- Original research article
A pulmonary rehabilitation program reduces levels of anxiety and depression inCOPD patients
Multidisciplinary Respiratory Medicinevolume 8, Article number: 41 (2013)
The presence of anxiety and depressive symptoms in COPD patients has beenacknowledged for many years. The preponderance of recent studies supportsthe utility of pulmonary rehabilitation programs to reduce the levels ofdepression and anxiety in these patients. The aim of this study is toinvestigate possible changes in levels of anxiety and depression amongpatients enrolled in a pulmonary rehabilitation program, along with the roleof disease severity in these changes.
In 101 COPD patients, who attended a pulmonary rehabilitation program, levelsof trait anxiety (STAI) and depressive symptoms (BDI) were assessed at thebeginning and at the end of the program. Age, sex, level of education inyears and stage of disease severity were recorded.
Our study included 80 male and 21 female patients. Mean age and meaneducation level were 64.1 ± 8.1 and11.3 ± 4.1 years, respectively. Regarding COPDstaging, 11 patients suffered from mild, 16 from moderate, 47 from severeand 27 from very severe COPD. Significant decreases in anxiety (from 39.7 to34.0, p < 0.001) and depression rates (from 10.7 to 6.3,p < 0.001) were observed. A statistically significantreduction in anxiety and depression was revealed (p < 0.05)atall stages of COPD.
Pulmonary rehabilitation programs should be offered to all COPD patientsirrespective of disease severity, since they all lead to improvement inanxiety and depressive symptoms.
Over the last decades, therapeutic evolution in healthcare,in conjunction with anincrease in average life expectancy, resulted in a significant and gradualdiminution in medical emergencies but simultaneously gave rise to chronicprogressive and debilitating diseases.
Gradual reintegration of the chronically suffering patients in family, social andprofessional environment is nowadays a challenge for the therapeutic team. Socialintegration is continuously threatened by a constellation of factors concerning thenature of the disease and by the psychosocial parameters implicating the dynamictask of adjustment mechanisms that constitute the subjective experience of theillness.
It is well known that Chronic Obstructive Pulmonary Disease (COPD) is a disease withpsychological comorbidities. Several studies have suggested that the prevalence ofanxiety and depression among patients with COPD is substantially greater thanlifetime rates in the general population and higher than in patients with otherpulmonary diseases such as bronchial asthma and tuberculosis , or other chronic diseases such as chronic heart failure . International prevalence rates of clinical depression in COPD patientsrise above 30% and sometimes above 50% , whereas corresponding rates in the background population is around 6-8% . Studies in Greece also report high prevalence rates of depression inCOPD patients, often above 42% . Moreover, studies indicate rates of anxiety varying from 10% to 19% , which is higher than the prevalence rate of 15% mentioned in the generalpopulation . Additionally, one out of two patients with COPD disease appears tosuffer from general psychopathological symptoms .
Recent studies show a reduction in anxiety and depression symptoms among patientswith COPD that are enrolled in pulmonary rehabilitation programs [7–9]; nevertheless some authors believe that further studies are needed . Several studies have pointed out that the degree of psychologicalimprovement brought about by the program depends on disease severity stage. Thesestudies mostly deal with severe COPD (usually leaving out stage I disease) [11, 12].
The aim of this study is to investigate the change in anxiety and depressive symptomsamong patients with COPD disease who attended a pulmonary rehabilitation program,along with the effect of disease severity on this change. Specifically, we assessedwhether the rehabilitation program alters anxiety and depression in patients withCOPD, and if this change depends on disease stage, severity and gender.
The study lasted four years and involved all patients with COPD who attended apulmonary rehabilitation program and met the criteria for inclusion in thestudy. All interested patients with COPD (for whom there was no contraindicationsuch as angina pectoris, myocardial infarction, severe pulmonary hypertension,congestive heart failure, labile diabetes, inability to exercise due toorthopedic or other reasons, dementia or severe hypoxia caused by exercise andcorrected by O2 administration) were admitted to this rehabilitationprogram . The sample consisted of 101 COPD patients, 80 males and 21 females,who completed a three months program. Inclusion criteria were the following: ageless than 80 years, without other chronic comorbid medical conditions(cardiovascular diseases, major psychiatric disorders, etc.) and absence ofacute exacerbation of COPD during the last two months before starting theprogram. We excluded patients who did not meet the inclusion criteria(n = 12) as well as those who did not complete the rehabilitationprogram (n = 43).
