 \210\206V \210\206EELV \210\206P RV Pressure Volume TLC COPD \210\206V \210\206EELV \210\206P RV Pressure Fig. 5.2.5 Pressure-volume curves at rest (dotted) and on exercise (solid) in a normal indi vidual and a person with COPD showing the higher residual volume (RV) and total lung capaci ty (TLC), differential change in end-expiratory lung volume (EELV) and the reduced changes in volume(ZV) for a given transpleural pressure change (ZP). D HALPIN 96 COPD exacerbation Increased ventilatory drive - d PaO2 - i PaCO2 - d pH Tachypnoea (e.g. anxiety) Worsening expiratory flow limitation Dynamic hyperinflation (i EELV, d IC) Gas exchange Mechanical disadvantage Cardiovascular effects - i Pulmonary Neuromechanical uncoupling - Dyspnoea i VD/VD due to i PEEPi - d CDYN - i Elastic/threshold loading of inspiratory muscles constraint of VT arterial pressure d RV preload - i LV afterload Inspiratory muscle dysfunction Fig. 5.2.6 The pathophysiological consequences of worsening air \202 ow limitation and dyn amic hyperin \202 ation. Reproduced with permission from Thorax 2006; 61: 354 \200\223361. COPD is also associated with systemic endothelial dysfunction and central nervous system ab normalities (including depression) which may also be due to the effects of systemic in \202 ammation. MacNee W. Pathophysiology of cor pulmonale in chronic obstruc- tive pulmonary disease. Part One. Am J Respir Crit Care Med 1994; 150(3): 833 \200\223852. Magee F, Wright JL, Wiggs BR, et al. Pulmonary vascular structure and function in chronic o bstructive pulmonary disease. Thorax 1988; 43(3): 183 \200\223189. Further reading Agusti A. Thomas A. Neff lecture. Chronic obstructive pulmonary disease: a systemic disease. Proc Am Thorac Soc 2006; 3(6): 478 \200\223481. Niewoehner DE, Kleinerman J, Rice DB. Pathologic changes in the peripheral airways of young cigarette smokers. N Engl J Med 1974; 291(15): 755 \200\223758. O \200\231Donnell DE, Parker CM. COPD exacerbations. 3: Pathophysiology. Barbera JA, Roca J, Ferrer A, et al. Mechanisms of worsening gas exchange during acute exac erbations of chronic obstructive pulmonary disease. Eur Respir J 1997; 10(6): 1285 \200\223 1291. Thorax 2006; 61(4): 354 \200\223361. Saetta M, Di Stefano A, Maestrelli P, et al. Airway eosinophilia in chronic bronchitis duri ng exacerbations. Am J Respir Crit Care Med 1994; 150(6 Pt 1): 1646 \200\2231652. Gibson GJ. Pulmonary hyperin \202 ation a clinical overview. Eur Respir J 1996; 9(12):2640 \200\2232649. Saetta M, Turato G, Maestrelli P, et al. Cellular and structural bases of chronic obstructi ve pulmonary disease. Am J Respir Crit Care Med 2001; 163(6): 1304 \200\2231309. Hogg JC, Macklem PT, Thurlbeck WM. Site and nature of airway obstruction in chronic obstruc tive lung disease. N Engl J Med 1968; 278(25): 1355 \200\2231360. Shapiro SD. The macrophage in chronic obstructive pulmonary dis- Janssens JP, Pache JC, Nicod LP. Physiological changes in respiratory function associated w ith ageing. Eur Respir J 1999; 13(1): 197 \200\223205. Jeffery PK. Comparison of the struct ural and in \202 ammatory features of COPD and asthma. Giles F. Filley Lecture. Chest 2000 ; 117 (5 Suppl 1): 251S \200\223260S. ease. Am J Respir Crit Care Med 1999; 160(5 Pt 2): S29 \200\223S32. Stockley RA. Neutrophils and protease/antiprotease imbalance. Am J Respir Crit Care Med 1999; 160(5 Pt 2): S49 \200\223S52. MacNee W, Wiggs B, Belzberg AS, et al. The effect of cigarette smoking on neutrophil kineti cs in human lungs. N Engl J Med 1989; 321(14): 924 \200\223928. This page intentionally left blank J CALVERT 98 5.3 Investigations in COPD Investigations in COPD con \201 rm a diagnosis suspected on clinical grounds. Further inve stigations are used to de \201 ne the level of physiological compromise associated with th e condition and to de \201 ne interventions to be considered as part of the management pla n. The following categories of investigation will be considered: \200 lung function testi ng; \200 imaging: plain radiology; \200 cross sectional imaging; \200 oxygen assessme nt; \200 functional assessment & anthropometry; \200 bloods; \200 cardiac investigati ons. The carbon dioxide transfer coef \201 cient is also reduced in COPD and is a marker of the severity of emphysema. Imaging Radiological investigations are not required to make a diag- nosis of COPD however all patients should have a CXR to exclude other pathologies. Typical appearances of COPD on the plain radiograph include hyper-inflated lung fields (>7 posterior ribs visible overlyi ng the lung \201 elds), \202 attening of the diaphragm, horizontal ribs and narrowing o f the mediastinum. Bullae may be visible on some \201 elds. Care must be taken not to mis interpret these as evidence of a pneumothorax (Fig. 5.3.1). Lung function testing Diagnosis of COPD is suggested by a compatible