The Impact of Screening Programs for Anxiety and Depression on Incidence and Severity of COPD Exacerbations in Community-Dwelling Adults
Background: The impact that depression and/or anxiety screening has on prevalence and severity of COPD exacerbations has not been addressed. A systematic assessment addressing possible associations will be performed to inform guidelines and practice.
Purpose and methods: A search of electronic databases for articles published before March 2017 was performed. Longitudinal and retrospective studies as well as systematic reviews reporting an association between depression and anxiety and COPD, or that report their effect on exacerbation severity or prevalence, were eligible.
Results of Systematic Review: Nine studies were found revealing a positive association between depression and/or anxiety and COPD exacerbation and severity. Depression or anxiety consistently increased the risk of COPD exacerbation in the 3,426 participants who were followed for 1-3 years. Depression or anxiety were also associated with frequency of exacerbation among depressed COPD participants. When exacerbation required hospitalization, anxiety was associated with increased length of hospitalization. COPD also increased the risk of depression.
Conclusions and Implications: Depression and anxiety negatively affect prognosis of COPD, increasing the risk of exacerbation as well as frequency.
Keywords: Chronic obstructive pulmonary disease (COPD), depression and/or anxiety screening, screening programs, COPD exacerbations
The Global Initiative of Chronic Obstructive Lung Disease (GOLD) defines Chronic Obstructive Pulmonary Disease (COPD) as “the persistent airflow limitation that is usually progressive and associated with an enhanced inflammatory response in the airways and the lung to noxious particles and gases” (GOLD, 2017, pg. 2). COPD is the of third leading cause of death in the United States (Kochanek, Xu, & Tejeda-Vera, 2017) and according to the World Health Organization’s (WHO) predictions, COPD will be the third leading cause of death in the world by 2030 (WHO, 2017). COPD often has occurrences of symptom deterioration or exacerbations requiring treatment such as antibiotics or corticosteroids (Burge & Wedzicha, 2003). COPD exacerbations are responsible for significant health resource utilizations, mortality, reduced functional ability, and quality of life (Mittmann et al., 2008).
According to A. M. Yohannes, Willgoss, Baldwin, and Connolly (2010) the prevalence of anxiety and/or depression in COPD patients is as high as 40%. Anxiety and depression, common comorbidities of COPD, have been found to be associated with higher frequency and length of COPD hospitalizations (Dahlén & Janson, 2002). Despite increasing awareness of the impact that depression and/or anxiety have on COPD, depression and anxiety often go untreated and undetected (Maurer et al., 2008). An association between anxiety and/or depression and COPD exacerbations has been suggested for some time but evidence supporting this claim was limited (Catherine Laurin, Moullec, Bacon, & Lavoie, 2012). Xu et al. (2008) along with several other promising studies have produced substantial evidence to show a correlation between anxiety and/or depression and COPD exacerbations. Xu et al. (2008) suggests there may even be a causal relationship between anxiety and/or depression and COPD exacerbation.
Nursing is a profession in which the care of the patient is holistic. What affects the mind, body or spirit affects all three and assessing them all is essential to providing excellent care. Chronic progressive illnesses such as COPD impact the patient’s quality of life, limit their ability to perform activities of daily living, inhibit interactions with others due to activity limitations further limiting social support. When caring for patients in both inpatient and outpatient settings nurses play a vital role in evaluating each patient’s myriad of needs. Being aware of the positive correlation between depression and anxiety and COPD exacerbations will promote an awareness of the need to utilize depression and/or anxiety screening tools with patients with COPD. The question driving this systematic review is, “What is the impact of screening programs for anxiety and depression on incidence and severity of COPD exacerbations in community-dwelling adults with COPD?” The objective of this systematic review was to examine the impact of depression and/or anxiety screening on COPD exacerbation severity and prevalence.
A literature search was completed between February 1, 2017 and March 28, 2017 using the following databases: Academic Search Complete, CINAHL with Full Text, Health Source: Nursing/Academic Edition, PsycARTICLES, PsycINFO. The dates of the original search included publications between the years 1985 to 2017. Key words used included any Boolean operators or symbols: Depression or Anxiety, COPD or Congestive Pulmonary Obstructive Disease, Screening Programs. The initial search results yielded 1317 results. Search limits included: English language, peer-reviewed, Outpatient. The remaining 52 abstracts were reviewed based on the following inclusion criteria: adult 18 years or older, outpatient, COPD, depression and/or anxiety. Articles were also filtered based on the following exclusion criteria: inpatient, asthma, cancer, congestive heart failure, or panic. After reviewing all the abstracts and the full text of the articles, 48 articles were eliminated based on inclusion and exclusion criteria.