In order to determine COPD severity of our sample, a spirometric evaluationbefore and after bronchodilation(200 μg salbutamol) was performed. Wefollowed the Global Initiative for Chronic Obstructive Lung Disease (GOLD)diagnostic criteria, which classifies COPD severity [in relation to forcedexpiratory volume in 1 second (FEV1)/forced vital capacity (FVC)ratio (FEV1%) - percentage of predicted] into four stages: stage I(mild COPD): FEV1 > 80% predicted; stage II (moderateCOPD): FEV1 50% to 80% of predicted; stage III (severe COPD):FEV1 30% to 50% of predicted; and stage IV (very severe COPD):FEV1 < 30% of predicted . The spirometric evaluation of each patient was performed a few daysbefore he/she started the rehabilitation program.
Depression was assessed with the Beck Depression Inventory (BDI) , which is widely used, and has been standardized  and used in the Greek population previously . The BDI includes 21 items graded from 0 to 3. The inner coherencereliability is high and the re-test reliability ranges from 0.48 to 0.86 forclinical groups and 0.60 to 0.90 for non-clinical population. Its validity inrelation to an external criterion for depression, such as clinical diagnosis, isconsidered to be satisfactory. Anxiety was assessed with the SpielbergerState-Trait Anxiety Inventory (SSTAI) , one of the well-known and broadly used anxiety rating scales. Theinventory consists of 40 items, each one graded from 1 to 4. The SSTAIdifferentiates anxiety to (a) anxiety caused by a specific condition (statesubscale), and (b) anxiety as a more permanent characteristic of the personality(trait subscale). This second (trait) subscale was used in our study protocol.The SSTAI is considered as having a high inner coherence reliability andvalidity compared to clinical diagnosis. Also it has been standardized  and widely used in studies in the Greek population previously . Participants replied to the questionnaires in two phases, atbaseline and at discharge from the pulmonary rehabilitation program.
Pulmonary rehabilitation program
Patients of our study followed a pulmonary rehabilitation program for a period ofthree months, with three sessions per week, each lasting 50 minutes. Theprogram included respiratory physiotherapy, respiratory muscle training, aerobicexercise on a bicycle ergometer and on a treadmill and strengthening of musclegroups. The exercise was performed with oxygen supplementation whilesimultaneously recording heart rate and hemoglobin saturation. The minimum andmaximum number of sessions per patient was 34 and 39, respectively, with anaverage of 37 per patient.
The statistical program used was SPSS 16. The statistical analysis was performedusing x2 test, paired t-test, ANOVA, sample t-test,Pearson correlation and stepwise multiple regression. For regression models, anempirical approach was used after correlation analysis. Statistical significancewas set at p < 0.05.
The hospital ethics committee approved the study and all participants providedwritten informed consent. No financial support was necessary.
The demographic characteristics of our patients and their spirometric values aresummarized in Table 1. There were no differencesbetween genders regarding age, years of education and FEV1 percentageof predicted (t-test p > 0.05). With regard to theseverity of COPD according to GOLD classification, the number of patients withsevere COPD disease (47 patients, 46.5% of the total sample) was significantlyhigher than that of other subgroups (x2 p < 0.01, Table 1).
Changes in anxiety and depression
Mean depression and anxiety scores were significantly lower at discharge comparedto baseline for all our patients (paired t-testp < 0.05, Table 2). Same findings wererevealed for all subgroups (according to staging of COPD disease) of patientsand no statistical difference was identified when checking for mean individualchanges in depression and anxiety scores among all different disease severitysubgroups (ANOVA p > 0.05).
Mean BDI score, at baseline, for the total of our sample was 10.7, which issignificantly (sample t-test p < 0.05) higher than thecorresponding mean score (5.86)  in the general population. At discharge from the program, mean BDIscore was 6.33, not statistically different from the corresponding mean score inthe general population (sample t-test p > 0.05). Therate of patients who had depressive symptoms (BDI > 9)  at baseline was 47.5% (48 patients, Table 3) whereas at discharge it became 14.9% (15 patients,Table 3), which was a statistically significantreduction (x2 p <0.05).
