Patients With COPD With Higher Levels of Anxiety Are More Physically Active

Transcription

1 CHEST Originl Reserh Ptients With COPD With Higher Levels of Anxiety Are More Physilly Ative Huong Q. Nguyen, PhD, RN ; Vinent S. Fn, MD, MPH ; Jerld Herting, PhD ; Jungeun Lee, MS ; Musett Fu, RN, MM ; Zijing Chen, BS ; Soo Borson, MD ; Ruth Kohen, MD ; Gustvo Mtute-Bello, MD ; Genevieve Pglilun, MD ; nd Sndr G. Adms, MD COPD Bkground: Physil tivity (PA) hs een found to e n exellent preditor of mortlity eyond trditionl mesures in COPD. We imed to determine the ssoition etween depression nd nxiety with elerometry-sed PA in ptients with COPD. Methods: We performed ross-setionl nlysis of seline dt from 148 stle ptients with COPD enrolled in n ongoing, longitudinl, oservtionl study. We mesured PA (totl dily step ount) with Stepwth Ativity Monitor over 7 dys, depression nd nxiety with the Hospitl Anxiety nd Depression Sles (HADSs), dyspne with the Shortness of Breth Questionnire, nd funtionl pity with the 6-min wlk test. Results: Inresed nxiety ws ssoited with higher levels of PA suh tht for every one-point inrese in the HADS-Anxiety sore there ws orresponding inrese of 288 step ounts per dy ( steps, P,.001), fter djusting for ll other vriles. Higher levels of depressive symptoms were ssoited with lower PA ( steps, P 5.02) only when nxiety ws in the model. The intertion term for nxiety nd depression pprohed signifine ( 5 26, P 5.10), suggesting tht higher levels of nxiety mitigte the negtive effets of depression on PA. Conlusions: The inresed PA ssoited with nxiety in COPD is, to our knowledge, novel finding. However, it is unler whether nxious ptients with COPD re more restless, nd use inresed psyhomotor tivity s oping mehnism, or whether those with COPD who push themselves to e more physilly tive experiene more nxiety symptoms. Future studies should evlute for nxiety nd PA to etter inform how to improve linil outomes. Tril Registry : Cliniltrils.gov; No.: NCT ; URL: CHEST 2013; 144(1): Arevitions: 6MWT 5 6-min wlk test; CASCADE 5 COPD Ativity: Serotonin Trnsporter, Cytokine, nd Depression Study; HADS 5 Hospitl Anxiety nd Depression Sle; HADS-A 5 Hospitl Anxiety nd Depression Sle-Anxiety; HADS-D 5 Hospitl Anxiety nd Depression Sle-Depression; PA 5 physil tivity; SAM 5 Stepwth 3 Ativity Monitor Epidemiologi studies sed on self-reported physil tivity (PA) show tht higher levels of tiv ity re ssoited with lower risk of inident COPD in smokers nd in ptients who lredy hve COPD, nd with lower risk of ute exertions, hospitl dmissions, nd mortlity. 1-3 A reent, 4-yer, prospetive study of ptients with COPD showed tht ojetively mesured PA ws the est preditor of ll-use mortlity ompred with rod rnge of other prognosti ftors, inluding irflow ostrution, exerise performne, rdiovsulr sttus, nutritionl nd musulr sttus, systemi inflmmtion, helth sttus, depressive symptoms, nd dyspne. Eh inrese of 1,845 steps per dy ws ssoited with 51% lower risk of deth. 4 Ojetive mesures of PA pture wht ptients tully do vs wht they report doing or re ple of doing during lortory test. 5 Findings from these studies undersore the ritil importne of PA in COPD nd the need to etter understnd how modifile ftors suh s psyhologi well-eing influene PA. The prevlene of mjor depression in ptients with moderte to severe COPD is pproximtely 40%. 6 Nerly 20% of ptients hd episodes of moderte to severe depression prior to their COPD dignosis. 7 Anxiety disorders, whih hve onsiderle overlp journl.pulitions.hestnet.org CHEST / 144 / 1 / JULY Downloded From: y Dvid Kinnison on 07/08/2013

