Thomas Ritz, Ph.D.
Juliet Kroll, M.A.
Alexandra Kulikova, M.S.
Chelsey Werchan, M.A.
E. Sherwood Brown, M.D., Ph.D.
In this chapter we review psychiatric aspects of the common pulmonary disorders, as well as the use of psychiatric medications in patients with these disorders. Some lung diseases are discussed elsewhere in this book, including tuberculosis in Chapter 26 (“Infectious Diseases”), cystic fibrosis and childhood asthma in Chapter 32 (“Pediatrics”), sleep-related breathing disorders in Chapter 14 (“Sleep Disorders”), lung cancer in Chapter 22 (“Oncology”), lung transplant in Chapter 29 (“Organ Transplantation”), and ventilator issues in Chapter 28 (“Surgery”).
Asthma is a chronic inflammatory disorder of the airways that is characterized by variable airway obstruction and airway hyperresponsiveness to various trigger factors. Symptoms of asthma include shortness of breath, chest tightness, cough, and wheezing, as well as restrictions in physical, social, and occupational functioning (see Chapter 32 for a discussion of asthma in children). The prevalence of asthma has increased significantly in past decades. Worldwide, an estimated 300 million people have asthma, and deaths from asthma have been estimated at 250,000 cases annually (Global Initiative for Asthma 2012). Prevalence rates vary internationally from 1% to 18%. In children, asthma is the most common chronic disease. In the United States, racial and ethnic minorities, in particular Puerto Ricans, African Americans, and American Indians/Alaskan Natives, are disproportionately affected (Leong et al. 2012). In addition to substantial personal suffering, the economic costs of asthma are considerable, with estimated costs of $56 billion in 2007 in the United States alone, and are increasing (Centers for Disease Control and Prevention 2013).
Historically, asthma has been viewed as one of the seven prototypical psychosomatic illnesses. Earlier psychoanalytic theory of psychosomatic medicine advanced the notion that asthma was the outcome of a conflictual constellation in the mother–child relationship (Alexander 1950). With advances of the biomedical model of asthma, which emphasizes cellular and molecular processes, the focus of the field has shifted to empirical research more compatible with a biopsychosocial view of asthma etiology and its course (Ritz et al. 2013). Earlier clinical and epidemiological findings indicated that many asthma patients viewed psychological factors as primary or secondary triggers of their asthma exacerbations, although study findings pertaining to this perception have varied considerably (Weiner 1977). Systematic questionnaire surveys indicate that up to one-fourth of people with asthma believe that emotions and stress are among their top asthma triggers, and these perceptions are associated with diminished illness control and more emergency treatments, independent of possible mood disorder comorbidity (Ritz et al. 2016).
Ample research points to an elevated comorbidity of asthma and psychiatric illness, in particular anxiety (Katon et al. 2004; Roy-Byrne et al. 2008) and depression (Trojan et al. 2014). Comorbid panic disorder has been found in 6.5%–24% of adults and 0.6%–4.7% of children and adolescents (Katon et al. 2004). In a large-scale cross-national study, adults with self-reported asthma had significantly elevated odds of also being diagnosed with panic disorder/agoraphobia, generalized anxiety disorder, posttraumatic stress disorder, social phobia, dysthymia/major depressive disorder (MDD), or alcohol use disorder (Scott et al. 2007). For a similar range of disorders in adult patients, including bipolar disorder and binge-eating disorder, the likelihood of a subsequent diagnosis of asthma was also elevated (Alonso et al. 2014). Comorbidities appear to depend on race or ethnicity, with particularly high comorbidity of panic disorder among urban patients with asthma who were from Puerto Rico and the Dominican Republic (21.1%) compared with asthma patients who were African American (6.7%) (Feldman et al. 2010). Suicidality (Kuo et al. 2010) and schizophrenia (Pedersen et al. 2012) are also more common in asthma patients. Common underlying risk factors, such as a genetic predisposition to both types of disorders or perinatal factors, may explain these findings (Meuret et al. 2017). Psychological disorders may produce some of the distress that triggers asthma symptoms, and such disorders are associated prospectively with problems in asthma control, emergency room visits, and hospitalizations (Favreau et al. 2014; Schneider et al. 2008).