Changes in anxiety and depression per gender
Regarding anxiety scores our observations indicated that mean scores at baselinewere higher than the corresponding scores in the general population.Specifically, female patients of our sample had a mean STAI score of 42.62(versus 37.47  in the general female population, sample t-testp < 0.01), while men had an average of 38.87 (versus 34.54  in the general male population, sample t -test p <0.01). Atdischarge our study indicated reduced mean STAI scores for both female (36.29)and male patients (33.4). These scores were not statistically different from thecorresponding mean scores in the general population (sample t-testp > 0.05). The rate of female patients who had clinicallysignificant anxiety symptoms (STAI > 45) at baseline was 47.6%and was reduced to 19% at discharge (x2 p < 0.05). Regarding male patients of our sample,25% of them had clinically significant anxiety symptoms(STAI > 43) at baseline and the percentage was reduced to 12.5%at discharge (x2 p < 0.05).
A significant positive correlation was observed between anxiety and depressionscores both at baseline and at discharge from the program (Pearson correlationp < 0.01, Table 4).
A significant positive correlation was also observed between first and lastmeasuring for both anxiety and depression (Pearson correlationp < 0.01, Table 3), but no correlationwas found between FEV1% of predicted and anxiety – depressionscores (Pearson correlation p > 0.05, Table 4).
More in detail, we implemented stepwise multiple regression analysis usingvariation in depression as the dependent variable and controlling for gender,age, FEV1%, years of education and variation in anxiety (independentvariables). Gender, age, years of education and FEV1% were notinvolved in the variance of the dependent variable whereas variation in anxietyinterpreted 34.3% of variation in depression (f 1.97 = 50.62, p<0.01). Considering anxiety variation as the dependent variable and gender,age, years of education, FEV1% as independent variables the resultswere not different, since variation in anxiety scores was independent of gender,age and FEV1%, whereas variation in depression interpreted 34.3% ofvariation in anxiety (f 1.97 = 50.62, p <0. 01).
Summarizing the results of this study, we have shown that a rehabilitation programcan reduce the high levels of anxiety and depression in patients with COPD.Improvement occurs for patients in all disease stages (with no statisticallysignificant differences among them), irrespective of gender. This improvement is notdependent on disease stage, gender, age or years of education. Spirometry showed nocorrelation with either anxiety or depression in the course of the program andanxiety and depression were not correlated with the severity of COPD”.
Drug treatment encounters serious problems. Benzodiazepines may cause respiratorydepression and should be avoided . In addition, beta-blockers are contraindicated in these patients,despite their anxiolytic action, because of the potential risk ofbronchoconstriction . Atypical antipsychotics in very small doses can alleviate anxietysymptoms in these patients, but they should be used cautiously because of possibleneurological and cardiovascular side effects . In other studies SSRIs have been used (first-line drugs for themanagement of depression) [26–30]. Sertraline [28, 29], fluoxetine [26, 31] citalopram  and paroxetine  may improve quality of life, however it is noted that patients with COPDand psychiatric comorbidity are reluctant to take additional medications [26, 33].
Both individual and group therapy are useful for the treatment of patients with COPD . The comparison of individual and group intervention usually favors thelatter [35–41]. Group therapy is a financially attractive treatment approach thatrequires few therapists to treat more patients. Furthermore it seems that grouptherapy offers valuable treatment opportunities, which may be due to recognition ofshared experiences and emotions among its members in a situation resembling the realworld more accurately .
It is very likely that improvement of psychological symptoms in rehabilitationprograms is associated with both psychological, and biological parameters (which areclosely coupled with the effects of exercise and respiratory physiotherapy).
Biological mechanisms associated with exercise activity, including changes in centralmonoamine function [36–40], enhanced hypothalamic- pituitary- adrenal axis regulation, increasedrelease of endogenous opioids [42–49] and reduced systemic inflammation [49, 50], may affect depression and anxiety among patients undergoing PR. Inaddition, behavioral mechanisms [51–56] associated with exercise activity as active distraction from worryingthought patterns (rumination), increase in self- efficacy by providing patients witha meaningful mastery experience, provision of daily pleasant events and regularsocial contact and support, operate synergistically to produce reductions ofsymptoms.