2 with depressive symptoms, re lso prevlent in ptients with COPD, with estimtes rnging from 10% to 36%. 6,8,9 Ptients with higher levels of depressive symptoms report worse physil funtioning Similrly, studies tht hve mesured funtionl pity using lortory exerise tests (eg, 6-min wlk test [6MWT], symptom-limited yle, or tredmill) hve found tht depression is ssoited with worse funtionl pity. 12,15-17 In ontrst to these erlier reports tht mesured funtionl pity, more reent, ross-setionl study from Germny of 170 ptients with COPD found tht depressive symptoms were not ssoited with worse PA s mesured y elerometry fter djustment for numer of relevnt linil orreltes. 18 Unfortuntely, nxiety ws not mesured in this study y Wtz nd ollegues, 18 thus, we know very little out the reltionship etween nxiety (with or without depression) nd the level of PA in the dily lives of ptients with COPD. The viious dyspne-nxiety-deonditioning spirl hs long een knowledged for suset of ptients with COPD, yet the presumption tht nxiety ontriutes to inresed dyspne with onsequent redutions in PA hs not een formlly tested. 19,20 The reltionship etween nxiety in ptients with COPD nd funtionl pity remins unler. A similr numer of studies hve found tht higher nxiety levels re ssoited with worse funtionl pity, nd similr numer of studies report no reltionship etween nxiety nd funtionl pity We re not wre of ny pulished report on the reltionship etween nxiety nd ojetively onfirmed PA during the dily lives of ptients with COPD. Sine reent findings suggest tht omorid nxiety is ssoited with greter risk of mortlity for ptients with COPD, 27 more ttention should e direted t understnding nxiety in reltion to self-re ehviors Mnusript reeived August 1, 2012; revision epted Deemer 4, Affilitions : From the Deprtment of Reserh nd Evlution (Dr Nguyen), Kiser Permnente Southern Cliforni, Psden, CA; University of Wshington & Puget Sound Veterns Administrtion (Dr Fn), Settle, WA; University of Wshington (Drs Herting, Borson, Kohen, Mtute-Bello, nd Pglilun nd Mss Lee, Fu, nd Chen), Settle, WA; nd the University of Texs Helth Siene Center t Sn Antonio nd The South Texs Veterns Helth Cre System (Dr Adms), Sn Antonio, TX. Funding /Support : This work ws supported in prt y grnts from the US Ntionl Institutes of Helth (NIH) Ntionl Hert, Lung, nd Blood Institute [5R01HL093146] nd the NIH Ntionl Center for Reserh Resoures [UL1RR025014]. Dr Fn hs funding through the Deprtment of Veterns Affirs. Correspondene to: Huong Nguyen, PhD, RN, Deprtment of Reserh nd Evlution, Kiser Permnente Southern Cliforni, 100 S Los Roles, Psden, CA 91101; e-mil: huong.q2.nguyen@ kp.org 2013 Amerin College of Chest Physiins. Reprodution of this rtile is prohiited without written permission from the Amerin College of Chest Physiins. See online for more detils. DOI: /hest nd linil outomes. Therefore, the purpose of this ross-setionl study ws to determine the ssoition etween depression nd nxiety with elerometrysed, free-living, multory PA in ptients with COPD. Study Design nd Settings Mterils nd Methods The COPD Ativity: Serotonin Trnsporter, Cytokine, nd Depression Study (CASCADE) is n ongoing, multisite, prospetive, oservtionl study of sujets with COPD who re eing followed for 2 yers to study the iologi uses nd funtionl onsequenes of depression. This mnusript is ross-setionl, desriptive nlysis of dt from 148 sujets olleted t entry to CASCADE. This study ws pproved y the respetive institutionl review ords t three linil sites: the University of Wshington, Settle (pprovl numer 37332); the VA Puget Sound Helth Cre System (pprovl numer 00240); nd the University of Texs Helth Siene Center t Sn Antonio/South Texs Veterns Helth Cre System (pprovl numer HSC H), nd ws registered with ClinilTrils.gov (NCT ). 