Tilburg University
Patient reported outcomes and mental health in COPD
Pommer, A.M.
Publication date: 2014
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Link to publication in Tilburg University Research Portal
Citation for published version (APA):
Pommer, A. M. (2014). Patient reported outcomes and mental health in COPD. Ridderprint.
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PA
TIENT REPOR
TED OUT
COME
S AND MENT
AL HE
AL
TH IN C
OPD
An
toine
tte P
ommer
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Chronic Obstructive Pulmonary Disease (COPD) represents a major public health issue.1 It currently is the fourth leading cause of death in the world and according to the World Health Organization becoming the fifth most common worldwide burden of disease by the year 2020.1 At present, the global prevalence of clinically relevant COPD is estimated at 9‐ 10% of the adult population aged ≥ 40;2 in the Netherlands the prevalence of COPD is estimated at around two percent of the general population.3 COPD causes a significant strain on the health‐care systems; in 2003 the annual global cost per patient directly ascribed to COPD (e.g. due to exacerbations and hospitalization) varied between €380 (France) and €2995 (USA);4 in the Netherlands these costs were estimated at €440 per
patient per year.4 With a prevalence of COPD that equals approximately 2% of the Dutch
general population (16 million inhabitants) this would mean around €145 million a year. By 2007 the overall annual costs of COPD in the Netherlands had increased to €415 million.5 The annual worldwide COPD related socioeconomic costs (e.g. due to absenteeism and loss of productivity) even exceed those directly ascribed to COPD.4 Table 1. Classification of severity of airflow limitation in COPD In patients with FEV1/FVC < 0.70
FEV1 ≥ 80% predicted Mild GOLD I
50% ≤ FEV1 < 80% predicted Moderate GOLD II
30% ≤ FEV1 < 50% predicted
FEV1 < 30% predicted SevereVery severe GOLD IIIGOLD IV
COPD is characterized by “persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lungs to noxious particles or gases”.1 The degree of airflow limitation as derived from spirometry and expressed in the Forced Expiratory Volume in one second (FEV1) serves as the main indicator for a clinical diagnosis and the staging of COPD (Table 1).1 Though COPD usually is progressive by nature, exacerbations may accelerate disease progression; these are acute events “characterized by changes in the patient’s baseline dyspnoea, cough, and/or sputum beyond normal day to day variations that may warrant a change in regular medication”6 and often result in “reduced physical activity, worse quality‐of‐life (QoL), and
an increased risk of death”.7,8 Contrary to traditional thinking however, COPD is no longer
considered a “mere” pulmonary condition; mounting research has clearly demonstrated that many extra‐pulmonary systems and organs (e.g. cardiac) are involved in this progressive condition.9 Therefore, researchers have been investigating new ways to
classify COPD that go beyond impaired lung function and help guide more successful treatment strategies. This has resulted in a “phenotyping framework” that can be used to identify subcategories of patients “with unique prognostic or therapeutic characteristics”.10
Chap
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Chronic Obstructive Pulmonary Disease (COPD) represents a major public health issue.1 It currently is the fourth leading cause of death in the world and according to the World Health Organization becoming the fifth most common worldwide burden of disease by the year 2020.1 At present, the global prevalence of clinically relevant COPD is estimated at 9‐ 10% of the adult population aged ≥ 40;2 in the Netherlands the prevalence of COPD is estimated at around two percent of the general population.3 COPD causes a significant strain on the health‐care systems; in 2003 the annual global cost per patient directly ascribed to COPD (e.g. due to exacerbations and hospitalization) varied between €380 (France) and €2995 (USA);4 in the Netherlands these costs were estimated at €440 per
patient per year.4 With a prevalence of COPD that equals approximately 2% of the Dutch
general population (16 million inhabitants) this would mean around €145 million a year. By 2007 the overall annual costs of COPD in the Netherlands had increased to €415 million.5 The annual worldwide COPD related socioeconomic costs (e.g. due to absenteeism and loss of productivity) even exceed those directly ascribed to COPD.4 Table 1. Classification of severity of airflow limitation in COPD In patients with FEV1/FVC < 0.70
FEV1 ≥ 80% predicted Mild GOLD I
50% ≤ FEV1 < 80% predicted Moderate GOLD II
30% ≤ FEV1 < 50% predicted
FEV1 < 30% predicted SevereVery severe GOLD IIIGOLD IV
COPD is characterized by “persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lungs to noxious particles or gases”.1 The degree of airflow limitation as derived from spirometry and expressed in the Forced Expiratory Volume in one second (FEV1) serves as the main indicator for a clinical diagnosis and the staging of COPD (Table 1).1 Though COPD usually is progressive by nature, exacerbations may accelerate disease progression; these are acute events “characterized by changes in the patient’s baseline dyspnoea, cough, and/or sputum beyond normal day to day variations that may warrant a change in regular medication”6 and often result in “reduced physical activity, worse quality‐of‐life (QoL), and
an increased risk of death”.7,8 Contrary to traditional thinking however, COPD is no longer
considered a “mere” pulmonary condition; mounting research has clearly demonstrated that many extra‐pulmonary systems and organs (e.g. cardiac) are involved in this progressive condition.9 Therefore, researchers have been investigating new ways to
classify COPD that go beyond impaired lung function and help guide more successful treatment strategies. This has resulted in a “phenotyping framework” that can be used to identify subcategories of patients “with unique prognostic or therapeutic characteristics”.10
Chapter 1
10
meaningful outcomes such as symptoms, exacerbations, response to therapy, and rate of disease progression.10 However, when health care providers have to determine the severity of COPD, one difficulty is that many key COPD outcomes are patient‐reported outcomes, and that these patient reported outcomes depend on the way patients experience these symptoms and present them to the clinician. For example, dyspnoea, one of the core symptoms of COPD, is by definition “a subjective experience”.11 In addition, whether or not an exacerbation is diagnosed depends on the symptoms reported by the patient and whether or not (s)he seeks help for these symptoms.12 Moreover, the
reported impact of COPD varies greatly among patients, even when their objective physiological limitations are comparable. Therefore, the guidelines recommend a combined assessment of objective measures (e.g. lung function, exercise capacity) and patient reported outcomes (PRO) when disease progression and/or response to treatment are evaluated.13 Hence, COPD management, and disease management in general, is
largely focused on symptom relief and emphasizes the importance of patient reported outcomes (PRO’s).14 A Patient reported outcome refers to the “measurement of any
aspect of a patient’s health status that comes directly from the patient (i.e., without the interpretation of the patient’s responses by a physician or anyone else)”.15 PRO
instruments have the advantage of combining the effect of COPD on different pulmonary and extra‐pulmonary systems as experienced by the patient into a single score.13
Moreover, when evaluating response to treatment, PRO instruments can be particularly useful when a treatment has multiple small effects that can only be observed when registered collectively.13 Therefore the guidelines provided by the Global initiative for chronic Obstructive Lung Disease (GOLD) regard the use of PRO instruments an integral part of standard disease assessment.1 The present thesis focuses on patient reported outcomes and their relation to mental health in patients with COPD.
