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Alterations in Pulmonary Physiology with Lung Transplantation

Manish Mohanka, Amit Banga

10.1002/cphy.c220008

Source: Volume 13, Issue 1, January 2023

Published online: January 2023

Full Article on Wiley Online Library



Abstract

Lung transplant is a treatment option for patients with end‐stage lung diseases; however, survival outcomes continue to be inferior when compared to other solid organs. We review the several anatomic and physiologic changes that result from lung transplantation surgery, and their role in the pathophysiology of common complications encountered by lung recipients. The loss of bronchial circulation into the allograft after transplant surgery results in ischemia‐related changes in the bronchial artery territory of the allograft. We discuss the role of bronchopulmonary anastomosis in blood circulation in the allograft posttransplant. We review commonly encountered complications related to loss of bronchial circulation such as allograft airway ischemia, necrosis, anastomotic dehiscence, mucociliary dysfunction, and bronchial stenosis. Loss of dual circulation to the lung also increases the risk of pulmonary infarction with acute pulmonary embolism. The loss of lymphatic drainage during transplant surgery also impairs the management of allograft interstitial fluid, resulting in pulmonary edema and early pleural effusion. We discuss the role of lymphatic drainage in primary graft dysfunction. Besides, we review the association of late posttransplant pleural effusion with complications such as acute rejection. We then review the impact of loss of afferent and efferent innervation from the allograft on control of breathing, as well as lung protective reflexes. We conclude with discussion about pulmonary function testing, allograft monitoring with spirometry, and classification of chronic lung allograft dysfunction phenotypes based on total lung capacity measurements. We also review factors limiting physical exercise capacity after lung transplantation, especially impairment of muscle metabolism. © 2023 American Physiological Society. Compr Physiol 13:4269‐4293, 2023.

