher level of air pollution than the WHO s recommended target level for health protection and the trend is not expected to fall in near future. 18,19 In Hong Kong, study has also found a significant association between high levels of air pollution and increased admissions for COPD. 20 The direct health care costs and lost productivity due to air pollution effects have been estimated to be over HK$ 1.9 billion per year. 19 Although this cost estimation may contribute both cardiac impact and respiratory disease, more than half of the health care costs are due to respiratory problems. 1.2 Diagnosis of COPD A clinical diagnosis of COPD should be considered in any patients presented with dyspnoea, chronic cough or sputum production, and a history of exposure to risk factors for the disease as mentioned in 1.1 Spirometry is required to make the diagnosis in this clinical context. Forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) will be obtained during the investigation. The presence of post-bronchodilator FEV 1 /FVC < 0.7 (70% predicted) confirms the diagnosis of airflow limitation and thus of COPD. Since ratio of 70% is a simple and independent, but challenges have been raised among respiratory professions. Used of fixed ratio to define airflow limitation will 5

22 result in more frequent diagnosis of COPD in elderly 21, and less frequent diagnosis in adults younger than 45 years old 22, when compared to another cutoff value using lower limit of normal (LLN) of the ratio (FEV 1 /FVC). The LLN values are based on the normal distribution and classify the bottom 5% of the healthy population as abnormal. However, LLN values are reference-dependent among different population worldwide, therefore, using a fixed ratio will enhance the diagnostic simplicity and consistency among different populations. And as a physician, Spirometry finding is only one parameter to establish the diagnosis of COPD, which clinical symptoms and risk factor exposure should be considered too. The diagnosis ratio used in this paper will be a fixed ratio of 70% predicted in FEV 1 /FVC for the evaluation of burden and prevalence assessment. Severity of COPD is classified according to values of FEV 1 and according to GOLD guideline 1, the severity is classified as followed: In patients with FEV 1 /FVC <0.7: Table 1: COPD GOLD stage GOLD 1 Mild FEV 1 >=80% predicted GOLD 2 Moderate 50%<=FEV 1 <80% predicted GOLD 3 Severe 30%<=FEV 1 <50% predicted GOLD 4 Very Severe FEV 1 <30% predicted 6

23 1.3 Scope of problem of COPD worldwide COPD prevalence worldwide The COPD prevalence data worldwide show remarkable variation due to differences in survey methods, diagnostic criteria, and analytic approaches. 23 Self-reporting by a doctor in diagnosis of COPD or equivalent condition poses significant under-estimation. As a chronic disease, COPD imposes a huge burden worldwide and this burden will increase in ageing population. 24 A systematic review and meta-analysis of papers published from 1990 to 2004 found 37 estimates for the global prevalence of COPD and yield a pooled prevalence rate estimate of 7.6% (95%CI: %) 23. The prevalence rate in people aged 65 and over was estimated to be higher than other age groups at 14.2% (95% CI: %). Pooled prevalence rate of COPD based on Spirometry tests was 9.2% (95%CI: %) which was higher than that from self-reported diagnoses indicating that self reported prevalence tended to under-estimate the true prevalence. Another study showed, worldwide prevalence rate of moderate to severe COPD among those aged 40 and above was 10.1%. 25 The Americas had the highest COPD prevalence rate of 1.5% in 2004 among all WHO sub-regions, followed by Europe (1.3%) and Western Pacific (1.2%). 26 Although Europe has relatively low prevalence rate, it steadily climbing up from 1990 to

24 1.3.2 Mortality of COPD worldwide The global Burden of Disease Study projected that the COPD, previous ranked 6 th as a cause of death in 1990, will become the 3 rd leading cause of death worldwide by A newer projection even estimated COPD will be the 4 th leading cause of death in This significant increasing mortality maybe related to the expanding epidemic of smoking in low and middle income countries, and also reduced mortality from other common disease in the aging population. However, under-recognition and under-diagnosis of COPD still affect the accuracy of mortality data 29, therefore caution is needed for analysis Service utilization arising from COPD worldwide In USA, the rate of hospital discharges from COPD as the principal diagnosis increased from 1.7 per 1000 in 1992 to 2.3 per 1000 in About 64% of COPD hospital episodes were reported in the population aged 65 and above, with COPD hospitalization rate being approximately 11.6 per In UK, the mean length of stay in hospital increased from 7.5 days in 1998/1999 to 7.8 days in 2002/2003, followed by a reduction to 5.9 days in 2008/2009. Over 60% of the admission in COPD was patients aged 65 and above. 31 While in Australia, the numbers of patient days in hospital per episode aged 65 and above were of 8.2 8

25 days in 1998/1999 to 7.2 days in 2007/ Economic Burden and Disability-adjusted Life Years (DALYs) worldwide In the developed countries, COPD plays a significant economic burden. In European Union, the total costs of respiratory disease are estimated to be about 6.5% of the total health care budget, with COPD accounting for 56% (38.6 billion Euros). 33 In the United States the estimated direct coasts of COPD are $29.5 billion and the indirect costs $20.4 billion. 34 Expenses will be alerted if the disease severity increases or repeated hospitalization or ambulatory oxygen cost etc. Medical costs increased from stage I disease (hospital costs US$680) to stage III (hospital costs US$6,770) COPD 35, in addition if oxygen therapy is used in more severe patients, diagnosed as stage II to III were much higher (from US$ 699 to US$ 2,012). Also, the economic value of the care-provider and the family members are always under-estimate into the true cost of the COPD expenditures. In UK, the mean annual direct costs per COPD patients was 819 in 2000/2001, while indirect costs such as productivity loss accounted for another 820per patient. 36 In Australia, on average, the direct health care costs per COPD patients were AU$723.9 in 2008, of which AU$399.4 was attributed to hospitalization. 37 In term of healthy life lost, WHO estimated COPD caused more than 26 million 9