MEASURING PATIENT REPORTED OUTCOMES IN COPD
It is well known that diagnostic information alone is neither sensitive nor specific enough to predict health care needs and utilization, and treatment outcomes; these are largely determined by a person’s functional status.16 The World Health Organization has
developed an “International Classification of Functioning, Disability and Health” (ICF), in order to classify the elements that constitute functional state.16 The ICF is based on the
Bio‐psychosocial Model and describes functional state from three different perspectives: 1. “body functions and structures”; 2. “the range of activities the individual can or cannot carry out”; and 3. “participation in society”.16,17 These aspects are interrelated and
dependent on environmental and personal factors.16 To evaluate an individual’s functional
status both objective measures of functional state and subjective patient reported outcomes such as self‐perceived well‐being are required.16 Therefore, in order to develop a valid and reliable PRO instrument, it is very important that patients are involved in the whole process, from generating the items to evaluating the tool.18 This patient
involvement can be established through focus group discussions in which patients are invited to express their opinions and discuss their experiences. Over the years a dozen different respiratory and disease‐specific patient reported outcome instruments have been developed.19 It is beyond the scope of this thesis to discuss them all in detail, however, the best known and most influential instruments are discussed.
Fletcher’s Medical Research Council (MRC) dyspnoea scale
One of the first respiratory specific health status instruments was Fletcher’s Medical Research Council (MRC) dyspnoea scale, which grades the effect of breathlessness on daily activities.20 Though the MRC dyspnoea scale is still a highly recommended and frequently
used instrument1, breathlessness is only one of the many disabling aspects that affect
daily living in patients with COPD. In addition the scale appears to be rather insensitive to subtle changes in breathlessness.21 This has resulted in a demand for new instruments
that measure different aspects of health status and are sensitive to subtle changes in health status. Since then, various multidimensional disease‐specific instruments have been developed.
St. George’s Respiratory Questionnaire (SGRQ)
Among the most widely used multidimensional instruments to measure health status in respiratory patients is St. George’s Respiratory Questionnaire (SGRQ)22, the scale is
available in over 77 languages23 and the original article has been cited in over a 100 publications. The SGRQ contains 76 items that can be divided into three subscales: symptoms activity and impact. Each item has a weighted score that resulted from visual analogue scales. These empirically derived item‐weights are meant to reflect the level of distress associated with the symptom or state described in the corresponding item.24 Higher scores indicate worse health status.22 By incorporating weighted item scores the developers of the SGRQ made a first attempt to include the patients’ perspective into the developmental process of a PRO instrument. A large body of research has provided evidence supporting the validity and reliability of the SGRQ and its sensitivity to changes in health status. It was found that the overall minimal clinical important difference was estimated at around 4 units on a scale of 100.25 However, due to its length and the rather
complex scoring algorithm that resulted from the weighted item coefficients, both clinicians and patients found the SGRQ too complicated for use in everyday clinical practice.26 Therefore, shorter more feasible questionnaires were required.
Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT)
At present the Clinical COPD Questionnaire (CCQ)27 and COPD Assessment Test (CAT)28 are
the best known brief, COPD specific instruments; both scales are highly recommended by the GOLD guidelines1. The CCQ is a 10 item multi‐dimensional instrument that includes
Chap
meaningful outcomes such as symptoms, exacerbations, response to therapy, and rate of disease progression.10 However, when health care providers have to determine the severity of COPD, one difficulty is that many key COPD outcomes are patient‐reported outcomes, and that these patient reported outcomes depend on the way patients experience these symptoms and present them to the clinician. For example, dyspnoea, one of the core symptoms of COPD, is by definition “a subjective experience”.11 In addition, whether or not an exacerbation is diagnosed depends on the symptoms reported by the patient and whether or not (s)he seeks help for these symptoms.12 Moreover, the
reported impact of COPD varies greatly among patients, even when their objective physiological limitations are comparable. Therefore, the guidelines recommend a combined assessment of objective measures (e.g. lung function, exercise capacity) and patient reported outcomes (PRO) when disease progression and/or response to treatment are evaluated.13 Hence, COPD management, and disease management in general, is
largely focused on symptom relief and emphasizes the importance of patient reported outcomes (PRO’s).14 A Patient reported outcome refers to the “measurement of any
aspect of a patient’s health status that comes directly from the patient (i.e., without the interpretation of the patient’s responses by a physician or anyone else)”.15 PRO
instruments have the advantage of combining the effect of COPD on different pulmonary and extra‐pulmonary systems as experienced by the patient into a single score.13
Moreover, when evaluating response to treatment, PRO instruments can be particularly useful when a treatment has multiple small effects that can only be observed when registered collectively.13 Therefore the guidelines provided by the Global initiative for chronic Obstructive Lung Disease (GOLD) regard the use of PRO instruments an integral part of standard disease assessment.1 The present thesis focuses on patient reported outcomes and their relation to mental health in patients with COPD.
