Lung Function Testing in Chronic Obstructive Pulmonary Disease

Lung function testing has undisputed value in the comprehensive assessment and individualized management of chronic obstructive pulmonary disease, a pathologic condition in which a functional abnormality, poorly reversible expiratory airway obstruction, is at the core of its definition. After an overview of the physiologic underpinnings of the disease, the authors outline the role of lung function testing in this disease, including diagnosis, assessment of severity, and indication for and responses to pharmacologic and nonpharmacologic interventions. They discuss the current controversies surrounding test interpretation with these purposes in mind and provide balanced recommendations to optimize their usefulness in different clinical scenarios.

Key points

  • Expiratory airflow limitation is the defining physiologic abnormality of chronic obstructive pulmonary disease (COPD).

  • Increase in resting lung volumes with further hyperinflation, when expiratory airflow limitation and increased ventilation are combined, has deleterious consequences for the sensory-perceptual and mechanical responses to physical activity.

  • Lung function tests allow a detailed evaluation of the physiologic consequences of airway, alveolar, capillary, and respiratory muscle abnormalities induced by COPD.

  • Physiologic parameters from pulmonary function tests are clinically relevant for diagnosis, assessment of disease severity, individualized management, and evaluation of the effect of treatment.

  • Important complementary information can be obtained by integrated cardiopulmonary exercise testing, which includes noninvasive measurements of pulmonary gas exchange and lung mechanics, and exertional dyspnea ratings.


Chronic obstructive pulmonary disease (COPD) is characterized by inflammatory injury of airways, lung parenchyma, and pulmonary vasculature secondary to noxious environmental exposures (eg, tobacco smoking, biomass, and fuel burning) in interaction with individual factors (eg, genetics, prematurity, small lung size). A physiologic abnormality, poorly reversible expiratory airflow limitation on spirometry, is a key defining feature of the disease. Most of the currently available pulmonary function tests (PFTs) were developed and clinically validated in patients with COPD. In fact, no other chronic respiratory disease has been so thoroughly studied from the physiologic standpoint as COPD. Accordingly, PFTs remain central to the accurate diagnosis, assessment of disease severity, and evaluation of the effects of treatments in this highly prevalent disease ( Table 1 ). The current review discusses the practical applications of PFTs; thus, the authors specifically avoid detailed physiologic discussions, technical considerations, or epidemiologic implications of abnormal physiologic tests. They address specific scenarios in which PFTs can impact clinical decision making and help clinicians frame an individualized patient-centered approach to COPD management ( Box 1 ).

Table 1

Summary of the expected results of pulmonary function tests in different clinical scenarios involving patients with chronic obstructive pulmonary disease

Test Diagnostic Workup Assessment of Disease Severity Main Effects of BDs
Key findings

  • ↓ Post-BD FEV 1 /FVC

  • ↓ FEV 1

  • ↑ FEV 1 used by regulatory bodies

Secondary findings

  • ↓ FEF 25%–75% , ↓ FEF 25%–75% /FVC, ↓ FEV 1 /FEV 6 , ↓ FEV 3 /FEV 6

  • As disease progresses, ↓ FVC may reflect worsening gas trapping

  • ↑ FVC and/or SVC may indicate less gas trapping

Lung volumes
Key findings

  • ↑ RV

  • ↑ RV, ↓ IC (and ↓ IC/TLC)

  • ↓ RV, ↑ IC (and ↑ IC/TLC)