26 disability-adjusted life years worldwide in 2000, 38 and it is projected that DALYs lost to COPD would be nearly 52 million in 2030 (7 th leading cause of DALYs lost) Scope of problem in Hong Kong and Asia-pacific regions COPD prevalence in Hong Kong Older people would have a higher prevalence rate of COPD as showed in a worldwide trend, and in Hong Kong, the population is rapidly ageing. The population aged 65 and above nearly doubled from 482,800 in 1990 to 916,600 in 2010, 39 and projected that in 2036, there will be 2,389,100 people aged 65 and above in Hong Kong. 40 In Hong Kong, the prevalence rate can be estimated by self-reported data or clinical diagnosis based on Spirometric data, but central registry is lacking, and the prevalence of COPD may includes other respiratory diseases e.g. chronic bronchitis, emphysema, bronchiectasis etc. Many studies have tried to look into the prevalence by mean of self-reporting approach: a population health survey (PHS) conducted in was first to estimate the prevalence rate of self-reported COPD in population aged 15 years and above and found it to be 1.4%. 41 It also reveals an increased trend in age-specific prevalence when in elderly. The prevalence rate of self-reported COPD among those aged 65 and above was estimated to be 4.6%. 41 Another local study revealed that the prevalence rate 10

27 of chronic bronchitis or emphysema among elderly aged 70 and above increased from 8.1% in to 9.0% in But if the prevalence rate is calculated based on Spirometric result (FEV 1 /FVC <0.7), among the 165 subjects with aged 70 and above, there was 10.9% in If the prevalence rates are calculated based on the staging severity of COPD after Spirometry confirmation, the overall prevalence rate among people aged 60 and above to be 25.9% 43 (FEV 1 /FVC <0.7). Prevalence of moderate (stage II) to very severe (stage IV) COPD was about 14.1%. 43. Interestingly, if the definition of COPD was changed to the LLN values of the FEV 1 /FVC ratio as mentioned in Section 1.2 previously, the prevalence rate among those aged 60 or above was still as high as 12.4%. From the two studies, prevalence based on either definition (FEV 1 /FVC <0.7 or LLN values of FEV 1 /FVC) by Spirometry, was higher than self reported prevalence, this implies that under-diagnosis of COPD is common among Hong Kong. A study quoted from a cohort of an elderly health centre in Hong Kong, suggests an under-estimation is possible about 6.1% among people aged 65 and above attending the elderly health centre. 44 Based on the prevalence of risk factors, a projection model estimated that the prevalence rate of moderate to severe COPD among the population aged 30 and above in 2000 was relatively low in Hong Kong (3.5%) as compared with those in other Asia-Pacific countries, such as China (6.5%), Japan (6.1%) and Australia 11

28 (4.7%). The prevalence rate in Singapore (3.5%) was the same as in Hong Kong Mortality of COPD in Hong Kong In Hong Kong, COPD (ICD-9: or ICD-10: J40-J47) has been the 6 th leading cause of death. In 2008, there were 2,103 deaths from COPD, accounting for 5.1% of all deaths. 46 The age adjusted COPD mortality rate increased slightly in the early 80s, then followed a decreasing trend in general, with the exception of a peak in Similar to the worldwide figures, the greatest number of deaths from COPD in Hong Kong occurs in those 65 years and above, the proportion of deaths increased from 70% in 1981 to 94% in Also the COPD mortality for those aged 65 and above was per 100,000 accounting for 6.0% of all deaths within the age group. When compared to other Asian countries, Hong Kong has similar age-adjusted COOD mortality rate compared to Australia (5%) 48, and Singapore (4.6%) 49, but lower than those in China (43.6%) Disability and Health related Quality of Life of COPD in Hong Kong Cost in dealing with disability is one of the indirect costs to COPD. A study performed in 2006 by Lee, Lee & Mackenzie, on groups of severe to very severe 12

29 COPD patients, reported a mean Barthel Index score of (out of a maximum of 20) and 73.2% of these older COPD patients had mild to severe functional limitations as defined by the Barthel Index. 51 Similar situations have been observed in oversea studies among COPD population, The mean Barthel score in an Italian study in COPD patients was 89.7 (out of a maximum of 100) whereas healthy subjects was In Singapore, it was estimated that about 11.6% of Chinese COPD patients aged 55 and above had functional disability (needing help in one or more of the ten selected basic ADL), as compared to 5.5% among those without COPD Service utilization arising from COPD in Hong Kong COPD exacerbation is one of the main reasons for hospitalization and service utilization in Hong Kong. In 2001, COPD ranked first in terms of number of public hospital episodes among people aged above 65 years (30,530 episodes). Patients aged 65 years and above diagnosed with COPD occupied 238,022 bed-stays and there were 11,336 COPD patients who stayed in public hospitals. 54 The age-adjusted hospitalization rates of COPD (ICD-9: , 496) remained stable in 1997 to 2002, but a drop in 2003 (possibly due to severe acute respiratory syndrome), and gradual increased again in 2004 and The overall decreasing trend over 1997 to