MEASURING PATIENT REPORTED OUTCOMES IN COPD
It is well known that diagnostic information alone is neither sensitive nor specific enough to predict health care needs and utilization, and treatment outcomes; these are largely determined by a person’s functional status.16 The World Health Organization has
developed an “International Classification of Functioning, Disability and Health” (ICF), in order to classify the elements that constitute functional state.16 The ICF is based on the
Bio‐psychosocial Model and describes functional state from three different perspectives: 1. “body functions and structures”; 2. “the range of activities the individual can or cannot carry out”; and 3. “participation in society”.16,17 These aspects are interrelated and
dependent on environmental and personal factors.16 To evaluate an individual’s functional
status both objective measures of functional state and subjective patient reported outcomes such as self‐perceived well‐being are required.16 Therefore, in order to develop a valid and reliable PRO instrument, it is very important that patients are involved in the whole process, from generating the items to evaluating the tool.18 This patient
involvement can be established through focus group discussions in which patients are invited to express their opinions and discuss their experiences. Over the years a dozen different respiratory and disease‐specific patient reported outcome instruments have been developed.19 It is beyond the scope of this thesis to discuss them all in detail, however, the best known and most influential instruments are discussed.
Fletcher’s Medical Research Council (MRC) dyspnoea scale
One of the first respiratory specific health status instruments was Fletcher’s Medical Research Council (MRC) dyspnoea scale, which grades the effect of breathlessness on daily activities.20 Though the MRC dyspnoea scale is still a highly recommended and frequently
used instrument1, breathlessness is only one of the many disabling aspects that affect
daily living in patients with COPD. In addition the scale appears to be rather insensitive to subtle changes in breathlessness.21 This has resulted in a demand for new instruments
that measure different aspects of health status and are sensitive to subtle changes in health status. Since then, various multidimensional disease‐specific instruments have been developed.
St. George’s Respiratory Questionnaire (SGRQ)
Among the most widely used multidimensional instruments to measure health status in respiratory patients is St. George’s Respiratory Questionnaire (SGRQ)22, the scale is
available in over 77 languages23 and the original article has been cited in over a 100 publications. The SGRQ contains 76 items that can be divided into three subscales: symptoms activity and impact. Each item has a weighted score that resulted from visual analogue scales. These empirically derived item‐weights are meant to reflect the level of distress associated with the symptom or state described in the corresponding item.24 Higher scores indicate worse health status.22 By incorporating weighted item scores the developers of the SGRQ made a first attempt to include the patients’ perspective into the developmental process of a PRO instrument. A large body of research has provided evidence supporting the validity and reliability of the SGRQ and its sensitivity to changes in health status. It was found that the overall minimal clinical important difference was estimated at around 4 units on a scale of 100.25 However, due to its length and the rather
complex scoring algorithm that resulted from the weighted item coefficients, both clinicians and patients found the SGRQ too complicated for use in everyday clinical practice.26 Therefore, shorter more feasible questionnaires were required.
Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT)
At present the Clinical COPD Questionnaire (CCQ)27 and COPD Assessment Test (CAT)28 are
the best known brief, COPD specific instruments; both scales are highly recommended by the GOLD guidelines1. The CCQ is a 10 item multi‐dimensional instrument that includes
Chapter 1
12
result of their disease”.27 The CCQ was developed as an instrument to use in daily clinical
practice.27 Because patient involvement had become one of the key elements in the developmental process of PRO instruments interviews and focus group discussions were conducted to generate potentially relevant items to be included in the CCQ. However, following the focus group discussions, the eventual content and structure of the CCQ were determined by experts without considering which issues were most relevant from a patient’s perspective. Moreover, the psychometric properties of the CCQ were not thoroughly investigated.18 In addition, the GOLD guidelines indicate that further research
is required “to validate the discriminative performance and practical implications of the CCQ in detecting exacerbations in daily care”1. Testing the stability and content of the
scale structure could result in a new understanding of the practical implications of the CCQ in detecting exacerbations in daily care.
The CAT is a relatively new eight item uni‐dimensional instrument to assess the impact of COPD on health status by measuring COPD related symptoms.28 Results of a recent
systematic review have supported the validity of the CAT.19 Analogous to the CCQ, the
developmental process of the CAT started with a qualitative study consisting of individual interviews and focus group discussions with both patients and healthcare providers to discuss what determines health status in people with COPD, and the way these patients experience their condition.29 The initial qualitative study resulted in 21 eligible items;
these were studied in a subsequent quantitative study that performed psychometric and Rasch analyses and reduced the 21 item instrument to an eight item uni‐dimensional scale.28 However, although the CAT is a well‐developed and psychometrically sound instrument, the lack of specific subscales may result in a loss of valuable information. A multi‐dimensional scale provides the opportunity to focus on specific aspects of health status, and help to individualize disease management and treatment goals. Hence, a new, multi‐dimensional instrument based on the patient’s perspective obtained from focus group discussions, and tested with rigorous statistical techniques appropriate for scale development could add valuable knowledge to current clinical practice.