symptom and exposure h istory and is con \201 rmed by the presence of air- \202 ow obstruction on lung function testing. Current UK Guidelines (NICE)(1) suggest performing lung function measurements in p atients over the age of 35 who have smoked and who describe symptoms of regular cough, whee ze, sputum production, or exertional dyspnoea. Spirometry Air \202 ow obstruction is con \201 rmed by the presence of a FEV1 of less tha n 80% predicted (de \201 ned using reference values based on a patients height, sex and ag e) and an FEV1 to FVC ratio of 70% or less. Classi \201 cation of disease severity in guid elines is based on patients FEV1 \200\223 though this may not re \202 ect degree of funct ional impairment. The severity strati- \201 cation developed by GOLD is given in Table 5. 3.1. Table 5.3.1 MRC dyspnoea scale Fig. 5.3.1 CXR showing changes consistent with COPD. Score De \201 nition 1 Not troubled by breathlessness except on strenuous exercise High resolution CT scanning (Fig. 5.3.2) may also be con- sidered. This permits identi \201 cation of large bullae or upper zone predominant emphysematous changes which may be am enable to surgery. 2 Short of breath when hurrying or walking up a slight hill 3 Walks slower than contemporaries on the level because of breathlessness, or has to stop to catch breath when walking at own pace 4 Stops for breath after about 100m or after a few minutes on the level 5 Too breathless to leave the house, or breathless when dressing or undressing Further investigations: Where there is diagnostic uncertainty and asthma is being considere d in the differential diagnosis a peak \202 ow (PEF) diary showing greater than 20% varia bility in PEF may pro- vide additional diagnostic information. Where uncertainty still exis ts reversibility testing may be carried out using spirometry pre- and post-inhaled bron- ch odilator or steroid challenge (30mg prednisolone for 10 days). A positive test is one where FEV1 improves by >15% and the magnitude of the change is at least 150ml. Where the patient \200\231s symptoms are in excess of the meas- ured spirometry detailed lung function measu rements can be made. TLC, RV and FRC are all characteristically increased in COPD and are r elated to the degree of hyperin \202 ation of the lungs. Fig. 5.3.2 Typical appearance of emphysema on HRCT. CHAPTER 5.3 Investigations in COPD 99 A-1 antitrypsin In subjects with proven COPD aged <45 assay of -1 anti- trypsin should be considered. This is an anti-proteinase inhibitor inherited on chromosome 14. 70 variants h ave been identi \201 ed. Normal variants are labeled M. The com- monest abnormal variants are designated S and Z. Subjects inheriting 2 normal versions are designated PiMM. Abnor- m al subjects may be homozygous or heterozygous for the abnormal forms of the enzyme so enzym e activity is quoted when abnormal results are quoted. -1 AT is also present in the liver so LFTs should be checked in abnormal subjects. Oxygen assessment Routine measurement of arterial blood gasses is not rec- ommended and sho uld be reserved for those with resting oxygen saturations, measured using pulse oximetry, o f less than 93% or if carbon dioxide retention is suspected. Arterial blood gasses are requ ired for assessment for long- term oxygen therapy. Mortality is improved by administra- tio n of oxygen for >15 hours per day at a rate suf \201 cient to improve pO2 to >8KpA in pati ents with chronic obstructive pulmonary disease with PaO2 < 7.3 kPa when breathing air duri ng a period of clinical stability or in patients with COPD with PaO2 7.3 \200\2238 kPa in t he presence of co-morbidities such as secondary polycythaemia, nocturnal hypoxia, periphera l oedema, pulmonary hypertension. Ambulatory oxygen may also be considered in some patients . It is usually only appropriate for those with oxygen desatu- rations of more than 4% to b elow a saturation of 90% who experience an improvement in oxygenation and exercise capacity with supplementary oxygen. Due to the subjective nature of improved exercise capacity it i s recommended that assessment for ambulatory oxygen be conducted in a blinded manner using air and oxygen cylinders. Cardiac investigations Electrocardiography A number of abnormalities may be noted on the EC G of subjects with severe COPD including right axis devia- tion (a mean electrical axis of the heart to the right of +90 ), right bundle branch block (QRS width >120ms and rSR patte rn in V1) or prominent p-waves (p-pulmonale \200\223 tall peaked p-waves in leads II, III and aVF). Echocardiography In subjects in whom cor-pulmonale is suspected the degree of pulmonary hyp ertension may be estimated by measure- ment of the velocity of the tricuspid regurgitant je t. Pulmo- nary hypertension is present when mean pulmonary artery pressure exceeds 25 mmHg at rest or 30 mmHg (4000 Pa) with