30 was statistically significant. Women showed a decreasing trend while men did not have similar trend. Men had a much higher hospitalization rates than women. In 2005, the COPD hospitalization rate (per 1000) for men aged 65 to 74 was 13.8, while that for women was only But this information was from primary diagnosis of COPD admission which many of patients were admitted due to other causes but with secondary diagnosis as COPD. More than 4% of the annual bed-stays were used by COPD patients and those aged 65 years used the majority of bed-stays. The average number of bed-stays per episode slightly decreased from 7.4 days in 2007 to 7.0 in For those who aged 66 and above, they spent more than one week in hospital per episode, or a total of 2 to 3 weeks a year (17.8 days in 2006). 56 In China, the number of hospital discharges of COPD cases nearly doubled from 173,248 in 2006 to 337,781 in The older population aged 60 and above takes up 70% of all COPD hospital discharge. Also the average length of hospital stay in COPD patients was 11.2 days in Economic Burden from COPD in Hong Kong There are not much researches or studies particularly targeted on calculation of the economic burden of COPD patients in Hong Kong. Only limited data can be 14

31 retrieved, a study by Cadenza funded by the Hong Kong Jockey Club Charities Trust, based on the assumption of standard public ward fee of HK$3,300 per day, calculated that, in 2006, about HK$ 985 million were spent on COPD hospitalization. 86% of which was for people aged 65 and above, accounting for HK$ 844 million. On average, the annual costs of hospital admissions to each COPD patients were in sum approximately HK$ 56,051, while the costs for older patients increased to approximately HK$ 66,287. The authors postulated the total costs of hospitalization by 2036, in patients of COPD aged 65 and above would increase to approximately HK$ 7.8 billion. The costs will be further increased to 3 to 8 times from moderate severity COPD to more severe patients. Besides, smoking is the major risk factor of COPD. In 1998, the smoking-attributable public hospital costs of COPD in the population aged 35 and above were estimated to be HK$ 430 million, accounting for one third of all tobacco-related diseases and majority of the costs were utilized for treating patients aged 65 years and above, particularly male Comorbidities of COPD COPD is not a disease that affects only the pulmonary system, it is increasing recognized that comorbidities include the influence on cardiac function and gas 15

32 exchanges. 59 The inflammatory mediators of COPD patients in the circulation may contribute to skeletal muscle wasting and cachexia, and may initiate or worsen comorbidities such as ischemic heart disease, heart failure, osteoporosis, normocytic anaemia, diabetes, metabolic syndrome, and depression. These comorbidities play a significant major impact on quality of lift and survival to the COPD patients. 60 Therefore, COPD patients should not only be taken care of their lung condition, handling their comorbidities are same important. 1.6 Management of COPD Pharmacological treatment Pharmacologic therapy for COPD patients are used for symptoms reduction, frequency and severity of exacerbation reduction, health status and exercise tolerance improvement etc. But there is no conclusive evidence that the existing medication for COPD would modify the long term decline in lung function when tested as a primary and secondary outcome in clinical trials 61,62 except the smoking cessation intervention. The choice of different medication depends on the availability in the locality, cost of medication and patient s response. Therefore, it is patient-specific treatment choice and different patients with the same severity may treatment in a slightly different approach and medication choice. The main route of 16

33 drug administration in COPD medication is inhaled route, therefore puff technique training is essential in all COPD patients who started this mode of drug delivery. 63 Spacer devices are available for those patients who are not able to have good coordination with the puff device namely Metered-dose inhaler (MDI), so that medication can still be delivered in a secure manner in dose and prevention of uneven drug efficaciousness Smoking cessation program It is one of the most important parts in the overall management of COPD because it has the greatest influence on the natural history of the disease. Nicotine replacement Products in any form (nicotine gum, inhaler, nasal spray, transdermal patch, sublingual tablets, or lozenge) reliably increases the long term cessation rate of smoking Medical contraindications to this treatment includes coronary artery disease, untreated peptic ulcer disease, and recent myocardial infarction or stroke. 67 Newer agents like Varenicline 68, bupropion 69 and nortriptyline 70 were found to have the ability to increase the long term quit rate in smoking cessation. Pharmacological treatment alone was definitely not enough to tackle this chronic disease as tobacco dependence. Counseling delivered by physicians and other health professionals significantly increases quit rates over self-initiated strategies

34 And there is a dose-response relationship counseling intensity and the cessation success. 72,73 Helping patients to identify the problem, assessing the willingness to make a quit attempt, assist the patient s quit plan and arrange follow-up are all patients are suitable strategies that a physician can employ. In some multicenter controlled clinical trial, combination of physician advice, group support, skills training, and nicotine replacement therapy can achieve an abstinence rate of 35% in 1 year and a sustained abstinence rate of 22% at 5 years Bronchodilator therapy Bronchodilator will increase the FEV 1 or change other spirometric variables, by altering the airway smooth muscle tone, so as to improve the emptying of the lungs, reduction of lung hyperinflation at rest and during exercise. 75,76 The dose-response relationships using FEV 1 as the outcome are relatively flat with all classes of bronchodilators. Toxicity is also dose related. Most commonly used item is beta 2 Agonist, namely salbutamol and indacaterol, which could be used as needed basis or regularly basis for symptoms control. 77 Indaceterol is a novel long acting beta 2 -agonist with a duration of action of 24 hours. 78 Another class of bronchodilator is the anticholinergics, namely ipratropium, oxitropium and tiotropium bromide. They block the muscarinic receptors and relax smooth muscles 18