Longitudinal studies have additionally demonstrated associations among stress, psychiatric disorders, and asthma onset. Panic disorder in early adulthood was related to a greater likelihood of developing asthma 20 years later (Hasler et al. 2005), while early adulthood asthma was predictive of later onset of panic disorder. A meta-analysis of longitudinal studies confirmed the bidirectional nature of the association between distress and atopic disorders (allergic disorders, characterized by type I hypersensitivity reactions, in that sample mostly asthma), with a stronger role of atopic disease in predicting subsequent psychological distress than the reverse (Chida et al. 2008). Perinatal factors may account for some of these associations. Stress during pregnancy, such as negative life events, anxiety, and depression, has been linked to childhood asthma and atopic illness in a number of studies (Andersson et al. 2016). Blood cord mononuclear cells of mothers with higher prenatal stress show signs of elevated inflammatory cytokine responses when challenged with antigens, a characteristic that could affect early-life programming of lung structure and function (Wright 2010). A variety of early-life challenges, such as parental mental illness, parenting problems, and exposure to domestic or neighborhood violence, have also been found to predict childhood asthma prospectively, sometimes in interaction with other environmental exposures (Exley et al. 2015). Recent research suggests that alterations of the lung or intestinal microbiome through psychological stress may also constitute a common risk factor for both affective disorders and asthma (Trueba et al. 2016). Overall, these findings indicate that psychosocial factors and mental health–related factors are critical players in asthma etiology, manifestation, and management and are important in the early stages of asthma development.
Influences of psychosocial factors on asthma unfold directly through their impact on pathophysiological processes or affect the illness indirectly through health behaviors and illness management. Airway and immune system function are susceptible to direct psychological influences, through nervous system and endocrine pathways. Vagal excitation and hyperventilation-associated negative affect lead to bronchoconstriction that is clinically significant in approximately one-fourth of patients (Isenberg et al. 1992; Ritz 2012) and can produce asthma symptoms. Stressful life episodes have been demonstrated to exacerbate asthma in children within a few days of stressor onset (Sandberg et al. 2004), and studies with sensitized mice show differential upregulation of allergy-relevant cytokine production depending on the acute versus chronic character of stressors (Kang and Weaver 2010). Immune cells of asthmatic children from low socioeconomic status (SES) families exposed to chronic stress respond to antigen stimulation with an elevated production of inflammatory cytokines (Marin et al. 2009). Downregulation of messenger RNA of beta-adrenergic and glucocorticoid receptors that are potentially relevant for lung health has been shown in children with chronic stress and low SES (Miller and Chen 2006). Sputum analysis of asthma patients during stressful periods (e.g., exams) demonstrated that allergy-relevant cytokine production is also elevated in the airways upon allergen challenge (Liu et al. 2002). Some of the allergic inflammatory processes correlate with overactivation in distinct areas of the limbic system (Rosenkranz et al. 2012). The well-documented facilitation of respiratory infections through stress could also mediate asthma exacerbations, given the importance of infections as asthma triggers (Trueba and Ritz 2013).
Interaction with comorbidity or underlying risk factors may worsen the impact of stress in asthma, as has been shown for depression (Miller et al. 2009) and for polymorphisms of glucocorticoid and beta2-receptor genes (Rehm et al. 2012). Influences of stress on asthma can be counterbalanced by resilience factors, such as positive life experiences (Sandberg et al. 2002). Because psychobiological processes are superimposed on specific developmental trajectories of lung mechanics and immune system development and are embedded in a multitude of physical and social environmental disease mediators and moderators, the multilevel framework of a biopsychosocial asthma analysis is required (Wright and Subramanian 2007).
