Although many different factors may be involved in the development of COPD, smoking is the most significant. Exposure to tobacco smoke provokes a series of inflammatory processes involving the small as well as the large airways and can also impair host defence mechanisms. 

In predisposed individuals this leads to pathological processes that we have come to recognize as chronic bronchitis and emphysema. It is important to note that bronchial inflammation can be detected long before the disease is evident clinically[1] and persists long after the cessation of smoking,[2] and that the inflammatory processes of COPD are readily distinguishable from those of asthma.[3,4]

Physiological defects
Airflow limitation and hyperinflation
Expiratory airflow limitation is the principal physiological defect in COPD. Intrinsic airway factors re­late to bronchial wall inflammation and include mucosal inflammation/edema, bronchial wall remodeling/fibrosis, and increased mucosal secretions. 

Extrinsic factors involve the loss of elastic tissue support for small airways and the dynamic expiratory compression of these airways.[5,6] Other factors such as respiratory muscle dys­function can further limit airflow in some patients. 
Hyperinflation can also occur in COPD, leading to an increase in functional residual capacity (FRC)—the amount of air that remains in the lungs at the end of tidal exhalation. 

This can lead to gas trapping and an increase in residual volume (RV). As a consequence, there is an augmentation of the inspiratory work of breathing, which is an important factor in producing dyspnea. As the expiratory time is essential for lung emptying, factors that decrease this time, such as an increasing respiratory rate during exercise, result in a progressive in­crease in FRC (Figure 1 [10]).[7] This phenomenon is called dynamic hyperinflation, and is largely responsible for exercise limitation in COPD.[7-11]

Gas exchange disturbances
Perturbations in gas exchange are caused primarily by regional inequalities of ventilation and perfusion (VQ mismatching).[12] This process commonly produces hypoxemia, but in more advanced disease can also contribute to hypercapnia and chronic respiratory acidosis. Other contributing factors to gas exchange disturbances in advanced COPD are pulmonary hypertension and impaired cardiac function, which can lead to reduced mixed venous oxygenation.

Ventilatory muscle dysfunction
A number of factors contribute to ventilatory muscle dysfunction in COPD. A major factor is a consequence of hy­perinflation, which limits force generation and endurance,[13] and places the inspiratory muscles at a mechan­ical disadvantage. 

Other factors include nutritional alterations, a sustained inflammatory response that affects the contractile apparatus, tissue hypoxia, and loss of muscle mass.[14,15] These factors also affect other skeletal muscles, which may further contribute to exercise limitation.[16,17]

Cardiovascular disturbances
Cardiovascular disturbances are common in COPD and may represent a complication of COPD itself or may be triggered by the same factor, that is, smoking. Recently it has been proposed that lung inflammation may directly affect atherogenesis by driving systemic inflammation.

Pulmonary hypertension is a late complication of COPD and independently worsens its prognosis.[18-24] A major factor is chronic hypoxia, which can result in pulmonary vasoconstriction. Other factors include endothelial dysfunction, remodeling of pulmonary arteries, and pulmonary capillary bed destruction. 

Right ventricular dysfunction and failure (cor pulmonale) may eventually develop and add to the morbidity and mortality of this disease.

Reduced exercise capacity
Deconditioning may result from lack of physical activity and can be an independent factor in exercise limitation. Fortunately, this is amenable to a pulmonary rehabilitation program. Management of deconditioning, like the management of other physio­logical defects of COPD, begins with assessment of function.

Assessment of airflow limitation and hyperinflation
Spirometry with measurements derived from a maximal forced ex­piratory maneuver is the most clinically relevant test in assessing COPD. Airway obstruction is diagnosed when the FEV₁/FVC (forced expiratory volume in 1 second to forced vital capacity) ratio is less than 0.7 L, a situation usually accompanied by a reduction in FEV₁ to less than 80% of predicted (Figure 2 [11]). 

FEV₁ has tra­ditionally been used to grade severity of COPD (see Table 2 [12] from Pharmacological management of stable chronic obstructive pulmonary disease [13]).[25-26] In COPD the expiratory flow-volume curve is characteristically concave (Figure 3 [14]). This appearance is typical for emphysema (but not specific) and implies the dynamic airway collapse with forced exhalation.[27] Significant response to bronchodilators, defined as an in­crease in FEV₁ by 12% and 180 mL, is common in asthma but uncommon in COPD. 

New technology has allowed the development of portable hand-held spirometers that are robust, simple to use, and reasonable in cost ($500 to $1500), making spirometry a test that can be performed in the office setting. Accreditation can be obtained in BC through the Diagnostic Accreditation Program, and once you have the re­quired pulmonary function test (PFT) credentials you may bill for performing this test. Spirometry should be routine in COPD for the following:

• Diagnosis (particularly of early disease or to differentiate from asthma).

• Establishing severity. 

• Determining prognosis.

• Monitoring disease progression and response to therapy. 