exercise. Functional assessment Selection for interventions such as pulmonary rehabilita- tion is bas ed on an assessment of patients lung function and their functional capacity. The most commo nly used tool is the MRC dyspnoea scale (Table 5.3.1). Further reading Chronic obstructive pulmonary disease. National clinical guideline on manag ement of chronic obstructive pulmonary disease in adults in primary and secondary care. Tho rax 2004; 59 (Suppl 1): 1 \200\223232. Anthropometry BMI is calculated as weight (Kg)/height2(m). Low BMI (<25 kg/m2) or a loss of >1 unit in BMI is associated with increased mortality whilst a >2kg weight gain following nutritional supplementation is associated with improved mortality. Prescott E, Almdal T, Mikkelsen KL, et al. Prognostic value of weight change in chronic obs tructive pulmonary disease: results from the Copenhagen City Heart Study. Eur Respir J 2002 ; 20(3): 539 \200\223544. Hematological investigation Full blood count The combination of hypoxia and carboxyhaemoglo bin in COPD can lead to polycythaemia which is marked by an increased hemoglobin and haemat ocrit >60%. In subjects with headache, visual disturbance or other features of hyperviscosi ty symptoms can be improved by phlebotomy. Schols AM, Slangen J, Volovics L, et al. Weight loss is a reversible factor in the prognosi s of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157(6 Pt 1): 17 91 \200\2231797. P CALVERLEY 100 5.4 Pharmacological therapy (including cor pulmonale) Pharmacological treatment plays a central role in COPD management but it is not the only tr eatment approach and should be used in conjunction with other therapies such as pulmonary r ehabilitation. The emphasis of treatment changes as the disease progresses and a more aggre ssive approach to symptomatic treatment is now recommended. It is important to understand w hat treatment is designed to do and how effective it is likely to be. At present much thera py has relatively non-speci \201 c bene \201 ts on a range of clinical endpoints while th e side effects experienced appear to be individual to the treatment used. Problem based (Fig. 5.4.1): This is the management approach adopted by NICE. It allows iden ti \201 cation of patient-base problems and individualized treatment regi- mens to control these separately. Types of treatment Smoking cessation aids Nicotine replacement therapy (NRT): these can be given by patch, gum and inhaler routes. Like other smoking ces- sation aids they should be used as part of a goal-directed smoking cessation program. Quitting is more likely in patie nts with less nicotine dependence (longer time to \201 rst cigarette in day) and NRT appr oximately doubles quit rates in the general population. Classi \201 cation of severity Spirometric (Table 5.4.1) \200\223 the approach developed by GOLD and modi \201 ed by the ATS/ERS and NICE is used. This defines the disease in term s of the severity of air \202 ow limitation and comprises a threshold FEV1/FVC less than 0 .7 and a reduction in the percent predictive FEV1. It is useful prognostically but does not describe symptom intensity or the degree to which health status is impaired. Bupropion This antidepressant drug increases quit rate above placebo and has been shown to bene \201 t smoking cessation in COPD patients. It can provoke anxiety and insomnia. Perce ived risks of cardiovascular complications have limited its use although it is dif \201 cu lt to be sure that this was a causal relationship. Patient with COPD Assess symptoms/problems Manage those that are present as below Patients with COPD should have access to the wide range of skills available from a multidis ciplinary team Respiratory failure Cor pulmonale Smoking Breathlessness Frequent exacerbations Abnormal BMI Chronic productive cough Anxiety & depression & excercise limitation Palliative care Fig. 5.4.1 Management of stable COPD. A general approach to COPD management based on the in dividual patient \200\231s problems. Although these are generally paralleled by the severit y of air \202 ow obstruction this relationship is not strong enough to base therapy solely on this measurement. CHAPTER 5.4 Pharmacological therapy (including cor pulmonale) 101 Table 5.4.1 Spirometric classi \201 cation of COPD severity Beta-agonists \200 These can be given orally although this route is not rec- I: Mild FEV1/FVC < 70% or lower limit of normal FEV1 > 80% predicted FEV1/FVC < 70% or lower limit of normal 50% < FEV1 < 80% predicted FEV1/FVC < 70% or lower limit of normal 30% < FEV1 < 5 0% predicted FEV1/FVC < 70% or lower limit of normal FEV1 < 30% predicted or FEV1 < 50% ommended. They are most commonly administered as short-acting drugs with a duration of action of 3 \200\2234 hours (salbutamol, tearbutline) or as long-acting inhaled agents with a 12-hour d uration of action (salmeterol, formoterol). Formoterol has a faster onset of action but the potential for improved symptom control in COPD has not been tested. II: Moderate III: Severe IV: Very Severe All these drugs are available in dry powder form and salbutamol and salmeterol can also be used as CFC-free metered dose inhalers. All produce bronchodilation of modest degree (150 \200\223250ml depending on the patient population). Varencline The most effective drug to date to augment quit rates in healthy subjects: This partial A-antagonist has not yet been tested in COPD although studies are on-going. It is w ell tolerated and was superior to bupropion in healthy sub- jects in previous randomized st udies. The longer-acting agents improve exercise tolerance and reduce end-exercise breathlessness, decrease the likelihood of exacerbations and improve quality of life. Bronchodilator drugs (Table 5.4.2) Table 5.4.2 Commonly used drugs in COPD management Drug Inhaler (mcg) Solution for Nebuliser (mg/ml) Oral Vials for Injection (mg) Duration of action (hours) B2-agonists Short-acting Salbutamol (albuterol) 100,200 (MDI & DPI) 5 5mg (Pill) Syrup 0.024% 0.1, 0.5 4 \200\2236 Terbutaline 400,500 (DPI) 2.5, 5 (Pill) 0.2, 0.25 4 \200\2236 Long-acting Formoterol 4.5 \200\22312 (MDI & DPI) 12+ Salmeterol 25 \200\22350 (MDI & DPI) 12+ Anticholinergics Short-acting Ipratropium bromide 20, 40 (MDI) 0.25 \200\2230.5 6 \200\2238 Oxitropium bromide 100 (MDI) 1.5 7 \200\2239 Long-acting Tiotropium Combination short-acting B2-agonists plus anticholinergic in one inhaler 200/80 (MDI) Fenoterol/Ipratropium 18 (DPI) 24+ 1.25/0.5 6 \200\2238 Salbutamol/Ipratropium 75/15 (MDI) 0.75/4.5 6 \200\2238 Methylxanthines Aminophylline 200 \200\223600 mg (Pill) 240 mg Variable, up to 24 Theophylline (SR) 100 \200\223600 mg (Pill) Variable, up to 24 Inhaled glucocorticosteroids Beclomethasone 50 \200\223400 (MDI & DPI) 0.2 \200\2230.4 Budesonide 100, 200, 400 (DPI) 0.20, 0.25, 0.5 Fluticasone 50 \200\223500 (MDI & DPI) Triamcinolone Combination long-acting B2-agonists plus glucocorticosteroids in one inhaler 4.5/160, 9/320 (DPI) Formoterol/budesonide 100 (MDI) 40 40 Salmeterol/ \202 uticasone 50/100, 250, 500 (DPI) 25/50, 125, 250 (MDI) Systemic glucocorticosteroids Prednisone 5 \200\22360 mg (Pill) P CALVERLEY 102 These effects seem to relate to the longer duration of action. Single inhaler combination treatments: \200 Salbutamol + ipratropium: this combination tr eatment improves FEV1 more than either drug alone but must be used four times daily and is being withdrawn because no CFC-free alternative can be formulated. Nebulised salbutamol is the most widely used beta-agonist given by this route but there is no good evidence that this is superior to using this agent through a metered dose inhaler. It is widely used in high doses in exacerbations. \200 Typical side effects are palpitati ons, tachycardia and increased somatic tremor. Previous concerns about car- diovascular saf ety of long-acting inhaled salmeterol have been resolved by the good safety pro \201 le of these drugs in the TORCH study. LABA/ICS (salmeterol, \202 uticasone SFC or budesonide for- moterol BF): \200 These dru gs are available in dry powder form and in the case of SFC in metered dose inhalers as well . They are given twice daily. SFC can decrease airway in \202 ammation in COPD. Both drug combinations are better than their indi- vidual components in improving FEV1, reducing exac erba- tion treatment and sustaining improved health status. \200 There is evidence of a r eduction in mortality compared with placebo or inhaled steroid monotherapy when the SFC com bination is given. Like LABA alone, hospitalisa- tion was reduced in patients randomized to SFC in the TORCH study. Anti-cholinergic drugs \200 Ipratropium is the typical short-acting agent (4 \200\2236 ho urs duration of action) while tiotropium produces sustained bronchodilatation for at least 24 hours after inhaling a single dose. The side-effect profile is similar with dry mouth th e most common complaint. Ipratropium has a bitter taste and there is a potential for glauco ma and prostatism, although these problems are very infrequent. Agents with less evidence for ef \201 cacy Leukotriene receptor antagonist: there are no g ood data to suggest these agents are bene \201 cial. Mucolytic/anti-oxidant drugs: mainten ance drug use of a simple mucolytics such as bromhexol appears ineffective. Systematic revi ews suggested a reduction in exacerbation frequency from using these drug classes, principa lly due to an effect of N-acetylcysteine. This drug has antioxidant properties and similar effects are likely with carbocysteine and erdosteine, the latter two being available in the UK. NAC reduced exacerbations in patients not receiving inhaled steroids in one adequate c onducted randomized control trial. More data