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Anxiety and Chronic Obstructive Pulmonary Disease: Prevalence, Impact, and Treatment

Wake Forest University School of Medicine, Department of Psychiatry and Behavioral Medicine, Medical Center Boulevard, Winston-Salem, NC.

Gretchen A. Brenes, PhD, Wake Forest University School of Medicine, Department of Psychiatry and Behavioral Medicine, Medical Center Boulevard, Winston-Salem, NC 27157.

	ABSTRACT

TOP ABSTRACT INTRODUCTION EPIDEMIOLOGY OF ANXIETY IN... IMPACT OF ANXIETY ON... MANAGING ANXIETY IN PATIENTS... DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
OBJECTIVE: This article reviews the prevalence of anxiety disorders in patients with chronic obstructive pulmonary disease (COPD) as well as the impact of comorbid anxiety on quality of life in patients with COPD. Published studies on three types of treatments for anxiety are then reviewed: psychopharmacology, psychotherapy, and pulmonary rehabilitation programs.

MATERIALS AND METHODS: A PubMed search was conducted of the literature from 1966 through 2002 using the keywords anxiety, chronic obstructive pulmonary disease, respiratory diseases, obstructive lung diseases, and pulmonary rehabilitation. Any articles that discussed the prevalence of anxiety symptoms or anxiety disorders among patients with COPD, the impact of anxiety on patients with COPD, or the treatment of anxiety in COPD patients were included in this review.

RESULTS: Anxiety disorders, especially generalized anxiety disorder (GAD) and panic disorder, occur at a higher rate in patients with COPD compared with the general population. Not surprisingly, anxiety has a significant and negative impact on quality of life of COPD patients. Nonetheless, few studies have examined pharmacological, psychotherapeutic, or pulmonary rehabilitation treatments for anxiety disorders in the context of COPD. Trials of nortriptyline, buspirone, and sertraline have been found to reduce symptoms of anxiety. Similarly, cognitive–behavioral programs that focus on relaxation and changes in thinking also produced declines in anxious symptoms. Finally, multicomponent pulmonary rehabilitation programs can also result in reductions in anxious symptoms.

CONCLUSIONS: Studies examining the treatment of anxiety disorders in patients with COPD are promising, yet their efficacy needs to be established. The long-term effects of treatment of anxiety disorders on quality of life of COPD patients have yet to be explored.

Key Words: anxiety disorders, • chronic obstructive pulmonary disease.

Abbreviations: COPD = chronic obstructive pulmonary disease;; FEV₁ = forced expiratory volume in 1 second;; GAD = generalized anxiety disorder;; STAI = State Trait Anxiety Inventory;; SSRI = selective serotonin reuptake inhibitor;; PMR = progressive muscle relaxation.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION EPIDEMIOLOGY OF ANXIETY IN... IMPACT OF ANXIETY ON... MANAGING ANXIETY IN PATIENTS... DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
Chronic obstructive pulmonary disease (COPD) consists of a number of conditions characterized by airway inflammation and destruction of the pulmonary parenchyma. These processes lead to the clinical hallmarks of COPD, which are airflow limitation and dyspnea or shortness of breath. Some patients will have sufficient destruction of alveoli to produce hypoxemia, which further contributes to dyspnea and decreased exercise capacity (1). The largest cause of COPD is smoking, because it produces accelerated decreases in forced expiratory volume in 1 second (FEV₁) (1). Approximately 14 to 20 million people in the United States have COPD, and it is the fourth leading cause of death (2,3). Among older adults (65 years or older), approximately 34.1 people per 1000 have COPD (4).

	EPIDEMIOLOGY OF ANXIETY IN PATIENTS WITH COPD

TOP ABSTRACT INTRODUCTION EPIDEMIOLOGY OF ANXIETY IN... IMPACT OF ANXIETY ON... MANAGING ANXIETY IN PATIENTS... DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
Rates of anxiety disorders in patients with COPD, particularly generalized anxiety disorder (GAD) and panic disorder, are much higher than in the general public (Table 1). Yellowlees and colleagues found that 34% of patients with COPD met diagnostic criteria for either panic disorder or GAD (5). The prevalence of GAD among patients with COPD ranges from 10% to 15.8% when using standard diagnostic procedures (5–7) compared with lifetime rates of 3.6% to 5.1% in the general public (8,9). Thus, GAD is at least three- times more prevalent in COPD patients than in the general United States population. Aghanwa et al. (6) found a prevalence rate of GAD of 10% among COPD patients in Nigeria compared with 3.3% in their sample of healthy controls. Rates of panic disorder are also higher in this population. Karajgi and colleagues (10), using the Structured Clinical Interview for DSM-III-R, found a prevalence rate of 8% for panic disorder which is 5.3-times as high as in the general population (11). They were careful not to confuse a panic attack with an episode of anxiety secondary to pulmonary dysfunction by excluding any panic attacks and anxiety that occurred in situations associated with pulmonary problems (eg, exertion) from their diagnosis (10). Moore and Zebb (12) found an even higher rate of panic disorder (32%) using self-report measures of panic disorder symptoms based on DSM-IV criteria for panic disorder. Also, Porzelius and colleagues (13) found that 37% of patients reported that they had experienced a panic attack in the previous 3 weeks. Not only is anxiety highly common among COPD patients but the reverse is also true. The lifetime prevalence of respiratory disease is higher in people with panic disorder (47%) than with other psychiatric diagnoses (14).