Whereas some psychosocial factors may affect biological pathways directly, others may affect asthma indirectly through adverse health behaviors or compromised management (Chen et al. 2007). Stress can influence dietary behaviors and substance use, giving rise to adverse influences on asthma through obesity (Sivapalan et al. 2015) or smoking (Bakakos et al. 2016). Seminal studies of “psychomaintenance” of asthma conducted in the early 1970s at the National Jewish Hospital in Denver, Colorado, demonstrated that aspects of anxiety indirectly influence asthma control through their effect on management variables (Kinsman et al. 1973). Thus, patients’ asthma-related fears were associated with physicians’ corticosteroid prescriptions. Patients’ beliefs about their illness and its treatment motivate and guide self-management behaviors and therefore influence asthma outcomes (Kaptein et al. 2010). As shown for Latino cultures (McQuaid et al. 2009), specific beliefs and concerns about medication can interfere with adequate asthma management. Patients’ perceptions of asthma symptoms are of great importance. A substantial proportion of patients inaccurately assess their dyspnea (Janssens et al. 2009); imaging studies examining cortical processing of the perception of dyspnea have identified neurophysiological pathways involving areas relevant to interoception (i.e., the perception of bodily responses such as respiration) and emotion, such as the insular cortex and amygdala (von Leupoldt et al. 2008). The close association between interoception and emotion is also reflected in the association of anxiety with enhanced processing of respiratory symptoms (von Leupoldt et al. 2011).
Beyond the first-line treatments of anti-inflammatory and bronchodilatory medication, multidisciplinary behavioral medicine team efforts should ideally address the need for education in asthma self-management and for adjunctive behavioral treatments (Ritz et al. 2013).
Asthma education is recognized as essential and effective in improving asthma control (Global Initiative for Asthma 2012; National Heart, Lung, and Blood Institute/National Asthma Education and Prevention Program 2007). Patients need training in the proper use of inhalers, self-monitoring of asthma symptoms or lung function, avoidance and management of triggering factors, and self-adjustment of medication using asthma action plans devised by their treating physician. Regular physical activity and exercise are also recommended, because they are safe for patients and improve fitness and asthma outcomes (Eichenberger et al. 2013). In daily life, physical activity is associated with bronchodilation; nevertheless, patients complain about symptoms, possibly because in stronger exercise, hyperreactive airways of asthma patients can also constrict, a response that can be controlled by bronchodilators or warm-up protocols (Ritz et al. 2010).
Because adherence to maintenance medication is often low, interventions have been devised to improve outcomes (Bårnes and Ulrik 2015). However, intervention effects on overall adherence levels and asthma outcomes have remained disappointing, and new intervention modes utilizing electronic monitoring, smartphone applications, and the Internet are now being explored. Training in accurate perception of airway obstruction using feedback from self-measurements of lung function has shown promise for improving medication adherence and reducing underperception of airway status in minority children with asthma (Feldman et al. 2012).
A range of behavioral interventions with varying support by psychophysiological rationales have also been tested. Studies of relaxation training, yoga, and meditation have produced mixed results (Lahmann et al. 2009; Pbert et al. 2012; Posadzki and Ernst 2011), which is not surprising, given that physical activation, rather than deactivation, dilates the airways. By contrast, various forms of breathing training show more promise, with clinical trial evidence supporting slow abdominal breathing (Thomas et al. 2009), slow breathing with heart rate variability feedback (Lehrer et al. 2004), and hypoventilation training with (Ritz et al. 2014) or without (Bruton and Lewith 2005) feedback of end-tidal carbon dioxide levels. Although some of these techniques also yield effects on lung function, benefits are seen mostly for asthma symptoms, quality of life, and bronchodilator or maintenance medication needs.
More comprehensive programs of psychotherapy have been tested to address common psychiatric asthma comorbidities, such as panic or depression, and the negative effect of these symptoms on asthma outcomes. These interventions typically target both general concerns of patients and asthma-specific concerns, such as hyperventilation (Lehrer et al. 2008). For example, Parry et al. (2012) randomly assigned 94 high-anxiety asthma patients to either intervention or control groups to compare the effectiveness of anxiety self-management education in reducing asthma-specific fear. The patients who received the cognitive-behavioral therapy (CBT) intervention showed lower levels of asthma-specific panic fear at the end of the treatment, as well as at the 6-month follow-up, suggesting the efficacy of CBT in managing comorbid asthma and anxiety. However, no asthma-specific illness outcomes were reported. In another study, adults with persistent asthma showed improvements in quality of life and asthma control following a six-session self-regulation intervention that focused on identifying goals, problems, and barriers to asthma management (Baptist et al. 2013). Thus, CBT is associated with positive effects on anxiety, asthma control, and quality of life for patients with asthma (Kew et al. 2016).
