advances in chronic obstructive pulmonary disease

CLINICAL PERSPECTIVES

Advances in chronic obstructive pulmonary diseaseC. F. McDonald and Y. Khor

Respiratory and Sleep Medicine, Austin Hospital, Melbourne, Victoria, Australia

Key wordsCOPD, chronic obstructive pulmonary disease,

chronic, lung disease, update.

CorrespondenceChristine F. McDonald, Respiratory and Sleep

Medicine, Austin Hospital, Studley Road,

Heidelberg, Vic. 3084, Australia.

Email: [email protected]

Received 13 November 2012; accepted 28 May

2013.

doi:10.1111/imj.12219

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow

limitation in the presence of identifiable risk factors. Inflammation is the central patho-

logical feature in the pathogenesis of COPD. In addition to its pulmonary effects, COPD

is associated with significant extrapulmonary manifestations, including ischaemic heart

disease, osteoporosis, stroke and diabetes. Anxiety and depression are also common.

Spirometry remains the gold standard diagnostic tool. Pharmacologic and non-

pharmacologic therapy can improve symptoms, quality of life and exercise capacity and,

through their effects on reducing exacerbations, have the potential to modify disease

progression. Bronchodilators are the mainstay of pharmacotherapy, with guidelines

recommending a stepwise escalating approach. Smoking cessation is paramount in

managing COPD, with promotion of physical activity and pulmonary rehabilitation

being other key factors in management. Comorbidities should be actively sought and

managed in their own right. Given the chronicity and progressive nature of COPD,

ongoing monitoring and support with timely discussion of advanced-care planning and

end-of-life issues are recommended.

Background and epidemiology

Chronic obstructive pulmonary disease (COPD) repre-sents a spectrum of lung diseases characterised by persis-tent airflow limitation due to varying combinations ofsmall-airways disease (obstructive bronchiolitis) andemphysema. It is a major cause of morbidity and disabil-ity, having a prevalence of around 10% in those agedover 40 years.1,2 By 2030 COPD is predicted to havebecome the third-leading cause of death worldwide, with90% of those deaths occurring in low- and middle-income countries. In Australia, COPD is responsible for4% of all deaths in recent years and is the only majorcondition for which the burden of disease continues toincrease as our population ages.3 Australian death ratesfrom COPD per head of male population have declinedsubstantially since their peak in the 1970s, reflectingchanges in tobacco consumption. By contrast, femaledeath rates peaked in the 1990s and have stabilised,reflecting the increased uptake of smoking by womenover the last 3–4 decades.3

Cigarette smoking is the most important risk factor forCOPD. Although traditional teaching suggested 10–15%of smokers develop COPD, recent studies indicate somedegree of airflow limitation is present in up to 50% ofsmokers, with clinically significant COPD being present inaround 25%.4 It is increasingly recognised that a signifi-cant proportion of patients with COPD are non-smokers.5

This proportion is generally higher in developing coun-tries where exposure to biomass smoke for heating andcooking is common (for example up to nearly 70% ofpeople in India with COPD are non-smokers),5 but is stillsignificant in the developed world, with just under 40% ofpeople in a recent New Zealand study being never-smokers,6 and overall international figures ranging from25% to 45%.7 Other risk factors include maternalsmoking, long-standing asthma and respiratory symp-toms, exposure to second-hand smoke and occupationalexposures to dusts and fumes. Genetic susceptibility is animportant factor in disease development, with the mostwell-established genetic factor, α1-antitrypsin deficiency,being present in 1–2% of individuals with COPD.

Diagnosis

Spirometry is required to make a diagnosis of COPD. Amedical history and clinical examination may suggest thediagnosis, but they are not reliable predictors of airflowobstruction. In the presence of symptoms such as

Funding: None.Conflict of interest: Christine McDonald has served on advisoryboards for GlaxoSmithKline, Novartis, Pfizer; received confer-ence support from Nycomed; has given presentations at educa-tional meetings sponsored by Boehringer Ingelheim andNovartis.