are needed before these can be con \201 dentl y recommended. Erdosteine may enhance recov- ery from exacerbations treated with antibiotic s and is cur- rently licensed for this indication. Maintenance antibiotics: this treatment is not currently recommended although it is the study of several clinical trials. Tiotropium consistently increases FEV1 by 150 \200\223300ml, improves exercise tolerance, r educes breathlessness, decreases the number of exacerbations and improves quality of life. Nebulised ipratropium is often used often used together with nebulised salbutamol in exac- erbations although the evidence base for this is not strong. Theophylline Xanthine derivatives have been widely used as bronchodi- lators in COPD but ha ve a narrow \200\230therapeutic window \200\231. High doses can produce headache, nausea a nd vomiting with more toxic side effects such as ventricular tachycardia and convulsions po ssible. Lower doses may have an anti- in \202 ammatory action and as monotherapy can have clinical bene \201 ts but good comparative studies with the agents above are currently lac king and theophylline remains a third-line supplementary treatment. Corticosteroids \200 Oral corticosteroids are not used in the management of stable diseas e. They are associated with signi \201 cantly increased healthcare use and specifically wi th oste- oporosis and skeletal muscle weakness. General treatment approaches Smoking cessation This is relevant at all stages of COPD but i t is in \202 uenced by the degree of dependence on tobacco. Tobacco depen- dence is a rela psing and remitting condition and repeated attempts at quitting are required. Care is best delivered in conjunction with a smoking cessation councilor and a choice of treatment indiv idualized to the patient \200\231s need. Inhaled corticosteroids: Fluticasone propionate and budesonide are the most widely used dru gs although new longer acting formulations of beclomethasone are being developed. These age nts are not licensed for mon- otherapy in COPD and do not modify airway histology in this d isease despite their other anti-in \202 ammatory properties. However, they do produce smal l but consist- ent improvements in post-bronchodilator FEV1 and are associated with fewer c linical exacerbations and better health status. Rescue therapy This is commonly recommended for patients with acute symptomatic deteriorati on. This idea has been borrowed from asthma and has not been thoroughly tested in COPD. In general it is better to provide sustained bronchodilatation, as acute within day variation in air \202 ow obstruction is not seen in COPD. Previous concerns about the risk of progressive meta- bolic bone disease, skin bruising or eye complications have been down played after the TORCH trial although local hoarseness and weakness of the voice can be trou- blesome in individual patients. Bronchodilator therapy AUTHOR \200\231S TIP Consider using long-acting inhaled bronchodilators in all patients wit h persistent exercise limitation/exercise- induced breathlessness on a daily basis and in t hose in whom pulmonary rehabilitation is used to augment physical activity. Physician diagnosed pneumonia is signi \201 cantly more likely to occur in patients taking inhaled corticosteroids alone or in combination with other treatments. This does not trans late into worse mortality or health status but these drugs do not reduce the frequency of h ospitalization. CHAPTER 5.4 Pharmacological therapy (including cor pulmonale) 103 Osteoporosis is seen in both men and women irrespec- tive of their prior inhaled corticoste roid use and can affect around a third of patients with severe disease. A low threshold for starting bone protection in these patients is needed, particularly in those who have requi red courses of oral corticosteroids. There are no clear data about the relative bene \201 ts of long-acting beta-agonists and a nti-cholinergics, although the latter tend to produce better results when used as monothera py. It is important to ensure that patients com- plaining of exacerbations have long-acting bronchodilator therapy as a \201 rst-line treatment approach. Cataracts are frequent and not necessarily related to steroid use either. Awareness of visu al impairment is relevant in patients over 65 years. Supplementary inhaled corticosteroid These are useful in patients who exacerbate despite ad e- quate bronchodilator treatment. The addition of an inhaled corticosteroid to a long-acti ng beta-agonist seems to be preferred by patients to monotherapy with tiotropium and may be associated with a better quality of life. More data are needed before this distinction can be considered com- pletely established. Combinations of bronchodilator and inhaled cortico steroid may improve exercise tolerance although whether this is greater than use of the bro