The fact that patients participate in a pulmonary rehabilitation program, which, withthe necessary modifications, works in a way that refers to the functioning of groupsformed by people sharing common characteristics , acts therapeutically. Moreover, it is well knownthat the sense ofbelonging to a group is often beneficial, as it provides the opportunity forparticipants to trigger interactions and through this process to identify elementsof personal experience among others, and to process them in a healthier way .
The results of this study are consistent with reports of strong evidence ofpsychological/psychiatric benefits of pulmonary rehabilitation [58–61], (such as improved mood and anxiety) in patients with COPD [62, 63]. This study is in accordance with previous findings indicating thatpatients with less favorable psychological conditions may also benefit from arehabilitation program .
An additional finding is that the effectiveness of a pulmonary rehabilitation programin reducing stress and depressive symptoms experienced by patients with COPD, isundeniable, regardless of disease stage, patients’ gender, age or educationlevel.
Furthermore, this study is in agreement with findings of other related works [29, 30] that reported anxiety and depression as being the major comorbidityproblem in patients with COPD. However, the prevalence of comorbidity seems to varywidely among different researchers [25, 65–67]. The acceptance of common assessment tools for stress and depression inpatients with COPD could mitigate the problem.
The fact that the predicted FEV1% and severity of COPD showed nocorrelation with anxiety or depression has been observed in other studies [6, 68]. These observations are consistent with the hypothesis that the predictedFEV1% does not reflect all aspects of the disease . It is likely that patients interpret disease seriousness subjectively,which contributes to the development of the levels of anxiety and depressivesymptoms.
Limitations of the study
The purpose of this study was to assess whether a brief three monthrehabilitation program can improve levels of anxiety and depression in patientswith COPD without being able to answerbut only to speculate on the reasons forthis improvement. Subsequent studies should focus on exploring the causes of theimprovement.
This was a short-term before-and-after design study (which is most useful indelineating immediate effects of short-term programs). Although it might be moreuseful in COPD patients to assess longer-term repercussions of therehabilitation program this was beyond the scope of this study (after all over alonger time period of time conditions may change and obscure any intervention'seffects by threatening the study's internal validity). The fact that the numberof men was unequal to that of women may actually underestimate baseline anxietyand depression scores, since women tend to have higher levels of both, but sucha choice would have eliminated the representativeness of the sample (women withCOPD, despite a steady increase in number, still remain fewer than men). Animportant problem in the study is that a substantial number of patients havechosen to discontinue the rehabilitation program and a subsequent study shouldexamine whether psychological factors are involved in patients attrition.Understanding the problem should not aim at excluding patients with COPD fromrehabilitation programs, but to create individualized interventions both beforeand during rehabilitation.
Our study supports that pulmonary rehabilitation programs should be offered to allCOPD patients regardless of disease severity, since they all get improvements inanxiety and depressive symptoms. Further research would be useful to confirm thesefindings and to focus on the possibilities of intervention and rehabilitation inpatients with mild COPD.
Moussas G, Tselebis A, Karkanias A, Stamouli D, Ilias I, Bratis D, Vassila-Demi K: A comparative study of anxiety and depression in patients with bronchialasthma, chronic obstructive pulmonary disease and tuberculosis in a generalhospital of chest diseases. Ann Gen Psychiatry. 2008, 7: 7-10.1186/1744-859X-7-7.
Yohannes AM, Willgoss TG, Baldwin RC, Connolly MJ: Depression and anxiety in chronic heart failure and chronic obstructivepulmonary disease: prevalence, relevance, clinical implications andmanagement principles. Int J Geriatr Psychiatry. 2010, 25: 1209-1221. 10.1002/gps.2463.
Maurer J, Rebbapragada V, Borson S, Goldstein R, Kunik ME, Yohannes AM, Hanania NA, ACCP Workshop Panel on Anxiety and Depression in COPD: Anxiety and depression in COPD: current understanding, unanswered questions,and research needs. Chest. 2008, 134 suppl: 43S-56S.
