Copyright #ERSJournalsLtd 2004 EurRespir J 2004;23: 932– 946 EuropeanRespiratory Journal DOI: 10.1183/09031936.04.00014304 ISSN0903-1936 Printedin UK –allrights reserved

ATS/ ERSTASKFORCE

Standardsfor the diagnosisand treatment of patientswith COPD: asummaryof the ATS/ERSposition paper

B.R. Celli*, W. MacNee*,andcommittee members

Committeemembers: A Agusti, A Anzueto, B Berg, A S Buist, P M A Calverley, N Chavannes, T Dillard, B Fahy, A Fein, J Heffner, S Lareau, P Meek, F Martinez, W McNicholas, J Muris, E Austegard, R Pauwels, S Rennard, A Rossi, N Siafakas, B Tiep, J Vestbo, E Wouters, R ZuWallack

*P ulmonaryand Critical C are D ivision, St Elizabeth s’ Medical Center, Tufts U niversity School of Medicine, Boston, Massachusetts, USA

# Respiratory Medicine ELE GI, Colt R esearch Lab Wilkie Building, CONTEMedical Schoo l, T eviot Place, Edinburgh, UK CONTENTSNTS

Background...... 932 Managementof stab eCOPD:surgery in and for Goals and objectives 933 COPD...... 938 Participants 933 Surgery in COPD 938 Evidence, methodology and validation 933 Surgery for COPD 938 Concept of a "live",modular document 933 Managementof stab e COPD: s eep...... 938 Organisation of the document 933 Managementof stab eCOPD:air-trave ...... 939 De® nitionof COPD...... 933 Exacerbationof COPD: de® nition, eva uation and Diagnosisof COPD...... 933 treatment ...... 939 Epidemio ogy,risk factors andnatura history De® nition 939 ofCOPD ...... 934 Assessment 940 Patho ogyand pathophysio ogyin COPD ...... 934 Indication for hospitalisation 940 C inica assessment, testingand differentia diagnosisof Indications for admission to specialised or intensive COPD...... 934 care unit 940 Medicalhistory 935 Treatment of exacerbations 940 Physicalsigns 935 Exacerbationof COPD: inpatient oxygen therapy. . . 940 Smokingcessation ...... 935 Setting and adjusting oxygen¯ ow 941 Brief intervention 935 Monitoring following hospital discharge 941 Managementof stab eCOPD:pharmaco ogica therapy 936 Exacerbationof COPD: assisted venti ation...... 942 Bronchodilators 936 Indications for mechanicalventilation 942 Glucocorticoids 936 Modes of mechanicalventilation 942 Outcomes of frequently used drugs 936 Criteria for hospital discharge 942 Combination therapy 937 Follow-up evaluation 943 Managementof stab e COPD: ong-termoxygen Ethica and pa iativecare issues inCOPD ...... 943 therapy...... 937 Integrateddisease management for primarycare in Managementof stab e COPD: pu monary COPD...... 943 rehabi itation...... 937 Referral indications 943 Managementof stab eCOPD:nutrition ...... 938 Conc usions...... 944

Background been enough advances inthe ®eld to require an update, especially adapted to the particular needs of the ATS/ERS The Standards for the Diagnosis and Treatment of Patients constituency 3) Itallowsfor the creation of a "live" modular with COPD document 2004 updates the position papers on document based on the web;it should provide healthcare chronic obstructive pulmonarydisease ( COPD)published by professionals and patients witha user friendly and reliable the American Thoracic Society (ATS) and the European authoritative source of information 4) The care of COPD Respiratory Society (ERS)in1995 [1,2] Both societies felt should be comprehensive, is often multidisciplinaryand the need to update the previous documents due to the rapidlychanging 5) Both the ATS and the ERS acknowledge following 1) The prevalence and overall importance of the recent dissemination of the Global Initiative of Obstruc- COPD as ahealth problem is increasing 2) There have tive Lung Disease (GOLD)[3]as amajorworldwide

*Pulmonaryand Critical Care Division, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA #Respiratory Medicine ELEGI, Colt Research Lab Wilkie Building, Medical School, Teviot Place, Edinburgh, UK Correspondence: B R Celli, St Elizabeth’s Medical Center, 736 Cambridge St, Boston MA 02135, USA Fax:1 6175627756 E-mail: bcelli@cchcs org ATS/ERSCOPD STANDARDS 933 contribution to the battle against COPD However, some Concept of a "live",modulardocument speci® crequirements ofthe members of both societies require adaptation ofthe broad GOLD initiative Those requirements Understanding that medicine and,in particular, the area of include speci® crecommendations on oxygen therapy, pulmo- COPD is constantly undergoing changes, the ATS and the nary rehabilitation, noninvasive ventilation,surgery inand ERS considered that it was time to develop new instruments for COPD,sleep, air travel, and end-of-life In addition, capable of adjusting to the changes Assuch, this is the ®rst special emphasis has been placed on issues related to the habit statement conceived to be primarilybased on the web and of smokingand its control capable of being changed asneeded Toachieve this goal,the organisations have developed a COPD task force composed ofthree members from each society whose of® ce willlast for 3 yrs The maintask of the members is to constantly review Goalsand objectives advances inthe ®eld of COPD and to propose changes to the modules of the document Asiscustomary inboth organisa- The maingoals of the updated document are to improve tions, the need to do so mayarise from the membership the qualityof care provided to patients with COPD and to through the current existing mechanisms One of the members develop the project using adisease-oriented approach To of the task force from each society willrepresent the society achieve these goals,both organisations have developed a on the executive GOLD committee The overall goalis to modularelectronic web-based document withtwo compo- attempt to maintaina synchronous ¯owwith the wider objec- nents 1) A component for health professionals that intends tives of GOLD to: raise awareness of COPD;inform on the latest advances in the overall pathogenesis, diagnosis,monitoring and manage- ment of COPD;and promote the concept that COPD is a Organisationof the document treatable disease 2) A component for the patient that intends to: provide practical information on allaspects of COPD; and The document has two distinct components The ® rst, promote ahealthy lifestyle to allpatients af¯icted withthe directed at patients and their needs, whichcan be accessed disease from the ATS/ERS website (www copd-ats-ers org) and from the website of each society (www ersnet org and www thoracic org), is not the subject of this summary The second is directed at healthcare practitioners and allthose interested in Participants the professional issues related to COPD This summary highlightsthe contents of the document for health practi- The committee members whowere involvedin the produc- tioners, but the readers are encouraged to access the tion of this document are clinicians,nurses, respiratory thera- document via the website, where an easy navigationaltool pists and educators interested inthe ®eld of COPD The current willallow you to explore its contents The reader is also Standards for the Diagnosis and Treatment of Patients with encouraged to access the patient document inorder to COPD document is unique inthat it also had input from familiarise themselves withits content Itwas designed for patients suffering from COPD Thecommittee members were and withpatients so as to serve as areliable resource for proposed and approved bythe ATS and ERS The members everyone were selected because of their expertise and willingnessto participate inthe generation of the document A unique feature of this project was the development of apatient De® nitionof COPD document that could serve as aformal source of information for the patients, thereby makingthem partners inthe effort to Chronic obstructive pulmonarydisease ( COPD) is a decrease the burden of the disease preventable and treatable disease state characterised by air¯ow limitation that is not fullyreversible The air¯ ow limitationis usuallyprogressive and is associated withan abnormalin¯ ammatory response of the lungs to noxious Evidence,methodology and validation particles or gases, primarilycaused by cigarette smoking Although COPD affects the lungs,it also produces signi®cant Several well-accepted guidelines served as the blueprint for systemic consequences the document Namely, the ATS and the ERS standards of 1995 [1,2] and the GOLD initiativepublished in2001 [3] At the initialmeeting, each member of the committee was Diagnosisof COPD assigned aspeci® csection of the document and was asked to select asubcommittee to gather literature and review the The diagnosis of COPD should be considered inany existing evidence The document was discussed infour group patient whohas the following:symptoms of cough; sputum meetings, and the content and validityof each section was production; or dyspnoea; or history of exposure to risk fac- thoroughly reviewed The ®nalstatement is the product of tors for the disease those discussions and has been approved by allthe members The diagnosis requires spirometry; apost-bronchodilator of the committee Several of the basic source documents forced expiratory volumein one second ( FEV1)/forced vital reviewed have used an evidence-based approach, and the capacity (FVC) 40 7con® rms the presence of air¯ow committee utilised those references as asource of evidence limitationthat is not fullyreversible (table 1) Spirometry wherever appropriate should be obtained inall persons withthe followinghistory: The draft document was reviewed by adiverse group of exposure to cigarettes; and/or environmental or occupational experts whose input was also considered Peer review was pollutants; and/or presence of cough, sputum production or identi® ed by the ATS and ERS,and the ®naldocument was dyspnoea Spirometric classi® cation has proved useful in submitted for review and approval by the Board of Directors predicting health status [4],utilisation of healthcare resources of the ATS and the Executive Committee ofthe ERS [5],development of exacerbations [6,7] and mortality [8]in 934 B R CELLI ET AL