ncho- dilator than alone is not clear. Hospitalization is reduced with this regimen. Wasting of the peripheral muscle is important for prog- nosis and daily function. Reversing this is dif \201 cult and no speci \201 c drugs have been shown to augment muscle functi on yet. In patients with milder disease, obesity can be a complicating factor which requires speci \201 c advice and management. Cor pulmonale \200 This is a pathological term which describes right ven- tricular hypert rophy secondary to pulmonary cir culatory disorders. COPD is the commonest cause of this bu t there is an impression that this is becoming less frequent, at least in the developed wor ld. It can be diagnosed in vivo with cardiac MRI. The diagnosis is normally based on clinic al assessment \200\223 ankle swelling and raised JVP in a patient with persistent hypoxemi a together with ECG evidence of right heart strain and p-pulmonale with or without echocard iographic dysfunction. Severe disease Patient admitted to hospital should have maximal treat- ment as their risk o f future exacerbations is greater and hospitalization is associated with a worse outcome. T he combination of a long-acting anti-cholinergic, beta-agonist and inhaled corticosteroid i s likely to be the preferred maintenance regimen. There are some data which support the val ue to patients of this approach. Prevention of exacerbations All the long-acting inhaled bronchodilators and inhaled cor- ti costeroids do this, as does the combination of these regimes. Treatment should also include routine adminis tration of in \202 uenza vaccination and pneumococcal vaccination. There are good data to support the use of the latter as a way of decreasing pneumonias and hospit alisations. Whether the addition of other therapies will be synergistic or will address epi sodes not currently well prevented remains to be seen. In COPD, hypoxemia is the major factor that leads to cor pulmonale and its correction is th e most effective treatment. Although this does not lead to regression of severe pulmonary h ypertension it can prevent its pro- gression. Two randomized controlled trials reported ove r 25 years ago have shown that patients with a PaO2 less than 7.3kPa live longer if given d omiciliary oxygen. These changes are not necessarily correlated with physi- ological improv ements in the pulmonary circulation. Oxygen is best delivered from an oxygen concentrator u sing a face mask or nasal prongs, whichever is complied with the better. Patients should be assessed when clinical stable to con \201 rm the presence of persistent hypoxemia and tha t the prescribed oxygen concentration achieves a PaO2 above 8.0kPa without producing hyperc apnia. Careful expla nation of the purposes of oxygen treat- ment is important. It is unlik ely to improve exertional breathless ness and the patient should know this. Ambulatory oxyg en should be provided for patients who are likely to leave their home or undertake signi \201 - cant amounts of exercise. Assessing progress Unlike bronchial asthma where symptom control can be readily assessed, t reatment for COPD involves modi \201 cation of persistent symptoms which do not always dis appear. Treatment tends to be cumulative. Focused questions which identify speci \201 c ac tivities that limit the patient and enquiry after episodes of symptomatic deterioration, ev en if they did not lead to a treatment change, provide the best way of clinically assessing progress. Assessing the risk to the patient of complications (largely based on a combinati on of base- line FEV1, MRC breathlessness score and body mass index together with walking d istance where available) should help stratify how intensive treatment may need to be and wh ether additional therapy should be used earlier. Medical therapy has a limited role here. Diuretics are still used to reduce signi \201 can t peripheral oedema while ACE inhibitors are widely prescribed and likely to be effective, although large clinical studies con \201 rming this are absent. The use of other cardiac d rugs, such as dig- oxin is not recommended unless the patient has atrial fibrillation. Vaso dilators of whatever type including inhaled NO all worsen gas exchange signi \201 cantly i n cor pulmonale due to COPD. No studies have yet shown that giving these drugs has a bene \201 cial effect on the nat- ural history. AUTHOR \200\231S TIP Disease management is more like cardiovascular preven- tion than asthm a control where treatment is given to obtain a long-term goal rather than an immediate symp - tomatic improvement. The relationship between early symptom improvement and reductions in subsequent complications has not been de \201 ned yet. Co-morbidities Co-morbidities are much commoner in COPD than previ- ously realized. \200 Occult cardiac disease is particularly common and a low FEV1 is almost as