Wells KB, Golding J, Burnan MA: Psychiatric disorder in a sample of the general population with and withoutchronic medical conditions. Am J Psychiatry. 1998, 145: 976-979.
Tselebis A, Gournas G, Tzitzanidou G, Panagiotou A, Ilias I: Anxiety and depression in Greek nursing and medical personnel. Psychol Rep. 2006, 99: 93-96.
Tselebis A, Bratis D, Kosmas E, Harikiopoulou M, Theodorakopoulou E, Dumitru S, Moussas G, Karkanias A, Ilias I, Siafakas N, Vgontzas A, Tzanakis N: Psychological symptom patterns and vital exhaustion in outpatients withchronic obstructive pulmonary disease. Ann Gen Psychiatry. 2011, 10: 32-10.1186/1744-859X-10-32.
Emery CF, Schein RL, Hauck ER, MacIntyre NR: Psychosocial and cognitive outcomes of a randomized trial of exercise amongpatients with chronic obstructive pulmonary disease. Health Psychol. 1998, 17: 232-240.
Griffiths TL, Burr ML, Campbell IA, Lewis-Jenkins V, Mullins J, Shiels K, Turner-Lawlor PJ, Payne N, Newcombe RG, Ionescu AA, Thomas J, Tunbridge J: Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: arandomised controlled trial. Lancet. 2000, 355: 362-368. 10.1016/S0140-6736(99)07042-7.
Guell R, Resqueti V, Sangenis M, Morante F, Martorell B, Casan P, Guyatt GH: Impact of pulmonary rehabilitation on psychosocial morbidity in patients withsevere COPD. Chest. 2006, 129: 899-904. 10.1378/chest.129.4.899.
Ries AL, Bauldoff GS, Carlin BW, Casaburi R, Emery CF, Mahler DA, Make B, Rochester CL, Zuwallack R, Herrerias C: Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based Clinical PracticeGuidelines. Chest. 2007, 131 (5 Suppl): 4S-42S.
Güell R, Resqueti V, Sangenis M, Morante F, Martorell B, Casan P, Guyatt GH: Impact of pulmonary rehabilitation on psychosocial morbidity in patients withsevere COPD. Chest. 2006, 129: 899-904. 10.1378/chest.129.4.899.
Withers NJ, Rudkin ST, White RJ: Anxiety and depression in severe chronic obstructive pulmonary disease: theeffects ofpulmonary rehabilitation. J Cardiopulm Rehabil. 1999, 19: 362-365. 10.1097/00008483-199911000-00007.
Hui KP, Hewitt AB: A simple pulmonary rehabilitation program improves health outcomes andreduces hospital utilization in patients with COPD. Chest. 2003, 124: 94-97. 10.1378/chest.124.1.94.
Global Initiative for Chronic Obstructive Lung Disease: Global Strategy for the Diagnosis, Management, and Prevention of ChronicObstructive Pulmonary Disease (GOLD).http://www.goldcopd.org,
Beck AT, Steer RA: Manual for the Revised Beck Depression Inventory. 1987, San Antonio, TX: Psychological Corporation
Donias S, Demertzis I: Validation of the Beck depression inventory. Proceedings of the 10th Hellenic Congress of Neurology and Psychiatry:1983. Edited by: Varfis G. 1983, Thessaloniki, Greece: University Studio Press, 486-492.
Tselebis A, Moulou A, Ilias I: Burnout versus depression and sense of coherence: A study in Greek nursingstaff. Nurs Health Sci. 2001, 3: 69-71. 10.1046/j.1442-2018.2001.00074.x.
Spielberger GD, Gorush RL, Lusshene RE: The State-Trait Anxiety Inventory. 1970, Palo Alto, CA: Consulting Psychologists Press
Liakos A, Giannitsi S: The validity of the Greek modification of the Spielberger anxiety scale. Encephalos. 1984, 21: 71-76.
Tselebis A, Papaleftheris E, Balis E, Theotoka I, Ilias I: Smoking related to anxiety and depression in Greek medical staff. Psychol Rep. 2003, 92: 529-532. 10.2466/pr0.2003.92.2.529.