Table 1. –SpirometricclassiŽ cation of chronicobstructive country, 50± 75%of the costs are for services associated with pulmonary disease (COPD) exacerbations Tobacco smoke is by far the most important risk factor for COPD worldwide Other important risk factors Severity Postbronchodilator FEV1 % pred are occupational exposures, socio-economic status and gene- FEV1/FVC tic predisposition

# COPD has avariable natural history and not allindividuals At risk 40 7 580 followthe same course [14] The often-quoted statistic that Mild COPD 40 7 580 only15± 20%of smokers develop clinicallysigni® cant COPD Moderate COPD 40 7 50± 80 mayunderestimate the tollof COPD Severe COPD 40 7 30± 50 Itis increasingly apparent that COPD often has its roots Very severe COPD 0 7 530 4 decades before the onset of symptoms [15] Impaired growth FEV1:forcedexpiratory volume in one second; FVC:forcedvital of lungfunction during childhoodand adolescence, caused by capacity #:patientswho smoke or haveexposure to pollutants, have recurrent infections or tobacco smoking,may lead to lower cough,sputum or dyspnoea maximallyattained lungfunction inearly adulthood [16,17] This abnormalgrowth will,often combined witha shortened plateau phase inteenage smokers, increase the risk of COPD COPD Itis intended to be applicableto populations [9]and The risk factors for COPD are shown intable 2and they not to substitute clinicaljudgment inthe evaluation of the are separated into host factors and exposures severity of disease inindividual patients Itis accepted that asingle measurement of FEV1 incom- pletely represents the complex clinicalconsequences of COPD A staging system that could offer acomposite picture of Patho ogyand pathophysio ogy in COPD disease severity is highlydesirable, although it is currently unavailable However, spirometric classi® cation is useful in COPD comprises pathologicalchanges infour different predicting outcomes such ashealth status and mortality,and compartments of the lungs (central airways,peripheral air- should be evaluated Inadditionto the FEV1,the body mass ways,lung parenchyma and pulmonaryvasculature), which index (BMI)[10,11] and dyspnoea [12]have proved useful in are variablypresent inindividuals with the disease [18±22] predicting outcomes such as survival,and this document Tobacco smokingis the mainrisk factor for COPD, recommends that they be evaluated inall patients although other inhalednoxious particles and gases maycontri- BMI is easily obtained by dividingweight (in kg) over bute This causes an in¯ammatory response inthe lungs, height (in m2) Values 521 kg·m-2 are associated withincre- whichis exaggerated insome smokers, and leads to the ased mortality characteristic pathologicallesions of COPD Inadditionto Functional dyspnoea can be assessed by the Medical in¯ammation, an imbalanceof proteinases and antiprotei- Research Councildyspnoea scale as follows 0:not troubled nases inthe lungs,and oxidative stress are also important in withbreathlessness except withstrenuous exercise 1: troubled the pathogenesis of COPD [23] The different pathogenic by shortness of breath when hurrying or walkingup aslight mechanisms produce the pathologicalchanges which,in turn, hill 2:walks slower than people of the same age due to give rise to the followingphysiological abnormalities in breathlessness orhas to stop for breath when walkingat own COPD:mucous hypersecretion and cilliarydysfunction; pace on the level 3:stops for breath after walkingabout air¯ow limitationand hyperin¯ation; gas exchange abnormali- 100 mor after afew minutes on the level 4:too breathless to ties; pulmonaryhypertension; and systemic effects [24,25] leave the house or breathless when dressing or undressing Poorly reversible air¯ow limitationassociated withbronch- iectasis, cystic ®brosis and ®brosis due to tuberculosis are not C inica assessment, testingand differentia diagnosisof included inthe de® nitionof COPD,and should be considered COPD inits differential diagnosis Patients presenting withair¯ ow limitation at arelatively COPD runs an insidiouscourse, measured over years, with early age (4th or 5th decade) and particularly those witha an often undiagnosed initialphase Its presence can be familyhistory of COPD should be tested for a1-antitrypsin suspected after adirected clinicalevaluation and then con- de® ciency ®rmed physiologicallywith simple spirometry Chest radio- graphy helps indifferential diagnosis (table 3), and other tests maybe useful to better determine the phenotype and physio- logicalcharacteristics of individualpatients Epidemio ogy,risk factors andnatura historyof COPD Some patients withasthma cannot be distinguished from

COPD isaleadingcause of morbidityand mortality world- wide,and results inan economic and social burden that is both substantial and increasing The prevalence and morbid- Table 2. –Riskfactors for chronic obstructive pulmonary ity data greatly underestimate the total burden of COPD disease because the disease is usuallynot diagnosed untilit is Host factors Exposures clinicallyapparent and moderately advanced In people aged 25± 75 yrs inthe USA,the estimated prevalence of Geneticfactors Smoking mild COPD (de® ned as FEV1/FVC 570% and FEV1 580% Sex Socio-economicstatus predicted) was 6 9%and of moderate COPD (de® ned as Airwayhyperreactivity, Occupation FEV1/FVC570% and FEV1 480%pred) was 6 6%,according IgE and asthma Environmentalpollution to National Health and Nutrition Examination Survey Perinatalevents and childhood illness (NHANES) COPD is the fourth-leading cause of death in Recurrentbronchopulmonary infections the USA and Europe, and COPD mortality infemales has Diet more than doubled over the last 20 yrs [13] Currently, COPD is amore costly disease than asthma and,depending on Ig:immunoglobulin ATS/ERSCOPD STANDARDS 935

