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Chronic Obstructive Pulmonary Disease

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Abstract

COPD is characterized by airflow limitation that is not fully reversible. The morphological basis for airflow obstruction results from a varying combination of obstructive changes in peripheral conducting airways and destructive changes in respiratory bronchioles, alveolar ducts, and alveoli. A reduction of vascularity within the alveolar septa has been reported in emphysema. Typical physiological changes reflect these structural abnormalities. Spirometry documents airflow obstruction when the FEV1/FVC ratio is reduced below the lower limit of normality, although in early disease stages FEV1 and airway conductance are not affected. Current guidelines recommend testing for bronchoreversibility at least once and the postbronchodilator FEV1/FVC be used for COPD diagnosis; the nature of bronchodilator response remains controversial, however. One major functional consequence of altered lung mechanics is lung hyperinflation. FRC may increase as a result of static or dynamic mechanisms, or both. The link between dynamic lung hyperinflation and expiratory flow limitation during tidal breathing has been demonstrated. Hyperinflation may increase the load on inspiratory muscles, with resulting length adaptation of diaphragm. Reduction of exercise tolerance is frequently noted, with compelling evidence that breathlessness and altered lung mechanics play a major role. Lung function measurements have been traditionally used as prognostic indices and to monitor disease progression; FEV1 has been most widely used. An increase in FVC is also considered as proof of bronchodilatation. Decades of work has provided insight into the histological, functional, and biological features of COPD. This has provided a clearer understanding of important pathobiological processes and has provided additional therapeutic options. © 2014 American Physiological Society. Compr Physiol 4:1‐31, 2014.

