should preferentially be used for disability assessment. Both incremental and constant load endurance testing, using cycle ergometry or treadmill, are used extensively and these different approaches have the potential to produce different, but complimentary, clinical information. Estimations of symptom-limited, maximal oxygen consumption (Vo2max) during incremental cycle exercise testing is frequently used in the assessment of disability in patients with occupational lung diseases, but is used less extensively in COPD, where endurance tests may be preferable. Knowledge of the Vo2max and of the MET equivalents (metabolic rates based on multiples of the resting Vo2) of various activities of daily living permit a crude estimation of the patient's functional capacity. Precise stratification of the Vo2max vis-à-vis overall functional disability in individual patients with COPD is not available. However, generally speaking, a Vo2max of <15mL/kg/min in a patient with COPD represents severe functional disability. Standard cardiopulmonary exercise testing measures the following physiological responses: metabolic load (Vo2, Vco2), ventilation, breathing pattern, arterial oxygen saturation, heart rate, oxygen pulse, and blood pressure. More recently, other ventilatory parameters relevant to dyspnoea assessment, such as the exercise tidal flow-volume loop analysis relative to the maximal resting loop, are being used (Fig. 5.7) . This approach allows a more comprehensive evaluation of the ventilatory constraints that apply in a given individual compared with traditional estimates of ventilatory limitation such as the ventilatory index (i.e. estimated maximal ventilatory capacity minus peak ventilation). Repeated inspiratory capacity measurements during exercise allow an indirect assessment of the extent of dynamic hyperinflation which, as already mentioned, contributes importantly to both symptoms and exercise intolerance (Figs 5.6 and 5.8) [7,41].
Dyspnoea is measured during exercise using the Borg or visual analogue scales. Both scaling methods have been shown to be reliable (reproducible) and responsive (ability to detect change) in patient populations with CoPD [34,35]. Constant load cycle ergometry at 50-80% of the patient's predetermined maximal work rate has been shown to have excellent reproducibility and to be responsive to interventions such as bronchodilators, oxygen therapy, opiates, and exercise training . For the clinical assessment of bron-chodilator efficacy, comparisons of the dyspnoea (Borg) scale—time slopes at a standardized constant load (e.g. 75% peak Vo2) has been shown to be highly responsive, and concomitant quantitative flow-volume loop analysis allows additional insights into the mechanisms of functional improvement .
Does CT assessment of the extent of emphysema predict disability?
High resolution computed tomography (HRCT) has made it possible to quan tify, with considerable precision, the extent and pattern of emphysematous destruction of the lung in vivo [42,43]. Emphysema scores, based on the magnitude and distribution of low attenuation areas on HRCT, correlate well with morphometric measurements of microscopic emphysema in subsequently resected lungs. Several studies have shown reasonable correlations between HRCT derived emphysema scores and physiological indices such as the diffusion capacity for carbon monoxide (DLCO), lung volumes, and spirometric expiratory flow rates [42,43]. HRCT performed at end-inspiration correlates most closely with the extent of emphysema on pathological examination, whereas HRCT performed at end-expiration correlates best with measurements of airflow obstruction . Intensive research is currently underway on the potential role of HRCT in differentiating the various pathological components of COPD (i.e. emphysema, chronic bronchitis and asthma). However, the classical findings in chronic bronchitis of bronchial wall thickening and gas trapping at low lung volumes are unreliable and often absent. Given the heterogeneity of pathological abnormality in COPD, it is unlikely that refinements in HRCT quantification and differentiation will enhance our ability to predict disability in a given patient. However, preliminary studies suggest that HRCT assessments, in combination with detailed physiological measurements, have the potential to elucidate mechanisms of disability in individual COPD patients . For example, it has been shown that symptomatic patients with a history of cigarette smoking, who have only minor spirometric abnormalities, but with disproportionately reduced DLCO, may have a localized upper zone centrilobular emphysema on HRCT . Such patients may have significant ventilation/perfusion inhomogeneity and extensive small-airways dysfunction, not reflected by the FEV1. In these patients, the combination of excessive ventilatory stimulation (due to high physiological deadspace) can aggravate expiratory flow limitation and DH, with consequent premature ventilatory limitation, heightened dyspnoea and exercise intolerance .
Patients with both interstitial lung disease and emphysema may have normal expiratory flow rates and lung volumes. HRCT is useful in such patients to determine the relative extent of each disease and the likely contribution of each condition to the clinical and functional abnormality .