Table 3. –Differential diagnosis of chronicobstructive diseases; familyhistory of COPD or other respiratory diseases; pulmonary disease (COPD) co-morbidities; any unexplained weight loss; and exposure his- tory, smoking,and occupational and environmental exposures Diagnosis Suggestivefeatures Physicalsigns COPD Mid-lifeonset Slowlyprogressing symptoms A normalphysical examinationis commonin early COPD Longhistory of smoking [13] Asthe disease progresses, some signs become apparent Asthma Early onset and inadvanced stages manyare almost pathognomonic Varying symptoms Examinationshould aimat elicitingthe presence of respiratory Symptoms duringthe night/ early and systemic effects of COPD Allpatients should have their morning respiratory rate, weight and height, and BMI measured Presenceof allergy,rhinitis and/ or eczema A family history Smokingcessation Air¯ow limitation that islargely reversible Congestiveheart failure Finebasilar crackles on auscultation Cigarette smokingis an addiction and achronic relapsing Dilatedheart on chestradiography disorder, and is regarded as aprimary disorder by the Pulmonaryoedema Department of Health and Human Services Guidelines inthe Volumerestriction not air¯ ow USA [26,27] and by the World Health Organization ( WHO) limitationon pulmonaryfunction Therefore, treating tobacco use and dependence should be tests regarded as aprimary and speci® cintervention Smoking Bronchiectasis Large volumeof purulentsputum should beroutinely evaluated whenever apatient presents to a Commonlyassociated with bacterial healthcare facility and allsmokers should be offered the best infection chance to treat this disorder Coarsecrackles/ clubbingon The most comprehensive of the guidelines prepared on auscultation smokingcessation is "Treating Tobacco Use and Depen- Bronchialdilation and bronchial wall dence",an evidence-based guidelinesponsored by the US thickeningon chestradiography/ CT Department of Health and Human Services and released in Tuberculosis Onsetat allages 2000,which updates the previous evidence-based guideline Lungin® ltrate on chestradiography "Smoking Cessation" released in1996 The guidelineand the Microbiologicalcon® rmation meta-analyses on whichit is based are availableonline [28] Highlocal prevalence of tuberculosis The key ®ndings of this report are summarised intable 4 Obliterativebronchiolitis oungeronset and in nonsmokers Historyof rheumatoidarthritis/ fume exposure Hypodenseareas on expiration on Brief intervention CT suggestiveof bronchiolitis Diffusepanbronchiolitis Effectsmostly male nonsmokers The key steps inbrief intervention are as follows Ask: Almostall have chronicsinusitis systematically, identify alltobacco users at every visit, Diffusesmall centrilobular nodular implement an of® ce-wide system that ensures that tobacco opacitiesand hyperin¯ ation on use is queried and documented for every patient at every clinic chestradiography and HRCT visit Advise: strongly urge alltobacco users to quit,in aclear, strong and personalised manner Assess: determine will- CT:computedtomography; HRCT:highresolution computed to- ingness to make aquit attempt Assist: help the patient with mography aquit plan,provide practical counselling, provide treatment and social support, help the patient obtain extra treatment COPD withthe current diagnostic tests Themanagement of and social support, recommend the use ofapproved pharma- these patients should be similarto that of asthma cotherapy (except inspecial circumstances), and provide supplementary materials Arrange: schedule follow-upcontact, either inperson or via the telephone Medicalhistory Permanent remissions can be achieved ina substantial percentage of smokers withcurrently availabletreatments A directed medicalhistory should assess the following Successful treatment of this disorder can have asubstantial issues: symptoms of cough, sputum production and dyspnoea; bene® tinreducing manysecondary complications of which past medicalhistory of asthma, allergies and other respiratory COPD is one Allpatients willingto make aserious attempt

Table 4. –Key points of the Treating Tobacco Use and Dependence guidelines

Tobaccodependence is a chroniccondition that warrantsrepeated treatment untillong-term or permanentabstinence is achieved Effective treatmentsfor tobacco dependence exist and all tobacco users should be offeredthese treatments Cliniciansand healthcare delivery systems must institutionalise the consistent identi® cation, documentation and treatment of everytobacco userat everyvisit Brieftobacco dependence intervention is effectiveand every tobacco user should be offeredat leastbrief intervention Thereis astrongdose-response relationship between the intensity of tobaccodependence counselling and its effectiveness Threetypes of counsellingwere found to beespecially effective: practical counselling, social support as part of treatment andsocial supportarranged outside treatment Five® rst-linepharmacotherapies for tobacco dependence are effective: bupropion SR,nicotinegum, nicotine inhaler, nicotine nasal sprayand nicotine patch, and at leastone of thesemedications should be prescribed in theabsence of contraindications Tobacco-dependencetreatments are cost effective relative to othermedical and disease prevention interventions 936 B R CELLI ET AL to quit should be offered pharmacological support (nicotine reduction inresidual volumeand/ or adelay of the onset of replacement therapy and/or bupropion) [26,27] Smoking dynamichyperin¯ ation during exercise Both ofthese changes cessation activities and support for its implementation should contribute to areduction inperceived breathlessness [30,31] be integrated into the healthcare system Ingeneral, the more advanced the COPD,the more important the changes inlung volume become relative to those in FEV1 The clinicaluse of bronchodilator drugs is illustrated in Managementof stab eCOPD:pharmaco ogica therapy ® gure 1 Short-acting bronchodilators can increase exercise tole- Effective medications for COPD are availableand all rance acutely [30,31] Long-acting inhaled b-agonists improve patients whoare symptomatic merit atrial ofdrug treatment health status possibly to agreater extent than regular short- [1± 3] The medications for COPD currently availablecan reduce acting anticholinergics [32],reduce symptoms, rescue medica- or abolishsymptoms, increase exercise capacity, reduce the tion use and increase time between exacerbations compared number and severity of exacerbations, and improve health withplacebo [33±35] Combiningshort-acting bronchodilator status Atpresent, no treatment has modi®ed the rate of agents (salbutamol (albuterol)/ipratropium) produces a decline inlung function The inhaledroute ispreferred greater change inspirometry than either agent alone [34] The change inlungfunction after brief treatment withany Combininglong-acting b-agonists and ipratropium leads to drug does not help inpredicting other clinicallyrelated fewer exacerbations than either drug alone No good com- outcomes Changes in FEV1 followingbronchodilator thera- parative data between different long-acting b-agonists are py can be smallbut are often accompanied by larger changes presently available,although itis likelythat their effects will inlung volumes, which contribute to areduction inperceived be similar Combininglong-acting b-agonists and theophyl- breathlessness Combiningdifferent agents produces agreater lineappears to produce agreater spirometric change than change inspirometry and symptoms than single agents alone either drug alone [35] Tiotropiumimproves health status and reduces exacerbations and hospitalisations compared with both placebo and regular ipratropium [36,37] Bronchodilators Theophyllineis aweak bronchodilator, whichmay have some anti-in¯ammatory properties Its narrow therapeutic Three types ofbronchodilator are incommon clinical use: index and complex pharmacokinetics make its use dif® cult, b-agonists, anticholinergic drugs and methylxanthines Despite but modern slow-release preparations have improved this substantial differences intheir site of action withinthe cell problem and lead to more stable plasmalevels Generally, and some evidence for nonbronchodilator activity withsome therapeutic levels should be measured and patients should be classes of drug, the most important consequence of broncho- kept on the lowest effective dose (recommended serum level dilator therapy appears to be airwaysmooth muscle relaxa- 8± 14 mg·dL-1) tion and improved lungemptying during tidalbreathing The resultant increase in FEV1 maybe relatively smallbut is often accompanied by larger changes inlung volumes [29],with a Glucocorticoids Confirm diagnosis of COPD Glucocorticoids act at multiplepoints withinthe in¯am- matory cascade, although their effects in COPD are more modest ascompared withbronchial asthma Data from large Intermittent symptoms patient studies suggest that inhaledcorticosteroids can pro- cough, wheeze, SA-BD as needed . inhaled -agonist, anticholinergic duce asmallincrease inpostbronchodilator FEV1 and a small exertional dyspnoea reduction inbronchial reactivity instable COPD [38± 40] In patients withmore advanced disease (usually classi® ed as an FEV1 550%pred) there is evidence that the number of Persistent symptoms LA-BD/SA-BD Æ Ç + as needed exacerbations per year and the rate of deterioration inhealth dyspnoea, night reliever waking status can be reduced by inhaledcorticosteroids in COPD [38] Evidence from four large prospective 3-yr studies has Limited benefit? shown no effect of inhaledcorticosteroids on rate of change Yes of FEV1 inany severity of COPD [38± 41] When therapy is thought to be ineffective, atrial of with- Alternative class/combine classes drawingtreatment is reasonable Some patients willexacer- LA-BD+ICS bate when this occurs, whichis areason for re-instituting this therapy [42] The results of forthcoming large randomised Limited benefit? trials withmortality as an outcome willhelp clarify the role of Side-effects? inhaledglucocorticoids in COPD Yes Add/substitue oral theophylline Outcomes offrequently used drugs Fig 1 ± Algorithmfor pharmacologicaltreatment of chronic obstruc- tivepulmonary disease ( COPD) SA-BD:short-actingbronchodilator; LA-BD:long-actingbronchodilator; ICS:inhaledcorticosteroid Table 5summarises the effects of frequently used medica- Assess effectivenessby treatment response criteria Ifforcedexpira- tions inpatients with COPD Theevidence level was obtained tory volume 550%predicted and exacerbations of COPD requiring a from the GOLD document [3]using the same grade of courseof oral corticosteroid or antibioticoccurred at least once evidence, as follows Grade A:randomised clinicaltrial ( RCT), withinthe last year, consider adding regular ICS Alwaysensure the patientcan use an inhaled device effectively and understands its rich body of data Grade B: RCT,limitedbody of data purpose If an ICS anda long-acting b-agonistare used, prescribe a Grade C:nonrandomised trials, observational studies Grade combinationinhaler D:panel consensus ATS/ERSCOPD STANDARDS 937