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Internal Medicine Journal 43 (2013)

© 2013 The AuthorsInternal Medicine Journal © 2013 Royal Australasian College of Physicians854

shortness of breath, cough and/or sputum productionand a history of relevant exposure(s), an individual witha post-bronchodilator forced expiratory volume in onesecond (FEV1) to forced vital capacity (FVC) ratio (FEV1/FVC) of less than 0.7 (indicating airflow limitation that isnot fully reversible) is deemed to have COPD. This defi-nition is widely accepted because of its practicality, al-though its use may lead to overdiagnosis in the elderly (asFEV1 declines more rapidly with age than does FVC) andunderdiagnosis in younger adults. Consequently, someauthors recommend that a lower limit of normal (fifthpercentile of the normal distribution range of FEV1/FVCvalues) be applied. Unfortunately, by whatever definitionairflow obstruction is measured, spirometry continues tobe infrequently performed, even among those hospital-ised for ‘exacerbation of COPD’ in Australia. Only 51% ofa recently audited group of patients admitted to hospitalwith this diagnosis had undergone lung function testingin the 5 years prior to admission or during hospitalisa-tion.8 This lack of confirmatory testing contributes toboth under- and overtreatment of such patients.

Pathology

COPD is a chronic inflammatory airway disease, butdiffers significantly from asthma in that the inflammationis relatively resistant to treatment with corticosteroids.Exposure to noxious injury triggers a predominantlyneutrophilic infiltration with activation of the innateimmune response. An inflammatory cascade ensues,with induction of type 1 and type 17 T helper cells andthe subsequent development of transforming growthfactor β-induced small-airway fibrosis and matrixmetalloproteinase elastic tissue destruction.9 Theseresponses appear to perpetuate even after removal of theinitial stimulus10 and may be associated with ‘spillover’ ofthe inflammatory response from the lungs to the systemiccirculation, leading to potential downstream effects, suchas arterial stiffness and its consequences. Parenchymaldestruction is associated with loss of lung tissue elasticityand small-airways collapse during exhalation, leading toso-called ‘gas trapping’, while goblet cell metaplasia andimpaired mucociliary function contribute to excessmucus accumulation and worsening obstruction.

Overlap of COPD and asthma

The definition of COPD is quite broad and may include avariety of patients with distinct clinical and other featureswho may both present differently and respond differentlyto treatment (so-called ‘clinical phenotypes’). Manypatients with COPD will report a history of asthma. Thisdual diagnosis or ‘overlap syndrome’ may be recognised

through symptoms associated with variable airflowobstruction as well as incomplete reversibility of airflowobstruction on lung function testing.11 There is increasingevidence that patients with COPD and asthma experiencemore rapid disease progression than those with eitherdisease alone. Airway hyperresponsiveness and an asthmadiagnosis have been associated with a greater decline inFEV1 in both smokers and non-smokers. Patients withoverlap syndrome have worse health-related quality oflife and experience more frequent and severe respiratoryexacerbations, despite younger age and reduced lifetimesmoking exposure, when compared with those withCOPD alone.12 The evidence base for management of thissubgroup of patients is relatively limited, as they arecommonly excluded from clinical trials.

Systemic effects and comorbidities

It has been proposed that the term ‘chronic systemicinflammatory syndrome’ be applied to COPD in order tohighlight the underlying inflammatory responsecommon to both COPD and many of its associatedcomorbidities, which are also commonly associated withsmoking.13 Features include systemic oxidative stress,changes in vasomotor and endothelial function andenhanced circulating concentrations of procoagulantfactors.13 Using a UK-wide validated primary care data-base, Feary et al. observed a fivefold increase in risk ofcardiovascular disease, a threefold increase in risk ofstroke and a twofold increase in risk of diabetes inpatients with physician-diagnosed COPD.14 Suggestedmechanisms, over and above smoking, that may beimplicated in these interactions include increased aorticstiffness and associated left ventricular dysfunction, aswell as increased platelet activation.15 Of note is the factthat having COPD increases the risk of lung cancer by upto 4.5-fold among long-term smokers.16 Consideringlung- and non-lung-related manifestations of COPD as a‘syndrome’ akin to the way in which we think of themetabolic syndrome, for example, may encourage inves-tigation and appropriate management of some of themore common comorbidities described in associationwith COPD, including those mentioned as well as osteo-porosis, hyperlipidaemia, hypertension, skeletal muscleabnormalities, anxiety and depression.