28 Prtiipnts We reruited prtiipnts from queries of medil reords nd pulmonry funtion tests, hest linis from the three medil enters, reserh dtse mintined y the investigtors, pulmonry rehilittion progrms, etter-rethers groups, ommunity pulmonry prties, dvertisements, the CASCADE study wesite, nd other referrls. The inlusion riteri were s follows: (1) dignosis of COPD onfirmed y the following: postronhodiltor /FVC, 70%, moderte to very severe disese s defined y the GOLD (Glol Inititive for Chroni Ostrutive Lung Disese) riteri (, 80%), ge 40 yers, nd signifint history of urrent or pst igrette smoking (. 10 pk-yers); (2) stle disese with no ute exertions of COPD in the pst 4 weeks; nd (3) ility to spek, red, nd write English. We exluded ptients with ny of the following onditions: other hroni ostrutive lung diseses suh s sthm, ronhietsis, nd ysti firosis; idiopthi pulmonry firosis; unompensted ongestive hert filure (left-sided ventriulr dysfuntion); primry pulmonry vsulr disese; non-copd-relted hroni inflmmtory diseses; infetious disese; utoimmune disese; lung ner or metstti ner; hroni renl filure requiring dilysis; hroni unompensted liver disese; HIV/AIDS; hroni ntiioti use or ongoing infetion; hroni orl prednisone use; ipolr disese; psyhoti disorders; nd ny dementi. Proedures Informed onsent ws otined prior to lini ssessments, whih inluded preronhodiltor nd postronhodiltor spirometry, 6MWT, nd ompletion of questionnires. Prtiipnts were sked to wer n tivity monitor for 7 dys, eginning fter their initil lini visit. Two dys fter this lini visit, depression nd nxiety ssessment ws ompleted vi telephone y trined mentl-helth professionl. Mesures Demogrphi dt inluded self-reported ge, sex, edution, inome, living sitution, nd mritl sttus. Disese severity inluded self-report of hroni onditions (Chrlson omoridity index), 146 Originl Reserh Downloded From: y Dvid Kinnison on 07/08/2013

3 oxygen supplementtion, nd spirometry, whih ws performed ording to Amerin Thori Soiety stndrds 29 using n EsyOne spirometer (ndd Medil Tehnologies In ). Postronhodiltor vlues were used. Funtionl pity ws ssessed using the 6MWT ording to the Amerin Thori Soiety guidelines. 30 Dyspne ws mesured with the Shortness of Breth Questionnire. 31 Psyhologi well-eing ws mesured with the Hospitl Anxiety nd Depression Sle (HADS). 13 A sore 8 on either sle indites linilly relevnt nxiety (HADS-A) or depression (HADS-D). PA ws mesured with Stepwth 3 Ativity Monitor (SAM) (OrthoCre Innovtions LLC) fstened ove the right nkle. The SAM is dul-xis elerometer linked to miroproessor sensor tht ontinuously reords git yles (strides); stride ounts re douled to represent steps. The SAM hs een vlidted for use in ptients with COPD 32 nd is highly urte in mesuring steps ross rnge of speeds ompred with other elerometers on the mrket Prtiipnts were sked to wer the SAM during wking hours for 7 dys. The SAM ws progrmmed to reord in 1-min epohs; vlid dy ws defined s hving 10 h (600 min) of monitor wer. Totl step-ount per dy ws the primry PA vrile. Ptients wore the elerometer for medin of 7 dys. Sesonlity ws lso onsidered in the nlysis sine PA hs een shown to vry y seson. 