35 around bronchiole. Tiotropium is a long action anticholinergic which reduces exacerbations and related hospitalizations, improves symptoms and health status. 79 Long acting bronchodilators are more convenient and more effective at producing maintained symptom relief than short-acting bronchodilators. Other classes include methylxanthine, namely theophylline, in the form of oral medication. This is less effective and less well tolerated than inhaled long acting bronchodilators, 80 with also a narrow therapeutic window, as toxicity is dose related and near toxic dosage is easily reaching. 81 Problems include the development of atrial and ventricular arrhythmias and grand mal convulsions. Therefore, this is only used when inhalation route is compromised or product not immediately available Inhaled corticosteroid Regular use of inhaled corticosteroids improved symptoms, lung function, and QoL, and reduced the frequency of exacerbations in COPD patients, especially with FEV 1 <60% predicted Interestingly, some patients may have acute exacerbation if inhaled corticosteroids were withdrawal from treatment. However, the effects of inhaled corticosteroids on pulmonary and systemic inflammation in COPD patients are still controversial. Inhaled corticosteroid use is associated with higher prevalence of oral candidiasis, hoarse voice and skin bruising 85,61, and the risk of 19

36 pneumonia also increased However, currently, guideline still recommended the use of inhaled corticosteroid, but to balance the potential risk of pneumonia in that particular patient Combination therapy An Inhaled corticosteroid combined with a long acting beta 2 -agonist is more effective than the individual components in improving lung function and health status and reducing the rate of exacerbations in patients from moderate to very severe COPD. 83,84,86,89-91 Metaanalysis found that combination therapy may reduce mortality with a number needed to treat (NNT) of But the risk of pneumonia is also increased 93 despite the fact that compliance to both medication can be ensured and symptomatic improvement. Some studies are ongoing in evaluating the different treatment combination therapy in order to enhance the compliance and effectiveness in managing the symptoms and possibly alter the natural course of disease progression Oral Corticosteriod Oral corticosteroid is usually reserved for the use in acute exacerbation but not in long term maintenance use because it has numerous side effects. The side effect 20

37 includes muscle weakness and steroid myopathy which may further worsening the respiratory functionality 94-95, therefore, it should only be suggested to be prescribed under specialist hand Non Pharmacological treatment Pulmonary rehabilitation: Recent research has provided consistent evidence that pulmonary rehabilitation can considerably alleviate the burden of COPD by reducing respiratory symptoms such as dyspnea and by improving functional performance and QoL in patients with COPD Also, after pulmonary rehabilitation, improvement in symptoms of anxiety and depression were reported in several studies The component of various in different setting, but basically includes education, exercise training, motivation enhancement, crisis management and functional status assessment and maintenance. A multi-disciplinary approach would be adopted and is involving different specialist as a team, including nurses, physiotherapist, occupational therapist, dietitians, or social worker. The minimum length of an effective rehabilitation program is 6 week, but the longer the program, the more effective the results would be as shown in some studies

38 Oxygen Therapy The COPD patients who have resting oxygen saturation at or lower than 7.3 kpa (55mmHg), with or without hypercapnia confirmed twice over a three weeks period, warrant the use of long term oxygen therapy. With the use of duration greater than 15 hours each day, it is shown to have survival benefit in these particularly type of patients. 105 Stringent criteria should be met before the ambulatory oxygen is to be provided to patients, in order not to aggravate the paradoxic carbon dioxide retention secondary to excessive and unnecessary use of oxygen to COPD patients Ventilatory Support Non-invasive ventilation (NIV) is using more frequently in managing very severe COPD patients especially in combination with long term oxygen therapy when there are pronounced daytime hypercapnia. 107 Survival improvement was observed but it will not influence the quality of life of COPD patients Scope of Problem of Anxiety and depression among COPD Prevalence of Anxiety and depression Anxiety and depression are highly prevalent comorbidities in COPD, some 22

39 reviews in overseas reported prevalence rates of up to 75% for anxiety and up to 80% for depression among COPD patients Another study of 1,736 patients of COPD found 40% with depressive symptoms, 111 while other studies found ranging from 16-74% of significant depression of all COPD patients. 112,113 But most published studies have been of poor methodological quality, uncontrolled, with small sample size. 114 Anxiety has received less attention than depression among COPD population, despite the fact that anxiety and depression usually occur together in these patients. 115 In studies which the prevalence of anxiety among COPD patients has been assessed, the estimates have varied from 2 to 96% of all patients In stable COPD in out-patient setting, clinical prevalence of anxiety ranged from 13% to 55%, while that of depression ranged from 7% to 32% These 4 studies employed the same screening tool of HADS for depression and anxiety. Another systemic review 123 of 64 studies, with focus on severe stage of COPD, the prevalence of depression ranged from 37% to 71%, and with anxiety ranged from 50% to 70%, and it also found that the situation is more prevalent when compared to other chronic illness, e.g. cancer, AIDS, heart disease, and renal disease etc. 23