Acute exacerbations of COPD

An exacerbation of COPD is defined as an acute eventcharacterised by a worsening of the patient’s respiratorysymptoms that is beyond normal day-to-day variationsand necessitates a change in medication.17 COPD exacer-bations are associated with considerable morbidity,

Advances in COPD

© 2013 The AuthorsInternal Medicine Journal © 2013 Royal Australasian College of Physicians 855

mortality and healthcare costs. They are the secondleading cause of hospitalisations in Australia.18 Exacerba-tions become more frequent as the severity of COPDworsens.19 Following hospitalisation for an exacerbation,quality of life and lung function decline, and patients are atrisk for further serious exacerbations. A primary goal oftreatment in COPD is therefore to reduce exacerbations.Triggers for acute exacerbations include viral and bacterialinfections as well as environmental pollutants, heartfailure, pulmonary embolism and other factors.20 Prompttreatment with short-acting bronchodilators, antibiotics asappropriate and corticosteroids has been demonstrated tohasten resolution and reduce need for hospitalisation.21

Non-invasive ventilatory support is indicated for hype-rcapnic respiratory failure and is effective in avoidingintubation and reducing risk of death.22 Mortality afterhospitalisation for acute exacerbation may be as high as22% at 12 months,23 although more recent data suggest atrend towards improved outcomes.24 An admission tohospital with an exacerbation of COPD is a sentinel eventthat should give pause for review of current management,including preventive therapies. Such episodes should actas a trigger for discussion about advanced-care planningand wishes concerning non-invasive and invasive venti-lation should the need arise. Recent data suggest earlypulmonary rehabilitation following exacerbation andhospitalisation may decrease readmission, and NationalInstitute for Health and Care Excellence guidelinesrecommend this as standard of care.25

Management of stable COPD

Although severity of airflow obstruction is classifiedaccording to FEV1 (as a percentage of the predictednormal value), and spirometry is essential in determiningwhether the probable cause of respiratory symptoms isCOPD, clinical criteria, such as degree of breathlessnessinduced by daily activities and frequency of exacerba-tions, should also be used when evaluating overalldisease severity.26,27 Validated tools, such as the modifiedMedical Research Council breathlessness scale and theCOPD Assessment Test, may be helpful in assessingdisease impact and treatment response.17

The goals of management in stable COPD are to reducesymptoms, reduce the frequency and severity of exacer-bations, improve exercise tolerance and health-relatedquality of life, slow disease progression and reducemortality. Both pharmacologic and non-pharmacologicstrategies may be employed. Guidelines for COPD man-agement recommend a stepwise escalation of therapybased on disease severity. Two guidelines commonly usedin Australia are the Global Initiative for Chronic Obstruc-tive Lung Disease (GOLD) Strategy Document17 and the

locally developed COPD-X guideline.26 The recentlyupdated (2011) GOLD Document has adopted a newstratification for disease severity, based on exacerbationrates and symptom scores in addition to degree of airflowobstruction. This is not significantly different fromCOPD-X, which determines severity based on clinicalhistory and functional assessment as well as spirometryand emphasises consideration of the presence and treat-ment of complications and comorbidities in their ownright.

Smoking cessation

Preventing or limiting lung damage through smokingcessation should be the foremost goal for all physiciansmanaging COPD. Of course, all smokers should beencouraged to stop smoking, whether or not they haveCOPD. Smoking cessation reduces rate of decline of FEV1as well as improving respiratory symptoms and health-related quality of life. To date, smoking cessation andhome oxygen therapy (in severely hypoxaemic individ-uals) are the only strategies conclusively demonstrated toimprove mortality in COPD. Even brief counselling canbe effective. But additional strategies may be required forpatients who continue to smoke despite having lungdisease. All forms of nicotine replacement therapy (NRT)appear to assist smoking cessation in dependent smokers,and NRT is safe even in acute coronary syndromes.Agents such as the antidepressant and selectivecatecholamine reuptake inhibitor buproprion and theα4β2 nicotinic acetylcholine receptor partial agonistvarenicline are also effective. All pharmacologic therapiesmust be combined with support and counselling formaximum efficacy.26