COPD AND MENTAL HEALTH
The physical signs and symptoms and functional limitations that characterize COPD can affect all aspects of daily living. They frequently result in role‐changes and social isolation and are often accompanied by emotional difficulties. For example, the loss of mobility due to increasing breathlessness may cause people to quit tasks and activities that require physical effort. In addition, because smoking is one of the primary causes of COPD, many patients feel stigmatised as COPD is frequently regarded a self‐inflicted condition, which leads to feelings of guilt, shame, self‐blame and sometimes depression.30,31 Furthermore, the symptoms of COPD are often unpredictable, this may contribute to feelings of fear and anxiety. Hence, many patients with COPD also have to deal with mental health issues.32 For example, 42% of patients with COPD report a current or past psychiatric disorder,33 though prevalence rates vary widely due to different screening tools, sample sizes and patient samples.32 A meta‐analysis revealed that 25% of patients with COPD reported an elevated level of depressive symptoms;34 major depressive disorder or other mood disorders as diagnosed with diagnostic interviews were reported by 15% ‐17%35,36 of patients with COPD. The prevalence of symptoms of anxiety was 28%;37 clinically diagnosed anxiety disorders were reported by 16% of patients with COPD.38 These prevalence rates are substantially higher than those found in the general population where the prevalence of depression and anxiety disorders is around 2‐4%,39,40 but comparable to those reported
in different other chronic medical conditions such as diabetes or cardiovascular disease (10%‐14% depressive disorders, 14% anxiety disorders).39,41‐44
Although it is often thought that anxiety and depression are a direct result of the burden and complications caused by a chronic, progressive, and disabling condition such as COPD, a recent systematic review and meta‐analysis revealed that the association between depression, anxiety and adverse COPD outcomes is most probably bidirectional. Anxiety and depression can also be the cause of adverse COPD outcomes such as exacerbations, hospital (re)admission, and decreased health related quality of life.45‐49 Having COPD
increased the risk of developing anxiety or depression (RR, 1.69; 95% CI, 1.45‐1.96), and having co‐morbid depression and/or anxiety increased the risk of COPD outcomes (RR, 1.43; 95% CI, 1.22‐1.68) and possibly death (RR, 1.83; 95% CI, 1.00‐3.36).45 In addition, it is
well known that the burden of physical symptoms in medical illnesses is higher for those with co‐morbid depression and anxiety, even after controlling for disease severity,50 and early research has demonstrated that co‐morbid psychiatric disorders influence the outcomes of PRO measures.51 More specifically, COPD patients with co‐morbid depression and anxiety are at an increased risk of exacerbations (depression: RR, 1.12; 95% CI, 1.02‐ 1.24, depression and anxiety: RR, 1.18; 95% CI, 1.01‐1.38)52, report higher levels of functional disability, and worse quality of life.43 Furthermore, perceived functional
disability and quality of life are more dependent on co‐morbid depression and/or anxiety than physiological disease markers such as lung function.43 In addition, depression was
associated with an increased risk of hospitalisation (adjusted IRR, 1.72; 95% CI, 1.04‐ 2.85),53 worse functional status (12% to 37% higher scores on the SGRQ)54 and non‐
compliance with medical treatment (OR, 3.03; 95% CI, 1.96‐4.89);55 anxiety was associated
with an increased risk of re‐hospitalisation (HR, 1.76; 95% CI, 1.16‐2.68).56 Finally, smoking
is one of the main causes of COPD, and smoking cessation its primary treatment opportunity, depression however impedes smoking cessation57 thereby increasing the risk of
complications.
Chap
result of their disease”.27 The CCQ was developed as an instrument to use in daily clinical
practice.27 Because patient involvement had become one of the key elements in the developmental process of PRO instruments interviews and focus group discussions were conducted to generate potentially relevant items to be included in the CCQ. However, following the focus group discussions, the eventual content and structure of the CCQ were determined by experts without considering which issues were most relevant from a patient’s perspective. Moreover, the psychometric properties of the CCQ were not thoroughly investigated.18 In addition, the GOLD guidelines indicate that further research
is required “to validate the discriminative performance and practical implications of the CCQ in detecting exacerbations in daily care”1. Testing the stability and content of the
scale structure could result in a new understanding of the practical implications of the CCQ in detecting exacerbations in daily care.
The CAT is a relatively new eight item uni‐dimensional instrument to assess the impact of COPD on health status by measuring COPD related symptoms.28 Results of a recent
systematic review have supported the validity of the CAT.19 Analogous to the CCQ, the
developmental process of the CAT started with a qualitative study consisting of individual interviews and focus group discussions with both patients and healthcare providers to discuss what determines health status in people with COPD, and the way these patients experience their condition.29 The initial qualitative study resulted in 21 eligible items;
these were studied in a subsequent quantitative study that performed psychometric and Rasch analyses and reduced the 21 item instrument to an eight item uni‐dimensional scale.28 However, although the CAT is a well‐developed and psychometrically sound instrument, the lack of specific subscales may result in a loss of valuable information. A multi‐dimensional scale provides the opportunity to focus on specific aspects of health status, and help to individualize disease management and treatment goals. Hence, a new, multi‐dimensional instrument based on the patient’s perspective obtained from focus group discussions, and tested with rigorous statistical techniques appropriate for scale development could add valuable knowledge to current clinical practice.
