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Environmental Perturbations: Obesity

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Abstract

Obesity currently affects about one‐third of the U.S. population, while another one‐third is overweight. The importance of obesity for certain conditions such as heart disease and type 2 diabetes is well appreciated. The effects of obesity on the respiratory system have received less attention and are the subject of this article. Obesity alters the static mechanical properties of the respiratory system leading to a reduction in the functional residual capacity (FRC) and the expiratory reserve volume (ERV). There is substantial variability in the effects of obesity on FRC and ERV, at least some of which is related to the location rather than the total mass of adipose tissue. Obesity also results in airflow obstruction, which is only partially attributable to breathing at low lung volume, and can also promote airway hyperresponsiveness and asthma. Hypoxemia is common is obesity and correlates well with FRC, as well as with measures of abdominal obesity. However, obese subjects are usually eucapnic, indicating that hypoventilation is not a common cause of their hypoxemia. Instead, hypoxemia results from ventilation‐perfusion mismatch caused by closure of dependent airways at FRC. Many obese subjects complain of dyspnea either at rest or during exertion, and the dyspnea score also correlates with reductions in FRC and ERV. Weight reduction should be encouraged in any symptomatic obese individual, since virtually all of the respiratory complications of obesity improve with even moderate weight loss. © 2011 American Physiological Society. Compr Physiol 1:263‐282, 2011.

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Figure 1. Figure 1.

Some of the proteins produced by adipose tissue (adipokines). IL, interleukin; TNF, tumor necrosis factor; PBEF, pre‐B‐cell colony‐enhancing factor; TGF, transforming growth factor; PAI, plasminogen activator inhibitor; VEGF, vascular endothelial growth factor; IL‐1RA, interleukin‐1 receptor antagonist.

Reproduced with permission of the American Physiological Society from Figure of Shore
Figure 2. Figure 2.

Effects of lower thoracic (left) and abdominal (right) loading on the total respiratory static volume pressure curve in an anesthetized, paralyzed normal subject.

Reproduced with permission of the American Physiological Society from Figure of Sharp et al.
Figure 3. Figure 3.

Schematic representation of lung volumes in lean and obese subjects. TLC, total lung capacity; FRC, functional residual capacity; ERV, expiratory reserve volume; RV, residual volume.

Reproduced with permission of Elsevier from Figure of Shore and Johnston
Figure 4. Figure 4.

Pressure‐volume (PV) relationship of the lung and of the lean and obese chest wall showing how static lung volumes change when obesity alters the PV curve of the chest wall. Vrel, relaxation volume of the respiratory system, volume at which the inward recoil of the lung balances the outward recoil of the chest wall. Obesity‐related changes in the relaxation PV curve of the chest result in a reduction of Vrel.

Figure 5. Figure 5.

Flow volume loops during tidal breathing at rest, at anaerobic threshold (Vth), and at peak exercise, as well as the maximum expiratory flow volume loop of an obese subject who was flow limited during tidal breathing both at rest and during exercise (A), and one who was not (B).

Reproduced with permission of the Scandinavian Physiological Society from Figure of Romagnoli et al.
Figure 6. Figure 6.

Postural changes in mean total respiratory conductance (Grs) plotted against the midtidal lung volume (MTLV) in 10 obese subjects and 13 control subjects both sitting and supine. Symbols on horizontal axis indicate mean values of residual volume (RV). Control subjects are represented by closed symbols and obese subjects are represented by open symbols subjects. MTLV in control subjects was from records of tidal volume and inspiratory capacity, assuming that TLC measured by body plethysmography in the seated position fell by 200 ml when supine. In the obese subjects, TLC measured by multibreath helium dilution in both postures was used as the reference volume to derive MTLV.

Reproduced with permission of the American Physiological Society from Figure of Watson and Pride
Figure 7. Figure 7.