Pharmacotherapy

The aims of pharmacotherapy in COPD are to relievesymptoms (notably, breathlessness) and to preventdeterioration, either by reducing exacerbations or byreducing decline in quality of life, or both.Bronchodilators remain the mainstay of therapy forCOPD and include short- and long-acting β2 agonists(SABA and LABA) as well as short- and long-actingmuscarinic antagonists (SAMA and LAMA).They canimpact the gas trapping that is a feature of COPD, induc-ing improvements in inspiratory capacity and end-expiratory lung volume that may improve breathlessnessand exercise capacity even in the absence of a demon-strable ‘bronchodilator response’ on simple spirometrictesting. In addition to improving symptom control, bothLAMA and LABA have been shown to reduce exacerba-tions and hospitalisations and to improve lung function.27

McDonald & Khor


Despite the relative corticosteroid insensitivity of theinflammatory response in COPD, the addition of aninhaled corticosteroid is recommended in patients withmoderate to severe COPD, especially in those with recur-rent exacerbations, because of additional benefits interms of reduced exacerbations as well as improvedquality of life. These small additional benefits must bebalanced against an increased risk for pneumonia andlocal side-effects of dysphonia and upper-airway candidi-asis.28 Inhaler technique must be assessed regularly, andmedications reviewed and either continued or discon-tinued based upon treatment response and tolerability. Itis important that both patient and treating doctor areclear as to the expectations from treatment (for example,whether the treatment aims purely at symptom controlor is aimed at longer-term outcomes such as preventionof exacerbations and/or hospitalisations, or both).

Newer therapies

Indacaterol is a novel ‘ultra-LABA’ with 24-h bronchodi-lator efficacy allowing once-daily dosing. It may besuperior to conventional LABA in patients with moderateto severe COPD and is comparable in efficacy withtiotropium.29 The combination of indacaterol plustiotropium provides additional bronchodilation com-pared with each treatment alone.30 As understandingof COPD inflammatory pathways increases, newertherapies targeting inflammatory molecules have beendeveloped. Roflumilast, a selective phosphodiesterase-4inhibitor, has recently been approved for use in severalcountries for treatment of severe COPD (although not yetin Australia). It has been shown to be effective, withwell-tolerated side effects,31 and may be suited forpatients with severe COPD and frequent exacerbations.32

However, long-term data on efficacy and adverse eventsare not yet available, and its role in patients alreadyreceiving standard combination therapy is yet to be deter-mined.33 Although standard-dose theophylline is consid-ered a third- or fourth-line treatment in COPD, low-dosetheophylline has recently been raised as a possibleadjunct to current inhaled therapies, given experimentaldata demonstrating it enhances anti-inflammatory effectsof inhaled corticosteroids in COPD airways throughmodification of histone deacetylase-2. Nonetheless,large-scale clinical trials investigating exacerbationreduction through this mechanism are awaited.34 Giventhe known anti-inflammatory and immunomodulatoryeffects of macrolide antibiotics, several studies haveevaluated their effects on reducing COPD exacerbations.A recent study found a decreased rate of exacerbations inpatients treated with daily azithromcyin.35 Adverseeffects included ototoxicity and increased macrolide

resistance. Azithromycin is also associated with cardiactoxicity.36 It remains to be seen what the treatment effectof chronic macrolide therapy is in COPD patients treatedmaximally with conventional therapies and whetherbenefits will outweigh risks to the individual and thecommunity from their more widespread use.