40 Depressive symptoms maybe a spectrum of illness ranged from dysthymia (subclinical depression) to genius clinical depression. A study reported this situation and found that approximately one fourth of COPD patients actually have unrecognized subclinical depression and such patient groups are commonly to have a high physical disability and at risk to develop major clinical depression. 124 Depression and anxiety are often untreated or undertreated in patients with COPD. 125 Fewer than one third of patients were receiving appropriate treatment among those who have been diagnosed depression. 126,127 Some risk factors have been identified, however, due to different study methodology and patient selection groups, no consensus of definite risk factors being concluded. Different studies are trying to target on the risk factors of the COPD who develops anxiety and depression, including female gender 126, current smoking 126,128, low social class status 126, living alone 129, presence of comorbidities 129, moderate severity of COPD with FEV 1 less than 50% predicted 129, severe symptoms of dyspnoea 130 or patients who are using long term oxygen therapy 131 etc. Again, there is no consensus of definite risk factors for depression and anxiety in COPD. Spirometrically determined airflow limitation and the FEV 1 /FVC ratio were linked to generalized anxiety, but to none of the other mental health domains. 132 There 24

41 seems to be a relationship between depression and the severity of the COPD, with 25% of patients with severe COPD also having depression, 19.6% of those with mild COPD. 76 Some studies believe that lung function of the COPD patient is a good predictor of mental health, although some studies 135,118 believe that it is not related. In a metaanalysis study, depression and anxiety had among the highest correlations with various questionnaires for the assessment of health status and strongly impaired health status and OoL in patients with COPD. Others factors included dyspnea and exercise tolerance. But spirometric values are only weakly associated with the health status in COPD patients. 136 Some studies also found the association with poorer survival, longer hospitalization stay, persistent smoking, increased symptom burden etc Screening problem for Anxiety and Depression A wide range of screening and diagnostic tools have been used to assess psychological distress among COPD patients, for example, those measure symptom severity using self-report questionnaire or evaluate psychiatric disorders by using structured clinical interview. Sometimes, it is particularly difficult to detect the presence of anxiety or depression in the population of COPD patients, due to the overlapping symptoms typical of respiratory disease and psychiatric disorder. 118 The 25

42 gold standard for diagnostic criteria of depression is based on the DSM-IV by formal assessment with psychiatrists. But some other useful items are currently employed for making a diagnosis of depression and monitoring of the response to treatment, which emulates the DSM-IV, it is a nine item measure and called the Patient Health Questionnaire-9 (PHQ-9) 138. Other screening tools for depression included the Center for Epidemiologic Studies-Depression (CES-D) scale 139, Geriatric Depression Scale 140 Zung Self-Rating Depression Scale 141. For anxiety screening instrument, it has been receiving less attention, but still some reasonable choices for screening the anxiety are available, namely, the Hospital Anxiety and Depression Scale (HADS) 142, Depression Anxiety Stress Scale 143 and the Beck Anxiety Inventory 144. Again, there is no consensus as to which is the most appropriate approach. Choices of the screening tools are based on preference and language validation among different ethnicity and countries. 26

43 1.7.3 Impact of Anxiety and Depression to COPD patient Symptoms of anxiety and depression were shown to be associated with a worse course of disease, including reduced QoL and increased symptoms burden, health care use, and even mortality. 137,145,146 Depressive symptoms were more common in COPD than in coronary heart disease, stroke, diabetes, arthritis, hypertension and cancer in a US study. 111 Untreated or incompletely treated depression and anxiety have major impact to the medical treatment compliance, frequency of admission, duration of hospital stay, and primary care utilization. 126,128,121 Depressed patients in a chronic illness like COPD are usually appears sicker than their counterparts and have a lower compliance to medication treatment Also, physical functioning will be influenced by depression with reduced 12-minutes walking assessment for COPD patients. 152 Because of the compromising physical health, with the associated mood disorders, it will lead to an increasing risk of hospitalization and rehospitalization. 153,154 Therefore, it brings large burden to the health care systems and also society as a whole Management modalities of anxiety and depression patients in COPD Managing depression and anxiety in COPD is difficult. Many COPD patients have transient or transitory mood symptoms during or after an acute exacerbation that 27

44 will improve spontaneously as the physical status improved. No evidence that these time-limited minor depressive symptoms require specific treatment, only when they develop major depression or anxiety that treatments are warranted Pharmacological treatment: Evidence for antidepressant therapy in COPD is limited; it is even more scare for anxiolytic treatment. Clary and Mikkelsen have showed in their reviews that tricyclic antidepressant (TCA) medication has been useful in improving mood of patients in general, but with little effect on the COPD patients. 118,155 A reason would be the side effect profiles of TCA that made it not popular to be used. But other classes of antidepressant, selective serotonin reuptake inhibitor (SSRI) has been found in high efficacy in improving short term outcomes for depression, anxiety, panic attacks, cognitive function, and overall disability in COPD. 156 One of the major concern of pharmacological treatment is the compliance issue. Study on drug compliance issue on COPD is limited, but on asthma, this issue has been confirmed. Poor compliance (defined as having less than 70% of the inhaled medication) was associated with higher depression scores in asthma patients, 157,158 while anxiety was not associated with poor compliance. It is reasonable to postulate that anxiety will improve compliance because they are more anxious about their own health. 28