Due to the small number of articles identified on the topic of interest an additional search utilizing the same databases was performed during this time with the key words: depression and/or anxiety screening, COPD exacerbations. The initial search yielded 157 results. The same inclusion and exclusion criteria were applied. After reviewing the abstracts and the full text of these articles another 6 articles addressing the topic were discovered. Original research cited in these additional articles were also considered for inclusion in the systematic review. These studies were instrumental to the body of knowledge known about the topic. All the articles included in this review can be located utilizing the West Virginia Library online.
Nine studies were included that address the association and prevalence of depression and/or anxiety with COPD. Table 1 includes detailed information about the included articles. The studies were geographically dispersed, taking place in China, Canada, England, the United States, and Spain. The included quantitative literature varied in design and included five prospective studies, one retrospective study, and two meta-analysis.
The included studies recruited participants through convenience sampling using various methods including outpatient clinics, health care centers, a COPD study, an emphysema treatment trial, and a network of hospitals. The sample sizes for these studies were between 116 and 1134. No power analysis was performed for any of the studies. Some the studies required patients to be above 30 to 40 years of age whereas others placed a restriction on maximum age. Most studies required previous physician diagnosis of COPD confirmed upon entrance to the study by spirometry. Many studies evaluated FEV/FVC values to provide a baseline estimate of lung function and to evaluate the level of disease. All studies required participants to be fever free. Several studies required patients to have been free of exacerbation for a month prior to beginning the study. One study wanted participants to have a smoking history of 10 pack-years (C. Laurin et al., 2009).
The included studies used varying methods to operationalize depression and anxiety as well as COPD exacerbation. Depression and anxiety indicators were defined by psychiatric interview (C. Laurin et al. (2009), or psychometric instruments such as HADS, BDI, or other similar instruments in the remaining studies. COPD diagnosis was confirmed by various methods, such as one utilizing a pulmonologist (Jennings, DiGiovine, Obeid, & Frank, 2009). Three studies utilized spirometry testing with FEV/FVC ratio less than 0.7 (Montserrat-Capdevila et al., 2017; Quint, Baghai-Ravary, Donaldson, & Wedzicha, 2008; Xu et al., 2008). Another study used spirometry to measure FEV and FVC to establish a baseline value (C. Laurin et al., 2009). One study also evaluated the level of COPD progression utilizing the GOLD classifications (Montserrat-Capdevila et al., 2017). Five of studies were prospective following the patients for up to 2 years utilizing monthly phone calls as well as diary cards to help with recall regarding exacerbation symptoms, as well as medications received during their exacerbation (C. Laurin et al., 2009; Quint et al., 2008; Xu et al., 2008). Some of the studies differentiated the severity of the exacerbations based on whether the event required hospitalization. Exacerbation length was defined as the period beginning when medication for exacerbation was initiated and ending when medication was terminated. Statistical analysis was performed on results for each study to determine the significance of the findings and the effect of potential co-morbidities and other factors.
Six of the studies found that depression and anxiety were associated with increased risk of exacerbation (Atlantis, Fahey, Cochrane, & Smith, 2013; Jennings et al., 2009; C. Laurin et al., 2009; Montserrat-Capdevila et al., 2017; Quint et al., 2008; Xu et al., 2008). C. Laurin et al. (2009) found that patients with anxiety/depression had a higher annual rate of exacerbation (3.81 vs. 2.73; p= 0.009). Montserrat-Capdevila et al. (2017), Xu et al. (2008), and C. Laurin et al. (2009) found a correlation between depression and/or anxiety and increased frequency of exacerbations. Montserrat-Capdevila et al. (2017) found that patients with anxiety/depression (HAD) showed a higher incidence of frequent exacerbation (73.5%) compared with patients with no depression/anxiety (50.9%), (p<0.001). Xu et al. (2008) also found that COPD patients with depression had a higher incidence of frequent exacerbation compared with those with no depression (25 vs. 20%; p=0.003); evidence showed that COPD patients with anxiety also had a greater frequency of exacerbations compared with those without anxiety (27.2% vs. 20.2%; p=0.35). Montserrat-Capdevila et al. (2017) found that anxiety/depression doubled the risk of exacerbation frequency (OR 2.28; CI 1.17-4.42). Quint et al. (2008) found that increased depressive symptoms were associated with frequent exacerbations with baseline depression 12.5 (5.0-19.0) and exacerbation depression 19.5 (12.0-28.0) using the CES-D instrument. Jennings et al. (2009), Catherine Laurin et al. (2007), and Fan, Ramsey, Giardino, and et al. (2007) found that female COPD patients had increased depression and anxiety contributing to a higher frequency of female COPD patients with exacerbations.