predictive as rai sed cholesterol for its occurrence. P CALVERLEY 104 Further reading Calverley PM. Effect of corticosteroids on exacerbations of asthma and chro nic obstructive pulmonary disease. Proc Am Thorac Soc 2004; 1(3): 161 \200\223166. KEY FACT Engaging the patient Patients who comply with treatment, even when it is a placebo , do signi \201 cantly better than those who do not. Persuading people to comply with thei r treatment regimen is likely to be one of the best therapies we can use. Identifying indiv iduals with signi \201 cant depression and anxiety is important and the severity of the sy mp- toms should be treated on their own merits. Spending time explaining the nature of the disease to the patient, what it means and what their treatment is intended to achieve is al ways worthwhile, providing a realistic assess- ment of what can be done for them and when i t is going to be done will help build con \201 dence that all is not hopeless. Careful che cks to ensure the patient can use inhaled therapy are necessary and require repetition. Adv ice speci \201 c to the device employed is mandatory. Tracking their adherence with prescr ibed medication is a useful guide as to those who may have more problems in future, particu larly when less than 80% of the prescribed doses are taken. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and \202 uticasone propionate and s urvival in chronic obstructive pulmonary dis- ease. N Engl J Med 2007; 356(8): 775 \200\223 789. Celli BR, MacNee W. Standards for the diagnosis and treatment of patients with COPD: a summ ary of the ATS/ERS position paper. Eur Respir J 2004; 23(6): 932 \200\223946. National Institute for Clinical Excellence. Chronic obstructive pul- monary disease. Nation al clinical guideline on management of chronic obstructive pulmonary disease in adults in p rimary and secondary care. Thorax 2004; 59 (Suppl 1): 1 \200\223232. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and preve ntion of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Ca re Med 2007; 176(6): 532 \200\223555. Srivastava P, Currie GP, Britton J. Smoking cessation. BMJ 2006; 332(7553):1324 \200\2231326. Wedzicha JA, Seemungal TA. COPD exacerbations: de \201 ning their cause and prevention. Lancet 2007; 370(9589): 786 \200\223796. This page intentionally left blank R EVANS & M MORGAN 106 5.5 Non-pharmacological management for COPD In recent years it has become evident that COPD is a com- plicated systemic disease with co nsequences that go far beyond the damage to the airways. Pharmacological treat- ment for CO PD is disappointing in comparison to its central role in asthma. No pharmacological treatme nt convincingly modi \201 es the progress of the disease and the role of drug treatment is con \201 ned to amelioration of symptoms. The lack of effective pharmacological treatment has in the past resulted in a nihilistic attitude towards therapy that has only recently c hanged, alongside a greater understanding of the nature and development of disability in CO PD. The content of this chapter will cover the relevant areas of non-pharmacological treatm ent. Other important areas of non-pharmacological treatment such as smoking cessation and l ung volume reduction surgery are covered elsewhere in the book. \200 The nature and asses sment of disability in COPD. \200 Formal pulmonary rehabilitation. \200 Other forms of performance enhancement. \200 Self-management programs. Table 5.5.1 MRC Dyspnoea Scale Grade Degree of breathlessness related to activities 1 Not troubled by breathlessness except on strenuous exercise 2 Short of breath when hurrying or walking up a slight hill 3 Walks slower than contemporaries on the level ground because of breathlessness, or has to s top for breath when walking at own pace 4 Stops for breath after walking about 100m or after a few minutes on the level ground 5 Too breathless to leave the house, or breathless when dressing or undressing Other simple scales such as the Oxygen Cost Diagram exist but are not widely used. The attr action of the MRC scale is the simplicity to which it can be applied to clinical interview and broad acceptance of its validity. Health status \200 Quality of life (health status) questionnaires all differ in their con tent and emphasis. However, most disease- speci \201 c questionnaires contain domains that relate to activity limitation or dyspnoea on exertion. Nature and assessment of disability Breathlessness resulting in activity limitation (disabi lity) is a major feature of advanced COPD. In the early stages of the condition the mild ai r \202 ow obstruction may have no impact. However as air \202 ow obstruction or hyperin \202 ation pro- gresses, dyspnoea on exertion eventually becomes a signi \201 - cant featu re of daily life. These effects may be delayed until loss of airway function is quite