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease based on an inflammatory response of the lung to noxious particles or gases, often due to tobacco smoking or environmental exposures, such as smoke from open fireplaces or biomass fuel stoves in developing countries (Global Initiative for Chronic Obstructive Lung Disease 2017). The resulting airflow limitation is progressive and, in contrast to asthma, only partially reversible. Patients experience symptoms of persistent cough and dyspnea (an uncomfortable sensation of breathlessness). These symptoms are associated with limitations in daily activities and can generate considerable fear and distress, reducing quality of life considerably (von Leupoldt et al. 2012). Systemic inflammation may additionally contribute to COPD severity and the comorbidity commonly observed with other somatic diseases, including lung cancer, cardiovascular diseases, respiratory tract infections, skeletal muscle dysfunction, and diabetes. Late stages of COPD are characterized by insufficient gas exchange, hyperinflation of the lungs, respiratory muscle weakening, and emphysema, requiring long-term oxygen therapy, mechanical ventilation, or surgical procedures. In 2010, the worldwide prevalence of COPD was estimated at 11.7%, although rates vary widely across countries (Adeloye et al. 2015). The highest rates are found in older segments of the population, especially in individuals older than 60 years. COPD is a leading cause of morbidity and mortality, with rates increasing due to changes in world population demographics.
The prevalence of comorbid psychiatric symptoms, in particular mood and anxiety disorders, is generally high in COPD (Rapsey et al. 2015). Although prevalence rates vary considerably across studies, recent reviews estimate that approximately one-fourth of COPD patients experience clinically significant depression (Panagioti et al. 2014). Clinically significant anxiety is estimated to be two times more prevalent in patients with COPD than in the general population, with panic-related symptoms or panic disorder being up to 10 times more prevalent. These psychiatric comorbidities impact COPD management, with increased frequency of exacerbations, hospitalizations, and hospital readmissions due to anxiety and depression (Coventry et al. 2011; Laurin et al. 2012). Physical activity is also hampered by COPD (Spruit et al. 2010), further reducing both psychological and physical functioning. Consequently, quality of life of COPD patients with comorbid psychiatric diagnoses is impaired considerably (Blakemore et al. 2014). Psychiatric comorbidities often remain undetected (Kunik et al. 2005), further complicating patient management. Reasons for these comorbidities are likely multifactorial but include concerns about functional and social limitations, life-threatening states of dyspnea and suffocation, and end-of-life questions. Inflammatory mechanisms in COPD could constitute a psychobiological link to anxiety and depression (Barnes and Celli 2009), but research remains in its infancy. That retrospectively reported psychiatric diagnoses (in particular, depression, generalized anxiety disorder, and alcohol use disorder) are more common among individuals who subsequently develop COPD than among those who do not supports a potential etiological role of clinically significant emotional distress (Rapsey et al. 2015).
Qualitative research points to the importance of additional psychological considerations in COPD. Lindqvist and Hallberg (2010) identified six core areas of concern from patient interviews: “feelings of guilt due to self-inflicted disease,” “making sense of existence,” “adjusting to bodily restrictions,” “surrendering to fate,” “making excuses for smoking-related causes,” and “creating compliance with daily medication.” Feelings of guilt about one’s smoking habit and its effects on one’s health appear to be central, hindering acceptance of the chronic condition with its functional limitations and altered perspective on life. The psychological impact of exacerbations is also considerable, with patients experiencing lack of energy, anxiety, feelings of confinement, resignation, anger, and guilt (Kessler et al. 2006). Stronger emotional responses to their illness and a reduced feeling of control over COPD are linked to adverse management outcomes in COPD patients (Kaptein et al. 2008).