COPD AND MENTAL HEALTH
The physical signs and symptoms and functional limitations that characterize COPD can affect all aspects of daily living. They frequently result in role‐changes and social isolation and are often accompanied by emotional difficulties. For example, the loss of mobility due to increasing breathlessness may cause people to quit tasks and activities that require physical effort. In addition, because smoking is one of the primary causes of COPD, many patients feel stigmatised as COPD is frequently regarded a self‐inflicted condition, which leads to feelings of guilt, shame, self‐blame and sometimes depression.30,31 Furthermore, the symptoms of COPD are often unpredictable, this may contribute to feelings of fear and anxiety. Hence, many patients with COPD also have to deal with mental health issues.32 For example, 42% of patients with COPD report a current or past psychiatric disorder,33 though prevalence rates vary widely due to different screening tools, sample sizes and patient samples.32 A meta‐analysis revealed that 25% of patients with COPD reported an elevated level of depressive symptoms;34 major depressive disorder or other mood disorders as diagnosed with diagnostic interviews were reported by 15% ‐17%35,36 of patients with COPD. The prevalence of symptoms of anxiety was 28%;37 clinically diagnosed anxiety disorders were reported by 16% of patients with COPD.38 These prevalence rates are substantially higher than those found in the general population where the prevalence of depression and anxiety disorders is around 2‐4%,39,40 but comparable to those reported
in different other chronic medical conditions such as diabetes or cardiovascular disease (10%‐14% depressive disorders, 14% anxiety disorders).39,41‐44
Although it is often thought that anxiety and depression are a direct result of the burden and complications caused by a chronic, progressive, and disabling condition such as COPD, a recent systematic review and meta‐analysis revealed that the association between depression, anxiety and adverse COPD outcomes is most probably bidirectional. Anxiety and depression can also be the cause of adverse COPD outcomes such as exacerbations, hospital (re)admission, and decreased health related quality of life.45‐49 Having COPD
increased the risk of developing anxiety or depression (RR, 1.69; 95% CI, 1.45‐1.96), and having co‐morbid depression and/or anxiety increased the risk of COPD outcomes (RR, 1.43; 95% CI, 1.22‐1.68) and possibly death (RR, 1.83; 95% CI, 1.00‐3.36).45 In addition, it is
well known that the burden of physical symptoms in medical illnesses is higher for those with co‐morbid depression and anxiety, even after controlling for disease severity,50 and early research has demonstrated that co‐morbid psychiatric disorders influence the outcomes of PRO measures.51 More specifically, COPD patients with co‐morbid depression and anxiety are at an increased risk of exacerbations (depression: RR, 1.12; 95% CI, 1.02‐ 1.24, depression and anxiety: RR, 1.18; 95% CI, 1.01‐1.38)52, report higher levels of functional disability, and worse quality of life.43 Furthermore, perceived functional
disability and quality of life are more dependent on co‐morbid depression and/or anxiety than physiological disease markers such as lung function.43 In addition, depression was
associated with an increased risk of hospitalisation (adjusted IRR, 1.72; 95% CI, 1.04‐ 2.85),53 worse functional status (12% to 37% higher scores on the SGRQ)54 and non‐
compliance with medical treatment (OR, 3.03; 95% CI, 1.96‐4.89);55 anxiety was associated
with an increased risk of re‐hospitalisation (HR, 1.76; 95% CI, 1.16‐2.68).56 Finally, smoking
is one of the main causes of COPD, and smoking cessation its primary treatment opportunity, depression however impedes smoking cessation57 thereby increasing the risk of
complications.
Chapter 1
14
MODELS OF EXPLANATION
Different physiological and psychological models have been suggested to explain the association between COPD, depression and anxiety. As mentioned in the previous paragraph, a common model of explanation suggests that anxiety and depression are the direct result from having a progressive, irreversible, debilitating and stigmatising condition such as COPD.58 Other models suggest that anxiety, depression and COPD have a common underlying cause or mechanism. For example, the hyperventilation model suggests that both dyspnoea and anxiety are caused by the hyperventilation syndrome. Both COPD and panic disorder are characterized by dysfunctional breathing patterns which may result in hyperventilation which leads to hypocapnia which is associated with dyspnoea and symptoms of anxiety.58 The nicotine dependence model explains the association between
COPD and mental disorders through cigarette smoking (i.e. nicotine dependence). Cigarette smoking causes hypoxia which can induce depressed mood, in addition ±80% of COPD is caused by smoking.58 Still other models suggest that personal factors amplify
COPD outcomes through mechanisms such as illness perceptions and coping strategies. These cognitive behavioural models focus on the role of thoughts and beliefs and how these affect perceptions, guide decisions and influence outcomes. At the core of the cognitive behavioural models is the assumption that people construct models of the world around them and their own personal condition. When people suffer from a chronic condition the cognitive behavioural approach assumes that they constructs models (e.g. illness perceptions) of their symptoms to explain and/or predict events (i.e. exacerbations, etc.).59 Illness perceptions are defined as “idiosyncratic representations of symptoms and illness, formed on the basis of personal and observed encounters with illness as well as information from medical sources and from the “popular” media, friends, parents, the internet, and fellow patients”.60 These illness perceptions determine how someone copes with his/her condition and therefore eventually influence (disease) outcomes.60 Hence,
with regard to COPD, panic and anxiety may result from catastrophic cognitions and misinterpretations of physical symptoms such as breathlessness, thereby amplifying these symptoms and causing even more panic.58 RESEARCH OPPORTUNITIES Though it is generally accepted that there is a high prevalence of depressive disorders in patients with COPD little is known about the course of depression in this specific patient population. From the general population we know that depression often has a chronic or intermittent course61 with an average duration of three to six months per episode,62 of
which approximately 20% evolves into a chronic depression.63 A prospective study on the
course of depressive symptoms, and its determinants could provide knowledge about the course and risk factors of chronic/recurrent depressive symptoms, and may help clinicians in making clinical decisions. In addition, despite the extensive literature on the significant impairment caused by co‐morbid depression and anxiety, and the strong association
between depression and anxiety and important outcomes such as quality of life, exacerbations, and perceived functional disability43, a more psychologically based phenotype has never been suggested. The use of phenotypes is to accentuate differences between patients that relate to and therefore may predict clinically meaningful outcomes. Until now, the proposed phenotypes mainly focused on physiological characteristics. A study to explore the presence of a more psychological based phenotype may provide alternative explanations as to why some patients report worse health outcomes than others despite similar or even less physiological limitations.