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Figure 1. Figure 1. Changes in static pressure‐volume curves of the lung with aging. Reproduced by permission from (388).
Figure 2. Figure 2. Relationship between small airway thickening and degree of emphysema. Note that there was a significant correlation (continuous line) between small airway thickness and mean linear intercept (Lm) in centrilobular emphysema (CLE) but not in panlobular emphysema (PLE) or in α1‐antitrypsine (AAT) deficiency or nonsmoking controls (dashed lines). Reproduced by permission from (194).
Figure 3. Figure 3. Schematic representation of factors favoring (within ovals) and opposing (within rectangles) airway narrowing. Continuous and interrupted arrows denote positive and negative effects, respectively. The effect of airway smooth muscle (ASM) contraction is amplified by mucosal thickening and the presence of bronchial secretions. The loads external and internal to the airway wall are the mechanisms that tend to limit ASM shortening, thus opposing airway narrowing. In COPD, loss of lung elastic recoil (emphysema) and peribronchial alveolar attachments are the major culprits for reduced load on ASM. Reproduced by permission from (28).
Figure 4. Figure 4. Relationships between airway wall area and perimeter in membranous bronchi from COPD patients. (A) WAi is the area of the innerlayer, internal to airway smooth muscle (mucosa). (B) WAo is the outer layer, external to the airway smooth muscle (adventitia). (C) WAm is the area of airway smooth muscle. Note that only WAi was related to the obstruction observed in vivo (FEV1/FVC) and the regression line of WAj versus Pbrn was different between patients with an FEV1/FVC of 40% (dashed line) and patients with an FEV1/FVC of 80% (continuous line). Reprinted with permission of the American Thoracic Society from (383). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.
Figure 5. Figure 5. Upper panel. Area‐pressure curve of two hypothetical airways (dashed and dotted lines) from total lung capacity (TLC) to residual volume (RV). Continuous lines are iso‐flow curves derived by solving the Bernoulli equation and assuming that pressure drop from alveoli (left panel, horizontal arrow with equation) is mostly due to convective acceleration. PAlv is alveolar pressure. The maximum flow for each airway is determined at the intersection of airway pressure‐area (dashed line) and iso‐flow curves. Note that maximum flow (V·) is less if airway elastance (dPtm/dA) is less (upper panel, dotted curve) or iso‐flow curves are shifted to the left (Lower panels). This may be due to an additional pressure drop due to peripheral frictional losses (left panel) or to a decrease in lung elastic recoil (right panel).
Figure 6. Figure 6. Relationships between area (A), pressure, and flow (B) in peripheral and central airways. Note the greater compliance of peripheral airway at low pressures. Arrows indicate maximum flows at each pressure (or lung volume). Reproduced by permission from (29).
Figure 7. Figure 7. Frequency distributions of percentage and absolute changes in 1‐s forced expiratory volume (FEV1) as percentage change (A), absolute change (B) and absolute change in percentage predicted (C) after a bronchodilator test in COPD patients. Note that half of patients had increments of FEV1 exceeding the limits used to define positive response (200 mL and 12%). Reproduced by permission from (374).
Figure 8. Figure 8. Relationship between airway responsiveness to methacholine (PC20, concentration causing a 20% decrease of FEV1 in subjects with centrilobular emphysema (solid circles), panlobular emphysema (open circles), and nonsmokers (triangles). Reprinted with permission of the American Thoracic Society from (113). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.
Figure 9. Figure 9. Mechanisms of lung hyperinflation. Static hyperinflation occurs when the relaxation volume of the respiratory system is increased, for example, when elastic recoil of the lung is decreased (emphysema). Dynamic hyperinflation occurs when there is no time allowed for tidal expiration to reach the relaxation volume of the respiratory system (inset box), because (A) increase of tidal volume (VT), (B) decrease of expiratory time (TE), (C) expiratory flow limitation (EFL), (D) increase of time constant (τ), and (E) postinspiratory activity of inspiratory muscles (PIA).
Figure 10. Figure 10. Relationships between diaphragm tension and the lengths of muscle fibers (upper panel) or sarcomere (lower panel) in elastase‐induced emphysematous and control animals. Note the leftward shift of optimal length despite a constant sarcomere tension‐length relationship, thus allowing preservation of the force generation capacity in the presence of lung hyperinflation. Reproduced by permission from (365).
Figure 11. Figure 11. Comparison of maximal, partial, and tidal flow volume loops in a subject with severe COPD at rest (thin continuous line) and on incremental exercise (thick interrupted and continuous lines). Note the progressive reduction of forced expiratory flows and the increase in functional residual capacity during exercise. Reproduced by permission from (64).
Figure 12. Figure 12. Effect of smoking on lung function decline. Note the greater effect of early than late smoking on FEV1. Reprinted with permission of the American Thoracic Society from (336). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.
Figure 13. Figure 13. Hypothetical effects of lung volume reduction surgery (LVRS). (A) Effects of LVRS removing only nonfunctional cysts and bullae. The dashed line represents the static relationship between pleural pressure and lung volume from a hypothetical emphysema patient during a very slow (quasistatic) inspiration from residual volume (RV) to total lung capacity (TLC). VC is represented by the difference on the ordinate between TLC and RV. Maximal elastic recoil pressure is shown by the double‐headed arrows at TLC. The slope of the relationship is lung compliance. The line labeled ‘‘inspiratory muscle capacity’' represents the chest wall pressure‐volume relationship during maximal inspiratory muscle contraction. Effects of LVRS are shown by the thin vertical line. Because this LVRS removed only nonfunctional lung, which does not contribute to lung elastic properties, compliance is unchanged. RV is reduced, and TLC is reduced by a lesser amount because the muscles can stretch the remaining lung. The difference between them, the VC, increases. Recoil pressure also increases but does not cause the increase in VC. (B) Effects of LVRS in a hypothetical patient with diffuse emphysema. The resected lung includes parenchyma, which has some elastic recoil. Its removal thereby decreases the compliance of the remaining lung. The recoil pressure rises by more than in (A), but the VC improves by less. If LVRS impairs intrinsic muscle function, the curve labeled ‘‘inspiratory muscle capacity’' would shift downward. This also limits the improvement in VC. Reprinted with permission of the American Thoracic Society from (110). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.
Figure 14. Figure 14. Effect of lung volume reduction surgery (LVRS) on dynamic hyperinflation and breathlessness during exercise. (A) Resting and iso‐work end expiratory lung volume (EELV) in 12 patients before and after bilateral LVRS. Patients experiencing a < 20% improvement in FEV1 after surgery are illustrated by the solid symbols. A decrease in both resting and iso‐work EELV is noted consistently by all patients after LVRS independent of change in FEV1. (B) Change in Borg score for breathlessness from rest to iso‐work (ΔBorgIW) as a function of the change in EELV (ΔEELV) as a percentage of predicted TLC. The outlying subject could not interpret the BORG score. A direct relationship is noted in the other subjects suggesting that improvement in dyspnea directly relates to a decrease exertional EELV after bilateral LVRS. Reprinted with permission of the American Thoracic Society from (246). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.