Table 5. –Effectof commonly used medications on important clinicaloutcomes inchronicobstructive pulmonary disease

FEV1 Lung volume Dyspnoea HRQoL AE Exercise Disease Mortality Side-effects endurance modi® er by FEV1

Short-acting b-agonists es (A) es (B) es (A) NA NA es (B) NA NA Some Ipratropiumbromide es (A) es (B) es (A) No (B) es (B) es (B) No NA Some Long-acting b-agonists es (A) es (A) es (A) es (A) es (A) es (B) No NA Minimal Tiotropium es (A) es (A) es (A) es (A) es (A) es (B) NA NA Minimal Inhaledcorticosteroids es (A) NA es (B) es (A) es (A) NA No NA Some Theophylline es (A) es (B) es (A) es (B) NA es (B) NA NA Important

FEV1:forcedexpiratory volume in one second; HRQoL:health-relatedquality of life; AE:exacerbationof COPD; NA:evidencenot available GOLD gradelevels are indicated in brackets (see text for explanation)

Combinationtherapy despite the fact that it has aminimaleffect on pulmonary function measurements This re¯ects the fact that much of the Combiningmedications of different classes seems acon- morbidityfrom COPD results from secondary conditions, venient wayof delivering treatment and obtainingbetter whichare often treatable if recognised Examples of these results This includes better lungfunction and improved treatable conditions are cardiac deconditioning, peripheral symptoms [43±45] muscle dysfunction, and areduction intotal and lean body Data from trials combininglong-acting inhaled b-agonists mass, anxiety and poor coping skills Elements of compre- and inhaledcorticosteroids show asigni®cant additional hensive pulmonaryrehabilitation, includingpromoting a effect on pulmonaryfunction and areduction insymptoms in healthy lifestyle, stressing adherence to therapy and encourag- those receiving combinationtherapy compared withits com- ingphysical activity, should be incorporated into the care ponents [45] The largest effects interms ofexacerbations and of allpatients with COPD Pulmonaryrehabilitation is a health status are seen inpatients withan FEV1 550% pred, multidisciplinaryprogramme of care that is individually where combiningtreatment is clearly better than either tailored and designed to optimise physical and social component drug used alone performance, and autonomy Pulmonaryrehabilitation should be considered for patients with COPD whohave dyspnoea or other respiratory symp- Managementof stab e COPD: ong-termoxygen therapy toms, reduced exercise tolerance, arestriction inactivities because of their disease, or impairedhealth status There are Supplemental long-term oxygen therapy ( LTOT) improves survival,exercise, sleep and cognitive performance inhypox- Hypoxaemia from disease progression aemic patients [1±3, 45± 50] Reversal of hypoxaemiasuper- or recovering from acute exacerbation sedes concerns about carbon dioxide( CO2) retention Ê a,O2 <7.3 kPa, a,O2 <88% Arterial bloodgas ( ABG)assessment is the preferred or method to determine oxygen need because it includes acid- Ê a,O2=7.3–7.8 kPa + cor pulmonale, base information Arterial oxygen saturation as measured by polycythemia, with optimal medical pulse oximetry ( Sp,O2)is adequate for trending Physiological management indications for oxygen include aarterial oxygen tension (Pa,O2) 57 3 kPa (55 mmHg) The therapeutic goalis to Prescribe oxygen maintain Sp,O2 490%during rest, sleep and exertion If Ê a,O2 >8 kPa ( a,O2 >90%) oxygen is prescribed during an exacerbation, ABG should be during rest, sleep and exertion rechecked in30± 90 days Withdrawalof oxygen because of Titrate flow improved Pa,O2 inpatients whose need for oxygen was determined when ina stable state maybe detrimental rest ( a,O2 >90%) exertion add 1 L·min -1 Active patients require portable oxygen Oxygen sources sleep add 1 L·min -1 include gas, liquidand concentrator; whileoxygen delivery methods include nasal continuous ¯ow,pulse demand,reser- voir cannulae and transtracheal catheters [51] Patient educa- Hypoxaemia identified Yes Recheck ABG tion improves compliance during exacerbation? 30–90 days Figure 2shows a¯owchart for prescribing home oxygen therapy No Continue LTOT