45 Cognitive behavior therapy (CBT): Patients of chronic illness tend to interpret their life experiences in a distorted way to relate with emotional distress. CBT is a direct, reality- based therapy that involves educating the patient to aware and identifies the faulty thinking about the reason to cause their symptoms and correcting the thoughts to fit more closely with reality. In major depression, CBT may be used to supplement the effects of antidepressant therapy. 159 Study to compare CBT with COPD education in patients with anxiety and depressive symptoms, both treatments had a significant effect in improving quality of life and symptoms over 8 weeks and the improvements were maintained during follow-up period. 160 But whether this management can be generally applied to all COPD patients is still undefined Pulmonary rehabilitation (PR): As mentioned in 1.621, PR has been useful in managing COPD patients and to optimize their exercise capacity, and health-related quality of life, through a multidisciplinary approach. How it works in alleviating the symptoms of depression and anxiety is postulating, but generally accepted. The core components of PR comprise supervised exercise training, education, and psychological support

46 Therefore, skilled people in mental health care should be another important component within the multidisciplinary team. The successful PR starts from effective and optimal pharmacologic therapies, both in respiratory and mood medication. With the improvement in dyspnea and exercise tolerance during PR, subsequent engagement in supervised whole-body exercise training has been showed to improve symptoms of anxiety and depression as a consequence of training-related gains in functional capacity. 162,163 Also, during the education program in PR, it will promote cognitive restructuring by dispelling common misbelief or distorted belief in COPD to the mood problem and the self-management skills of their chronic illness to improve their confidence, control, and autonomy of their disease. 164 A well-structured, enjoyable PR appears to help patient from reducing the depressive symptoms and from a behavioral perspective, the exercise and respiratory therapy components of PR may be instrumental in helping patients to desensitize the excessive symptoms of dyspnoea. However, the duration of PR or the best composition of PR team is still lacking of concrete consensus and evidence. Therefore, the effect of PR is still subjected for further standardized evaluation. 30

47 1.7.5 Situation in Hong Kong In Hong Kong, limited researches have been targeted on the issue of mental health in COPD patients, especially on anxiety and depression. A study by Chinese University of Hong Kong targeted on two cohort studies by Mr and Ms Os, included three thousand nine hundred and ninety-eight Hong Kong men and women aged 65 to 92, and to assess their depression by face to face interviewed using the short form of a validated Chinese version of the Geriatric Depression Scale (GDS) while respiratory disease was assessed by subjects self-reports of any history of chronic respiratory disease. It found that 13.2% of the chronic respiratory disease patients recruited into the study showed symptoms of depression, with an odds ratio of 1.58 (95% CI = ) after adjustment was made for age, sex, cigarette smoking, alcohol drinking and history of cardiovascular disease when compared with controls. Among those who self-reported to have chronic respiratory diseases and screened to have depression (N=44), none were on anti-depressants or any psychotherapy. It suggest a phenomenon that, depression in patients with chronic respiratory disease were under-treated. 165 However, study targeted on the characteristics of these group of patient is lacking in Hong Kong. 31

48 1.7.6 Knowledge gaps of anxiety and depression From the above literature reviews, there is no definite prevalence of anxiety and depression among studies, the ranges varies among the different screening tools usage, different population size, different study design etc. Without a more comprehensive understanding of the situation, health policy and resource allocation can be difficult, especially in Hong Kong where the resource allocation is limited. Besides, the characteristics features of COPD patients that are associated with anxiety and depression are not clearly defined. One of the very important lacks in knowledge includes the situation between different severity of COPD to the anxiety and depression. As a common sense, the more severe the illness, the higher chance would this affect patient s mood; however, limited study is designed to target these conditions. With the knowledge gap to be filled-up, it is possible for physicians to be more caution when different stages of COPD patients presented to clinic, and further evaluations are warranted and maybe feasible for the diagnosis of any depression and anxiety. 32

49 Chapter 2 Study rationale, aim and objective 2.1 study rationale COPD is a heavy burden to the health care system especially when the ageing population becomes more prevalent. In Hong Kong, the population aged 65 and above nearly doubled from 482,800 in 1990 to 916,600 in 2010, 166 and projected that in 2036, there will be 2,389,100 people aged 65 and above in Hong Kong. 167 With local study suggests the prevalence rate of self-reported COPD among those aged 65 and above was estimated to be 4.6%, 168 and among those COPD patients, prevalence of moderate (stage II) to very severe (stage IV) COPD was about 14.1%. 169 Therefore, we would expect a huge burden towards our existing health care systems. What s more is that, the under-diagnosis of COPD is common among Hong Kong society with suggestion of about 6.1% among people aged 65 as quoted in one of the local study. 169 The demand of these large group of patients warrant our immediate concern before it overwhelms over health care system. Current evidence already showed heavy health service utilization among COPD patients. In 2001, COPD was already ranked first in terms of number of public 33

50 hospital episodes among people aged above 65 years (30,530 episodes). Patients aged 65 years and above diagnosed with COPD occupied 238,022 bed-stays and there were 11,336 COPD patients who stayed in public hospitals. 54 If we based on the assumption of standard public ward fee of HK$3,300 per day, calculated that, the postulated total cost of hospitalization by 2036, in patients of COPD aged 65 and above would increase to approximately HK$ 7.8 billion. 57 So methods to improve patient s symptoms and to reduce the frequency of hospitalization may lessen the economic burden of COPD. One of the major risk factor for COPD hospitalization is depression and anxiety. However, depression and anxiety are often untreated or undertreated in COPD patients, 170 fewer than one third of COPD patients have been receiving appropriate treatment as found in some studies. 126,127 Untreated or incompletely treated depression and anxiety have major impact to the medical treatment compliance, frequency of admission, duration of hospital stay, and primary care utilization. 121,126,128 Also, it may associated with poor quality of life and premature death. 280,170,171 Depressed patients in a chronic illness like COPD are usually appears sicker than their counterparts and have a lower compliance to medication treatment Surprisingly, not much studies have been performed in Hong Kong with major concern on mental comorbidities of COPD patients. If the situation of 34