Management of cardiac disease asa comorbidity

The importance of managing the common comorbiditiesin COPD, which may be considered either as ‘fellowtravellers’ or as components of a chronic systemicinflammatory complex, is increasingly recognised. Manypatients with COPD die from cardiovascular disease,and the prevalence of ventricular dysfunction inpatients with COPD ranges from 9% to 52%. Diagnos-ing cardiac disease in COPD is made more difficult bysimilar presenting features, which, in both cases, mayinclude breathlessness, fatigue and even chest discom-fort. Beta-blockers have proven mortality benefits incardiac disease, but their use remains low in patientswith COPD because of their potential to provoke acutebronchospasm and worsen respiratory symptoms. Con-cerns have been allayed to some extent by a recentmeta-analysis suggesting that cardioselective beta-blockers are safe and well tolerated even in patientswith severe airflow obstruction.37 Nonetheless, theincluded studies were of short duration in smallnumbers of patients, thus providing little guidanceabout long-term safety and potential morbidity. Recentlarge observational database studies of patients withCOPD added reassurance with the finding of beneficialeffects of beta-blockers on overall mortality, withoutadverse effects on lung function.38,39 European Societyof Cardiology guidelines assert that COPD is not a con-traindication to the use of beta-blockers.40 Althoughlow-dose initiation and gradual up-titration is recom-mended, and mild deterioration in pulmonary functionand symptoms should not necessarily prompt discon-tinuation, prudence would dictate a cautious approachin the absence of long-term prospective data.

Other comorbidities should be managed according toappropriate guidelines.

Vaccination

Influenza vaccine reduces the number of acute exacer-bations that occur in persons with COPD, but evidenceregarding its effects on hospitalisations and mortality isinconclusive. Pneumococcal vaccine reduces the inci-dence of invasive pneumococcal disease, but there is alack of evidence concerning its effect on morbidity or

Advances in COPD


mortality in people with COPD.41 National Health andMedical Research Council guidelines recommend yearlyinfluenza vaccinations and up-to-date pneumococcalvaccination for people with COPD.

Activity promotion, pulmonaryrehabilitation and disease management

When patients with COPD begin to feel short of breathwith activity, they typically reduce their activities andbecome more sedentary. COPD results in systemic func-tional limitations that lead to physical deconditioning andthe development of the so-called ‘dyspnoea spiral’: pro-gressive deconditioning and ever-worsening dyspnoea.Regular physical activity is recommended for all peoplewith COPD and has been associated with reduced risk ofhospital admissions.

In people with moderate to severe COPD, participationin outpatient pulmonary rehabilitation (generally around6–8 weeks of graded exercises and education incorporat-ing self-management education, provided by a multidis-ciplinary team) is associated with improved exercisecapacity, less breathlessness and better quality of life and,in those who have been hospitalised, with reduced hos-pital admissions and mortality.42

Action plans have been effective in asthma. Theyallow patients to develop coping skills, to anticipateearly exacerbation symptoms, to self-initiate appropriatetreatment and to seek medical advice prior to significantdeterioration. COPD exacerbations are common inpatients with moderate to severe COPD and may lead tohospitalisation. Trials assessing the effects of action plansin COPD management have shown conflicting results,with variable adjuncts to patient care in these trialslikely contributors. Those with positive results, such asexpedited exacerbation recovery and reduced hospitaladmissions, have included additional supports, such asintensive education and case management.43–45 In con-trast, action plans with limited or no self-managementeducation and no case management have little benefi-cial effect.46 In view of the healthcare cost implicationsof COPD exacerbations, various models of self-management have been initiated in national healthcaresystems, but the evidence for benefit has not beenconfirmed. Programmes may include self-managementeducation about disease, optimisation of evidence-basedmedications, information and support from case man-agers and institution of self-management principles. A2007 Cochrane meta-analysis concluded that self-management education in COPD was likely associatedwith reduced hospital admissions and no detrimentaleffects, but determined that larger randomised con-trolled trials were required before clear recommenda-

tions could be made.47 A recent UK study included ahigh-risk group of patients with COPD who had beenrecently hospitalised and reported no overall effect of aself-management programme on readmissions anddeath.48 However, only 42% of the patients were suc-cessful self-managers, and these individuals did haveimproved outcomes. A recent US study has raisedconcern.49 This multicentre trial of a comprehensiveCOPD care programme was discontinued prematurelyby the data monitoring committee after only 44% ofthe planned 960 patients were enrolled, because of anexcess of deaths in the intervention group (28 vs 10).The primary outcome of admission did not differbetween the groups. It is not clear why so many deathsoccurred in the intervention group. Although perhapsthis was a chance occurrence, more studies are neededto determine the role of disease management in COPD.