Secondary findings

  • ↑ FRC, ↑ TLC

  • ↑ FRC, ↑ TLC

  • ↓ FRC, ↓ TLC

Airway resistance
Key findings

  • ↑ sRaw

  • No current role

  • ↓ sRaw

Small airway function
SB N 2 washout

  • ↑ phase III slope

  • No current role

  • ↓ phase III slope

MB N 2 washout

  • ↓ LCI, ↓ S cond and/or ↓ S acin

  • No current role

  • ↑ LCI, ↑ S cond and/or ↑ S acin


  • X 5

  • X 5

  • ↓ Δ X rs

Arterial blood gases
Key findings

  • Variable

  • ↓ Pa o 2 , ↑ Pa co 2

  • Variable

Gas transfer
Key findings

  • ↓ DL CO and/or ↓ K CO

  • ↓ DL CO

  • No current role

RM strength

  • No current role

  • MIP may ↓ due to hyperinflation

  • MIP may ↑ due to lung deflation


  • Variable

  • ↓ 6-MWD. ↓ SpO 2

  • 6-MWD may or not ↑


  • ↓ ventilatory efficiency

  • ↑ operating lung volumes

  • ↑ dyspnea/WR and/or ventilation

  • ↑ operating lung volumes

  • ↑ dyspnea/WR and ventilation

  • ↓ operating lung volumes

  • ↓ dyspnea/WR and ventilation

Constant work rate

  • No current role

  • No current role

  • ↑ Tlim

  • ↑ IC and ↓ dyspnea at isotime

Abbreviations: ↑, increased; ↓, decreased; 6-MWD, 6-min walking distance; CO, carbon monoxide; K , transfer coefficient; LCI, lung clearance index; MB, multiple breath; Pa, arterial partial pressure; RM, respiratory muscle; SB, single breath; S cond , ventilation heterogeneity in the acinar airways; S cond , ventilation heterogeneity in the conducting (preacinar) airways; SpO 2 , oxygen saturation by pulse oximetry; sRaw, specific airway resistance; Tlim, time to exercise limitation; WR, work rate; X 5 , reactance at 5 Hz; Δ X rs , differences between inspiratory and expiratory phases of respiratory reactance.

Box 1

Expiratory airflow limitation

A physiologic abnormality, poorly reversible expiratory airflow limitation on spirometry, is a key defining feature of COPD.

Structural and physiologic Basis of respiratory dysfunction in chronic obstructive pulmonary disease


The small airways (ie, <2 mm diameter, noncartilaginous bronchioles) constitute the initial locus of inflammation and increased airway resistance in COPD. Several studies have shown evidence of active inflammation and obliteration of peripheral airways even in the earlier stages of the disease. Loss of alveolar attachments as a result of emphysema contributes to greater collapsibility of small airways on expiration and increased resistance to airflow. Airway narrowing owing to mucosal edema, mucus plugging, airway remodeling, and peribronchial fibrosis together with reduced lung elastic recoil predispose to dynamic airway closure. It follows that even during spontaneous tidal breathing, many patients generate the maximal possible flow rates at that particular lung volume, a phenomenon termed expiratory flow limitation (EFL).

The volume of air left in the lungs at the end of a quiet expiration is termed end-expiratory lung volume (EELV) and is used interchangeably with functional residual capacity (FRC). The relaxation volume ( Vr ) of the respiratory system refers to the equilibrium point where the algebraic sum of the outward recoil of the chest wall and the inward recoil of the lungs is zero. Consequently, the alveolar and mouth pressure are also zero at end-expiration. In COPD, emphysema can result in increased compliance, such that EELV exceeds the Vr , often termed “static” or resting lung hyperinflation. However, in patients with resting EFL, EELV is a dynamic variable that varies with the prevailing breathing pattern. In other words, EELV is dynamically as well as “statically” determined. Thus, when breathing frequency increases, expiratory time is often insufficient to allow EELV to decline to the natural Vr , contributing to lung hyperinflation. In such individuals with significant EFL and increased EELV at rest, alveolar and mouth pressure are still positive at the onset of inspiration. Lung hyperinflation places the inspiratory muscles, particularly the diaphragm, at a significant mechanical disadvantage by shortening its fibers, thereby decreasing its force-generating capacity. Moreover, it forces tidal breathing to occur closer to total lung capacity (TLC) and the upper, nonlinear, poorly compliant, portion of the respiratory system’s pressure-volume relaxation curve. High inspiratory threshold (auto-positive end-expiratory pressure effect) and elastic loading of the functionally weakened inspiratory muscles require a greater inspiratory neural drive or electrical activation to generate a given force, a key mechanism of dyspnea in these patients ( Fig. 1 ). ,

Fig. 1

Neuromechanical dissociation and dyspnea in COPD. Neural inputs that reach the somatosensory cortex and contribute to intensity and quality of dyspnea come from (i) increased central corollary discharge from brainstem and cortical motor centers; (ii) altered afferent information from receptors in the airways, lungs, locomotor, and respiratory muscles; and (iii) information from central and peripheral chemoreceptors regarding the adequacy of ventilation and gas exchange. When the mechanical/muscular response of the respiratory system is constrained in the face of increasing inspiratory neural drive (IND), the intensity of “respiratory discomfort” increases and the sense of “unsatisfied inspiration” dominates as neuromechanical dissociation occurs. Concomitant increased activation of limbic structures also likely contributes to “respiratory distress.” [H + ], hydrogen ion concentration; Pa co 2 , partial pressure of arterial carbon dioxide; Pa o 2 , partial pressure of arterial oxygen.

( Adapted from O’Donnell DE, Ora J, Webb KA, et al. Mechanisms of activity-related dyspnea in pulmonary diseases. Respir Physiol Neurobiol 2009;167(1):116-32; with permission.)