	IMPACT OF ANXIETY ON PATIENTS WITH COPD

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Anxiety has a negative impact on the quality of life of adults with COPD. It is associated with greater disability (7,22) and impaired functional status (23), specifically in the areas of general health, physical roles, emotional roles, social functioning, bodily pain, mental health function, and vitality (17). Even after statistically controlling for the effects of overall health status, including additional medical diseases, COPD severity, and dyspnea, anxiety remains significantly associated with decreased functional status (17,22). Anxiety has also been found to be related to the disease characteristics of COPD, including forced vital capacity (15), chest symptoms (8), and dyspnea (24–25). Finally, anxiety is a significant predictor of the frequency of hospital admission for acute exacerbations of COPD (19).

	MANAGING ANXIETY IN PATIENTS WITH COPD

TOP ABSTRACT INTRODUCTION EPIDEMIOLOGY OF ANXIETY IN... IMPACT OF ANXIETY ON... MANAGING ANXIETY IN PATIENTS... DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
Medications
Only a few studies have investigated the use of psychotropic medications in COPD patients, either in an attempt to reduce depressive or anxiety symptoms or in an attempt to reduce dyspnea in patients without comorbid mood or anxiety disorders (Table 2). Benzodiazepines are not recommended as first-line treatment in patients with COPD because they can decrease respiratory drive and compromise lung function, worsening exercise tolerance (26). One anxiolytic, buspirone, does not have the same sedating effects as the benzodiazepines. Argyropoulou et al. (27) conducted a double-blind randomized clinical trial in which 16 patients were randomized to either 20 mg/d of buspirone or placebo for 14 days. They found that buspirone produced significant decreases in anxiety and dyspnea, and improved exercise tolerance among COPD patients.

More recently, focus has shifted to the SSRIs. Smoller et al. (28) suggest that a link between anxiety and respiratory symptoms may be mediated by the serotonergic system. There is evidence that central control of respiration is modulated by serotonin by increasing sensitivity to carbon dioxide (29,30). Higher sensitivity to carbon dioxide has been associated with more dyspnea among patients with COPD (31). Furthermore, hypersensitivity to carbon dioxide has also been found in panic disorder (32).

Two studies report the findings from a series of case studies. Papp et al. (34) tested the safety and efficacy of sertraline (100 mg/d) in six COPD patients, three of whom had a comorbid anxiety disorder. None of the patients discontinued the medication and the patients with anxiety reported improvement. They concluded that COPD was not a contraindication for the use of sertraline in treating panic disorder. Similary, Smoller and colleagues (28) reported a series of case studies in which they treated seven COPD patients with sertraline (25–100 mg/d). Only one patient discontinued the medication because of feeling jittery. The other six patients reported significant improvement, including decreased anxiety. They too concluded that sertraline is well-tolerated in patients with COPD.

A total of four studies involving the use of psychotropic medications in patients with COPD were reviewed. Two small randomized clinical trials testing the efficacy of nortriptyline (33) and buspirone (27) found that the medications were effective in significantly reducing self-reported anxiety symptoms. Although positive effects were found after a 2-week trial of buspirone, it should be noted that this medication typically takes 2 to 4 weeks to reach full therapeutic levels. Two series of case reports (28,34) found that sertraline was effective in reducing anxiety symptoms. One third of these participants (4/13) had a clinically diagnosed anxiety disorder, and all were in remission at the time of follow-up. These studies provide some evidence that buspirone, nortriptyline, and sertraline are well-tolerated in patients with COPD and can reduce anxiety symptoms.