Treatment goals for COPD are focused on symptom relief, reduction of exacerbations, and slowing of progressive decline in lung function. Treatment goals additionally include improvement in exercise tolerance, daily life functioning, quality of life, and life expectancy (von Leupoldt et al. 2012). First-line pharmacological treatment of COPD with bronchodilators should ideally be complemented by multidisciplinary pulmonary rehabilitation, as recommended by current guidelines (Global Initiative for Chronic Obstructive Lung Disease 2017). This combination of interventions has demonstrated effectiveness in supporting most treatment goals, specifically improvements in exercise capacity and quality of life (Puhan et al. 2016). A review of rehabilitation programs observed that components have variably included optimization of medical treatment, exercise training, smoking cessation, patient education and self-management training, nutrition counseling, relaxation, breathing and respiratory muscle training, and psychosocial support (von Leupoldt et al. 2012). However, the effectiveness of individual components has often been difficult to determine. The exercise training component alone has been shown to yield substantial effects on physical activity levels (Lahham et al. 2016). Similarly, action plans to prevent exacerbations paired with brief self-management training have been beneficial in reducing inpatient care (Howcroft et al. 2016). Smoking cessation is promoted as the intervention with the greatest potential to change the natural course of COPD (Global Initiative for Chronic Obstructive Lung Disease 2017). However, many patients continue to smoke despite their condition. Controlled studies indicate that cessation success rates are often lower than those in the general population, but significant gains in life expectancy, pulmonary function, symptom and exacerbation reduction, and slowing of decline in lung function can be achieved with successful long-term abstinence (von Leupoldt et al. 2012).
Although improvements in anxiety and depression have been reported in response to the multimodal treatment described above, other interventions target these comorbidities more directly. Therapy with antidepressants has so far not shown beneficial effects on depression in COPD (Yohannes and Alexopoulos 2014). CBT has been adapted to address COPD problem areas by specifically targeting catastrophizing of symptoms, avoidance of physical activity, and dysfunctional illness or treatment perceptions. Recent reviews have varied in their conclusions, with some showing significant psychological improvements with CBT and others not (Coventry et al. 2013; Farver-Vestergaard et al. 2015; Panagioti et al. 2014), particularly in comparison with exercise interventions. However, CBT programs have varied widely in components and administration formats (individual, group, and/or telephone-assisted). Interventions targeting more circumscribed problem areas, such as panic disorder and catastrophic misinterpretations of symptoms, may be more promising (Livermore et al. 2010). Coventry et al. (2013) pointed out that cognitive limitations in older patients may complicate use of CBT. Interventions have also lacked a more systematic approach for addressing existential questions that may arise from the irreversibility of loss in health and functioning and an end-of-life perspective, an area for which future acceptance-based treatment modalities may be particularly suited.
Adjunctive behavioral treatment modalities have often been included in pulmonary rehabilitation programs, but tests of their individual contribution to treatment goals are less common. Compromised respiratory muscle function in COPD patients can lead to hypercapnia symptoms and reduced exercise capacity. Thus, training of inspiratory muscle strength by breathing through resistive loads has been shown to improve functional exercise capacity, dyspnea, and quality of life in individuals with COPD (Gosselink et al. 2011). Other breathing techniques, such as abdominal or pursed-lip breathing, aim to reduce dynamic hyperinflation of the chest and improve gas exchange; interventions providing training in these techniques have shown beneficial effects on physical activity in people with COPD (Holland et al. 2012). Although intervention effects are often difficult to separate from the effects of other elements in yoga and relaxation training, a recent meta-analysis pooling all available trials of relaxation techniques found significant benefits of these treatment packages for anxiety, depression, and quality of life in patients with COPD (Volpato et al. 2015). Studies of tai chi, a practice that involves both physical movement and breathing exercises, have shown modest improvements in physical activity and lung function in comparison with usual care (Ngai et al. 2016). Although these recent reviews suggest statistically significant effects from adjunctive behavioral modalities, the effects are often small and are not necessarily clinically significant. Substantial improvements in outcome variables with relaxation interventions compared with other standard interventions such as exercise training are typically not demonstrated. However, adding any kind of psychological intervention to exercise training can enhance its effect on clinical outcomes such as dyspnea, anxiety, and exercise capacity (Wiles et al. 2015).