advan ced. This is because people generally have a large reserve of pulmonary func- tion that may not be required by a modern lifestyle. In addition, people with exertional dyspnoea can li mit the sen- sation by avoiding the provoking stimulus. Subsequently the skeletal musculatu re may become de-conditioned as a con- sequence of activity avoidance and further compound the problem. Once disability ensues it can be compounded by loss of con \201 dence, low mo od and poor task performance. The onset of disability is therefore a complicated picture of airway pathophysiology that is compounded by skeletal muscle dysfunction and psychosocial in \202 uences. To date, the nature of the muscle dysfunction is thought probably to be co nsequent upon the de-conditioning. There is an argument for a speci \201 c in \202 ammato ry myopathy in COPD but this is dif \201 cult to sustain when muscle groups other than the quadriceps appear immune. Nevertheless the muscles in COPD are also vulnerable to the effe cts of hypoxia, poor nutrition and steroid medication or other potential myopathic agents. The most well known questionnaires are the Chronic Respiratory Questionnaire (CRQ) and the St George \200\231s respiratory questionnaire (SGRQ). These are both vali- dated and respon sive questionnaires that have been used as outcome assessments for studies of therapeutic i ntervention. The CRQ is a predominantly responsive questionnaire while the SGRQ has both discriminative and evaluative qualities. Other disease-speci \201 c questionnaires that speci \201 cally examine physical function ing such as the pulmonary function scale and dyspnoea questionnaire (PFSDQ) exist but are n ot so widely used All these questionnaires have value as outcome meas- ures in clinical trials. They can also be used for quality assurance purposes in a rehabilitation program. Unlike the MRC scale they do not have any value in the management of the individual case. Exercise tests Objective assessment of exercise capacity is possible with \201 eld and la boratory examinations. Well-known \201 eld walking tests that have been applied to COPD a re the 6-minute walk test (6MWT) and the shuttle walk tests. Assessing disability The relationship between airway function (FEV1) and dis- ability is po or and non-predictive. The assessment of dis- ability in COPD requires a speci \201 c appr oach. The options include dyspnoea scales, health status questionnaires and direct observat ion of exercise performance. 6MWT This simple self-paced walking test has been used exten- sively for evaluation. It has normal reference ranges and a de \201 ned minimally important clinical difference. Althou gh the test is in widespread use it has some disadvantages as a performance measure because of its vulnerability to learning and encouragement effects. The physiological challenge of the 6MWT is also unpredictable. Dyspnoea scales The MRC Dyspnoea Scale (Table 5.5.1) is the best known of simple rating sca les. This was originally developed as part of a wider questionnaire but has become a useful and rapidly applicable tool for clinical staging of disability. It is really an activity s cale rather than a dyspnoea scale. The format is simple with a 1 to 5 score. The modi \201 ed scale that is used in the USA has a 0 \200\2234 scale. The shuttle walk tests These were developed as the \201 eld equivalents of the maximal ca pacity and submaximal (endurance) laboratory exercise tests. The incremental shuttle walk t est (ISWT) involves walking around a coned 10m course at speeds that increase every minute. The endurance shuttle walk CHAPTER 5.5 Non-pharmacological management for COPD 107 test (ESWT) involves walking at a constant speed around the cones. Both are externally pace d and symptom limited. These tests are growing in popularity because they are less vulnerab le to the in \202 uences of learning and encourage- ment and the physiological challenge i s known. In contrast to the 6MWT, the ISWT has a graded physiological response. Recently a minimally clinical important difference has been de \201 ned. the form of cycling or brisk walking. Training schedules require a combination of intensity , duration and frequency. These principles are similar to exercise training in health. Pati ents with COPD can actually train at a higher relative proportion of their maximal oxygen u ptake than healthy people. This is because the usual cardiovascular limit to exercise is pr e-empted in many people with advanced COPD by a ventilatory limit imposed by dynamic hyperi n- \202 ation. Opinions vary as the correct prescription intensity of endurance training. Higher intensity (>60% VO2 peak) training produces better results, and genuine physiologi- cal training, than lower intensity training. However some health status bene \201 ts occu r even with low intensity activity.