36,37 Dt Anlysis We used desriptive sttistis to desrie the smple nd used Person orreltions for the ivrite orreltions. We used independent t tests to ompre highly nxious nd depressed prtiipnts to those with low levels of depression nd nxiety (HADS-A nd HADS-D 8) on totl step ounts. We used multivrite liner regression models to exmine the reltionships etween depression nd nxiety with totl step ounts. We performed dignosti tests to ensure tht the models met the ssumptions for liner regression (eg, prtil orreltion plots, stndrdized residuls, DFITs sttistis, leverge, nd influene). We lso log trnsformed the outome vrile, step ounts; the model remined roust to outliers. All nlyses were onduted using SPSS, version 15.0 (IBM). A P vlue,.05 ws onsidered sttistilly signifint. Results Ptient Chrteristis Tle 1 inludes the summry of the demogrphi nd seline hrteristis of the 148 ptients inluded in the nlysis. The ohort (78% men) hd men % predited of 42% nd few omoridities. Overll, prtiipnts were reltively high funtioning nd hd reltively low depressive nd nxiety symptoms. Approximtely 32% nd 29% of ptients sored higher thn 8 points on the HADS-A nd HADS-D, respetively. Men SAM wer time did not differ etween sujets who hd high- or low-nxiety symptoms (874 min vs 899 min, P 5.29) Bivrite Undjusted Assoitions PA s mesured y totl step ount hd smll to moderte signifint orreltions ( r , P,.05) with ge, sex, disese severity ( % predited nd oxygen supplementtion), 6MWT, dyspne, nd nxiety Vriles Tle 1 Smple Chrteristis (N 5 148) ( Tle 2 ). PA ws not signifintly orrelted with depressive symptoms ( r ). Depression nd nxiety were highly orrelted ( r ) s expeted, ut neither ws orrelted with funtionl pity. Ptients with high levels of nxiety (HADS-A. 8) rued n verge of 1,681 more steps per dy ompred with ptients who hd low or no nxiety (men SD, 7,215 4,189 vs 5,534 3,358, P,.01). Multivrite Regression Models Results Soiodemogrphis Age, men (SD), y 66.5 (8.8) Femle sex 33 (22) Edution High shool or less 38 (26) Some ollege or more 110 (74) Inome, USD, 20,000/y 68 (47) 20,000/y 79 (53) Mritl sttus Prtnered 79 (53) Unprtnered 69 (47) Live lone 37 (25) BMI, men (SD), kg/m (6.4) Disese severity /FVC, men (SD) 0.44 (0.12) % predited, men (SD) 41.7 (15.7) O 2 supplementtion 59 (40) 5 y sine COPD dignosis 76 (51) Numer of omoridities, men (SD) 0.75 (0.91) Physil funtioning, men (SD) 6MWT, ft 1,059 (416) Totl steps/d 6,079 (3,718) Psyhologi well-eing, men (SD) HADS-D sore, (4.0) HADS-A sore, (4.1) Symptoms, men (SD) Shortness of Breth Questionnire sore, (17.7) Dt given s No. (%) unless otherwise indited. 6MWT 56-min wlk test; HADS 5 Hospitl Anxiety nd Depression Sle; HADS-A 5 Hospitl Anxiety nd Depression Sle-Anxiety; HADS-D 5 Hospitl Anxiety nd Depression Sle-Depression; O 2 5 oxygen; USD 5 US dollrs. Results from the six multivrite regression models prediting PA-totl steps per dy with disese severity, dyspne, funtionl pity, nd psyhologi welleing re summrized in Tle 3. Model 1, whih inluded ge, sex, irflow ostrution, nd oxygen use, explined 20% of the vrine in totl steps. Models 2 nd 3 showed tht dyspne nd funtionl pity were signifintly ssoited with PA, djusting for ll vriles from model 1. In Model 4, dyspne nd funtionl pity remined signifintly ssoited with PA, wheres depression ws not. In model 5, depression ws signifintly ssoited with worse PA journl.pulitions.hestnet.org CHEST / 144 / 1 / JULY Downloded From: y Dvid Kinnison on 07/08/2013