Factors promoting airway narrowing in obesity. In the obese, functional residual capacity (FRC) is reduced leading to decreased peribronchial pressure. Tidal volume (VT) is also reduced. The decrease in VT reduces the amount of airway smooth muscle (ASM) strain that occurs with each breath. Less strain results in a fewer detachments of myosin from actin, and a stiffer muscle. The stiffer the muscle, the more difficult it is to strain it. There is increased pulmonary blood volume in obesity Consequent increases in pulmonary artery pressure will increase fluid flux into the pulmonary interstitium resulting in cuffing of fluid around airways. This uncouples the airways from the retractive forces of the lung parenchyma further increasing ASM shortening. There may also be increases in circulating factors, such as endothelin, that can directly constrict ASM. The result is more ASM shortening and consequent reductions in airway caliber.

Figure 8. Figure 8.

Changes in pulmonary resistance (RL) induced by intravenous administration of methacholine in obese ob/ob mice and their lean age‐ and gender‐matched wild‐type controls. Data are mean ± SE. *P < 0.05 vs. wildtype.

Adapted from Figure of Shore et al. , and Reproduced with permission of the American Physiological Society
Figure 9. Figure 9.

Odds ratios (adjusted for race/ethnicity, age, and smoking) for adult‐onset current asthma as a function of body mass index, stratified by abdominal obesity, among California Teachers Study cohort members. Errors bars indicate the upper limit of the 95% confidence interval.

Adapted from Table 3 of von Behren et al.
Figure 10. Figure 10.

Pao2 (left) and Paco2 (right) as a function of body mass index (BMI). Data are compiled from six studies in which either Pao2 or Paco2 or both were available on individual obese subjects in the seated upright posture. Each study is indicated by a different symbol: closed circles, Kaufman et al.; open circles, Holley et al.; closed squares, Said; open squares, Sampson and Grassino; closed triangles, Lotti et al.; open triangles, Fritts et al.

Figure 11. Figure 11.

Relationship between arterial Pao2 and expiratory reserve volume (ERV) in eight obese subjects. Regression line of closest fit is shown (y = 73.9 + 15.8x; n = 32; SD (from regression) ± 10‐8 mmHg). For key to symbols see Figure . Closed circles, sitting before fasting; open circles, sitting after fasting; closed triangles, supine before fasting; open triangles, supine after fasting.

Reproduced from Figure of Farebrother et al. with permission of the British Medical Association
Figure 12. Figure 12.

In vivo adipose tissue oxygen status. Body weight and adipose tissue po2 determined by a fluorometric tissue oxygen sensor for lean (control, C57BL/6J) and obese ob/ob mice as well as mice with diet‐induced obesity (DIO). (n = 4 per group; all data expressed as mean ± SEM).

Reproduced from Figure D of Rausch et al. with permission of the Nature Publishing Group
Figure 13. Figure 13.

Schematic diagram showing potential mechanisms whereby obesity may lead to visceral adipose tissue hypoxia, and subsequent adipocyte necrosis and macrophage recruitment. FRC, functional residual capacity; Pao2, arterial partial pressure for oxygen.

Figure 14. Figure 14.

Relationship between intensity of breathing and leg discomfort (assessed by the modified Borg scale) and work rate during symptom‐limited incremental cycle exercise in obese women (closed circles) and in normal weight women (open circles). Relationships between intensity of breathing discomfort and both Ve and Vo2 during exercise were similar in obese and normal weight women. Values are means ± SE. *P < 0.05 obese vs. normal weight at a standardized cycle work rate.

Reproduced from Figure of Ofir et al. with permission of the American Physiological Society


Figure 1.

Some of the proteins produced by adipose tissue (adipokines). IL, interleukin; TNF, tumor necrosis factor; PBEF, pre‐B‐cell colony‐enhancing factor; TGF, transforming growth factor; PAI, plasminogen activator inhibitor; VEGF, vascular endothelial growth factor; IL‐1RA, interleukin‐1 receptor antagonist.

Reproduced with permission of the American Physiological Society from Figure of Shore


Figure 2.