Ê a,O2 <7.3 or 7.3–7.8 kPa Managementof stab e COPD: pu monaryrehabi itation + cor pulmonale, polycythemia during rest, sleep and exertion? Pulmonaryrehabilitation is de® ned as "amultidisciplinary No programme of care for patients withchronic respiratory impairment that is individuallytailored and designed to optimise physical and social performance and autonomy " Yes Discontinue [52] Continue LTOT LTOT Pulmonaryrehabilitation results inimprovements inmulti- ple outcome areas of considerable importance to the patient, Fig 2 ± A ¯ow chartfor prescribinglong-term oxygen therapy includingdyspnoea, exercise ability,health status and (LTOT) Pa,O2:arterialoxygen tension; Sa,O2:arterialoxygen satura- healthcare utilisation [53±57] These positive effects occur tion; ABG:arterialblood gases 938 B R CELLI ET AL no speci® cpulmonaryfunction inclusioncriteria that indicate Spirometry, Í L,CO the need for pulmonaryrehabilitation, since symptoms and functional limitationsdirect the need for pulmonary FEV1 <60% pred or FEV1 >60% pred and rehabilitation Í L,CO <60% pred Í L,CO >60% pred The pulmonaryrehabilitation programme includes exercise training,education, psychosocial/behavioural intervention, Unusually Quantitative lung nutritional therapy, outcome assessment and promotion of ppo FEV1 >40% pred Consider decreased scan to predict and long-term adherence to the rehabilitation recommendations surgery exercise postoperative lung ppo Í L,CO >40% pred capacity function Î Ï O ,max >15 mL·kg-1·min-1 or ppo FEV1 <40% pred or 2 -1 -1 Managementof stab eCOPD:nutrition ppo Í L,CO <40% pred ppo Î Ï O2max >10 mL·kg ·min or Weight loss, as wellas adepletion of fat-free mass ( FFM), Measure aerobic stair climb >3 flights (54 steps) maybe observed instable COPD patients, irrespective of the capacity (stair climb degree of air¯ow limitation, and being underweight is associ- as alternate) ated withan increased mortality risk [58] Nutritional screening isrecommended inthe assessment of COPD Simplescreening can be based on measurements of Fig 3 ± Algorithmfor pre-operativetesting for lungresection DL,CO: BMI and weight change Patients are considered under- carbondioxide diffusing capacity of the lung; FEV1:forcedexpira- -2 toryvolume in one second; ppo: predicted postoperative; V’ O2,max: weight (BMI 521 kg·m ; age 450 yrs), normalweight ( BMI maximumoxygen consumption 21± 25 kg·m-2),overweight ( BMI 25± 30 kg·m-2) or obese (BMI 530 kg·m-2) Criteria to de® ne weight loss are weight loss 410%in the past 6months or 45%in the past month Trial (NETT)showed bene® ts for asubset of patients Weight loss and particularly muscle wasting contribute withnonhomogenous emphysema Figure 4summarises the signi®cantly to morbidity,disability and handicap in COPD strati® cation of the patients and the results of the trial for patients Weight loss and loss infat mass is primarilythe each of the groups Group B is comprised of those patients result ofanegative balance between dietary intake and energy withnonhomogenous emphysema of upper lobe predomi- expenditure, whilemuscle wasting is aconsequence of an nance and limitedexercise performance after pre-operative impairedbalance between protein synthesis and protein break- comprehensive rehabilitation Group C corresponds to down Inadvanced stages of COPD,both energy balance and patients withpredominant upper lobe emphysema and good protein balance are disturbed Therefore, nutritional therapy post-rehabilitation exercise capacity Group D corresponds to mayonly be effective if combined withexercise or other those patients withhomogenous emphysema and lowpost- anabolicstimuli [59, 60] rehabilitation exercise capacity Group E was characterised by homogeneous emphysema and good post-rehabilitation exercise capacity Finally,group A corresponds to those patients Managementof stab eCOPD:surgery in and for COPD witha very highrisk for lungreduction surgery [70] The results of this trial showed that patients ingroup B Surgery in COPD whounderwent surgery had alower mortality,better exercise capacity and health status than patients randomised to Patients witha diagnosis of COPD have a 2 7± 4 7-fold medicaltherapy The operated patients ingroups C and D increased risk of postoperative pulmonarycomplications didnot bene® tfrom improved survival but had signi®cant [61± 63] However, COPD isnot anabsolute contraindication improvements inexercise capacity and health status com- to any surgery The most important concept determining the pared to patients randomised to medicaltherapy The patients risk of surgery is that the further the procedure from the in group E had higher mortality and would,therefore, not be diaphragm,the lower the pulmonarycomplication rate candidates for LVRS The results inthis group are similarto Although the value of pre-operative pulmonaryfunction those observed inthe highest risk group ( A)whoshould not testing ingeneral surgery is debatable, pre-operative pulmo- be considered for surgery nary function studies have awell-documented role inthe Lung transplantation results inimproved pulmonary evaluation ofpatients undergoing lungsurgery [64±67] function, exercise capacity and qualityof life,however, its Smokingcessation at least 4± 8weeks pre-operatively and effects on survival remain controversial [71] Speci® cguide- optimisation of lungfunction can decrease post-operative lines for lungtransplantation in COPD are shown intable 7 complications Inaddition,early mobilisation,deep breath- ing,intermittent positive-pressure breathing, incentive spiro- metry and effective analgesia maydecrease post-operative Managementof stab e COPD: s eep complications Analgorithmfor pre-operative evaluation of patients Sleep in COPD is associated withoxygen desaturation, undergoing lungresection isshown in® gure 3 whichis predominantly due to the disease itself rather than to sleep apnoea [72] The desaturation during sleep maybe greater than during maximumexercise [73] In COPD, sleep Surgery for COPD qualityis markedly impaired,both subjectively and objec- tively [74] However, sleep apnoea syndrome is about as Bullectomy,lung volume reduction surgery and lung prevalent in COPD as ina general populationof similarage, transplantation mayresult inimproved spirometry, lung but oxygen desaturation during sleep is more pronounced volumes,exercise capacity, dyspnoea, health-related quality when the two conditions co-exist [75] of life and possibly survival inhighly selected patients [68±69] The clinicalassessment inall patients with COPD should Factors associated witha favourable or unfavourable out- include questions about sleep qualityand possible co-existing come inbullectomy are shown intable 6 sleep apnoea syndrome Sleep studies are not indicated in The recently completed National Emphysema Therapy COPD except inspecial circumstances These include:a clinical ATS/ERSCOPD STANDARDS 939

Table 6. –Factorsassociated with favourable or unfavourable outcome inclassicalbullectomy

Parameter Favourable Unfavourable

Clinical Rapidprogressive dyspnoea despite maximal medicaltherapy Older age Ex-smoker Co-morbidillness Cardiacdisease Pulmonaryhypertension 410% weightloss Frequentrespiratory infections Chronicbronchitis Physiological Normal FVC orslightly reduced FEV1 535% pred FEV1 440% pred Lowtrapped gas volume Littlereversibility Decreased DL,CO Hightrapped lung volume Normalor near normal DL,CO

Normal Pa,O2 and Pa,CO2 Imaging CXR Bulla 41/3hemithorax Vanishinglung syndrome Poorlyde® ned bullae CT Large andlocalised bulla with vascular crowding and Multipleill-de® ned bullae in underlying lung normalpulmonary parenchyma around bulla Angiography Vascularcrowding with preserved distal vascular branching Vague bullae;disrupted vasculature elsewhere Isotope scan Well-localisedmatching defectwith normal uptake and Absenceof target zones,poor washout in washoutfor underlying lung remaininglung

CXR:chestradiography; CT:computedtomography; FVC:forcedvital capacity; FEV1:forcedexpiratory volume in one second; DL,CO: carbon monoxidediffusing capacity of the lung; Pa,O2;arterialoxygen tension; Pa,CO2;arterialcarbon dioxide tension Tablemodi® ed from [68] suspicion of sleep apnoea or complications of hypoxaemia Managementof stab eCOPD:air-trave that are not explained bythe awake arterial oxygen levels, and pulmonaryhypertension out of proportion to the severity of Commercial airliners can cruise at 412,192 m (440,000 pulmonaryfunction derangement feet), as longas the cabin is pressurised from 1,829±2,438 m Management of sleep problems in COPD should particu- (6,000± 8,000feet) This is equivalent to an inspired oxygen larlyfocus on minimisingsleep disturbance by measures to concentration at sea level of ~ 15% [77] limitcough and dyspnoea, and nocturnal oxygen therapy may Patients with COPD can exhibit falls in Pa,O2 that average be indicated for nocturnal hypoxaemia[76] Hypnotics should 3 3 kPa (25 mmHg) [78] Pre-¯ight assessment can help be avoided,if possible, inpatients withsevere COPD determine oxygen needs and the presence of co-morbidities [79] Oxygen needs can be estimated by using the hypoxia inhalationtest or through the use of regression formulae However, it is currently recommended that the Pa,O2 during air travel should be maintainedabove 6 7 kPa (50 mmHg) Candidate [80] Treatment with2± 3 L·min-1 ofoxygen by nasal cannula for LVRS willreplace the inspired oxygen partial pressure lost at 2,438m (8,000 feet) compared to sea level [81] Forhigh-risk patients, the goalshould be to maintainoxygen pressure Yes Í L,CO 20% FEV1 20% during ¯ight at the same level atwhichthe patient is clinically pred? pred? stable at sea level Most airlines willprovide supplemental oxygen on request No No