Oxygen therapy

The use of domiciliary oxygen is common at the moresevere end of the COPD spectrum. In 2005 21 000 Aus-tralians were receiving domiciliary oxygen therapy, at anestimated annual cost of over A$32 million, with themajor indication being COPD.50 Long-term continuousoxygen therapy has been proven to offer survival benefitsin patients with COPD and severe hypoxaemia (PaO2 ≤55 mmHg or 55–59 mmHg with evidence of end-organdamage). However, the role of oxygen therapy in patientswith exertional desaturation, nocturnal hypoxaemia orresting mild to moderate hypoxaemia is less clear. Recentstudies suggest an absence of long-term effects on breath-lessness or quality of life from the use of ambulatoryoxygen therapy in normoxaemic or mildly hypoxaemicpatients with COPD who desaturate with exertion, eventhough they may demonstrate small acute benefitsduring laboratory-based exercise tests.51,52 Nonetheless,occasional so-called ‘n-of-1 trials’ may be of use in someindividuals.52 Isolated nocturnal hypoxaemia is notuncommon in COPD patients, particularly during rapideye movement sleep. However, it has not been shown tolead to worse quality of life, daytime hypoxaemia orpulmonary hypertension. Limited studies have not con-sistently shown beneficial effects in sleep quality, pulmo-nary haemodynamics or survival over 2 years withnocturnal supplemental oxygen.53–55 Similarly, patientswith COPD and resting mild-to-moderate hypoxaemiahave not shown a survival benefit with domiciliaryoxygen therapy. The currently recruiting US Long-termOxygen Treatment Trial (NCT00692198) may providemore data regarding the effects of domiciliary oxygen inthe latter patient subgroup.

McDonald & Khor


Non-invasive ventilation:acute versus stable

Non-invasive ventilation (NIV) is considered the standardof care for patients with acute exacerbations of COPDassociated with hypercapnic respiratory failure and aci-dosis. It has been shown to reduce mortality, need forintubation, treatment failure, treatment complicationsand length of hospital stay.22 Patients who survive afteran episode of acute hypercapnic respiratory failuretreated with NIV are at high risk of readmission andlife-threatening events during the following year.Although there are theoretical reasons why chronic NIVmay benefit such patients, results from randomised con-trolled trials have been conflicting. A systematic reviewconcluded there was no consistent clinically or statisti-cally significant effect of domiciliary NIV on lung func-tion, gas exchange, exercise tolerance, respiratory musclestrength or sleep efficiency.56 However, many includedstudies had small sample sizes, included patients withoutsignificant hypercapnia, were of limited duration and/orused low levels of inspiratory pressure support. An Aus-tralian study randomised 144 patients to receive homeNIV plus long-term home oxygen therapy versus oxygenalone.57 Home NIV was associated with an improvementin survival up to 3.5 years, at the expense of worsequality of life. In summary, NIV may be a therapeuticoption in stable COPD patients with chronic ventilatoryfailure, but further long-term randomised controlledtrials are awaited.

Interventional therapy: surgeryand devices

In patients with very severe COPD who remain incapaci-tated by dyspnoea despite maximal therapy, various sur-gical approaches have been trialled. Currently availablesurgical interventions include lung transplantation, lungvolume reduction surgery and bullectomy. Since the firstsuccessful clinical lung transplant in 1983, transplanta-tion has become a treatment option for selected patientswith end-stage COPD, with improved survival. However,transplantation is limited by donor availability, the needfor lifelong immunosuppression and its complicationsand the development of chronic allograft dysfunction inthe form of bronchiolitis obliterans. In patients withemphysema, lung volume reduction surgery (LVRS) isaimed at relieving the hyperinflation and gas trappingassociated with inadequate lung emptying and its associ-ated mechanical disadvantage. LVRS and bullectomy inselected patients have been shown to improve lung func-tion and exercise capacity in the long term, althoughperioperative morbidity (most commonly parenchymal

air leaks) and mortality are significant.58 The majority ofpatients with end-stage COPD are not suitable surgicalcandidates because of their physiological fragility.Current selection guidelines for LVRS are largely basedupon the results of the National Emphysema TreatmentTrial inclusion criteria and outcome data and includebilateral, upper-lobe-predominant emphysema with sig-nificant hyperinflation and air trapping and a lowmaximal workload after pulmonary rehabilitation.59