Figure 1. Figure 1. Systemic blood supply of the lung via bronchial circulation. Note that bronchial arteries enter the lung via the hilum and supply the nonrespiratory portions of the bronchial tree. Also note the bronchopulmonary anastomoses, which are the source of blood supply to bronchial artery territory of allograft after transplantation. Reprinted, with permission, from, Deffebach ME, et al., 1987 37/American Thoracic Society. Copyright © 2022 American Thoracic Society. All rights reserved.
Figure 2. Figure 2. Clinical manifestations of airway ischemia resulting from loss of bronchial arteries after lung transplantation, noted during fiberoptic bronchoscopy. Bronchial mucosal ischemia and sloughing (A), mucosal necrosis with black discoloration (B), and anastomotic dehiscence found on day 22 after transplantation surgery during evaluation for sudden shortness of breath and bilateral pneumothorax (C).
Figure 3. Figure 3. Loss of blood supply to the bronchial tree from bronchial circulation after lung transplantation. Panel A depicts dual blood circulation in lungs before transplant surgery. The most severe ischemic changes are noted immediately at or distal to the airway anastomosis (left bronchus in panel B), as it is furthest from the source of blood supply to the bronchopulmonary anastomoses. Bronchial airway microvasculature dropout before bronchiolitis obliterans syndrome (panels C and D). Reprinted, with permission, from Nicolls MR and Zamora MR, 2010 95/Wolters Kluwer Health, Inc.
Figure 4. Figure 4. Central airway stenosis in the region of right mainstem anastomosis at 5 months postlung transplant (A) for the same patient depicted in Figure 2A. Balloon dilation for airway stenosis was performed (B).
Figure 5. Figure 5. Distal airway stenosis in the region of right bronchus intermedius at 3 months after lung transplantation (A), and vanishing bronchus syndrome in the right lower lobe segments at 7 months in the same patient (B). Patient expired 9 months after transplant surgery.
Figure 6. Figure 6. Reduction in airway anastomotic complications was achieved by shortening donor bronchus to reduce risk zone for bronchial ischemia. The donor bronchus should be cut back as close as possible to the upper lobe bronchus origin (a). If donor bronchus cut at (b) level, there will be a risk zone for bronchial ischemia (gray zone). Reprinted, with permission, from Weder W, et al., 2009 146/European Association for Cardio‐Thoracic Surgery, Elsevier B.V. All rights reserved © 2008.
Figure 7. Figure 7. Acute pulmonary embolism affecting the lobar artery of the right lower lobe (A), with infarction and possible hemorrhage in the corresponding lung territory. Patient was over 6 years postlung transplant indicating inadequacy of dual circulation in long term.
Figure 8. Figure 8. Interrupted pulmonary lymphatic drainage and its pathological outcomes in lung transplant. (A) Lymphatic vessel (green) is inevitably interrupted during lung transplant surgery. (B) Under physiological condition, lymphatic vessels maintain tissue homeostasis by draining excessive fluid, immune cells, and hyaluronan (HA) from the interstitial space. (C) Lymphatic drainage is blocked after lung transplant. During rejection, there are aberrant accumulations of fluid and low‐molecular‐weight HA (LMW‐HA). In addition, an increased presence of immune cells is observed in the lung interstitium. LYVE, lymphatic vessel endothelial hyaluronan receptor. Reprinted, with permission, from Cui Y, et al., 2017 31/Copyright © 2022 American Thoracic Society. All rights reserved.
Figure 9. Figure 9. Primary graft dysfunction. Bilateral infiltrates on chest X‐ray in a 68‐year‐old bilateral lung transplantation recipient for interstitial lung disease at day 0 (A), and day 3 postsurgery (B).
Figure 10. Figure 10. Innervation of the lung allograft. Note that the postsynaptic neuron of the parasympathetic system resides in the ganglia which are present in the walls of small bronchi. Loss of inhibitory presynaptic parasympathetic fibers during lung transplantation results in denervation‐hypersensitivity of the postsynaptic neuron, and airway hyperreactivity on methacholine challenge tests. Reprinted, from Grace MS, et al., 2013 50. Open access article distributed under Creative Commons CC‐BY License from Pulmonary Pharmacology & Therapeutics.
Figure 11. Figure 11. Mucus plugging noted during bronchoscopy examination for a patient at 4 weeks postlung transplantation (A), with airway mucus cast (B).
Figure 12. Figure 12. Spirometry after lung transplantation. “Baseline” spirometry is the average of two highest spirometry readings achieved at least 3 weeks apart after lung transplantation. Panels A and B depict FEV1 and FVC respectively, as percent‐predicted after lung transplantation surgery. Reprinted, with permission, from Mason DP et al., 2008. 83/The Annals of Thoracic Surgery.
Figure 13. Figure 13. Bronchiolitis obliterans syndrome, the most common phenotype of chronic lung allograft dysfunction at 4 years after lung transplantation. Inspiratory images of transplanted left lung (A), and expiratory images with areas of air‐trapping (B). Changes result from inflammation and scarring in the small airways postlung transplant.
Figure 14. Figure 14. Coronal CT scan image depicting restrictive allograft syndrome in a bilateral lung transplant recipient after 6 years. Note the bands of fibrosis in lung parenchyma which result in restrictive physiology on pulmonary function testing.


Figure 1. Systemic blood supply of the lung via bronchial circulation. Note that bronchial arteries enter the lung via the hilum and supply the nonrespiratory portions of the bronchial tree. Also note the bronchopulmonary anastomoses, which are the source of blood supply to bronchial artery territory of allograft after transplantation. Reprinted, with permission, from, Deffebach ME, et al., 1987 37/American Thoracic Society. Copyright © 2022 American Thoracic Society. All rights reserved.


Figure 2. Clinical manifestations of airway ischemia resulting from loss of bronchial arteries after lung transplantation, noted during fiberoptic bronchoscopy. Bronchial mucosal ischemia and sloughing (A), mucosal necrosis with black discoloration (B), and anastomotic dehiscence found on day 22 after transplantation surgery during evaluation for sudden shortness of breath and bilateral pneumothorax (C).


Figure 3. Loss of blood supply to the bronchial tree from bronchial circulation after lung transplantation. Panel A depicts dual blood circulation in lungs before transplant surgery. The most severe ischemic changes are noted immediately at or distal to the airway anastomosis (left bronchus in panel B), as it is furthest from the source of blood supply to the bronchopulmonary anastomoses. Bronchial airway microvasculature dropout before bronchiolitis obliterans syndrome (panels C and D). Reprinted, with permission, from Nicolls MR and Zamora MR, 2010 95/Wolters Kluwer Health, Inc.