PULMONARY REHABILITATION (PR)
Due to the progressive, irreversible course of COPD, the primary focus of COPD management is slowing down disease progression, relief of symptoms, preventing exacerbations, promoting a healthy lifestyle by stimulating smoking cessation and improving exercise capacity.1 All these treatment goals are aimed at improving or
maintaining quality of life and health status. Besides smoking cessation pulmonary rehabilitation (PR) is the primary choice of intervention.64 PR is “a multidisciplinary program
of care for patients with chronic respiratory impairment that is individually tailored and designed to optimise physical and social performance and autonomy”.65 PR aims to
Chap
MODELS OF EXPLANATION
Different physiological and psychological models have been suggested to explain the association between COPD, depression and anxiety. As mentioned in the previous paragraph, a common model of explanation suggests that anxiety and depression are the direct result from having a progressive, irreversible, debilitating and stigmatising condition such as COPD.58 Other models suggest that anxiety, depression and COPD have a common underlying cause or mechanism. For example, the hyperventilation model suggests that both dyspnoea and anxiety are caused by the hyperventilation syndrome. Both COPD and panic disorder are characterized by dysfunctional breathing patterns which may result in hyperventilation which leads to hypocapnia which is associated with dyspnoea and symptoms of anxiety.58 The nicotine dependence model explains the association between
COPD and mental disorders through cigarette smoking (i.e. nicotine dependence). Cigarette smoking causes hypoxia which can induce depressed mood, in addition ±80% of COPD is caused by smoking.58 Still other models suggest that personal factors amplify
COPD outcomes through mechanisms such as illness perceptions and coping strategies. These cognitive behavioural models focus on the role of thoughts and beliefs and how these affect perceptions, guide decisions and influence outcomes. At the core of the cognitive behavioural models is the assumption that people construct models of the world around them and their own personal condition. When people suffer from a chronic condition the cognitive behavioural approach assumes that they constructs models (e.g. illness perceptions) of their symptoms to explain and/or predict events (i.e. exacerbations, etc.).59 Illness perceptions are defined as “idiosyncratic representations of symptoms and illness, formed on the basis of personal and observed encounters with illness as well as information from medical sources and from the “popular” media, friends, parents, the internet, and fellow patients”.60 These illness perceptions determine how someone copes with his/her condition and therefore eventually influence (disease) outcomes.60 Hence,
with regard to COPD, panic and anxiety may result from catastrophic cognitions and misinterpretations of physical symptoms such as breathlessness, thereby amplifying these symptoms and causing even more panic.58 RESEARCH OPPORTUNITIES Though it is generally accepted that there is a high prevalence of depressive disorders in patients with COPD little is known about the course of depression in this specific patient population. From the general population we know that depression often has a chronic or intermittent course61 with an average duration of three to six months per episode,62 of
which approximately 20% evolves into a chronic depression.63 A prospective study on the
course of depressive symptoms, and its determinants could provide knowledge about the course and risk factors of chronic/recurrent depressive symptoms, and may help clinicians in making clinical decisions. In addition, despite the extensive literature on the significant impairment caused by co‐morbid depression and anxiety, and the strong association
between depression and anxiety and important outcomes such as quality of life, exacerbations, and perceived functional disability43, a more psychologically based phenotype has never been suggested. The use of phenotypes is to accentuate differences between patients that relate to and therefore may predict clinically meaningful outcomes. Until now, the proposed phenotypes mainly focused on physiological characteristics. A study to explore the presence of a more psychological based phenotype may provide alternative explanations as to why some patients report worse health outcomes than others despite similar or even less physiological limitations.
PULMONARY REHABILITATION (PR)
Due to the progressive, irreversible course of COPD, the primary focus of COPD management is slowing down disease progression, relief of symptoms, preventing exacerbations, promoting a healthy lifestyle by stimulating smoking cessation and improving exercise capacity.1 All these treatment goals are aimed at improving or
maintaining quality of life and health status. Besides smoking cessation pulmonary rehabilitation (PR) is the primary choice of intervention.64 PR is “a multidisciplinary program
of care for patients with chronic respiratory impairment that is individually tailored and designed to optimise physical and social performance and autonomy”.65 PR aims to
Chapter 1 16 Part one: Measuring Patient Reported Outcomes in COPD Patients with COPD are generally treated in a primary care setting and the Clinical COPD Questionnaire is among the most widely used instruments to measure health status in general practice. However, although widely used its structure of three subscales has never been tested with appropriate statistical analyses while this could further enhance the usefulness of the CCQ through a better understanding of the underlying constructs. Therefore, in Chapter 2 the usefulness of the Clinical COPD Questionnaire in everyday clinical practice is evaluated by testing the psychometric properties of its latent structure in a sample of primary care patients with COPD. Subsequently, though many disease specific health status instruments have been developed none of these instruments is entirely based on patients self‐report. In Chapter 3 we describe the developmental process and first validation of a fully patient centred COPD specific instrument to measure COPD specific impairment from a patient’s perspective; the Patient centred COPD Questionnaire (PCQ). In addition to primary care patients with COPD, we also invited patients with COPD from hospital based care and tertiary care pulmonary rehabilitation to participate in focus group discussions, in order to capture the complete spectrum of disease severity in a way that exceeds lung function and reflects current clinical practice.
Part two: Patient Reported Outcomes and mental health
Depressive disorders or even clinically relevant depressive symptoms are closely related to COPD outcomes and many studies report high prevalence rates of clinically relevant depression in patients with COPD regardless of disease severity. However, less well understood are the course and nature of depression in patients with COPD. In Chapter 4 we study the prevalence, course and main baseline predictors of (chronic/recurrent) depressive symptoms over a 12 months period in primary care patients with asthma or COPD. In addition we distinguish between the core symptoms and other symptoms of depression in order to explore whether clinically relevant depressive symptoms actually reflect a potential co‐morbid depressive condition or are “merely” a sign of disease activity.
Subsequently, Chapter 5 focuses on a subsample of severely impaired COPD patients referred to an intensive tertiary care pulmonary rehabilitation centre in whom there is a discrepancy between objective disease measures and PRO’s. The relation between key PRO’s, such as self‐reported exacerbations and health status, and symptoms of psychopathology is studied in order to explore the evidence for a psychologically distressed phenotype that can serve as an explanation as to why there is a discrepancy between objective and subjective outcome measures. Finally, because health status is one of the main outcomes in COPD treatment, Chapter 6 focuses on the long‐term effectiveness with regard to health status of an intensive pulmonary rehabilitation program offered to COPD patients with severely impaired health. Although the beneficial short‐term effectiveness of pulmonary rehabilitation is well established, its long‐term
effects remain inconclusive, especially in patients with severely impaired health status who are often excluded from research trials. In Chapter 7 the main findings of the present thesis are discussed together with implications and suggestions for current clinical practice and future research.