In order to obviate the need for surgery, there has beenconsiderable recent interest in the development ofbronchoscopic techniques for lung volume reduction.Modalities employed have included endobronchial valvesor blockers, airway bypass, biologic sealants and airwayimplants. Endobronchial one-way valves block theairway leading to the targeted emphysematous lung.Apart from allowing air to be vented and preventingrefilling, these valves also allow expulsion of mucus tominimise postobstructive infection. Modest improve-ments in lung function, exercise tolerance and symptomshave been demonstrated in selected patients withadvanced heterogenous emphysema using endo-bronchial valves, although efficacy is variable andadverse effects include increased risk of COPD exacerba-tions, haemoptysis and pneumonia.60 Bronchoscopicthermal vapour ablation (BTVA) is a newer techniquethat utilises heated water vapour to induce thermal reac-tion and subsequent inflammatory response with perma-nent fibrosis and atelectasis, leading to reduction involume of the targeted regions. Australia was involved inthe first human study of BTVA for lung volume reductionin upper-lobe-predominant emphysema. Results indicatethat BTVA significantly improves lung function, symp-toms and exercise tolerance.61 The most common adverseeffects of BTVA are lower respiratory events, pneumoniaand haemoptysis. These complex procedures requirecareful patient selection and assessment by a multidi-sciplinary team at a specialised centre to ensure bestoutcomes.

Prognosis, palliative care andadvanced-care planning

Lung function impairment is a strong predictor of mor-tality; however, use of lung function alone to classifydisease severity does not capture the multidimensionalnature of COPD. In patients with established COPD avariety of indices has been proposed that enhance theability to predict mortality. Degree of hyperinflation asmeasured by inspiratory capacity/total lung capacity ratiois more closely associated with all cause and COPD mor-tality than FEV1.62 The BODE index, incorporating bodymass index, degree of obstruction as measured by FEV1,

Advances in COPD


dyspnoea score and exercise capacity as measured by 6minutes’ walk distance into a common index, enhancesthe ability to predict mortality.63 Further, the presence ofcomorbid disease increases the risk of both hospitalisationand mortality. The predominant causes of mortality inpatients with mild disease are cardiac disease and malig-nancy, while as COPD severity increases, deaths due torespiratory disease are increasingly common.

Severe dyspnoea, cough, fatigue, social isolation,anxiety and depression are all features of late-stage COPDthat adversely impact quality of life. The COPD diseasecourse is often punctuated by recurrent exacerbationsthat may require hospitalisation and consideration ofassisted ventilation. Hospitalisation for acute exacerba-tion increases subsequent mortality risk. As the diseaseprogresses a more palliative approach to care may beappropriate. Determining prognosis in end-stage COPD isdifficult; however, characteristics that should trigger dis-cussions about a palliative approach to care, advanced-care planning and end-of-life issues include FEV1 < 25%,oxygen dependence, respiratory failure, heart failure orother comorbidities, weight loss or cachexia, decreased

functional status, increasing dependence on others, andadvancing age.64 Ideally, end-of-life discussions, includ-ing resuscitation and intubation wishes, and advanced-care planning, including consideration of the confermentof a medical enduring power of attorney, should occur inan outpatient setting when the patient’s condition isrelatively stable.

Conclusion

COPD is a common disease associated with significantmorbidity and mortality. Spirometry is key to its diagnosisand is required in order to avoid under- andovertreatment. Smoking cessation and oxygen therapy inthose who are hypoxaemic may reduce mortality.Pharmacologic and non-pharmacologic therapy canimprove symptoms, quality of life and exercise capacityand, through their effects on reducing exacerbations,have the potential to modify disease progression.Comorbidities are common and require targetedtreatment.

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McDonald & Khor


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