Figure 4. Central airway stenosis in the region of right mainstem anastomosis at 5 months postlung transplant (A) for the same patient depicted in Figure 2A. Balloon dilation for airway stenosis was performed (B).


Figure 5. Distal airway stenosis in the region of right bronchus intermedius at 3 months after lung transplantation (A), and vanishing bronchus syndrome in the right lower lobe segments at 7 months in the same patient (B). Patient expired 9 months after transplant surgery.


Figure 6. Reduction in airway anastomotic complications was achieved by shortening donor bronchus to reduce risk zone for bronchial ischemia. The donor bronchus should be cut back as close as possible to the upper lobe bronchus origin (a). If donor bronchus cut at (b) level, there will be a risk zone for bronchial ischemia (gray zone). Reprinted, with permission, from Weder W, et al., 2009 146/European Association for Cardio‐Thoracic Surgery, Elsevier B.V. All rights reserved © 2008.


Figure 7. Acute pulmonary embolism affecting the lobar artery of the right lower lobe (A), with infarction and possible hemorrhage in the corresponding lung territory. Patient was over 6 years postlung transplant indicating inadequacy of dual circulation in long term.


Figure 8. Interrupted pulmonary lymphatic drainage and its pathological outcomes in lung transplant. (A) Lymphatic vessel (green) is inevitably interrupted during lung transplant surgery. (B) Under physiological condition, lymphatic vessels maintain tissue homeostasis by draining excessive fluid, immune cells, and hyaluronan (HA) from the interstitial space. (C) Lymphatic drainage is blocked after lung transplant. During rejection, there are aberrant accumulations of fluid and low‐molecular‐weight HA (LMW‐HA). In addition, an increased presence of immune cells is observed in the lung interstitium. LYVE, lymphatic vessel endothelial hyaluronan receptor. Reprinted, with permission, from Cui Y, et al., 2017 31/Copyright © 2022 American Thoracic Society. All rights reserved.


Figure 9. Primary graft dysfunction. Bilateral infiltrates on chest X‐ray in a 68‐year‐old bilateral lung transplantation recipient for interstitial lung disease at day 0 (A), and day 3 postsurgery (B).


Figure 10. Innervation of the lung allograft. Note that the postsynaptic neuron of the parasympathetic system resides in the ganglia which are present in the walls of small bronchi. Loss of inhibitory presynaptic parasympathetic fibers during lung transplantation results in denervation‐hypersensitivity of the postsynaptic neuron, and airway hyperreactivity on methacholine challenge tests. Reprinted, from Grace MS, et al., 2013 50. Open access article distributed under Creative Commons CC‐BY License from Pulmonary Pharmacology & Therapeutics.


Figure 11. Mucus plugging noted during bronchoscopy examination for a patient at 4 weeks postlung transplantation (A), with airway mucus cast (B).


Figure 12. Spirometry after lung transplantation. “Baseline” spirometry is the average of two highest spirometry readings achieved at least 3 weeks apart after lung transplantation. Panels A and B depict FEV1 and FVC respectively, as percent‐predicted after lung transplantation surgery. Reprinted, with permission, from Mason DP et al., 2008. 83/The Annals of Thoracic Surgery.


Figure 13. Bronchiolitis obliterans syndrome, the most common phenotype of chronic lung allograft dysfunction at 4 years after lung transplantation. Inspiratory images of transplanted left lung (A), and expiratory images with areas of air‐trapping (B). Changes result from inflammation and scarring in the small airways postlung transplant.


Figure 14. Coronal CT scan image depicting restrictive allograft syndrome in a bilateral lung transplant recipient after 6 years. Note the bands of fibrosis in lung parenchyma which result in restrictive physiology on pulmonary function testing.
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Article Title: Alterations in Pulmonary Physiology with Lung Transplantation
 

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Manish Mohanka, Amit Banga. Alterations in Pulmonary Physiology with Lung Transplantation. Compr Physiol 2023, 13: 4269-4293. doi: 10.1002/cphy.c220008