Advances in nuclear medicine and magnetic resonance imaging in COPD hold promise for the future. Single photon emission computed tomography (SPECT) ventilation images can be used to provide quantitative volumetric mapping of regional gas trapping . In this technique, equilibrium phase images with xenon-133 are used to generate 3D views of the total lung volume, while washout images provide 3 dimensional views of regional gas trapping. Static magnetic resonance imaging (MRI) allows three dimensional reconstructions of the chest wall and diaphragm, which may improve evaluation of structure-function relationships in COPD, and also provide reliable measurements of lung volumes in these patients (for example, pre and post surgical intervention) . Dynamic MRI during the breathing cycle has been used to depict asynchronous movement of the chest wall and diaphragm in severe emphysema, and improvement in respiratory mechanics with surgical intervention (lung volume reduction surgery) . Magnetic resonance ventilation imaging with hyperpolarized He-3 gas has shown potential to allow volumetric mapping of enlarged airspaces in COPD that are below the resolution capability of HRCT . High resolution volumetric MR imaging of regional pulmonary perfusion has also become possible.
Hence, there is reason for considerable optimism that highly accurate quantitative imaging of both structural and functional abnormalities in patients with COPD will be available in the future. How much this imaging will add to the clinical and functional assessment of disability in the patient with COPD remains to be seen.
Will it be possible to measure small-airway function in future?
It has long been recognized that small-airways disease may precede the overt clinical manifestations of chronic bronchitis and emphysema in smokers. Chronic bronchiolitis of small airways is an integral component of established COPD. There is little doubt that small-airways disease contributes importantly to both impairment and disability in COPD. However, the small airways have been termed the 'silent zone' because extensive narrowing of these peripheral airways contributes little change to measurements of overall airways resistance. A reliable test of small-airways dysfunction is therefore desirable. Moreover, given our increased understanding of the nature of the inflammatory process in small airways in COPD, and the development of new, non-steroidal anti-inflammatory (mediator antagonists) and bronchodilator therapies (tiotropium and long-acting beta agonists), the assessment of small-airway function is of obvious importance in ascertaining the eventual clinical utility of these agents.
The development of a simple reproducible test of small-airway function has remained an elusive goal, as witnessed by the plethora of physiological tests that are currently available in clinical practice or in the research setting . Examples include:
1 Expiratory flow-volume loops derived by variable-volume plethysmography;
2 Partial and maximal flow-volume loop isovolume comparisons;
3 Flow volume loops during helium breathing;
4 Tests of expiratory flow limitation such as negative expiratory pressure (NEP) application;
5 Tests of ventilation distribution (i.e. frequency dependence of compliance and closing volume);
6 Measurement of thoracic gas volumes (i.e. residual volume); and
7 Measurements of dynamic hyperinflation and dynamic elastance during exercise [7,41].
All of the above listed tests have limitations; many are technically demanding or are unavailable and, in particular, the responsiveness of these tests to various therapeutic interventions has not been established. To the extent that air trapping and lung hyperinflation fundamentally reflect small-airway dysfunction in COPD, then bronchodilator induced reduction in lung hyperinflation serves as an indirect measure of improved dynamic small-airway function . Recent innovations in HRCT permit precise morphometric assessments of higher generations of peripheral small airways than were, hitherto, possible [36,37]. Classical HRCT imaging features of smoking-related bronchiolitis— areas of ground glass opacity, centrilobular nodules and bronchial wall thickening—have been described. Unfortunately, however, HRCT is usually normal in this early stage of disease. It is conceivable that in the future, combined structural and functional assessments of small-airway disease, such as those alluded to above will increase our understanding of the mechanisms of disability in COPD.
Disability in COPD is complex and multifactorial, and this makes clinical evaluation a challenging task. However, recent advances in our understanding of the interface between pathophysiological impairment and functional disability in COPD has set the stage for the development of better evaluative methods. More research and dialogue is required to devise an acceptable staging system for disability in COPD, akin to that which is already available for other chronic diseases such as congestive heart failure. The comprehensive assessment of disability might incorporate the following elements:
1 Measurement of impairment: FEVj, inspiratory capacity, and DLCO, each expressed as percentage predicted;
2 Measurement of body mass index;
3 Measurement of exercise performance, together with exertional symptoms and ventilatory reserves;
4 Assessment of chronic activity-related dyspnoea using validated self-rated scales or multidimensional instruments; and
5 Measurement of disease-specific quality of life using validated questionnaires.
A composite score derived from the above listed components would permit stratification of patients with respect to disability level, and could also be used to facilitate the evaluation of the overall clinical impact of therapeutic interventions in patients with symptomatic COPD.
1 World Health Organization. International Classification of Impairments, Disabilities and Handicaps. Geneva: World Health Organization, 1980; 10-11 (26-31): 86-7.