Di Marco F, Verga M, Reggente M, Maria Casanova F, Santus P, Blasi F, Allegra L, Centanni S: Anxiety and depression in COPD patients: the roles of gender and diseaseseverity. Respir Med. 2006, 100: 1767-1774. 10.1016/j.rmed.2006.01.026.
Voekel M, Voelkel NF, MacNee W: Chronic Obstructive Lung Diseases 2. Psychosocial aspects of ChronicObstructive Pulmonary Disease. 2008, BC Decker Inc: City,
Man GCW, Hsu K, Spoule BJ: Effect of alprazolam on exercise and dyspnea in patients with chronicobstructive pulmonary disease. Chest. 1986, 90: 832-836. 10.1378/chest.90.6.832.
Cantor L, Jacobson R: COPD: How to manage comorbid depression and anxiety. J Fam Pract. 2003, 2: 11-
Mikkelsen RL, Middelboe T, Pisinger C, Stage KB: Anxiety and depression in patients with chronic obstructive pulmonary disease(COPD). A review. Nord J Psychiatry. 2004, 58: 65-70. 10.1080/08039480310000824.
Yohannes AM, Connolly MJ, Baldwin RC: A feasibility study of antidepressant drug therapy in depressed elderlypatients with chronic obstructive pulmonary disease. Int J Geriatr Psychiatry. 2001, 16: 451-454. 10.1002/gps.461.
Eiser N, Harte R, Spiros K: Effect of treating depression on quality-of-life and exercise tolerance insevere COPD. COPD. 2005, 2: 233-241. 10.1081/COPD-57596.
Papp LA, Weiss JR, Greenberg HE, Rifkin A, Scharf SM, Gorman JM, Klein DF: Sertraline for chronic obstructive pulmonary disease and comorbid anxiety andmood disorders. Am J Psychiatry. 1995, 152: 1531-
Smoller JW, Pollack MH, Systrom D, Kradin RL: Sertraline effects on dyspnea in patients with obstructive airwaysdisease. Psychosomatics. 1998, 39: 24-29. 10.1016/S0033-3182(98)71377-5.
Lacasse Y, Beaudoin L, Rousseau L, Maltais F: Randomized trial of paroxetine in end-stage COPD. Monaldi Arch Chest Dis. 2004, 61: 140-147.
Evans M, Hammond M, Wilson K, Lye M, Copeland J: Placebo controlled treatment trial of depression in elderly physically illpatients. Int J Geriatr Psychiatry. 1997, 12: 817-824. 10.1002/(SICI)1099-1166(199708)12:8<817::AID-GPS645>3.0.CO;2-4.
Silvertooth EJ, Doraiswamy PM, Clary GL, Babyak MA, Wilkerson N, Hellegars C, Palmer SM: Citalopram and quality of life in lung transplant recipients. Psychosomatics. 2004, 45: 271-272. 10.1176/appi.psy.45.3.271.
Yohannes AM, Connolly MJ: Do antidepressants work in patients with chronic obstructive pulmonarydisease with comorbid depression?. Expert Rev Respir Med. 2011, 5 (6): 727-729. 10.1586/ers.11.70.
Post L, Collins C: The poorly coping COPD patient: a psychotherapeutic perspective. Int J Psychiatry Med. 1981–1982, 11 (2): 173-182. 10.2190/VUVV-2RQV-AG30-DPL1.
Kunik ME, Braun U, Stanley MA, Wristers K, Molinari V, Stoebner D, Orengo CA: One session cognitive behavioural therapy for elderly patients with chronicobstructive pulmonary disease. Psychol Med. 2001, 31: 717-723.
Eiser N, West C, Evans S, Jeffers A, Quirk F: Effects of psychotherapy in moderately severe COPD: a pilot study. Eur Respir J. 1997, 10: 1581-1584. 10.1183/09031936.97.10071581.
de Godoy DV, de Godoy RF: A randomized controlled trial of the effect of psychotherapy on anxiety anddepression in chronic obstructive pulmonary disease. Arch Phys Med Rehabil. 2003, 84: 1154-1157. 10.1016/S0003-9993(03)00239-9.