51 our targeted population can be better understood, it will be easier to formulate the best patient oriented care and cost-utility planning. This inspires the initiation of this study to look into the current situation in Hong Kong, hoping to know better of our COPD patients. 2.2 Aim and objective The aim of the current study is to estimate the prevalence of depression and anxiety among different stages of COPD patients and to try to identify the possible risk factors associated with depression and anxiety of these particular groups of patients. We postulate that there will be a relationship between the severity of COPD to the prevalence of depression and anxiety. And, the situation of depression and anxiety among COPD patients in Hong Kong is expected to be prevalent. Primary Objective: 1. To understand the prevalence and relationship of anxiety and depression and the situation among different stage of COPD patient 35

52 Secondary objective: 1. To evaluate the association between the anxiety and depression in COPD patients among other comorbidities, COPD Assessment Test (CAT) score, age and gender and other demographic data. 2. To compare the two groups of patients (COPD clinic and COPD ward) of their anxiety and depression status 36

53 Chapter 3 Study Methodology 3.1 Study design An observation study with cross-sectional survey and interview to a group of COPD patients was developed to estimate the prevalence of psychological condition and the demographic data for these groups of patients. The study includes a patient interviews and data retrieved from epr (electronic patient record) under Hospital Authority medical systems. 3.2 Study population The targeted populations are those patients who have a preliminary diagnosis of COPD between the periods of March 2012 to June 2012; either attended the out-patient clinic of COPD in every Wednesday morning from 10am to 2pm in block k, 7/F or being discharged from COPD ward in block E, 3/F in Princess Margaret Hospital. Princess Margaret Hospital is a regional hospital which is one of the major hospitals in the Kowloon West cluster, that it serves a total population of more than fifty thousand. Potential patients should fulfill the inclusion criteria 37

54 before entering into the current study: Inclusion criteria: 1. Patient who has the diagnosis of COPD that is confirmed by spirometry as according to GOLD classification 2. Patients who are able to make valid consent of the study 3. Patients who are able to understand and complete the questionnaires either by filling them by themselves or with the assistance from respiratory research nurses But certain patients will be excluded in order not to bias the situation: Exclusion criteria: 1. Significant medical comorbidity or uncontrolled medical condition which may confound results, including symptomatic or untreated carcinoma, dementia, known chronic psychiatric illness which is on treatment already and any other condition as judged by the research nurses. 2. Patient is on any anxiolytic medication or anti-depressant before entering the study. 3. Any other condition which makes patient not able to provide a valid consent 38

55 3.3 Sampling procedure Patients were recruited into two different settings with the postulation that outpatients group would be more stable emotionally, while inpatients group will be more emotionally disturbed after an exacerbation: Out-patient setting: Respiratory research nurses would approach attendants on their follow-up on Wednesday, started from 10am to 1pm, in the COPD out-patient clinic. The COPD clinic is a designated clinic that serves mainly the patients with principle diagnosis of COPD. Patients would go to Block K, 7 th Floor to have their regular follow-up appointment. Two research nurses would approach patients before they met the doctors for consultation. They were interviewed for the purpose of this study and asked for their consent before the interview started. Private consultation room was designated to them to provide adequate privacy. Each interview took about minutes. After the interview, patients would be directed to see the doctors in a short period of time. For each out-patient session, there would be around patients attendance usually. In-patient setting: Respiratory research nurses would approach each patient who was going to be 39

56 discharged from COPD ward each day from Monday to Friday. COPD ward is located at 3 rd floor, block E, and patients will be handled by respiratory physicians as their medical officer. Those who were admitted into COPD ward had the main diagnosis of acute exacerbation of COPD. After patients were stabilized and, before they were allowed to be discharged, the nurses in the ward would inform the research nurses to attend the patients. The patients were introduced about this study and asked for their consent for interviews. They were allowed home in a short period of time after they have completed the interviews. For both setting, after we obtained the consent by the research nurses, we allowed the patients to choose whether they wanted to read and to fill in the questionnaire by themselves, or with the assistance from research nurses (mainly to speak out the questions and help them to fill in the blanket). We would record down all patients that research nurses have attended, even if they refused for the study. We would try to look for the reason why they refused by asking direct questions. 3.4 Outcome measures Demographic data were collected includes age, sex, smoking history, comorbidities other than COPD, religion status, numbers of sibling, housing environment, daytime 40

57 physical activities conditions etc. Comorbidities were retrieved from Hospital Authority electronic patient record (epr). Lung function assessment was retrieved for these patients within 3 years, if the patients have not had any lung function test before, we would arrange a new appointment for this patient. Three separated questionnaires were filled up by patient to assess their psychological situation, dyspnea severity and general well-being by Hospital Anxiety-Depression Score (HADS), Modified Medical Research Council (MMRC) dyspnea score and COPD Assessment Test (CAT). 3.5 Questionnaires Hospital Anxiety Depression Score (HADS), is a self-report or rater-administrated scale composed of 7 items measuring anxiety symptoms and 7 items measuring depressive symptoms experienced during the preceding week. 172 It has been widely used for screening tool for psychiatric morbidity in general hospital patients, also its validity to screen medical outpatients has been confirmed. 172 A score of greater or equal to 8 has been established as optimal values for detection of anxiety or depression in the screening. 172, 173,174 The Chinese-Cantonese version of the HADS was translated by Dr. CM Leung, has showed to demonstrate good internal consistency, with comparable linguistic, structural and scale equivalence to the 41