Xu et al. (2008), Atlantis et al. (2013), Jennings et al. (2009), Fan, Ramsey, Giardino, and et al. (2007) found that depressed patients had increased mortality. Xu et al. (2008) found that anxiety was associated with more event-based exacerbations as well as longer hospital stays. Further, patients with probable anxiety stayed in the hospital 1.92 times longer than patients with no anxiety (Xu et al., 2008).
Each study conducted a thorough collection of background information regarding their participant’s health history at the beginning of their prospective studies to reduce, acknowledge, or eliminate confounders to reduce bias. Xu et al. (2008) collected socioeconomic data, evaluated exercise capacity and self-efficacy, and assessed individual participant’s comorbidities associated with COPD exacerbations. The studies were mostly convenience samples so random sampling was not possible. Because many of the studies were prospective and the recipients were asked many of the same questions throughout the study, participants likely anticipated the questions. As a result, subsequent recipient responses may have been influenced by previous responses and participants might have become disinterested. C. Laurin et al. (2009) and Xu et al. (2008) reported some participants dying during the study due to COPD related complications, which may have impacted the results of the study. Xu et al. (2008) also noted loss to follow up with 40 of their participants who had severe COPD (FEV1% <30%) and who were significantly depressed. Missing data due to participant death or withdrawal impacts the final results of the study. Several studies utilized monthly phone calls to talk with patients about exacerbations due to concern that memory cards might not be utilized with concern for recall bias. Xu et al. (2008) and Montserrat-Capdevila et al. (2017) had 69% and 75% male participants in their studies affecting the generalizability of their study results.
A bidirectional relationship exists between anxiety and/or depression and COPD (Atlantis et al., 2013). Patients with COPD have an increased likelihood of developing depression (Atlantis et al., 2013). Patients with COPD who have also have depression have an increased risk of having an exacerbation. Patients with COPD and depression and/or anxiety also have an increased frequency of exacerbation. A correlation between increased depressive symptoms and exacerbation has also been found (Quint et al., 2008). COPD patients with anxiety have been shown to have longer hospital stays.
According to Atlantis et al. (2013) patients with COPD have a 55% to 69% increase in risk of developing depression. Given the evidence, anxiety and/or depression screening should be a fundamental component in the ongoing evaluation of COPD patients. Patients should have frequent evaluations beginning when depression is diagnosed, upon beginning anti-depressant medication, and when changes are made in dosage or type of anti-depressants. Due to other probable co-morbidities present, the cause of the depression maybe be difficult to determine, including not only this chronic illness but also loss of quality of life, social isolation, and loss of independence.
The nursing profession seeks to provide holistic care providing for the health of the whole patient, mind, body, and spirit. Nurses provide care to patients with chronic illnesses both inpatient as well as in the home. Evaluation tools such as PHQ-9, a depression screening tool, are being implemented by nurses in efforts to address undiagnosed depression in patients admitted to acute care hospitals. This tool should be utilized whenever there is a change in a patient’s psychiatric status. As the primary healthcare providers in home healthcare, bedside nurses can implement this same assessment tool and if there is a significant change in their assessment a primary care physician can be notified about a change in patient status so that adjustments to medication regimen can be made. This is a change in practice that can and should be implemented in inpatient care as well as home care nursing to address the mental health of COPD patients and other patients who suffer with chronic illness.
As nurses also provide ongoing education to patients about their illness, they can educate patients about the potential for developing depression as well. Nursing already plays a vital role in providing education about COPD and while assessing a patient nurses can provide education about how to maintain respiratory health at home, signs of worsening respiratory status, and importance of contacting their health provider early to prevent further complications. While assessing patients in the hospital or at home, nurses can provide education about the symptoms of depression, how to maintain psychological health, and the signs of worsening depression.