Cognitive and behavioral approaches
According to psychological theories of anxiety, individuals panic when they misinterpret bodily sensations as more dangerous than they truly are and as a signal of impending danger (35,36). When a patient with COPD experience dyspnea, he or she presumably makes incorrect interpretations (eg, "I am going to die") in response to the feeling of breathlessness. This in turn leads to a heightened state of physiological arousal accompanied by additional sensations and misinterpretations. While breathlessness may represent actual danger in patients with COPD, COPD patients with panic disorder have more negative cognitions than COPD patients without panic disorder, but they do not differ with respect to pulmonary functioning (12). This suggests that anxiety in COPD patients with panic disorder reflects inaccurate cognitions rather than greater disease severity. Cognitive and behavioral approaches to treating anxiety in patients with COPD have yielded mixed results (Table 3).

Kunik and colleagues (40) conducted a randomized controlled trial of cognitive–behavioral therapy. Fifty-six patients were randomized into the study and 48 completed all assessments. Participants in the experimental condition received 2 hours of group of cognitive–behavioral therapy that was led by a board-certified geropsychiatrist. Topics covered included the role of anxiety and depression in chronic medical illness, the three components of anxiety (thoughts, physiological feelings, behaviors), relaxation training including diaphragmatic breathing and postural changes, thought stopping, and an explanation of exposure. Participants were given workbooks as well as audio tapes of the coping skills and practice exercises, and were instructed to practice the techniques daily. They were also called once per week for 6 weeks, the purpose of which was to allow patients to ask questions, monitor compliance, and increase compliance with homework sessions. Participants in the education group met with a board-certified internist and discussed the process, etiology, and treatment of COPD. They were given time to ask questions and share their experiences of living with COPD. They too were called weekly and given a chance to ask questions about COPD. However, they did not receive any instruction in cognitive–behavioral techniques for managing anxiety. Participants in the experimental group demonstrated significantly lower scores on self-report measures of anxiety and depressive symptoms. This study suggests that cognitive–behavioral therapy can indeed decrease anxiety and depressive symptoms in patients with COPD.

Two studies, however, failed to find significant decreases in anxiety after a cognitive–behavioral intervention (41,42). Eiser and colleagues (41) conducted a small clinical trial (18 patients with COPD) in which cognitive–behavioral therapy was compared with a no treatment control group. The experimental group received six, 90-minute cognitive–behavioral group therapy sessions led by one of two psychiatrists. They explored the concept of anxiety, its links with breathlessness, ways of controlling anxiety, simple deep muscle relaxation, and distraction techniques. Participants were instructed to practice the breathing and relaxation exercises three times per day for 10 minutes and were given audio tapes of the exercise. The control group also went to the hospital for six visits, at which time measures of respiratory and physical function were administered; however, they received no treatment. Participants in the experimental condition experienced improvements in physical functioning. While they did experience a decline in anxiety, change in mean scores was not statistically significant. Lisansky and Clough (42) conducted a cognitive–behavioral self-help education program that consisted of eight weekly 90-minute sessions lead by nurses. Eight patients were provided information about COPD based on the book, To Air is Human (43), including the anatomy and physiology of the lung, pathophysiology of COPD, and treatment and home care (medications and oxygen therapy). The cognitive component of the intervention focused on automatic thoughts and how they influence feelings and behavior. Participants were provided with homework assignments designed to aid them in monitoring their irrational automatic thoughts, evaluating their validity, refuting them, and replacing them with more accurate thoughts. Recommended supplemental readings included the pamphlet Coping with Depression (44) and the book Feeling Good: The New Mood Therapy (45). The behavioral component of the intervention included diaphragmatic breathing, pursed lip breathing, progressive muscle relaxation, and goals for symptom management. By the end of the program, participants demonstrated decreases in irrational reasoning and psychosocial disability. No changes in anxiety symptoms were noted.

As with the medication trials, all of the psychotherapy studies reviewed were conducted with patients with COPD who were not formally diagnosed with clinical anxiety disorders. In two of the reports (37,38), progressive muscle relaxation was the sole intervention. Both studies demonstrated that participants had mastered the technique, and both found that progressive muscle relaxation reduced anxiety symptoms in patients with COPD. In the third study (40), a combination of cognitive and behavioral techniques was taught, and the authors report a significant reduction in anxiety symptoms. Two studies (41,42) found no effect of a CBT intervention on anxiety. However, these two studies had the smallest sample sizes and they used instruments with questionable validity, both of which reduce the power to detect true effects.