58 original. 175 However, there are concerns that the anxiety subscales in the HADS may be less useful in identifying geriatric patients with sensitivity of 41% and specificity of 76.6% when the cut-off at 8, as quoted in a study by Davis. 176 Also, as compared to the detection of psychiatric cases, the HADS performs poorly in identifying major depression as described by Silverstone, 177 the major deficiency was the inability to distinguish patients of adjustment disorder from major depression. The HADS was originally designed to detect minor depression in order to avoid the floor effect of most other rating scales, and would thus tend to be less sensitive to changes in the more serious depressions, i.e. the ceiling effect. 178 Despite the possible pitfall, the HADS remains a commonly used screening tool because of its ease to use and generally acceptable. For detail of the HADS, please refer to Appendix. COPD Assessment Test (CAT) is a short, simple and patient-completed questionnaire for COPD with good measurement properties, assessing the impact on health status. There are total 8 questions targeted on different area on health status of COPD patients. The total score is 40. A large validation study has been performed in 6 European countries by Prof. PW Jones, 179 which the internal consistency was excellent by Cronbach s α=0.8.test re-test in stable patietns was very good (intra-class correlation coefficient 0.8). Also in sample from the USA, the correlation 42

59 with the COPD-specific version of the St George s Respiratory Questionnaire was r =0.8. The different between a stable and exacerbation patients was 5 units of the 40-point scale. The Chinese version has been validated and provided a reliable measurement to COPD health status 180 For detail of the CATS, please refer to Appendix. MMRC dyspnoea scale The scale has been used for many years for grading the effect of breathlessness on daily activities of COPD patients. 181 It measures the perceived respiratory disability of the patients by indicating the extent to which their breathlessness affects their mobility. It grades from 1 to 5, with the 5 the greatest perceived limitation of activity due to shortness of breath. Well established relationship was found between the MRC dyspnea scale and walking test performance, 182 and a significant association between MRC grade and shuttle distance, St. George s Respiratory Questionnaire (SGRQ) and Chronic Respiratory Questionnaire (CRQ), mood state and Nottingham extended activities of daily living (EADL). 183 Therefore, this simple and validated scale is used in the study to assess the disability according to the dyspnea condition and also to complement FEV 1 in classification of COPD severity in the new COPD guideline in GOLD management plan. 43

60 3.6 Statistical method Analysis was carried out using SPSS. Quantitative variables were analysed using analysis of variance (ANOVA). For qualitative variables, either a X 2 or a Fischer exact test was used. The relationships between variables were evaluated using Pearson product moment correlation coefficients. A p value <0.05 was the criterion for statistical significance. 3.7 Ethics approval The study has been approved by the Ethics Committee Board of the Hospital Authority Kowloon West Cluster which rights of human subjects are protected and written informed consent was obtained from all patients who were included in our study. 44

61 Chapter 4 Result 4.1 Total number of collectible data There are total 260 patients are approached in the study, which 172 attempts in in-patient, while 88 attempts in out-patient setting. Among the 172 attempts in in-patient (IP) setting, 97 (97/172=56.4%) attempts met the exclusion criteria and 75 (75/172=43.6%) attempts were valid and patients were recruited into study when all inclusion criteria fulfilled. 47 (47/172=27.3%) attempts were excluded because patients refuse to consent after explanation given by respiratory nurses. 15 (15/172=8.7%) patients have terminal malignancy, namely Carcinoma of lung, stomach, prostate, rectum, bladder, larynx or esophagus. 12 (12/172=7%) patients cannot make valid consent or have underlying psychiatric conditions (e.g. Chronic schizophrenia) that need to be excluded. 9 (9/172=5.2%) attempts were excluded due to double counting as patient were admitted again within the study period and had the questionnaire filled once. 8 (8/172=4.7%) patients left before research nurses could approach before discharge. And the remaining 6 (4 depression and 2 anxiety) patients were known to have depression or anxiety, and treatments have been started. 45

62 Among the 88 attempts in out-patient (OP) setting, 12 (12/88=13.6%) attempts met the exclusion criteria and 76(76/88=86.4%) attempts were valid and patients were recruited into study when all inclusion criteria fulfilled. 6 (6/12=50.0%) patients refused to consent for the study, 4 (4/12=33.4%) patients have terminal malignancy, 1 (1/12=8.3%) patient already diagnosed to have depression and the remaining 1 (1/12=8.3%) patient was mentally not fit to make consent. Therefore, total 151 patients were recruited while, 75 patients and 76 patients were in in-patient setting and out-patient setting respectively. 4.2 Demographic of the recruited patients The total numbers of the recruited patients in out-patient setting and in-patient setting in figure 1: 46

63 Figure 1: Flow chart of eligible subjects 1 47: refuse to consent; 15: malignancy; 12: mentally not fit; 9: double entry due to repeated admission; 8: left before research nurse attempt; 6: Known depression or anxiety 2 6: refuse to consent; 4: malignancy; 1: mentally not fit; 1: Known depression or anxiety 47