Sarcoidosis is characterized by noncaseating granulomatous involvement of lymph nodes, lymphatic channels in the lung, and other tissues. Sarcoidosis affects black patients more frequently than white patients in the United States. In Europe, Swedish and Danish patients have high prevalence rates. Onset of the illness usually occurs between the ages of 20 and 40 years. Diagnosis may be delayed until characteristic findings are recognized on a chest X ray. The disease often follows a relapsing and remitting course, with recovery in 80% of patients, but about 5% die from sarcoidosis. Patients often have a dry cough, shortness of breath, fatigue, and weight loss. Lesions can affect the skin, bones, joints, skeletal muscles, and heart.
Sarcoidosis may affect the central nervous system (CNS) in 5% of patients (Krumholz and Stern 2014). Indirect evidence for the diagnosis comes from cerebrospinal fluid and brain magnetic resonance imaging. Pituitary involvement may result in diabetes insipidus or the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypercalcemia, hyperprolactinemia, menstrual cycle changes, or hypogonadism. There have been case reports of neurosarcoidosis causing cognitive deficits, delirium, seizures, dementia, mania, and psychosis. Psychotic symptoms generally remit rapidly with steroids.
Sarcoidosis rarely has been investigated from a psychological standpoint. A large study of members of the Dutch Sarcoidosis Society found that perceived stress was high and was related to depressive symptoms (De Vries and Drent 2004). In addition, psychiatric comorbidity was reported in 44% of Italian sarcoidosis patients, with MDD in 25%, panic disorder in 6.3%, bipolar disorder in 6.3%, generalized anxiety disorder in 5%, and obsessive-compulsive disorder in 1.3% (Goracci et al. 2008). Depression is associated with poorer quality of life in sarcoidosis (Yeager et al. 2005).
Many individuals experience symptom patterns that mimic asthma or COPD. Such symptoms include the experience of disabling breathlessness, chronic cough, “air hunger,” and suffocation. Consideration of alternative diagnoses that may present in a manner similar to asthma is essential for correct diagnosis and treatment. Inappropriate treatment with medications such as systemic corticosteroids can result in deleterious side effects, ineffective treatment, and even morbidity (Benninger et al. 2011; Idrees and FitzGerald 2015).
In many respiratory conditions, chronic cough—defined as cough that is present for at least 4 weeks in children and 8 weeks in adults—is often the only symptom. However, chronic cough may also be present in the absence of any pulmonary or extrapulmonary (e.g., gastroesophageal reflux disease) etiology. In these cases, chronic cough, when unresponsive to medical management, is categorized as somatic cough disorder (previously psychogenic cough) or tic cough (previously known as habit cough) (Haydour et al. 2014; Vertigan et al. 2015). The American College of Chest Physicians (CHEST) Guideline and Expert Panel Report concluded that only low-quality evidence exists to support the definition or diagnosis of somatic cough disorder or tic cough (Vertigan et al. 2015). Somatic cough disorder is broadly indicated by core features, including chronic persistence, nonresponsiveness to medical treatment, daytime occurrence, absence at night, and the potential of a barking or honking sound. Tic cough is further classified as a psychogenic cough with single dry coughs (tics) that are suppressible, distractible, suggestible, and variable (Vertigan 2017). Despite low-quality evidence and lack of control groups, CHEST guidelines recommend nonpharmacological trials of hypnosis, suggestion therapy, combinations of reassurance and counseling, or referral to a psychologist or psychiatrist for treatment (Haydour et al. 2014; Vertigan et al. 2015).
The term hyperventilation syndrome was first introduced by Kerr et al. in 1937 and has since garnered both attention and controversy, with little consensus among definitions of symptomatology or diagnostic criteria (Bass 1997; Kerr et al. 1938). Hyperventilation arises when breathing occurs in excess of metabolic demand, which acutely leads to dyspnea and anxiety, and reduction of the partial pressure of carbon dioxide (pCO2) (Wilhelm et al. 2001). Symptoms of hyperventilation include breathlessness out of proportion to actual physical effort, chest pain that is usually atypical in angina, dizziness, paresthesias, fatigue, and palpitations (Tavel 1990). Terms used to describe this collection of symptoms have included dysfunctional breathing, behavioral breathlessness, neurocirculatory asthenia, and psychogenic dyspnea (Howell 1990; Jones et al. 2013). Problematic hyperventilation is estimated to occur in up to 10% of the general population, more commonly in children and adolescents, and even more commonly in those who also have asthma (D’Alba et al. 2015; Gridina et al. 2013).