4 Tle 2 Bivrite Correltions (N 5 148) Vrile Totl Steps Age Sex FEV1 % Predited O2 Use 6MWT Dyspne HADS-D HADS-A Totl steps/d 1.00 Age Sex % predited O 2 use MWT Dyspne HADS-D HADS-A See Tle 1 legend for expnsion of revitions. P,.01. P,.05. P,.001. ( steps, P 5.02) nd nxiety ws onversely ssoited with higher levels of PA ( 5 288, P,.001) fter djusting for ll other vriles. In seprte model, we lso tested the intertion etween nxiety nd depression nd found positive oeffiient, leit not signifint t.05 ( 5 26, P 5.10), suggesting tht if ptient ws depressed, higher levels of nxiety would mitigte the negtive effets of depression on PA. Sine dyspne ould potentilly medite the reltionship etween nxiety nd PA, we tested for this effet in two wys. First, we removed dyspne from model 6 nd found tht the oeffiients were silly similr to model 5, suggesting tht dyspne did not medite the reltionship etween nxiety nd PA. Seond, nxiety did not hve signifint reltionship with dyspne ( P 5.22), nother generl riterion for Tle 3 Multivrite Regression Models Prediting Physil Ativity, Totl Steps per Dy (N 5 148) Unstndrdized Coeffiients Stndrdized Coeffiients Vrile SE P Vlue R 2 R 2 Model Age, per y ,.001 Mle sex % predited ,.001 O 2 use Model Dyspne, SOBQ ,.001 Model Dyspne, SOBQ MWT, ft ,.001 Model Dyspne, SOBQ MWT, ft ,.001 Depression, HADS-D Model Dyspne, SOBQ MWT, ft ,.001 Depression, HADS-D Anxiety, HADS-A ,.001 Model MWT, ft ,.001 Depression, HADS-D Anxiety, HADS-A R 2 5 hnge in R 2 ; SOBQ 5 Shortness of Breth Questionnire. See Tle 1 legend for expnsion of other revitions. For eh 1% hnge in. Models 2-5 inluded ge, sex, % predited, nd supplementl O 2 use. Dyspne exluded from model 6; ompring models 5 nd 6 provides test of medition to exmine whether dyspne medites the reltionship etween the nxiety nd physil tivity. 148 Originl Reserh Downloded From: y Dvid Kinnison on 07/08/2013

5 dyspne to e viewed s mediting ftor. The ddition of sesonlity did not hnge ny of the oeffiients for ll models nd thus the presented dt do not inlude sesons. Disussion A key novel finding of this study is tht nxiety ws signifintly nd independently ssoited with inresed multory PA in ptients with severe COPD, even fter djusting for relevnt ovrites inluding demogrphis, disese severity, funtionl pity, dyspne, nd depression. To our knowledge, this finding hs not een pulished elsewhere. We performed numer of dignosti tests to ensure tht the models met the ssumptions for liner regression, nd, thus, we elieve these findings re vlid nd not due to dt errors or rtifts. Also, the inresed PA in ptients with higher nxiety levels ws not due to inresed wer time, s ptients with high nd low levels of nxiety wore the devie for the sme durtion. We lso found tht depression ws ssoited with less PA only when we djusted for nxiety. The disovery tht for eh one-point inrese in nxiety sore on the HADS-A in these ptients with COPD, there ws orresponding inrese of 288 steps per dy surprised us. These findings re espeilly interesting, sine pulished dt suggest positive reltionship etween nxiety nd dyspne, 26,38 whih re presumed to er negtive onsequenes on PA in ptients with COPD. 39 Inresed dyspne nd low levels of nxiety were ssoited with deresed dily step ounts (dt not shown), ut found no indition of n intertion. In ddition, test for dyspne s meditor of the reltionship etween nxiety nd PA ws negtive, suggesting tht nxiety nd PA re diretly relted. Interestingly, our novel finding in ptients with COPD is supported y two smll studies of primtes nd dults with pni disorder. Vinot nd ollegues 40 found tht in nonhumn primtes, nxiety ws ssoited with greter spontneous loomotor tivity. A study y Skmoto nd