The current literature on the subject COPD and depression and/or anxiety presents limitations. Some of the larger studies had participant populations which were predominantly male. Power analyses were not completed in the studies which would greatly improve the ability to limit the influence of atypical data and increase confidence in the results. The sample population for the included studies utilized a convenience sampling approach which raises concerns about whether they are a representative sample of this patient population. Qualities or unknown factors present in the specific population examined in these studies may limit the generalizability of the results. Though many factors were examined including socioeconomic, and social support, the studies included did not address the impact of the physical home environment for the participants. This is not surprising due to economic limitations of research but given the impact of environment on respiratory illness this is a factor that is essential to be addressed in further studies.
Conclusions and Implications
Evidence produced in the included studies demonstrate that depression and/or anxiety play a clinically significant role in COPD exacerbations both in frequency and severity of exacerbations. According to Kunik et al. (2005) less than 50% of patients with COPD and depression are being recognized due to lack of depression and/or anxiety screening. Over 10 years ago Kunik et al. (2005) recognized that no studies examining the prevalence of anxiety and/or depression in persons with COPD were occurring in the community setting outside of the clinic or inpatient setting. After reviewing the available literature found during in this search this continues to be true. The reasons for this may be many, including logistical challenges, higher staff requirements, expense, and lack of sufficient technology. Regardless, this data is pertinent to the topic and needed in order to understand the relationship between increased symptoms of depression and COPD exacerbation. The intent of this systematic review was to address the impact of depression/anxiety screening on COPD exacerbation and severity in a community environment. This area of study has yet to be explored.
Nursing and technology will likely play a role in future research on this subject. With the advent of health applications, patients with COPD could be enrolled in research completed at home where they could fill out a daily or weekly questionnaire about their COPD and depression. Data collected with this level of frequency would likely be able to detect changes in depression and change in COPD symptoms. Nurse researchers in cooperation with home health agencies could conduct monthly in home assessment of patients who indicate that they are experiencing depression along with COPD to track increasing symptoms of depression to correlate whether patients may be experiencing increasing symptoms of exacerbation coinciding with increasing symptoms of depression or because of increasing symptoms of depression. Research utilizing a health app could take place in both rural or metropolitan settings whereas a metropolitan environment would be less costly for in home assessment.
Protocols and order sets need to be established by advance practice nurses (APRN) providing primary care to COPD patients so that for every visit patients are screened for depression and referrals made to psychiatry to assist in managing newly diagnosed or unmanaged depression and anxiety.
Atlantis, E., Fahey, P., Cochrane, B., & Smith, S. (2013). Bidirectional Associations Between Clinically Relevant Depression or Anxiety and COPD: A Systematic Review and Meta-analysis. Chest, 144(3), 766-777. doi:http://dx.doi.org/10.1378/chest.12-1911
Burge, S., & Wedzicha, J. (2003). COPD exacerbations: defintions and classifications. European Respiratory JournalS Supplement, 46s-53s.
Dahlén, I., & Janson, C. (2002). Anxiety and Depression are Related to the Outcome of Emergency Treatment in Patients with Obstructive Pulmonary Disease. Chest, 122(5), 1633-1637. doi:http://dx.doi.org/10.1378/chest.122.5.1633
Fan, V. S., Ramsey, S. D., Giardino, N. D., & et al. (2007). Sex, depression, and risk of hospitalization and mortality in chronic obstructive pulmonary disease. Archives of Internal Medicine, 167(21), 2345-2353. doi:10.1001/archinte.167.21.2345
Jennings, J. H., DiGiovine, B., Obeid, D., & Frank, C. (2009). The Association Between Depressive Symptoms and Acute Exacerbations of COPD. Lung, 187(2), 128-135. doi:10.1007/s00408-009-9135-9
Kochanek, K. M., S., Xu, J., & Tejeda-Vera, B. (2017). National Vital Statistics Report Deaths: Final Data for 2014. www.cdc.gov. Retrieved from https://www.cdc.gov/nchs/data/nvsr/nvsr65/nvsr65_04.pdf
Kunik, M. E., Roundy, K., Veazey, C., Souchek, J., Richardson, P., Wray, N. P., & Stanley, M. A. (2005). Surprisingly High Prevalence of Anxiety and Depression in Chronic Breathing Disorders. Chest, 127(4), 1205-1211. doi:http://dx.doi.org/10.1016/S0012-3692(15)34468-8
Laurin, C., Labrecque, M., Dupuis, G., Bacon, S. L., Cartier, A., & Lavoie, K. L. (2009). Chronic obstructive pulmonary disease patients with psychiatric disorders are at greater risk of exacerbations. Psychosomatic medicine, 71(6), 667-674.