The efficiency of pulmonary gas exchange in COPD is compromised by several mechanisms :

  • Inhomogeneity of alveolar ventilation (VA) distribution caused by vastly dissimilar mechanical time constants (product of resistance and compliance) for emptying of alveolar units in different lung regions;

  • Regional lung hyperinflation with extrinsic compression of adjacent parenchyma, blood vessels, and small airways; and

  • Heterogeneity of alveolar and vascular destruction owing to emphysema and vascular inflammation.

Overall, there is a trend for patients with predominant emphysema to show more extensive areas of high VA/capillary perfusion (Qc) ratios, whereas those with predominant chronic bronchitis may have low VA/Qc regions as a result of increased small airways resistance and mucus plugging. However, it is clear that in many patients with COPD lacking specific phenotypical characteristics, VA/Qc abnormalities can be quite heterogenous. Vascular injury may occur before, simultaneously, or after the described small airway abnormalities; increased intimal thickness owing to deposition of extracellular matrix proteins and muscle cell proliferation contributes to increased pulmonary vascular resistance. , Compensatory adaptations of the central respiratory controller can preserve arterial oxygenation and acid-base status in patients with less severe COPD. However, these compensatory adjustments fail to varying degrees with disease progression. Thus, abnormalities in ventilatory control, critical respiratory muscle weakness, and the negative mechanical effects of lung hyperinflation culminate in decreased VA leading to variable degrees of hypoxemia and ultimately to CO 2 retention ( Box 2 ).

Box 2

Consequences of lung hyperinflation

Lung hyperinflation shortens the inspiratory muscles’ fibers: high inspiratory threshold and elastic loading of the functionally weakened inspiratory muscles require a greater inspiratory neural drive to generate a given force, a key mechanism of dyspnea in COPD.


Resting physiologic abnormalities are substantially amplified during the stress of exercise in patients with COPD. Exercise intolerance in COPD, however, is characteristically multifactorial with the exact mechanisms varying widely across the spectrum of disease severity and among patients with similar degrees of resting respiratory impairment. During exercise when ventilation increases, temporary and variable increase in EELV above its resting value occurs (dynamic lung hyperinflation [DH]), because of the combination of tachypnea and EFL. DH is manifest as a progressive reduction of inspiratory capacity (IC) and inspiratory reserve volume (IRV) at relatively low exercise intensities in the setting of largely preserved TLC. Acute-on-chronic lung hyperinflation during exercise amplifies elastic and inspiratory threshold loading of the already burdened inspiratory muscles and results in intolerable dyspnea and exercise limitation ( Fig. 2 ). ,

Fig. 2

Operating lung volumes at rest and during exercise ( left ) and the corresponding respiratory system pressure-volume relationship ( right ) in ( A ) a healthy subject and ( B ) a patient with COPD. In the healthy subject, EELV decreases during exercise, leading to a higher IC. In the COPD patient, EELV increases and IC is reduced. In COPD, the patient breathes at a higher, less compliant portion of the P-V curve where the work of breathing is increased. As a result, there is less “room” for VT expansion (lower IC) and a lower IRV is reached at lower exercise intensity.

( Adapted from O’Donnell DE. Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3(2):180-4; with permission.)

In patients with mild-to-moderate COPD, 1 consistent abnormality has been the finding of higher than normal ventilation ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
V ˙
E)-carbon dioxide production ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-2-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
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CO 2 ) relationship (ventilatory inefficiency) ( Fig. 3 ) secondary to

  • Increased physiologic dead space (high dead space ventilation [VD]/tidal volume [VT] ratio); and/or

  • Altered chemosensitivity with mild alveolar hyperventilation, potentially leading to a chronically reduced arterial partial pressure of CO 2 (Pa co 2 ).

Fig. 3

Average effect of aging, smoking, mild COPD, and moderate COPD on <SPAN role=presentation tabIndex=0 id=MathJax-Element-3-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
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CO 2 nadir, a metric of exercise ventilatory inefficiency. The modulating influence of airflow obstruction (AO) and decrements ( downward arrow ) in lung DL CO in smokers are also shown. Values are mean ± standard deviation. GOLD, Global Initiative for Chronic Obstructive Lung Disease.

( From Neder JA, Berton DC, Müller P de T, et al. Ventilatory Inefficiency and Exertional Dyspnea in Early Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2017;14:S22-29; with permission.)

Preservation of the arterial partial pressure for oxygen (Pa o 2 ) during exercise in these patients is a result of compensatory increases in inspiratory neural drive and <SPAN role=presentation tabIndex=0 id=MathJax-Element-4-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
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E to overcome a high VD/VT. In addition, altered afferent feedback from ergo-receptors responding to early metabolic acidosis (deconditioning) or mechanical distortion in active peripheral muscles, together with increased sympathetic nervous system activation, can directly stimulate ventilation. Increased return of poorly oxygenated mixed venous blood during exercise (because of reduced O 2 delivery or increased extraction) to areas of low VA/Qc in the lungs may precipitate (or worsen) arterial hypoxemia.