There is no clearly elucidated pathophysiology underlying hyperventilation, which can occur in both acute and chronic forms (Gardner 1996). Acute hyperventilation is easily diagnosed due to rapid breathing (tachypnea) or frequent deep breaths; chronic hyperventilation is more problematic, requiring more nuanced diagnosis to identify the subtleties of a modest increase in respiratory rate or tidal volume. Affected individuals frequently seek medical care and undergo extensive and expensive testing in attempts to identify an organic cause of symptoms (Decuyper et al. 2012).
Many physicians regard hyperventilation as a manifestation of anxiety, but a more complex interaction may be involved among organic respiratory, physiological, and psychiatric disturbances that induce symptomatic hypocapnia (i.e., deficiency of carbon dioxide in arterial blood) (Gardner 1996). Chronic hyperventilation is often observed in anxiety disorders, particularly panic disorder, where it generates several characteristic physical symptoms, including shortness of breath and dizziness (Meuret and Ritz 2010). Anxious patients with complaints of air hunger often take large “sigh” breaths, which results in overbreathing and induces hypocapnia. Additionally, neuroticism is viewed as a risk factor for the development of hyperventilation because it is strongly associated with self-reported hyperventilation symptoms (Decuyper et al. 2012).
Hyperventilation and anxiety can function in both a bidirectional and progressive manner, with symptoms of anxiety influencing breathing patterns, and hyperventilation symptoms generating psychological distress. Primary treatment for hyperventilation includes psychoeducation and interventions targeted at reducing hyperventilation. These interventions include diaphragmatic breathing, cognitive training, and hypoventilation training (Jones et al. 2013; Meuret et al. 2010).
Vocal cord dysfunction (VCD) was first described in the 1840s and occurs when abnormal adduction of the vocal cords during the inspiratory phase of the respiratory cycle produces airflow obstruction at the larynx (Dunn et al. 2015). VCD can mimic persistent asthma in up to 10% of patients seeking evaluation; if not diagnosed appropriately, VCD is often treated with asthma medications, with significant resulting morbidity and costs (Traister et al. 2016). Symptoms of VCD include wheezing, coughing, shortness of breath, chest tightness, and dyspnea. VCD can also be comorbid with asthma, with some studies showing that more than 50% of patients with VCD have an additional asthma diagnosis (Newman et al. 1995). The exact cause of VCD is not established but is likely multifactorial (Goldberg and Kaplan 2000). Factors predictive of VCD include younger age, female sex, high body mass index, history of childhood sexual trauma, and presence of anxiety or depression (Goldberg and Kaplan 2000; Idrees and FitzGerald 2015; Li et al. 2016). The condition is largely treated with breathing strategies aimed at reducing laryngeal muscle tone, and psychological interventions may also be useful in management of both adult and pediatric patients; however, continued research with longitudinal study designs is needed (Guglani et al. 2014).
Systemic corticosteroids are frequently prescribed for patients with pulmonary diseases. Long-term corticosteroid use is associated with side effects, such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis and immune system, glaucoma, cataracts, truncal obesity, thinning and bruising of the skin, and loss of bone mineral density.
Corticosteroids are also associated with an increased risk of depression, mania, and mixed episodes (Judd et al. 2014) Acute, high-dose corticosteroid therapy appears to be more strongly associated with mania or hypomania, while chronic, lower-dose therapy may be more associated with depression. Psychotic symptoms, including delusions, hallucinations, and disorganized thought processes, also can occur. The most common neuropsychiatric effects of corticosteroids may be cognitive changes. The hippocampus, a brain region involved in memory, appears to be particularly sensitive to corticosteroid effects, with some studies showing volume decreases (Brown 2009; Brown et al. 2004). Diffuse cognitive changes, including delirium, are also reported during corticosteroid therapy (Fardet et al. 2012). Dose is the most definitively established risk factor for psychiatric side effects of corticosteroids. Even inhaled corticosteroids can cause HPA axis suppression at higher doses, as well as psychiatric side effects. Corticosteroid-induced psychiatric symptoms and their treatment are discussed in detail in Chapter 24 (“Rheumatology”).