Figure 1. Changes in static pressure‐volume curves of the lung with aging. Reproduced by permission from (388).


Figure 2. Relationship between small airway thickening and degree of emphysema. Note that there was a significant correlation (continuous line) between small airway thickness and mean linear intercept (Lm) in centrilobular emphysema (CLE) but not in panlobular emphysema (PLE) or in α1‐antitrypsine (AAT) deficiency or nonsmoking controls (dashed lines). Reproduced by permission from (194).


Figure 3. Schematic representation of factors favoring (within ovals) and opposing (within rectangles) airway narrowing. Continuous and interrupted arrows denote positive and negative effects, respectively. The effect of airway smooth muscle (ASM) contraction is amplified by mucosal thickening and the presence of bronchial secretions. The loads external and internal to the airway wall are the mechanisms that tend to limit ASM shortening, thus opposing airway narrowing. In COPD, loss of lung elastic recoil (emphysema) and peribronchial alveolar attachments are the major culprits for reduced load on ASM. Reproduced by permission from (28).


Figure 4. Relationships between airway wall area and perimeter in membranous bronchi from COPD patients. (A) WAi is the area of the innerlayer, internal to airway smooth muscle (mucosa). (B) WAo is the outer layer, external to the airway smooth muscle (adventitia). (C) WAm is the area of airway smooth muscle. Note that only WAi was related to the obstruction observed in vivo (FEV1/FVC) and the regression line of WAj versus Pbrn was different between patients with an FEV1/FVC of 40% (dashed line) and patients with an FEV1/FVC of 80% (continuous line). Reprinted with permission of the American Thoracic Society from (383). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.


Figure 5. Upper panel. Area‐pressure curve of two hypothetical airways (dashed and dotted lines) from total lung capacity (TLC) to residual volume (RV). Continuous lines are iso‐flow curves derived by solving the Bernoulli equation and assuming that pressure drop from alveoli (left panel, horizontal arrow with equation) is mostly due to convective acceleration. PAlv is alveolar pressure. The maximum flow for each airway is determined at the intersection of airway pressure‐area (dashed line) and iso‐flow curves. Note that maximum flow (V·) is less if airway elastance (dPtm/dA) is less (upper panel, dotted curve) or iso‐flow curves are shifted to the left (Lower panels). This may be due to an additional pressure drop due to peripheral frictional losses (left panel) or to a decrease in lung elastic recoil (right panel).


Figure 6. Relationships between area (A), pressure, and flow (B) in peripheral and central airways. Note the greater compliance of peripheral airway at low pressures. Arrows indicate maximum flows at each pressure (or lung volume). Reproduced by permission from (29).


Figure 7. Frequency distributions of percentage and absolute changes in 1‐s forced expiratory volume (FEV1) as percentage change (A), absolute change (B) and absolute change in percentage predicted (C) after a bronchodilator test in COPD patients. Note that half of patients had increments of FEV1 exceeding the limits used to define positive response (200 mL and 12%). Reproduced by permission from (374).


Figure 8. Relationship between airway responsiveness to methacholine (PC20, concentration causing a 20% decrease of FEV1 in subjects with centrilobular emphysema (solid circles), panlobular emphysema (open circles), and nonsmokers (triangles). Reprinted with permission of the American Thoracic Society from (113). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.