DH and ventilatory inefficiency are not independent: high <SPAN role=presentation tabIndex=0 id=MathJax-Element-5-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
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E- <SPAN role=presentation tabIndex=0 id=MathJax-Element-6-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>V˙
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CO 2 and the consequent increased stimulus for inspiratory neural drive and ventilation accelerate the rate of DH leading to earlier attainment of critical inspiratory mechanical constraints because the end-inspiratory lung volume approaches, TLC and IRV disappear ( Fig. 4 ). Low IC decreases the reserve for VT expansion, which, in turn, tends to increase VD/VT, potentially compromising CO 2 elimination. As COPD worsens, and the relative contribution of mechanical constraints to dyspnea and exercise intolerance increases markedly, deterioration of pulmonary gas exchange and acid-base balance increases metabolic demand in the setting of a reduced capacity of the respiratory system to adequately respond.

Fig. 4

Select panels from cardiopulmonary exercise tests in COPD (solid symbols) compared with healthy controls (open symbols). ( A ) Dyspnea intensity and ( B ) ventilatory response to exercise are higher in COPD stimulated in part by increased ( C ) ventilatory inefficiency. As mechanical constraints develop during exercise, a rapid shallow breathing pattern emerges in COPD ( D , E ) and critical reduction in IRV ( F ) occurs. F b, breathing frequency; V E , minute ventilation. * p<0.05: patients versus controls.

( Adapted from Faisal A, Alghamdi B, Ciavaglia CE, et al. Common mechanisms of dyspnea in chronic interstitial and obstructive lung disorders. Am J Respir Crit Care Med. 2016;193(3):299-309; with permission.)

Exertional dyspnea increases steeply during exercise as inspiratory neural drive progressively increases in the face of demand-capacity imbalance. Thus, a high inspiratory neural drive in COPD patients stems from (see Fig. 1 ; Box 3 ) the following:

  • Increased efferent output from central chemosensitive receptors in the medulla responding to altered afferent inputs owing to the effects of increased wasted ventilation, early metabolic acidosis, critical arterial O 2 desaturation, increased ergo-receptor activation, sympathetic nervous system overactivation, and altered cardiovascular afferent activity; and/or

  • Increased cortical motor command output owing to increased respiratory muscle loading and functional weakness secondary to accelerated dynamic mechanical abnormalities.

Box 3

Dynamic hyperinflation

Acute-on-chronic lung hyperinflation during exercise amplifies elastic and inspiratory threshold loading of the already burdened inspiratory muscles and results in intolerable exertional dyspnea and exercise limitation.

Lung function tests in the diagnostic assessment of chronic obstructive pulmonary disease

The prevalence of COPD varies widely across the globe. Underdiagnosis and overdiagnosis have been estimated between 10% and 95% and 5% and 60%, respectively. , These discrepancies are largely ascribed to differences in defining criteria for poorly reversible airflow obstruction within the framework of COPD diagnosis.

Current Controversies in Defining Airflow Limitation

Forced expiratory volume in 1 second/forced vital capacity cutoff

During a forced expiratory maneuver from TLC to residual volume (RV), the largest fraction of exhaled volume (forced vital capacity, FVC) occurs at the earliest phase of expiration (ie, forced expiratory volume in 1 second, FEV 1 ) with the subsequent exhaled volume decreasing with increased time of the expiratory maneuver. It follows that the FEV 1 /FVC ratio is greater than 0.5 in most normal healthy individuals. Complicating the use of the FEV 1 /FVC ratio thresholds in the diagnosis of COPD are the naturally occurring changes in pulmonary function with age. With aging, loss of lung elastic recoil occurs, resulting in a decreasing FEV 1 /FVC ratio. Thus, whereas ratios near 0.85 are seen in normal children, values less than 0.6 might lie within the expected range in the very old. Ratios ≥0.7 are observed in most middle-aged subjects ( Fig. 5 ). Expiratory airflow limitation arises in COPD when the pathologic loss of lung elastic recoil and/or small airway obstruction and increased airway collapsibility on expiration slows the rate of lung emptying (see Structural and physiologic basis of respiratory dysfunction in chronic obstructive pulmonary disease: Rest ); consequently, flows are reduced for a given volume. It follows that an FEV 1 lower than expected for FVC after bronchodilator (BD) and a FEV 1 /FVC ratio below a critical defined threshold are thought to reflect the presence of airflow limitation in these subjects. ,

Aug 16, 2020 | Posted by in GENERAL | Comments Off on Lung Function Testing in Chronic Obstructive Pulmonary Disease
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