ollegues 41 found tht smll smple of dults (14 women, two men) with pni disorder symptoms hd high loomotor tivity s mesured y wrist tigrphy. Thus, it is plusile tht the inresed spontneous psyhomotor tivity is ehviorl mnifesttion of the restlessness ssoited with inresed nxiety, oping mehnism, or tht ptients with high level of nxiety do not effetively leverge energy onservtion strtegies nd re ruing steps with nongol-direted multory tivities. It is lso possile tht ptients who re nxious nd hypervigilnt my see lung disese s something tht they n nd should onquer nd tht the inresed PA my reflet this effort to mintin high level of tivity t ll osts. The linil implitions for these oservtions re interesting euse nxiety s omorid disorder is ssoited with inresed mortlity, 27 while inresed PA is ssoited with lower mortlity 4 in ptients with COPD. Perhps mild levels of nxiety tht result in higher dily step ounts nd less sedentry time my e slurious 42 ; this onjeture would need to e onfirmed in future studies. The ssoitions mong PA, depression, nd use of supplementl oxygen lso deserve ttention. Similr to the study y Wtz nd ollegues, 18 we lso found tht depression ws not signifint preditor of PA. However, when we djusted for nxiety in the finl model, high level of depressive symptoms ws ssoited with worse PA. Depression nd nxiety pper to hve different effets on PA with nxiety, ttenuting the negtive impt of depression on totl step ounts. Our findings suggest tht future predition models of PA should inlude djustments for nxiety. Use of supplementl oxygen ws not ssoited with fewer totl-step ount in our study. This finding is somewht ontrry to typil ssumptions y liniins tht ptients who rry or roll their oxygen tnks re less likely to e physilly tive, ut is onsistent with one other pulished study. 43 Limittions Our findings my hve limited generlizility to other ptients with COPD who experiene omoridities tht hve n underlying inflmmtory proess, sine we exluded these individuls from the prent study. In ddition, ptients who were using prednisone hronilly were exluded. Alterntively, these exlusions my hve provided level of ontrol over other omoridities to isolte the effets of nxiety on PA. This ws ross-setionl nlysis, thus, it is not ler if inresed PA is ehviorl mnifesttion of nxiety or oping mehnism for nxiety, or if ptients who push to remin tive experiene more nxiety due to inresed dyspne with tivities. In ddition, it is possile tht we did not hve suffiient power in this study to detet n intertion etween inresed dyspne nd low levels of nxiety. Another limittion is tht our tivity monitor my hve lso ptured involuntry nonmultory tivity tht is typilly ssoited with highly nxious sttes. Our smple ws predominntly men, tended to hve higher funtioning, hd low men sores for nxiety nd depression, ws ommitted to longitudinl reserh study, nd thus my not e representtive of the lrger popultion of ptients with COPD. Future investigtions ould exmine hnge in nxiety stte nd its reltionship with PA. Additionl sptil-lotion dt (eg, GPS to tringulte with elerometer dt) will help estlish whether the inresed PA is ourring outdoors or indoors ssoited with tivities of dily living. journl.pulitions.hestnet.org CHEST / 144 / 1 / JULY Downloded From: y Dvid Kinnison on 07/08/2013