THE SETTING OF THE PRESENT THESIS
The present thesis mainly focuses on Primary and highly specialised care and is the result of a collaboration between Tilburg University, PoZoB and “Schoondonck, centre for pulmonary rehabilitation”. PoZoB is a large primary care organization in the south of The Netherlands that supports approximately 250 GP’s in organizing their care for patients with a chronic disease through disease management programs targeted at specific conditions.67 In 2008 PoZoB started a disease management program for patients with
asthma and mild to moderate COPD (GOLD‐I or GOLD‐II), named the “ASCOZOB” program. Patients with asthma or COPD are enrolled in the ASCOZOB program. After a formal diagnosis the patient is referred to a specialized primary care nurse who invites him/her twice a year for a general examination and to discuss optimal treatment, treatment compliance and self‐management. In addition, smoking cessation, consultation with a dietician, temporary physiotherapy and interventions to support reactivation can be offered when necessary.68 Within the ASCOZOB program asthma and COPD, though different entities, are taken together because in Primary Care it is often difficult to differentiate between these two conditions. Although lung function is assessed annually and findings are interpreted according to the guidelines, the distinction between the two conditions in Primary Care remains less clear and may vary during the first onset of the symptoms. The content of the ASCOZOB program is based on what the asthma and COPD guidelines describe as necessary for optimal treatment in a Primary Care setting.69 Revant Schoondonck is a centre offering both inpatient and outpatient comprehensive PR based in highly specialised care to patients with COPD reporting severely impaired health status and high levels of healthcare utilization.7 Revant Schoondonck offers a 12 week
interdisciplinary rehabilitation program of 20‐25 hours a week. The PR program contains individual and group modules that are aimed at improving symptoms, exercise capacity and health status.7 More specifically, patients receive exercise training to improve their
Chap
Part one: Measuring Patient Reported Outcomes in COPD
Patients with COPD are generally treated in a primary care setting and the Clinical COPD Questionnaire is among the most widely used instruments to measure health status in general practice. However, although widely used its structure of three subscales has never been tested with appropriate statistical analyses while this could further enhance the usefulness of the CCQ through a better understanding of the underlying constructs. Therefore, in Chapter 2 the usefulness of the Clinical COPD Questionnaire in everyday clinical practice is evaluated by testing the psychometric properties of its latent structure in a sample of primary care patients with COPD. Subsequently, though many disease specific health status instruments have been developed none of these instruments is entirely based on patients self‐report. In Chapter 3 we describe the developmental process and first validation of a fully patient centred COPD specific instrument to measure COPD specific impairment from a patient’s perspective; the Patient centred COPD Questionnaire (PCQ). In addition to primary care patients with COPD, we also invited patients with COPD from hospital based care and tertiary care pulmonary rehabilitation to participate in focus group discussions, in order to capture the complete spectrum of disease severity in a way that exceeds lung function and reflects current clinical practice.
Part two: Patient Reported Outcomes and mental health
Depressive disorders or even clinically relevant depressive symptoms are closely related to COPD outcomes and many studies report high prevalence rates of clinically relevant depression in patients with COPD regardless of disease severity. However, less well understood are the course and nature of depression in patients with COPD. In Chapter 4 we study the prevalence, course and main baseline predictors of (chronic/recurrent) depressive symptoms over a 12 months period in primary care patients with asthma or COPD. In addition we distinguish between the core symptoms and other symptoms of depression in order to explore whether clinically relevant depressive symptoms actually reflect a potential co‐morbid depressive condition or are “merely” a sign of disease activity.
Subsequently, Chapter 5 focuses on a subsample of severely impaired COPD patients referred to an intensive tertiary care pulmonary rehabilitation centre in whom there is a discrepancy between objective disease measures and PRO’s. The relation between key PRO’s, such as self‐reported exacerbations and health status, and symptoms of psychopathology is studied in order to explore the evidence for a psychologically distressed phenotype that can serve as an explanation as to why there is a discrepancy between objective and subjective outcome measures. Finally, because health status is one of the main outcomes in COPD treatment, Chapter 6 focuses on the long‐term effectiveness with regard to health status of an intensive pulmonary rehabilitation program offered to COPD patients with severely impaired health. Although the beneficial short‐term effectiveness of pulmonary rehabilitation is well established, its long‐term
effects remain inconclusive, especially in patients with severely impaired health status who are often excluded from research trials. In Chapter 7 the main findings of the present thesis are discussed together with implications and suggestions for current clinical practice and future research.
THE SETTING OF THE PRESENT THESIS
The present thesis mainly focuses on Primary and highly specialised care and is the result of a collaboration between Tilburg University, PoZoB and “Schoondonck, centre for pulmonary rehabilitation”. PoZoB is a large primary care organization in the south of The Netherlands that supports approximately 250 GP’s in organizing their care for patients with a chronic disease through disease management programs targeted at specific conditions.67 In 2008 PoZoB started a disease management program for patients with
asthma and mild to moderate COPD (GOLD‐I or GOLD‐II), named the “ASCOZOB” program. Patients with asthma or COPD are enrolled in the ASCOZOB program. After a formal diagnosis the patient is referred to a specialized primary care nurse who invites him/her twice a year for a general examination and to discuss optimal treatment, treatment compliance and self‐management. In addition, smoking cessation, consultation with a dietician, temporary physiotherapy and interventions to support reactivation can be offered when necessary.68 Within the ASCOZOB program asthma and COPD, though different entities, are taken together because in Primary Care it is often difficult to differentiate between these two conditions. Although lung function is assessed annually and findings are interpreted according to the guidelines, the distinction between the two conditions in Primary Care remains less clear and may vary during the first onset of the symptoms. The content of the ASCOZOB program is based on what the asthma and COPD guidelines describe as necessary for optimal treatment in a Primary Care setting.69 Revant Schoondonck is a centre offering both inpatient and outpatient comprehensive PR based in highly specialised care to patients with COPD reporting severely impaired health status and high levels of healthcare utilization.7 Revant Schoondonck offers a 12 week
interdisciplinary rehabilitation program of 20‐25 hours a week. The PR program contains individual and group modules that are aimed at improving symptoms, exercise capacity and health status.7 More specifically, patients receive exercise training to improve their
Chapter 1
18
they may benefit most from PR. A recent retrospective observational study on the outcome of PR in this severely impaired subcategory of patients with COPD demonstrated that patients referred to PR based in highly specialised care indeed obtain substantial benefits.7 Studies on the long‐term benefits of PR in this subcategory of patients have not yet been conducted, though these could enhance COPD management for the most severe patients and may unveil new treatment opportunities to maintain obtained benefits.