Kunik ME, Veazey C, Cully JA, Souchek J, Graham DP, Hopko D, Carter R, Sharafkhaneh A, Goepfert EJ, Wray N, Stanley MA: COPD education and cognitive behavioral therapy group treatment forclinically significant symptoms of depression and anxiety in COPD patients;a randomized controlled trial. Psychol Med. 2008, 38: 385-396.
Brook D: Exploring Group Therapies. Psychiatric Times. 2003,http://www.psychiatrictimes.com/articles/exploring-group-therapies,
Dishman RK: Brain monoamines, exercise, and behavioral stress: animal models. Med Sci Sports Exerc. 1997, 29 (1): 63-74. 10.1097/00005768-199701000-00010.
Ransford CP: A role for amines in the antidepressant effect of exercise: a review. Med Sci Sports Exerc. 1982, 14 (1): 1-10. 10.1249/00005768-198201000-00001.
Dunn AL, Reigle TG, Youngstedt SD, Armstrong RB, Dishman RK: Brain norepinephrine and metabolites after treadmill training and wheelrunning in rats. Med Sci Sports Exerc. 1996, 28 (2): 204-209. 10.1097/00005768-199602000-00008.
Jacobs BL: Serotonin, motor activity and depression-related disorders. Am Sci. 1994, 82: 456-463.
Chaouloff F: Effects of acute exercise on central serotonergic systems. Med Sci Sports Exerc. 1997, 29 (1): 58-62. 10.1097/00005768-199701000-00009.
Raglin JS, Morgan WP: Influence of exercise and quiet rest on state anxiety and blood pressure. Med Sci Sports Exerc. 1981, 19 (5): 456-463.
Carr DB, Bullen BA, Skrinar GS, Arnold MA, Rosenblatt M, Beitins IZ, Martin JB, McArthur JW: Physical conditioning facilitates the exercise-induced secretion ofbeta-endorphin and beta-lipotropin in women. N Engl J Med. 1981, 305 (10): 560-563. 10.1056/NEJM198109033051006.
Farrell PA, Gates WK, Maksud MG, Morgan WP: Increases in plasma beta endorphin/beta-lipotropinimmunoreactivity aftertreadmillrunning in humans. J Appl Physiol. 1982, 52 (5): 1245-1249.
Gambert SR, Hagen TC, Garthwaite TL: Exercise and the endogenous opioids. N Engl J Med. 1981, 305: 1590-1591.
Pitsavos C, Chrysohoou C, Panagiotakos DB, Skoumas J, Zeimbekis A, Kokkinos P, Stefanadis C, Toutouzas PK: Association of leisure-time physical activity on inflammation markers(C-reactive protein, white cell blood count, serum amyloid A, andfibrinogen) in healthy subjects (from the ATTICA study). Am J Cardiol. 2003, 91 (3): 368-370. 10.1016/S0002-9149(02)03175-2.
Church TS, Barlow CE, Earnest CP, Kampert JB, Priest EL, Blair SN: Associations between cardiorespiratory fitness and C-reactive protein inmen. Arterioscler Thomb Vasc Biol. 2002, 22 (11): 1869-1876. 10.1161/01.ATV.0000036611.77940.F8.
Morrow J, Nolen-Hoeksema S: Effects of response to depression on the remediation of depressive affect. J Pers Soc Psychol. 1990, 58 (3): 519-527.
Nolen-Hoeksema S, Morrow J: A prospective study of depression and posttraumatic stress symptoms after anatural disaster: the 1989 Loma Prieta earthquake. J Pers Soc Psychol. 1991, 61 (1): 115-121.
McAuley E, Jerome GJ, Marquez DX, Elavsky S, Blissmer B: Exercise self-efficacy in older adults: social, affective, and behavioralinfluences. Ann Behav Med. 2003, 25 (1): 1-7. 10.1207/S15324796ABM2501_01.
Craft LL: Exercise and clinical depression: examining two psychological mechanisms. Psychol Sport Exerc. 2003, 6: 151-171.