No Upper lobe Exacerbationof COPD: de® nition, eva uation and Yes Homogenous predominant emphysema? emphysema? treatment

Yes Yes No De® nition Group A Anexacerbation of COPD isan event inthe natural course of the disease characterised by achange inthe patient ’s Low post- Low post- rehabilitation rehabilitation Table 7. –Disease-speciŽc guidelines forcandidate selection exercise exercise forlung transplantation in chronicobstructive pulmonary capacity? capacity? disease patients

Yes No Yes No FEV1 425% pred(without reversibility) and/ or Restingroom air Pa,CO2 47 3 kPa (55 mmHg) and/or Group BGroup CGroup DGroup E Elevated Pa,CO2 withprogressive deterioration requiring long-term oxygen therapy Fig 4 ± Schematicalgorithm from the National Emphysema Therapy Elevatedpulmonary arterial pressure with progressive deterioration Trial for Lung Volume Reduction Surgery (LVRS) (see text) FEV1: forcedexpiratory volume in one second; DL,CO:carbondioxide FEV1:forcedexpiratory volume in one second; Pa,CO2:arterialcarbon diffusingcapacity of thelung Modi®ed from[69] dioxidetension 940 B R CELLI ET AL

baseline dyspnoea, cough and/or sputum beyond day-to-day Table 9. –Indications forhospitalisation of patients with a variabilitysuf® cient to warrant achange inmanagement COPD exacerbation There is no agreed classi® cation of exacerbations The followingoperational classi® cation of severity can help rank Thepresenceof high-riskco-morbid conditions, including the clinicalrelevance of the episode and its outcome Level I: pneumonia,cardiac arrhythmia, congestive heart failure, diabetesmellitus, renal or liver failure treated at home Level II:requires hospitalisation Level III: Inadequateresponse of symptomsto outpatientmanagement leads to respiratory failure Markedincrease in dyspnoea Inabilityto eat orsleepdue to symptoms Assessment Worseninghypoxaemia Worseninghypercapnia Changesin mentalstatus Several clinicalelements must be considered when evaluat- Inabilityof thepatient to carefor her/ himself(lack of homesupport) ingpatients withexacerbations These include the severity of Uncertaindiagnosis the underlying COPD,the presence of co-morbidity and the Inadequatehome care history of previous exacerbations The physical examination should evaluate the effect of the episode on the haemody- namicand respiratory systems The diagnostic procedures to be performed depend on the setting of the evaluation [82,83] personnel, skillsand equipment exist to identify and manage The pharmacological treatment of patients withan exacer- acute respiratory failure successfully bation of COPD isbased on the same medications utilised in Indications for ICU or special care unit admissioninclude the management of the stable patient [1±3] However, the the following:impending or actual respiratory failure; pre- evidence supports the use of systemic glucocorticosteroids sence of other end-organ dysfunction, i e shock, renal, liver [84± 88] or neurological disturbance; and/or haemodynamicinstability Table 8shows the elements of the clinicalevaluation and diagnostic procedures that are usuallyinformative inpatients Treatment ofexacerbations withexacerbations according to the severity ofthe episode The treatment of exacerbations has to be based on the Indicationfor hospitalisation clinicalpresentation ofthe patient, as shown intables 10,11 and 12 Table 9provides reasonable guidelines for patient hospita- lisation Based onexpert consensus, they consider the severity of the underlying respiratory dysfunction, progression of Exacerbationof COPD: inpatient oxygen therapy symptoms, response to outpatient therapy, existence of co- morbidconditions and the availabilityof adequate home care During asevere exacerbation, ABGsshould be monitored for Pa,O2,arterial carbon dioxidetension ( Pa,CO2) and pH Indicationsfor admissionto specialised or intensive care The Sp,O2 should be monitored for trending and adjusting unit oxygen settings The goalof inpatient oxygen therapy is to maintain Pa,O2 48 kPa (60 mmHg) or Sp,O2 490%in order to The severity of respiratory dysfunction dictates the need for prevent tissue hypoxiaand preserve cellular oxygenation Due admissionto an intensive care unit ( ICU) Depending on the to the shape of the oxyhaemoglobindissociation curve, increa- resources availablewithin an institution, admissionof sing the Pa,O2 to values much greater than 8k Pa (60 mmHg) patients withsevere exacerbations of COPD to intermediate confers little added bene® t(1± 2vol%) and mayincrease the or special respiratory care units maybe appropriate if risk of CO2 retention, whichmay lead to respiratory acidosis

Table 8. –Clinicalhistory, physical Ž ndings and diagnostic procedures in patients with exacerbation of chronicobstructive pulmonary disease (COPD)

Level I Level II Level III

Clinicalhistory Co-morbidconditions # + +++ +++ Historyof frequentexacerbations + +++ +++ Severity of COPD Mild/moderate Moderate/severe Severe Physical® ndings Haemodynamicevaluation Stable Stable Stable/unstable Useaccessoryrespiratory muscles, tachypnoea Not present ++ +++ Persistentsymptoms after initialtherapy No ++ +++ Diagnosticprocedures Oxygen saturation es es es Arterialblood gases No es es Chestradiograph No es es Blood tests¶ No es es Serumdrug concentrations + Ifapplicable Ifapplicable Ifapplicable Sputumgram stainand culture No§ es es Electrocardiogram No es es

+ :unlikelyto be present; ++ :likelyto be present; +++ :verylikely to be present #:themore common co-morbid conditions associated with poor prognosisin exacerbations are congestive heart failure, coronary artery disease, diabetes mellitus, renal and liver failure; ¶:bloodtests includecell bloodcount, serum electrolytes, renal and liver function; +:serumdrug concentrations, consider if patientsare using theophylline, warfarin, carbamezepine,digoxin; §:considerif patienthas recently been on antibiotics ATS/ERSCOPD STANDARDS 941