2 Wolkove N, Dajczman E, Colacone A, Kreisman H. The relationship between pulmonary function and dyspnoea in obstructive lung disease. Chest 1989; 96: 1247-51.
3 Hay JG, Stone P, Carter J, Church S et al. Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease. Eur Respir J1992; 5: 659-64.
4 Bauerle O, Chrusch CA, Younes M. Mechanisms by which COPD affects exercise tolerance. Am J Respir Crit Care Med 1998; 157: 57-68.
5 Chrystyn H, Mulley BA, Peake MD. Dose-response relation to oral theophylline in severe chronic obstructive airways disease. Br Med J1988; 297: 1506-10.
6 Belman MJ, Botnick WC, Shin JW. Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996; 153: 967-75.
7 O'Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation and endurance during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 158: 1557-65.
8 Meek PM, Schwartzstein RMS, Adams L et al. Dyspnoea mechanisms, assessment and management: a consensus statement (American Thoracic Society). Am J Respir Crit Care Med 1999; 159: 321-40.
9 O'Donnell DE, Bertley JC, Chau LL, Webb KA. Qualitative aspects of exertional breathlessness in chronic airflow limitation: pathophysiologic mechanisms. Am J Respir Crit Care Med 1997; 155: 109-15.
10 O'Donnell DE. Exertional breathlessness in chronic respiratory disease. In Mahler DA, ed. Lung Biology in Health and Disease, Vol. III: Dyspnoea. New York: Marcel Dekker Inc, 1998; 97-147.
11 Pride NB, Macklem PT. Lung Mechanics in Disease. In: AP Fishman., eds. Handbook of Physiology, Section 3, Vol.
III Part 2: The Respiratory System. Bethesda MD: American Physiological Society, 1986; 659-92.
12 Stokes WA. A treatise on the diagnosis and treatment of diseases of the chest. Part 1: Diseases of the Lung and Windpipe. London: The New Sydenham Society 1937: 168-9.
13 Dodd DS, Brancatisano T, Engel LA. Chest wall mechanics during exercise in patients with severe chronic airflow obstruction. Am Rev Respir Dis 1984; 129: 33-8.
14 O'Donnell DE, Webb KA. Exertional breathlessness in patients with chronic airflow limitation: the role of hyperinflation. Am Rev Respir Dis 1993; 148: 1351-7.
15 O'Donnell DE, Revill S, Webb KA. Dynamic hyperinflation in exercise intolerance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164: 770-7.
16 Martinez FJ, Montes de Oca M, Whyte RI, Stetz J, Gay SE, Celli BR. LungVolume reduction improves dyspnoea, dynamic hyperinflation and respiratory muscle function. Am J Respir Crit Care Med 1997; 155: 1984-90.
17 Laghi F, Jurban A, Topeli A et al. Effect of lung Volume reduction surgery on neuromechanical coupling of the diaphragm. Am J Respir Crit Care Med 1998; 157: 475-83.
18 Dillard TA, Piantadosi S, Rajogopal KR. Prediction of ventilation at maximal exercise in chronic airflow obstruction. Am Rev Respir Dis 1985; 132: 230-5.
19 Jones NL, Jones G, Edwards RHT. Exercise tolerance in chronic airway obstruction. Am Rev Respir Dis 1971; 103: 477-91.
20 Levison H, Cherniack RM. Ventilatory cost of exercise in chronic obstructive pulmonary disease. J Appl Physiol 1968; 25: 21-7.
21 Jones NL. Pulmonary gas-exchange during exercise in patients with chronic airway obstruction. Clin Sci 1966: 3139-50.
22 O'Donnell DE, Webb KA. Breathlessness in patients with severe chronic airflow limitation: physiologic correlates. Chest 1992; 102: 824-31.
23 Leblanc P, Bowie DM, Summers E, Jones NL, Killian KJ. Breathlessness and exercise in patients with cardiorespiratory disease. Am Rev Respir Dis 1986; 133: 21-5.
24 O'Donnell DE, McGuire M, Samis L, Webb KA. The impact of exercise reconditioning on breathlessness in severe chronic airflow limitation. Am J Respir Crit Care Med 1995; 152: 2005-13.
25 Swinburn CR, Wakefield JM, Jones PW. Relationship between ventilation and breathlessness during exercise in chronic obstructive airways disease is not altered by prevention of hypoxemia. Clin Sci 1984; 67: 515-9.
26 O'Donnell DE, Bain DJ, Webb KA. Factors contributing to relief of exertional breathlessness during hyperoxia in chronic airflow limitation. Am J Respir Crit Care Med 1997; 155: 530-5.