6 Conlusions We onlude tht nxiety is ssoited with inresed dily PA in seleted smple of ptients with COPD. It is unler whether ptients with COPD who hve higher levels of nxiety re more restless nd use inresed psyhomotor tivity s oping mehnism, or whether those with COPD who push themselves to e more physilly tive experiene more nxiety symptoms. The linil implitions of these oservtions re interesting euse nxiety s omorid disorder is ssoited with inresed mortlity in ptients with COPD, wheres inresed PA is ssoited with lower mortlity in tht group. Bsed on our results, future COPD studies should inlude ojetive mesures of PA nd systemti evlutions for nxiety to etter inform liniins out how to improve the mngement nd linil outomes of these ptients. Aknowledgments Author ontriutions: Dr Nguyen hd full ess to ll of the dt in the study nd tkes responsiility for the integrity of the dt nd the ury of the dt nlysis. Dr Nguyen: ontriuted to the study design, dt nlysis nd interprettion, nd preprtion of the mnusript nd served s prinipl uthor. Dr Fn: ontriuted to the study design, dt nlysis nd interprettion, nd preprtion of the mnusript. Dr Herting: ontriuted to the study design, dt nlysis nd interprettion, nd preprtion of the mnusript. Ms Lee: ontriuted to dt quisition, nlysis, nd interprettion nd preprtion of the mnusript. Ms Fu: ontriuted to dt quisition, nlysis, nd interprettion nd preprtion of the mnusript. Ms Chen: ontriuted to dt quisition, nlysis, nd interprettion nd preprtion of the mnusript. Dr Borson: ontriuted to the study design, dt interprettion, nd preprtion of the mnusript. Dr Kohen: ontriuted to the study design, dt interprettion, nd preprtion of the mnusript. Dr Mtute-Bello: ontriuted to the study design, dt interprettion, nd preprtion of the mnusript. Dr Pglilun: ontriuted to dt interprettion nd preprtion of the mnusript. Dr Adms: ontriuted to the study design, dt interprettion, nd preprtion of the mnusript. Finnil/nonfinnil dislosures: The uthors hve reported to CHEST the following onflits of interest: Dr Adms hs reeived reserh grnts from the Ntionl Institutes of Helth, Veterns Affirs Coopertive Studies Progrm; Byer AG; Boehringer Ingelheim GmBH; Centoor Bioteh In (now Jnssen Bioteh In); GlxoSmithKline pl; Novrtis AG; Pfizer, In; nd Shering- Plough Corp (now Merk & Co In); nd hs reeived honorri for speking t ontinuing edution progrms (unrestrited grnts for ontinuing edution) from the following: AstrZene Phrmeutils pl; Byer AG; Boehringer Ingelheim GmBH; GlxoSmithKline pl; Novrtis AG; Pfizer, In; nd Shering-Plough Corp (now Merk & Co In). The other uthors hve reported to CHEST tht no potentil onflits of interest exist with ny ompnies/orgniztions whose produts or servies my e disussed in this rtile. Role of sponsors: The sponsors hd no role in the design of the study, the olletion nd nlysis of the dt, or the preprtion of the mnusript. Other ontriutions: The views expressed in this rtile re those of the uthor nd do not neessrily reflet the position or poliy of the Deprtment of Veterns Affirs. The uthors would like to express their hertfelt grtitude to ll the study prtiipnts. Referenes 1. Gri-Aymerih J, Frrero E, Félez MA, Izquierdo J, Mrrdes RM, Antó JM ; Estudi del Ftors de Ris d Aguditzió de l MPOC investigtors. Risk ftors of redmission to hospitl for COPD exertion: prospetive study. Thorx ;58(2): Gri-Aymerih J, Lnge P, Benet M, Shnohr P, Antó JM. Regulr physil tivity redues hospitl dmission nd mortlity in hroni ostrutive pulmonry disese: popultion sed ohort study. Thorx ;61(9): Gri-Aymerih J, Lnge P, Benet M, Shnohr P, Antó JM. Regulr physil tivity modifies smoking-relted lung funtion deline nd redues risk of hroni ostrutive pulmonry disese: popultion-sed ohort study. 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