Lewinsohn PM, Gotlib IH: Behavioral theory and treatment of depression. Handbook of depression. Edited by: Beckham EE, Leber WR. 1995, New York: Guildford Press, 352-375. 2
Bartoholomew JB, Ciccolo JT: Exercise, depression, and cognition. Exercise and its mediating effects on cognition. Edited by: Spirduso WW, Poon LW, Chodzko-Zajko W. 2008, Champaign, IL: Human Kinetcs, 2
Tselebis A, Moussas G, Bratis D: Psychological intervention in a COPD rehabilitation programme [in ModernGreek]. Pneumonologika Themata. 2006, 21-23.
Lacasse Y, Maltais F, Goldstein RS: Pulmonary rehabilitation: an integral part of the long-term management ofCOPD. Swiss Med Wkly. 2004, 134 (41–42): 601-605.
Paz-Dıaz H, Montes de Oca M, Lopez JM, Celli BR: Pulmonary rehabilitation improves depression, anxiety, dyspnea and healthstatus in patients with COPD. Am J Phys Med Rehabil. 2006, 86 (1): 30-36.
Pantou I, Harikiopoulou M, Bratis D: European Respiratory Society, Annual Congress. The impact of rehabilitation-induced symptomatic, functional andpsychological outcomes on health-related quality of life. 2006,
Coventry PA, Bower P, Keyworth C, Kenning C, Knopp J, Garrett C, Hind D, Malpass A, Dickens C: The effect of complex interventions on depression and anxiety in chronicobstructive pulmonary disease: systematic review and meta-analysis. PLoS One. 2013, 8 (4): e60532-10.1371/journal.pone.0060532.
White RJ, Rudkin ST, Ashley J, Stevens VA, Burrows S, Pounsford JC, Cratchley G, Ambler NR: Outpatient pulmonary rehabilitation in severe chronic obstructive pulmonarydisease. J R Coll Physicians Lond. 1997, 31: 541-545.
Pantou I, Harikiopoulou M, Mpletsa M: European Respiratory Society, Annual Congress. Does the severity of chronic obstructive pulmonary disease reflect on theoutcomes of pulmonary rehabilitation?. 2007,
Trappenburg JC, Troosters T, Spruit MA, Vandebrouck N, Decramer M, Gosselink R: Psychosocial conditions do not affect short-term outcome of multidisciplinaryrehabilitation in chronic obstructive pulmonary disease. Arch Phys Med Rehabil. 2005, 86 (9): 1788-1792. 10.1016/j.apmr.2005.03.030.
Edmunds M, Scudder L: Examining the Relationships Between COPD and Anxiety and Depression. Heart Lung. 2009, 38: 34-47. 10.1016/j.hrtlng.2008.02.005.
Kunik ME, Roundy K, Veazey C, Souchek J, Richardson P, Wray NP, Stanley MA: Surprisingly high prevalence of anxiety and depression in chronic breathingdisorders. Chest. 2005, 127: 1205-1211. 10.1378/chest.127.4.1205.
Hill K, Geist R, Goldstein RS: Anxiety and depression in end-stage COPD. Eur Respir J. 2008, 31 (3): 667-677. 10.1183/09031936.00125707.
Tselebis A, Kosmas E, Bratis D, Moussas G, Karkanias A, Ilias I, Siafakas N, Vgontzas A, Tzanakis N: Prevalence of alexithymia and its association with anxiety and depression ina sample of Greek chronic obstructive pulmonary disease (COPD)outpatients. Ann Gen Psychiatry. 2010, 9: 16-10.1186/1744-859X-9-16.
Papaioannou AI, Loukides S, Gourgoulianis KI, Kostikas K: Global assessment of the COPD patient: Time to look beyond FEV1?. Respir Med. 2009, 103: 650-660. 10.1016/j.rmed.2009.01.001.
The authors declare that they have no competing interests.
AT conceived the experiment, designed the study, performed the psychologicalmeasures, collected data, carried out the statistical analysis and drafted thepaper; DB performed the psychological measures, carried out the statistical analysisand drafted the paper; AP and GM helped draft the paper; II carried out thestatistical analysis and helped draft the paper; EK performed the physical measuresand helped draft the paper; MH, ET and SD performed the physical measures; NS and AVsupervised the study; NT carried out the statistical analysis, helped draft thepaper and supervised the study. All authors read and approved the finalmanuscript.