Laurin, C., Moullec, G., Bacon, S. L., & Lavoie, K. L. (2012). Impact of Anxiety and Depression on Chronic Obstructive Pulmonary Disease Exacerbation Risk. American Journal of Respiratory and Critical Care Medicine, 185(9), 918-923. doi:10.1164/rccm.201105-0939PP
Maurer, J., Rebbapragada, V., Borson, S., Goldstein, R., Kunik, M. E., Yohannes, A. M., & Hanania, N. A. (2008). Anxiety and depression in COPD: current understanding, unanswered questions, and research needs. Chest, 134(4 Suppl), 43s-56s. doi:10.1378/chest.08-0342
Mittmann, N., Kuramoto, L., Seung, S. J., Haddon, J. M., Bradley-Kennedy, C., & FitzGerald, J. M. (2008). The cost of moderate and severe COPD exacerbations to the Canadian healthcare system. Respiratory Medicine, 102(3), 413-421. doi:http://dx.doi.org/10.1016/j.rmed.2007.10.010
Montserrat-Capdevila, J., Godoy, P., Marsal, J. R., Barbé, F., Pifarré, J., Alsedà, M., & Ortega, M. (2017). Overview of the Impact of Depression and Anxiety in Chronic Obstructive Pulmonary Disease. Lung, 195(1), 77-85. doi:10.1007/s00408-016-9966-0
Quint, J. K., Baghai-Ravary, R., Donaldson, G. C., & Wedzicha, J. A. (2008). Relationship between depression and exacerbations in COPD. European Respiratory Journal, 32(1), 53-60. doi:10.1183/09031936.00120107
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|Year||Author, Journal, title||Country||Purpose||Sample Description including Ages,
|Design||Depression/Anxiety Screening Tool||Findings||Comments|
|2000||Abebaw M. Yohannes, Baldwin, and Connolly (2000), Clinical Gerontology, Mood disorders in elderly patients with COPD||Perform a meta-analysis of anxiety and depression in COPD pts||78 years, range 40-93||Meta-analysis of 11 studies||HAD, BASDEC, MMPI, BDI STAI, DSMIII||Prevalence of Depression 40%, Anxiety and Depression common in COPD patient,||Screening tools for depression not routinely used in clinical practice, symptoms masked by physical symptoms|
|2005||Kunik et al. (2005), Chest, Surprisingly High Prevalance of Anxiety and Depression in Chronic Breathing Disorders||United States||Assess the prevalence, screening, and recognition of depression and anxiety, in persons with Chronic breathing disorders||64.2 (range not given)||(X)(I) Cross sectional design N=1,334
|Prime-MD (phone contact), in person interview BDI-II and BAI=, those with significant depression and confirmed COPD were interviewed with SCID||High prevalence of anxiety and depression found in chronic breathing disorders
Providers recognizing < 40% of anxiety/depression disorders in COPD pts
|Va patients, mostly males participanting in study, non clinical or inpatient setting|
|2007||Fan et al. (2007), Arch Intern Med, Sex, Depression and Risk of Hospitalization and Mortality in Chronic Obstructive Pulmonary Disease||United States||Determine whether depressive or anxiety symptoms associated with COPD hospitalization and mortality||66.8 (range not given)||(L)Prospective Cohort study over 3 years looking a 1- and 3-year mortality as well as COPD or Respiratory related hospitalizations of ED visits. M(L), (I), (E)Longitudinal over 2 years, N=610, outpatient||BDI for depression, STAI for anxiety||40% mild to moderate depression, only 24.5% were taking antidepressant. 26.9% Hospitalized or seen in ED for COPD, 30.5% hospitalized for respiratory causes. 3 yr mortality higher for BDI 11<||High prevalence of depressive symptoms among patients with severe COPD with few receiving antidepressants. Found no correlation between depressive symptoms with COPD exacerbations|
|2008||Quint et al. (2008), European Respiratory Journal, Relationship between depression and exacerbations in COPD||England||Assess whether depression was related to exacerbation frequency||70.9±8.6||(L) Prospective Cohort study N=169,outpatient, followed over 1-yr, all pt FEV to FVC ratio <70%, no exacerbation in the previous month, also looking at CRP and IL-6||HADS, SDS, MMPI, BDI, CES-D – was used to measure frequency and duration of symptoms||15 had clinical depression, 61 frequent exacerbators, positive relationship between depressed and exacerbation frequency, more frequent exacerbators more depressed||Increased in depression for infrequent exacerbators verses frequent exacerbators. No link between systemic inflammation and depression. Study not designed to look at clinically meaningful changes in depression|