Table 10. –Level I:outpatient treatment Table 12. –Level III:treatment in patients requiring specialor intensive care unit Patient education Checkinhalation technique Supplementaloxygen Consideruse of spacerdevices Ventilatorysupport Bronchodilators Bronchodilators # Short-acting b2-agonist and/oripratropium MDI with spacer Short-acting b2-agonist (salbutamol(albuterol)) and ipratropium orhand-held nebuliser as needed MDI withspacer, two puffs every 2± 4h Consideradding long-acting bronchodilator if patient is not Ifthepatient is ontheventilator, consider MDI administration using one Considerlong-acting b-agonist Corticosteroids(the actual dosemay vary) Corticosteroids Prednisone30± 40 mg orally ·day-1 for10± 14 days Ifpatienttolerates oral medications, prednisone 30± 40 mg Considerusing an inhaledcorticosteroid orally·day-1 for10± 14 days Antibiotics Ifpatientcannot tolerate, give theequivalent dose i v for up to May beinitiatedin patients with altered sputum characteristics + 14 days Choiceshould be based on local bacterial resistance patterns Considerusing inhaled corticosteroids by MDI orhand-held Amoxicillin/ampicillin ¶,cephalosporins nebuliser Doxycycline Antibiotics(based on localbacteria resistance patterns) Macrolides§ Choiceshould be basedon localbacteria resistance patterns Ifthepatient has failed prior antibiotic therapy consider: Amoxicillin/clavulanate Amoxicillin/clavulanate Respiratory¯ uoroquinolones(gati¯ oxacin, levo¯ oxacin, Respiratory¯ uoroquinolones ƒ moxi¯oxacin) If Pseudomonas spp and/orother Enterobactereaces spp are MDI:metered-doseinhaler #:salbutamol(albuterol), terbutaline; +: suspected,consider combination therapy purulenceand/ orvolume; ¶:dependingon local prevalence of bacterial § b-lactamases; :azithromycin,clarithromycin, dirithromycin, roxithro- MDI:metered-doseinhaler mycin; ƒ:gati¯oxacin, levo¯ oxacin, moxi¯ oxacin recovery is complete Patients withhypoxaemia at discharge [89, 90] The maindelivery devices include nasal cannula and mayrequire short-term oxygen therapy as the effects of the venturi masks Alternative delivery devices include nonre- exacerbation are clearing After 30± 90 days, oxygen mayno breather masks, reservoir cannulae, nasal cannulae or transtra- longer berequired; thus re-evaluation of the patient ’s oxygen cheal catheters Asageneral principle,prevention of tissue hypoxia supercedes CO2 retention concerns If CO2 retention occurs, monitor for acidemia Ifacidemiaoccurs, consider noninva- Assess patient sive or invasive mechanical ventilation Obtain ABG Begin O2 Settingand adjusting oxygen ¯ ow Assure Pa,O2 >8 kPa Adjust O to Sa,O 90% Figure 5shows analgorithmfor correcting hypoxaemiain 2 2 the COPD patient Hypercapnia? (Pa,CO >6.7 kPa) Monitoringfollowing hospital discharge 2 No Yes Patients maybe started on oxygen for the ®rst time during hospitalisation for an acute exacerbation and discharged before pH <7.35? Yes Table 11. –Level II:treatment forhospitalised patient No change in (with Pa,O2 oxygen setting >8 kPa) Bronchodilators No Short-acting b2-agonist and/or Ipratropium MDI withspacer or hand-held nebuliser as needed Reassess ABG in Maintain O2 Supplementaloxygen (if saturation 590%) 1–2 h Sa,O2 90% Corticosteroids Ifpatienttolerates, prednisone 30± 40 mg orally ·day-1 for Yes 10± 14 days Hypercapnia? Reassess ABG in 2 h Ifpatientcan not tolerate oral intake, equivalent dose i v for Pa,CO2 >6.7 kPa up to 14 days Considerusing inhaled corticosteroids by MDI orhand-held No Consider nebuliser pH <7.35? Yes (with Pa,O mechanical ventilation Antibiotics(based on local bacteria resistance patterns) Maintain O2 2 >8 kPa) NPPV or intubation May beinitiatedin patientsthat have achangein theirsputum Sa,O2 90% # characteristics No Choiceshould be based on local bacteria resistance patterns No change in Amoxicillin/clavulanate oxygen setting Respiratory¯ uoroquinolones(gati¯ oxacin, levo¯ oxacin, moxi¯oxacin) Fig 5 ± Algorithmto correct hypoxaemia in an acutely ill chronic If Pseudomonas spp and/orother Enterobactereaces spp are obstructivepulmonary disease patient ABG:arterialblood gas; Pa,O2:

suspected,consider combination therapy arterialoxygen tension; O2: oxygen; Sa,O2:arterialoxygen saturation;

Pa,CO2:arterialcarbon dioxide tension; NPPV:noninvasivepositive MDI:metered-doseinhaler #:purulenceand/ or volume pressureventilation 942 B R CELLI ET AL and medicalstatus should be completed Ifthe patient no NPPV requires the same level of supervision as conventional longer meets the prescribing criteria for LTOT,oxygen should mechanical ventilation be discontinued, as there is no proven survival bene® tfor Contraindications for NPPV include the following:respira- patients withmild hypoxaemia [91] Patients recovering from tory arrest; cardiovascular instability(hypotension, arrhyth- an exacerbation maybene® tfrom pulmonaryrehabilitation mias,myocardial infarction); impairedmental status, Some patients whoneeded oxygen prior to hospitalisation somnolence, inabilityto cooperate; copious and/or viscous may,over time,increase their Pa,O2 to the point that they no secretions withhigh aspiration risk; recent facial or gastro- longer qualifyfor oxygen This phenomenon is thought to be oesophageal surgery; craniofacial trauma and/or ®xed naso- due to areparative effect of LTOT Withdrawingoxygen pharyngeal abnormality;burns; and extreme obesity from these patients maynegate the reparative effect and cause NPPV can be considered successful when ABGs and pH the patient’sstatus to deteriorate to the point of meeting the improve,dyspnoea is relieved, the acute episode resolves physiologicalrequirement for oxygen Consequently, these without the need of endotracheal intubation,mechanical patients should continue their oxygen therapy without inter- ventilation can be discontinued and the patient is discharged ruption, as withdrawingtheir oxygen mightbe detrimental from the hospital [92, 93] One-year mortality was reported to be lower inpatients receiving NPPV for exacerbations of COPD,as compared to both conventional mechanical ventilation [100]and optimal Exacerbationof COPD: assisted venti ation medicaltherapy alone [101] Figure 6illustrates auseful ¯ow-chart for the use of NPPV inexacerbation of COPD complicated by acute respiratory M via echanical ventilation can be administered noninvasive failure or invasive ventilation Noninvasive is preferred whenever possible Mechanical ventilation,either "invasive" or "non- invasive",is not atherapy but it is aform of life support until Invasive ventilation Intubation should be considered in the cause underlying the acute respiratory failure is reversed patients withthe following 1) NPPV failure: worsening of withmedical therapy [94±96] Patients considered for mechan- ABGs and or pH in1± 2h;lack of improvement in ABGs and icalventilation should have ameasurement of ABGs or pH after 4 h 2) Severe acidosis (p H57 25) and hypercapnia (Pa,CO2 48 kPa (60 mmHg)) 3) Life-threatening hypoxaemia (arterial oxygen tension/inspiratory oxygen fraction 526 6 kPa (200 mmHg)) 4) Tachypnoea 435 breaths·min-1 Indicationsfor mechanicalventilation

The institution of mechanical ventilation should be consi- Criteria for hospitaldischarge dered when,despite optimalmedical therapy and oxygen administration there is acidosis (p H57 35) and hypercapnia Asageneral rule, patients hospitalised for an acute (Pa,CO2 46± 8 kPa (45± 60 mmHg)) and respiratory frequency exacerbation can beconsidered for discharge once the reasons 424 breaths·min-1

Exacerbation of COPD requiring ventilatory support Modesof mechanical ventilation

Mechanical ventilation can be delivered as follows 1) Contraindication Through anendotracheal tube, by passing the upper airway, for NPPV? i e "conventional " or "invasive" mechanical ventilation 2) Without the use of an endotracheal tube, i e "noninvasive " Yes No mechanical ventilation or NIMV,whichcan be instituted in two modes: noninvasive positive pressure ventilation ( NPPV) (nasal or face masks); or negative pressure ventilation ( e g Intubate NPPV with iron lung,not recommended) MV monitoring