REFERENCES
1. From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014. Available from http://www.goldcopd.org/.2. Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM. Global burden of COPD: systematic review and meta‐analysis. Eur Respir J 2006;28:523‐532
3. Boezen HM, Postma DS, Smit HA, Poos MJJC. Hoe vaak komt COPD voor en hoeveel mensen sterven eraan? Rijksinstituut voor Volksgezondheid en Milieu [internet]. 2006 [last visited may 18 2014]. Available from www.rivm.nl
4. Wouters EFM. Economic analysis of the confronting COPD survey: an overview of results. Respir Med 2003;97 Suppl C:S3‐S14
5. Suijkerbuijk AWM, De Wit GA, Wijga AH, et al. Maatschappelijke kosten van astma, COPD en respiratoire allergie. Ned Tijdschr Geneesk 2013;157:A6462
6. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
Am J Respir Crit Care Med 2007;176:532‐555
7. Van Ranst D, Otten H, Meijer JW, van ’t Hul AJ. Outcome of pulmonary rehabilitation in COPD patients with severely impaired health status. Int J Chron Obstruct Pulmon
Dis 2011;6:647‐657
8. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128‐1138
9. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J 2009;33:1165‐1185
10. Han MK, Agusti A, Calverly PM, et al. Chronic obstructive pulmonary disease phenotypes. The future of COPD. Am J Respir Crit Care Med 2010;182:598‐604 11. Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society
statement: update on the mechanisms, assessment, and management of dyspnea.
Am J Respir Crit Care Med 2012;185:435‐452
12. Jones P, Higenbottam T. Quantifying of severity of exacerbations in chronic obstructive pulmonary disease. Adaptations to the definition to allow quantification. Proc Am Thorac Soc 2007;4:597‐601 13. Jones P, Miravitlles M, van der Molen T, Kulich K. Beyond FEV1 in COPD: a review of patient‐reported outcomes and their measurement. Int J Chron Obstruct Pulmon Dis 2012;7:697‐709 14. Gold PM. The 2007 GOLD guidelines: a comprehensive care framework. Respir Care 2009;54:1040‐1049
15. Committee for Medicinal Products for Human Use. "Reflection paper on the regulatory guidance for the use of health‐related quality of life (HRQL) measures in the evaluation of medicinal products." London, European Medicines Agency (2005). 16. Üstün TB, Chatterji S, Bickenbach J, Kostanjsek N, Schneider M. The international
classification of functioning, disability and health: a new tool for understanding disability and health. Disabil Rehabil 2003;25:565‐571
Chap
they may benefit most from PR. A recent retrospective observational study on the outcome of PR in this severely impaired subcategory of patients with COPD demonstrated that patients referred to PR based in highly specialised care indeed obtain substantial benefits.7 Studies on the long‐term benefits of PR in this subcategory of patients have not yet been conducted, though these could enhance COPD management for the most severe patients and may unveil new treatment opportunities to maintain obtained benefits.
REFERENCES
1. From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014. Available from http://www.goldcopd.org/.2. Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM. Global burden of COPD: systematic review and meta‐analysis. Eur Respir J 2006;28:523‐532
3. Boezen HM, Postma DS, Smit HA, Poos MJJC. Hoe vaak komt COPD voor en hoeveel mensen sterven eraan? Rijksinstituut voor Volksgezondheid en Milieu [internet]. 2006 [last visited may 18 2014]. Available from www.rivm.nl
4. Wouters EFM. Economic analysis of the confronting COPD survey: an overview of results. Respir Med 2003;97 Suppl C:S3‐S14
5. Suijkerbuijk AWM, De Wit GA, Wijga AH, et al. Maatschappelijke kosten van astma, COPD en respiratoire allergie. Ned Tijdschr Geneesk 2013;157:A6462
6. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
Am J Respir Crit Care Med 2007;176:532‐555
7. Van Ranst D, Otten H, Meijer JW, van ’t Hul AJ. Outcome of pulmonary rehabilitation in COPD patients with severely impaired health status. Int J Chron Obstruct Pulmon
Dis 2011;6:647‐657
8. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128‐1138
9. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J 2009;33:1165‐1185
10. Han MK, Agusti A, Calverly PM, et al. Chronic obstructive pulmonary disease phenotypes. The future of COPD. Am J Respir Crit Care Med 2010;182:598‐604 11. Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society
statement: update on the mechanisms, assessment, and management of dyspnea.
Am J Respir Crit Care Med 2012;185:435‐452
12. Jones P, Higenbottam T. Quantifying of severity of exacerbations in chronic obstructive pulmonary disease. Adaptations to the definition to allow quantification. Proc Am Thorac Soc 2007;4:597‐601 13. Jones P, Miravitlles M, van der Molen T, Kulich K. Beyond FEV1 in COPD: a review of patient‐reported outcomes and their measurement. Int J Chron Obstruct Pulmon Dis 2012;7:697‐709 14. Gold PM. The 2007 GOLD guidelines: a comprehensive care framework. Respir Care 2009;54:1040‐1049
15. Committee for Medicinal Products for Human Use. "Reflection paper on the regulatory guidance for the use of health‐related quality of life (HRQL) measures in the evaluation of medicinal products." London, European Medicines Agency (2005). 16. Üstün TB, Chatterji S, Bickenbach J, Kostanjsek N, Schneider M. The international
classification of functioning, disability and health: a new tool for understanding disability and health. Disabil Rehabil 2003;25:565‐571