More detailed lung function tests are available in most PFT labs. These are utilized in select instances in COPD. Most commonly this occurs when there is a reduction in FVC and a need to determine whether there is a concomitant restrictive disorder such as interstitial lung disease. In pure COPD, FVC is modestly decreased if there is air trapping and hyper­inflation (RV increased). 

Diffusing capacity (DLco) is very sensitive in detecting gas exchange abnormalities. It is usually reduced in emphysema (whereas it is normal or high in asthma) and correlates reasonably well with the pathological severity of emphysema.[28] 

Full pulmonary function tests should therefore be considered when spirometry indicates a reduced FVC to determine if there is a restrictive disorder present, and when spirometry is normal despite the presence of dyspnea to determine if there is an impairment in DLco that might suggest another pulmonary parenchymal or vascular disorder.

Peak expiratory flow rate 
Peak expiratory flow rate (PEFR) testing provides a simple, readily available measure of airflow. PEFR, however, may underestimate airflow ob­struction in COPD as it is predominantly a measure for the large airways. Furthermore, the reproducibility and reliability of PEFR testing is inferior to spirometry. We therefore advise against its use for routine assessment of COPD (in contrast to asthma) although it may have some merit as a serial measurement for a given individual.[29-30]

Radiological tests
Chest radiography may show features of hyperinflation such as flattening of the diaphragms with increased anteroposterior diameter on a lateral film, but this is not sensitive or specific for COPD. Although not routinely indicated, a CT chest scan may on occasion be of use in the characterization of COPD (emphysema).[31]

Assessment of gas exchange disturbances
Pulse oximetry can be done in the ambulatory setting to reliably quantitate oxygen saturation. Arterial blood gas measurement can be considered in patients with Sao₂ of less than 92% (or FEV₁ of less than 40%) to more precisely assess the degree of hypoxemia and hypercapnia.[32] 

Both tests can be used to determine the potential role of domiciliary oxygen. The portability of pulse oximetry makes it applicable in the quantitation of hypoxemia with exertion and during sleep.

Assessment of ventilatory muscle dysfunction
Tests for ventilatory muscle function may be considered in select cases, including those where ventilatory muscle involvement is suspected in a neuromuscular disorder, or where dyspnea or hypercapnia are out of proportion to the patient’s FEV₁.[12] Other assessment methods for muscle dysfunction may include measuring lung volumes (restrictive disorder), blood gases (elevated Paco₂), and maximal inspiratory and expiratory pressures. EMG and nerve conduction studies may also be considered.

Assessment of cardiovascular disturbances
Clinical evaluation, chest X-ray, EKG, and echocardiography with Echo-Doppler estimation can be used in patients with suspected cardiac disorders or pulmonary hypertension to assess the pulmonary artery systolic pressure and ventricular function.[27]

Assessment of reduced exercise capacity
Dyspnea scale 
The Medical Research Council dys­pnea scale is a simple clinical tool used to assess shortness of breath and disability during activity (Figure 4 [15]).[25] This scale has been found to cor­relate with the patient’s quality of life and may be of use in predicting mortality.[25]

6-minute walk test 
The 6-minute walk test is a standardized lab test in which the patient walks unassisted for 6 minutes and the distance is measured. The normal distances walked are about 500 m for women and about 580 m for men, with a change of 40 m in a properly performed test considered significant. The 6-minute walk test distance (degree of reduction) correlates well with functional disability and provides prognostic information.[33-34]

Cardiopulmonary exercise testing 
The cardiopulmonary exercise test (CPET) objectively measures maximum exercise capacity. When exercise capacity is reduced, CPET can assist in identifying the organ system responsible. The measure of peak oxy­gen uptake during incremental testing is an independent prognostic factor in COPD.[20] 

Dynamic hyper­inflation can be demonstrated by per­forming re­peated inspiratory capacity maneuvers and by comparing the exercise tidal flow-volume loops with the baseline maximal flow-volume loop (Figure 5 [16]). CPET can assist with patient selection for pulmonary re­habilitation, lung volume reduction surgery, and suitability for pulmonary resection.

Conclusions
COPD is an inflammatory airway disease with a complex pathophysiology. This disorder leads to airway obstruction and often to hyperinflation, which along with gas exchange abnormalities interact to cause dyspnea and functional limitation. Spirometry is a widely available tool that quantifies the abnormalities in COPD and can be fundamental in diagnosing, monitoring, and establishing the prognosis of individuals with this condition. 

More detailed lung function testing may have utility, but is not generally required. Measures of oxygenation (oximetry and arterial blood gases) can be used to monitor disease severity and to determine the appropriateness of domicillary oxygen. Such measurements should play as fundamental a role in the management of COPD as the monitoring of blood sugar does in diabetes.

Competing interests
None declared.

Dr Al Talag is a fellow in the division of Respirology Medicine at the University of British Columbia. 

Dr Wilcox is a respirologist at St. Paul's Hospital, associate professor of medicine at UBC, the director for Respirology Training at UBC, and the medical director of the Pulmonary Function Laboratory St. Paul’s Hospital.