|2008||Xu et al. (2008), Independent Effect of Depression and Anxiety on COPD Exacerbations and Hospitalization||China||Investigate the independent effect of depression and anxiety on COPD Exacerbations and hospitalizations||67.0±10.7||(L), (I) Prospective Cohort for 12 month period, physician diagnosed COPD, FEV/FVC ration <0.7 FEV <80%, no asthma, N= 491 Outpatient||HADS,||Depressed patients had more exacerbations, lower self-efficacy or social support, the depressed patients had more mortality, symptom and event based exacerbations and longer hospital stays; depression identified in stable COPD significantly associated with higher risk of exacerbation and hospitalizations, anxiety linked with increased overall length of event based exacerbations||Monitored monthly by phone after initial evaluation, assessed symptom based and event based exacerbations|
|2008||Jennings et al. (2009), The Association Between Depressive Symptoms and Acute
Exacerbations of COPD
|United States||Measure the depressive symptoms in
outpatients with stable COPD and then prospectively
evaluate the frequency of and risk for exacerbations during
the next year.
|67.1 ± 9.2||Retrospective Cohort Study
1 year study
|SF-36, BDI, MH||Strong correlation between depressive symptoms and increased rate of COPD exacerbations. Depressed patient had a higher number of exacerbations in the 1 year interval of the study||Smoking an independent risk factor for exacerbations of COPD and a causal relationship between smoking and depression.|
|2009||C. Laurin et al. (2009), Psychosomatic Medicine, COPD Patients with Psychiatric Disorders are a Greater Risk of Exacerbation||Canada||Assess the extent to which psychiatric disorders and risk and frequency of COPD exacerbation||66±8||(I),(SS),Prospective followed for about 2yrs, N=116, outpatient convenience sample, followed monthly to collect information regarding exacerbations||ADIS||Pt with psychiatric disorders exhibited significantly higher annual rate of exacerbations, more frequent and increased risk of exacerbation, focused primarily on patients treated in an outpatient setting||19 patients died during follow-up period, including 17 from COPD, average patient had 6.2 exacerbations/yr|
|2013||Atlantis et al. (2013), Bidirectional Associations Between Clinically Relevant Depression or Anxiety and COPD||Aim to determine depression or anxiety predicts COPD outcomes, depression or anxiety comorbidity predicts mortality, COPD predicts new depression or anxiety events to information guidelines and practice||42-72||Systematic Review and Meta-analysis. Searched electronic databases before 2012. Longitudinal studies in the adult population reporting the association between clinically relevant depression or anxiety performing statistical analysis||HADS, DSM-IV, BDI, PDA, GHQ, ESAS. MH||Confirm that depression or anxiety confers an increased risk of COPD outcomes and possibly death. COPD increases risk of developing depression. Pt with COPD and anxiety or depression had a 31% increased risk of exacerbation. COPD and Depression 83% Increased risk of mortality||Limited number of high quality studies.|
|2017||Montserrat-Capdevila et al. (2017), Lung, Overview of the Impact of Depression and Anxiety in COPD||Spain||Determine if the presence of anxiety and depression is associated with greater risk of frequent exacerbations||69.5±12||Prospective Cohort N=512 followed for 2 years Exacerbation defined as event that required abx, systemic corticortoids or hospitalization
Prevalence of depression at beginning og study 15.6%
|HADS||Anxiety/Depression strongly associated with moderate/severe frequent exacerbations OR=2.28
Anxiety/Depression doubled the risk of frequent exacerbation in the 2 yr study
|Being overweight also correlated with exacerbations OR=2.78
Anxiety and Depression associated with activation of hypothalamic-pituitary adrenal Axis causing an increase in systemic inflammatory response, weakening the immune response
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