Weaning Noninvasive positive pressure ventilation NPPV is by far the Improvement in most popular mode of providingnoninvasive ventilation It is pH, Ê a,CO2 typicallyadministered as acombinationof continuous positive clinical status airwaypressure ( CPAP)plus pressure support ventilation (PSV) [94± 98] ABG improve because of an increase inalveolar No ventilation without signi®cant modi®cations inthe alveolar Yes ventilation/perfusion mismatching and gas exchange inthe Intubate lungs [99] Continue NPPV MV 48 h ABGsare fundamental for the correct assessment and guidance of therapy Once baseline ABGsare obtained, if the 2-h T-tube trial pH is 57 35 inthe presence of hypercapnia, NPPV should be delivered ina controlled environment such as intermediate Wean to complete Success Failure ICUsand/or high-dependency units If the pH is 57 25, NPPV disconnection should be administered inthe ICU and intubation should be Discontinue MVNPPV readily available The combinationof some CPAP (e g 4± 8 cmH O) and PSV (e g 10± 15 cmH O)provides the most 2 2 Fig 6 ± Flow-chartfor theuse of noninvasive positive pressure effective mode of NPPV ventilation( NPPV)duringexacerbation of chronic obstructive pulmo- Patients meeting exclusion criteria should be considered for narydisease ( COPD)complicatedby acute respiratory failure MV: immediateintubation and ICU admission Inthe ®rst hours, mechanicalventilation; Pa,CO2:arterialcarbon dioxide tension ATS/ERSCOPD STANDARDS 943 for admissionare controlled and/or reversed Based on [103, 104] Neglect inoffering patients and their families consensus, conditions that need to be met when considering appropriate resources for supportive end-of-life care results in patients for discharge include:symptoms returning to base- unnecessary admissions to acute care hospitals for worsening line,including eating, sleeping, etc ;haemodynamicstability; respiratory symptoms oxygenation returning to baseline; inhaled b-agonist therapy required less frequently; abilityto resume ambulation;ability to eat and sleep without frequent awakeningby dyspnoea; Integrateddisease management for primarycare in off-parenteral therapy for 12± 24h;patient (or home care- giver) understands correct use of medications; follow-upand COPD homecare arrangements have been completed ( e g visiting nurse, oxygen delivery, mealprovisions etc ) Disease management can be regarded as an integrated and systematic approach inwhich healthcare providers work together inacoordinated and cooperative manner to produce an optimaloutcome for aparticular patient with COPD, throughout the entire continuum of care [105] Theconcept of Follow-upevaluation the disease as acontinuum isdepicted in®gure 7 This ® gure also represents the navigationtool for the web-based Once discharged, the patient should be followed There are Standards for the Diagnosis and Treatment of Patients with no studies that have addressed the speci® cschedules more COPD document 2004 likelyto result ina positive outcome, but patients with Integrated care for COPD involves the patient and ateam frequent exacerbations are more likelyto relapse Likewise, ofclinicalprofessionals workingin primary care, cooperating patients whohave developed respiratory failure requiring withsecondary care and rehabilitation services Optimal admissionto an ICU carry avery highmortality risk Based disease management involves redesigning standard medical on this, the guidelines for the re-evaluation of patients care to integrate rehabilitative elements into asystem of admitted for exacerbation of COPD should include:reassess- patient self-management and promotion of ahealthy lifestyle ment within4 weeks; evaluation of improvement insymptoms The followingaspects are important: smokingcessation for and physical exam;assessment of need for supplemental allpatients whosmoke; early diagnosis and secondary oxygen; repeat examinationif previous abnormalities were prevention (healthy lifestyle, vaccinations, exercise); educa- present; assessment of abilityof the patient to cope withthe tion and self-management; pulmonaryrehabilitation; mon- environment; an understanding and re-adjustment of the itoring and early recognition of exacerbation; implementation treatment regimen of rapid action plan;careful attention to end-of-life issues; palliativecare

Ethica and pa iativecare issues inCOPD Referral indications

Patients with COPD experience acute exacerbations of their Referral to specialist care is indicated for COPD patients disease, whichmay produce respiratory failure and apossible withthe following:disease onset at age 540yrs; frequent need for either ventilatory support or accepting death No exacerbations (two or more per year) despite adequate clinicalfeatures can identify patients withrespiratory failure treatment; rapidlyprogressive course of disease (decline in whowill experience more burden than bene® tfrom life sup- FEV1,progressive dyspnoea, decreased exercise tolerance, portive care unintentional weight loss; severe COPD (FEV1550% pred) Ifthe patient has, or can have, clear preferences about despite optimaltreatment; need for LTOT;onset of co- treatment, respect for the patient requires that care providers morbidillness (osteoporosis, heart failure, bronchiectasis, give effect to the patient ’s views Autonomy of the patient is lungcancer); evaluation for surgery the predominant ethical principle that drives end-of-life decision-making inmany societies Allhealthcare providers should assist patients during stable periods ofhealth to think about their advance care planning Clinical presentation by initiatingdiscussions about end-of-life care These discus- At riskSymptomatic Exacerbations Respiratory sions should prepare patients withadvanced COPD for a failure life-threatening exacerbation of their chronic disease, while assisting them to go on livingand enjoyinglife Pulmonary Interventions rehabilitation provides an important opportunity to assist advance care planningfor patients withmoderate-to-severe Smoking cessation COPD Educational programmes on advance care planning withinpulmonary rehabilitation increase the adoption rate for Disease management instruments of advance care planningand patient-physician discussion about end-of-life care [102] Patients whochoose to Pulmonary rehabilitation refuse life supportive care orhave it withdrawnrequire expert delivery of palliativecare Other options Patients with COPD sometimes qualifyfor formal hospice services, especially when they are havingrepeated exacerba- tions and very poor measures on tests of pulmonaryfunction Disease progression Symptoms Nevertheless, manypatients willhave afatal exacerbation FEV1 withina short time of havingfairly good function, so one cannot waitto consider using hospice untildeath is nearly certain Opportunities for hospice care are frequently neg- Fig 7 ± Continuumof care for chronicobstructive pulmonary disease lected for patients comingto the end of life with COPD (COPD) FEV1:forcedexpiratory volume in one second 944 B R CELLI ET AL

Conc usions 15 Anto JM, Vermeire P, Vestbo J, Sunyer J Epidemiologyof chronicobstructive pulmonary disease Eur Respir J 2001; This summary presents an overview of the entire document 17: 982± 994 for the health practitioner, whichis readily availableonline 16 Fletcher CM, Tinker CM, Peto R, Speizer FE The natural (www copd-ats-ers, www ersnet org and www thoracic org) historyof chronicbronchitis and emphysema Oxford, This summary does not include any reference to the patient Oxford University Press, 1976 document, which,due to its inherent characteristics, cannot 17 Gold DR, Wang X, Wipyj D, Speizer FE, Ware JH, Dockery be presented ina conventional format The readers are DW Effectsof cigarettesmoking on lung function in adolescentboys and girls N Engl J Med 1996; 335: 931± 937 encouraged to visit the website to access both fulldocuments 18 Saetta M, Di Stefano A, Turato G, et al CD8+ The committee that developed this document fullyunder- T-lymphocytesin peripheral airways of smokerswith chronic stands that the ®eld is rapidlychanging and that individual obstructivepulmonary disease Am J Respir Crit Care Med components of this document need to be updated periodically 1998; 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