Pulmonary rehabilitation
There is also evidence that comprehensive interventions that include an exercise component can improve symptoms of anxiety among patients with COPD (Table 4). Emery (46) tested a 30-day rehabilitation program that included aerobic exercise, strength training, education about COPD, psychosocial counseling, and stress management. Sessions were held 5 days per week for 4 hours each. They began with respiratory therapy, warm-up exercises, and 45 minutes of aerobic exercise (rapid walking, riding on a stationary bicycle, arm ergometry). Participants then participated in upper-body muscle strengthening exercises and pool exercises. The instructional component consisted of daily lectures on topics such as medication usage and physiology. The psychosocial counseling and stress management sessions were held twice per week for 45 minutes. They included progressive muscle relaxation training and cognitive–behavioral strategies for coping with stress. Participants in this program were 64 patients with COPD who all received the intervention. Emery found that his program produced significant declines in anxiety symptom severity.

These studies demonstrated that exercise alone, as well as a combination of exercise, education, and stress management (including progressive muscle relaxation), produces declines in anxiety symptoms. According to cognitive-behavioral models of anxiety, physical sensations and anxiety are strongly linked. The exercise component may act as a type of exposure therapy breaking the link between physical sensations and anxiety.

	DISCUSSION

TOP ABSTRACT INTRODUCTION EPIDEMIOLOGY OF ANXIETY IN... IMPACT OF ANXIETY ON... MANAGING ANXIETY IN PATIENTS... DISCUSSION ACKNOWLEDGMENTS REFERENCES

 
There are a number of methodological issues that need to be addressed in future studies. The use of randomized controlled trials to test the efficacy of interventions should be considered. Random assignment of participants to treatment conditions allows for the assumption of treatment equivalency. Variations in outcomes are assumed to be the result of the treatment condition rather than other factors. Researchers also need to use assessment instruments that have demonstrated reliability and validity. Lisansky and Clough assessed anxiety with the Symptom Questionnaire (49), an infrequently used measure, and no validity information about this measure was provided. Thus, it is not known if the lack of significant effect on anxiety is due to the way anxiety is measured or if the intervention itself is unsuccessful. Similarly, Eiser et al. (41) suggested that the Hospital Anxiety and Depression Scale (50) may not have been sensitive enough to detect change in anxiety severity in their study. Also, consistent use of standardized and reliable instruments as outcome measures will allow for cross-study comparisons of outcomes.

Researchers need to make sure that participants understand and appropriately use the techniques they are taught to ensure treatment integrity. Renfroe (37) and Gift and colleagues (38) were the only researchers to provide evidence that their participants had mastered the techniques of the intervention. They identified specific criteria for heart rate, respiration rate, and body temperature that participants had to meet to determine that they had indeed mastered the relaxation exercise. If mastery of the techniques is not assessed, it will not be known if positive outcomes are caused by nonspecific factors or to the actual intervention. Conversely, if no effects are found, it will not be known if the intervention itself is inadequate or if the participants are not properly using the techniques.

Sample size and sample selection also must be given careful consideration. Most of the studies published to date have relied on small sample sizes (28,34,41,42). With a small sample size, power is reduced, decreasing the likelihood that a significant difference will be detected when one truly exists. Thus, studies with meaningful results may not be statistically significant (41,42). Related to this, much of the existing research is based on convenience samples which may not be representative. Using a convenience sample may also bias the study. Individuals with low levels of anxiety at baseline have little room for improvement.

To date much of the research has focused on interventions that involve multiple treatment components, such as relaxation techniques and cognitive restructuring. Dismantling studies are needed to determine which components of these multicomponent interventions are most effective. For example, it is not known which portions of Kunik’s (40) intervention are the most efficacious and which techniques are not needed. A randomized controlled trial would allow researchers to compare and contrast different components of treatments to determine which are the most efficacious.

There are a number of additional directions for future research. First, researchers need to examine the efficacy of these treatments among patients with comorbid anxiety disorders and COPD. With the exception of one study (34), the studies to date have not formally assessed participants for clinical anxiety disorders. Rather, they have focused on self-reported anxiety symptom severity. Also, many of the studies did not select samples with high levels of self-reported anxiety, as this was not the focus of many of the reported studies. In fact, most of the participants were within the normal range of anxiety. Second, trials of pharmacologic agents to treat anxiety in this population are significantly lacking. Additional studies are needed to study effective treatments for anxiety in COPD patients. Third, the long-term effects of anxiety treatment on quality of life among COPD patients have yet to be determined. With the exception of one case series presentation (28), all of the follow-up assessments occurred immediately on completion of the intervention, precluding any conclusions regarding the long-term effects of the intervention. Finally, the use of other ancillary treatments, such as family education and support groups, should be examined.

	ACKNOWLEDGMENTS

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The work of Brenes was supported through Brooks Scholar Academic Medicine Award.

Received for publication August 27, 2002.

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