Other medications used for pulmonary diseases also have psychiatric side effects. Theophylline and beta2-adrenergic agonists are sometimes associated with anxiety, insomnia, restlessness, agitation, and depression. Theophylline may even be associated with an increased risk of suicidal ideation (Favreau et al. 2012). Initial reports suggested that leukotriene inhibitors may cause psychiatric symptoms, such as agitation, insomnia, anxiety, depression, and suicidal ideation, although more recent analyses do not suggest a link with completed suicide (Gibbons and Mann 2011). Other than dose reduction or discontinuation, no known treatments have been established for psychiatric side effects of these medications.
Psychiatric disorders are common among people with pulmonary diseases. The symptoms may be influenced by disability, activity limitations, and changes in quality of life, as well as breathlessness and medication side effects. In general, pharmacological treatment of psychiatric disorders such as depression, anxiety, and psychosis in this population is similar to that in other patient populations. However, the likelihood that patients with chronic respiratory diseases are already taking several medications increases the risk of additive side effects (e.g., QTc prolongation) and drug–drug interactions, particularly for drugs metabolized by the cytochrome P450 system. When possible, clinicians should avoid prescribing psychiatric medications that depress the respiratory system (e.g., benzodiazepines); if used, these agents should be prescribed at the lowest dosage that provides symptom relief. Sedating medications are contraindicated in hypercapnic patients (i.e., those with chronically elevated pCO2) because they can suppress hypoxic respiratory drive.
Although limited, there is also evidence suggesting potential benefits of pharmacotherapy in managing adult respiratory asthma and its psychiatric comorbidities. A randomized 12-week clinical trial of citalopram in 82 adults with both asthma and MDD showed reductions in oral corticosteroid use and depression symptom scores in patients receiving citalopram vs. placebo (Brown et al. 2005). Additionally, trends toward reductions in depression scores, as well as a correlation between changes in asthma (based on the Asthma Control Questionnaire and pulmonary function [FEV1% of predicted]) and changes in depressive symptoms, have been observed in small proof-of-concept randomized trials of escitalopram and bupropion in outpatients with asthma and MDD (Brown et al. 2007, 2012). These studies may have meaningful clinical implications for the management of both asthma and MDD with antidepressant medications; however, physiological mechanisms that drive the relationship between both conditions and the medication response remain unclear.
A recent meta-analysis concluded that benzodiazepines are safe and effective as hypnotics in less severe COPD (Lu et al. 2016); however, they also have a higher rate of adverse respiratory events (Chung et al. 2015; Ekström et al. 2014). Benzodiazepines have not been shown to be effective in relieving breathlessness in advanced COPD (Simon et al. 2016); low-dose opioids are suggested as a safer and more effective alternative (Ekström et al. 2014). Antipsychotic use has been associated with an acute and dose-dependent increased risk of acute respiratory failure in patients with COPD (Wang et al. 2017). Chronic antipsychotic use uncommonly causes laryngeal and other respiratory dyskinesias. Additional research, including larger-scale clinical studies that incorporate integrative approaches to pulmonary disease management, is needed to improve our understanding of the interaction between respiratory disease and psychiatric illness and to create better-targeted treatment approaches.
In this chapter, we discussed the nature, prevalence, and treatment of psychiatric disorders frequently observed in patients with pulmonary diseases. The symptoms and treatment outcomes of many pulmonary diseases are strongly influenced by mood, emotions, and the presence of psychiatric comorbidities and are mediated by biological factors, as well as through treatment adherence and overall functioning and quality of life. The management of psychiatric disorders in this population can include both psychosocial approaches and pharmacotherapy. When psychiatric medications are given, an appreciation of the potential for side effects and drug–drug interactions is essential.
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