Figure 9. Mechanisms of lung hyperinflation. Static hyperinflation occurs when the relaxation volume of the respiratory system is increased, for example, when elastic recoil of the lung is decreased (emphysema). Dynamic hyperinflation occurs when there is no time allowed for tidal expiration to reach the relaxation volume of the respiratory system (inset box), because (A) increase of tidal volume (VT), (B) decrease of expiratory time (TE), (C) expiratory flow limitation (EFL), (D) increase of time constant (τ), and (E) postinspiratory activity of inspiratory muscles (PIA).


Figure 10. Relationships between diaphragm tension and the lengths of muscle fibers (upper panel) or sarcomere (lower panel) in elastase‐induced emphysematous and control animals. Note the leftward shift of optimal length despite a constant sarcomere tension‐length relationship, thus allowing preservation of the force generation capacity in the presence of lung hyperinflation. Reproduced by permission from (365).


Figure 11. Comparison of maximal, partial, and tidal flow volume loops in a subject with severe COPD at rest (thin continuous line) and on incremental exercise (thick interrupted and continuous lines). Note the progressive reduction of forced expiratory flows and the increase in functional residual capacity during exercise. Reproduced by permission from (64).


Figure 12. Effect of smoking on lung function decline. Note the greater effect of early than late smoking on FEV1. Reprinted with permission of the American Thoracic Society from (336). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.


Figure 13. Hypothetical effects of lung volume reduction surgery (LVRS). (A) Effects of LVRS removing only nonfunctional cysts and bullae. The dashed line represents the static relationship between pleural pressure and lung volume from a hypothetical emphysema patient during a very slow (quasistatic) inspiration from residual volume (RV) to total lung capacity (TLC). VC is represented by the difference on the ordinate between TLC and RV. Maximal elastic recoil pressure is shown by the double‐headed arrows at TLC. The slope of the relationship is lung compliance. The line labeled ‘‘inspiratory muscle capacity’' represents the chest wall pressure‐volume relationship during maximal inspiratory muscle contraction. Effects of LVRS are shown by the thin vertical line. Because this LVRS removed only nonfunctional lung, which does not contribute to lung elastic properties, compliance is unchanged. RV is reduced, and TLC is reduced by a lesser amount because the muscles can stretch the remaining lung. The difference between them, the VC, increases. Recoil pressure also increases but does not cause the increase in VC. (B) Effects of LVRS in a hypothetical patient with diffuse emphysema. The resected lung includes parenchyma, which has some elastic recoil. Its removal thereby decreases the compliance of the remaining lung. The recoil pressure rises by more than in (A), but the VC improves by less. If LVRS impairs intrinsic muscle function, the curve labeled ‘‘inspiratory muscle capacity’' would shift downward. This also limits the improvement in VC. Reprinted with permission of the American Thoracic Society from (110). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.


Figure 14. Effect of lung volume reduction surgery (LVRS) on dynamic hyperinflation and breathlessness during exercise. (A) Resting and iso‐work end expiratory lung volume (EELV) in 12 patients before and after bilateral LVRS. Patients experiencing a < 20% improvement in FEV1 after surgery are illustrated by the solid symbols. A decrease in both resting and iso‐work EELV is noted consistently by all patients after LVRS independent of change in FEV1. (B) Change in Borg score for breathlessness from rest to iso‐work (ΔBorgIW) as a function of the change in EELV (ΔEELV) as a percentage of predicted TLC. The outlying subject could not interpret the BORG score. A direct relationship is noted in the other subjects suggesting that improvement in dyspnea directly relates to a decrease exertional EELV after bilateral LVRS. Reprinted with permission of the American Thoracic Society from (246). Official journal of the American Thoracic Society. Copyright © 2013 American Thoracic Society.
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Vito Brusasco, Fernando Martinez. Chronic Obstructive Pulmonary Disease. Compr Physiol 2014, 4: 1-31. doi: 10.1002/cphy.c110037