27 Light RW, Muro JR, Sato RI, Stansbury DW, Fischer CE, Brown SE. Effects of oral morphine on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1989; 139: 126-33.
28 Lane R, Cockcroft A, Adams L, Guz A. Arterial oxygen saturation and breathlessness in patients with chronic obstructive airways disease. Clin Sci 1987; 72:693-8.
29 Somfay A, Porszasz J, Lee SM, Casaburi R. Dose-response effect of oxygen on hyperinflation and exercise endurance in non-hypoxemic COPD patients. Eur Resp J 2001; 18: 77-84.
30 Jones PW, Huszczuk A, Wasserman K. Cardiac output as a contributor of ventilation through changes in right ventricular load. J Appl Physiol 1982; 53: 218-24.
31 Gift AG, Cahill CA. Psychophysiologic aspects of dyspnoea in chronic obstructive pulmonary disease: a pilot study. Heart Lung 1990; 19: 252-7.
32 McGavin CR, Artvinli M, Naoe H, McHardy GJ. Dyspnoea, disability and distance walked: comparison of estimates of exercise performance in respiratory disease. Br Med J1978; 2: 241-3.
33 Guyatt GH, Puglsey SO, Sullivan MJ et al. Effect of encouragement on walking test performance. Thorax 1984; 39: 818-22.
34 Borg G, Simple rating methods for estimation of perceived exertion. Wenner-
Gren Center Int Symp Series 1976; 28: 39-47.
35 Gift AG. Validation of a vertical visual analogue scale as a measure of clinical dyspnoea. Rehab Nurs 1989; 14: 313-25.
36 Stevens D, Elpern E, Sharma K, Szidow D, Ankin M, Kesten S. Comparison of hallway and treadmill six minute walk tests. Am J Respir Crit Care Med 1999; 160: 1540-3.
37 Singh SJ, Morgan MD, Scott S, Walters D, Hardman AE. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax 1992; 47: 1019-24.
38 Singh SJ, Morgan MD, Hardman AE, Rowe C, Bardsley PA. Comparison of oxygen uptake during a conventional treadmill test and the shuttle walking test in chronic airflow limitation. Eur Resp J 1994; 7: 2016-20.
39 Revill SM, Morgan MD, Singh SJ, Williams J, Hardman AE. The endurance shuttle test. A new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease. Thorax 1999; 54: 213-22.
40 Revill SM, Singh SJ, Morgan MD. Randomized controlled trial of ambulatory oxygen and an ambulatory ventilator on endurance exercise in COPD. Respir Med 2000; 94: 778-83.
41 O'Donnell DE. Exercise Limitation and Clinical Exercise Testing in Chronic Obstructive Pulmonary Disease. In: Wiseman IM, Zebellos RJ, eds. Clinical Exercise Testing. Prog Respir Res: Karger, 2002: 32, 138-58.
42 Nakano Y, Sakai H, Muro S et al. Comparison of low attenuation areas on computed tomographic scans between inner and outer segments of the lung in patients with chronic obstructive pulmonary disease: incidence and contribution to lung function. Thorax 1999; 54: 384-9.
43 Klein JS, Gamsu G, Webb WR, Golden JA, Muller NL. High resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusion capacities. Radiology 1992; 182: 817-21.
44 Genevois PA, de Vuyst P, Sy M, Scillia P et al. Pulmonary emphysema: Quantitative CT during expiration. Radiology 1996; 199: 825-9.
45 Wiggins J, Strickland B, Turner-Warwick M. Combined cryptogenic fibrosing alveolitis and emphysema: The value of high-resolution computed tomography in assessment. Respir Med 1990; 84: 365-9.
46 Suga K, Kume N, Nishigauchi K et al. Three-dimensional surface display of dynamic pulmonary xenon-133 SPECT in patients with obstructive lung disease. J Nucl Med 1998; 39: 889-93.
47 Gierada DS, Hakimian S, Slone RM, Yusen RD. MR analysis of lung Volume and thoracic dimensions in patients with emphysema before and after lung Volume reduction surgery. Am J Roentgenol 1998; 170: 707-14.
48 de Lange EE, Mugler JP, Brookeman JR et al. Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas. Radiology 1999; 210: 851-7.
49 Anthonison NR. Tests of mechanical function. In: AP Fishman, ed. Handbook of Physiology Vol. III Part 2: The Respiratory System. Mechanics of Breathing, American Physioloical Society. Baltimore, Maryland: Williams & Wilkins Co, 1986, 753-84.
Was this article helpful?