Effects of lower thoracic (left) and abdominal (right) loading on the total respiratory static volume pressure curve in an anesthetized, paralyzed normal subject.

Reproduced with permission of the American Physiological Society from Figure of Sharp et al.


Figure 3.

Schematic representation of lung volumes in lean and obese subjects. TLC, total lung capacity; FRC, functional residual capacity; ERV, expiratory reserve volume; RV, residual volume.

Reproduced with permission of Elsevier from Figure of Shore and Johnston


Figure 4.

Pressure‐volume (PV) relationship of the lung and of the lean and obese chest wall showing how static lung volumes change when obesity alters the PV curve of the chest wall. Vrel, relaxation volume of the respiratory system, volume at which the inward recoil of the lung balances the outward recoil of the chest wall. Obesity‐related changes in the relaxation PV curve of the chest result in a reduction of Vrel.



Figure 5.

Flow volume loops during tidal breathing at rest, at anaerobic threshold (Vth), and at peak exercise, as well as the maximum expiratory flow volume loop of an obese subject who was flow limited during tidal breathing both at rest and during exercise (A), and one who was not (B).

Reproduced with permission of the Scandinavian Physiological Society from Figure of Romagnoli et al.


Figure 6.

Postural changes in mean total respiratory conductance (Grs) plotted against the midtidal lung volume (MTLV) in 10 obese subjects and 13 control subjects both sitting and supine. Symbols on horizontal axis indicate mean values of residual volume (RV). Control subjects are represented by closed symbols and obese subjects are represented by open symbols subjects. MTLV in control subjects was from records of tidal volume and inspiratory capacity, assuming that TLC measured by body plethysmography in the seated position fell by 200 ml when supine. In the obese subjects, TLC measured by multibreath helium dilution in both postures was used as the reference volume to derive MTLV.

Reproduced with permission of the American Physiological Society from Figure of Watson and Pride


Figure 7.

Factors promoting airway narrowing in obesity. In the obese, functional residual capacity (FRC) is reduced leading to decreased peribronchial pressure. Tidal volume (VT) is also reduced. The decrease in VT reduces the amount of airway smooth muscle (ASM) strain that occurs with each breath. Less strain results in a fewer detachments of myosin from actin, and a stiffer muscle. The stiffer the muscle, the more difficult it is to strain it. There is increased pulmonary blood volume in obesity Consequent increases in pulmonary artery pressure will increase fluid flux into the pulmonary interstitium resulting in cuffing of fluid around airways. This uncouples the airways from the retractive forces of the lung parenchyma further increasing ASM shortening. There may also be increases in circulating factors, such as endothelin, that can directly constrict ASM. The result is more ASM shortening and consequent reductions in airway caliber.



Figure 8.

Changes in pulmonary resistance (RL) induced by intravenous administration of methacholine in obese ob/ob mice and their lean age‐ and gender‐matched wild‐type controls. Data are mean ± SE. *P < 0.05 vs. wildtype.

Adapted from Figure of Shore et al. , and Reproduced with permission of the American Physiological Society


Figure 9.

Odds ratios (adjusted for race/ethnicity, age, and smoking) for adult‐onset current asthma as a function of body mass index, stratified by abdominal obesity, among California Teachers Study cohort members. Errors bars indicate the upper limit of the 95% confidence interval.

Adapted from Table 3 of von Behren et al.


Figure 10.

Pao2 (left) and Paco2 (right) as a function of body mass index (BMI). Data are compiled from six studies in which either Pao2 or Paco2 or both were available on individual obese subjects in the seated upright posture. Each study is indicated by a different symbol: closed circles, Kaufman et al.; open circles, Holley et al.; closed squares, Said; open squares, Sampson and Grassino; closed triangles, Lotti et al.; open triangles, Fritts et al.



Figure 11.

Relationship between arterial Pao2 and expiratory reserve volume (ERV) in eight obese subjects. Regression line of closest fit is shown (y = 73.9 + 15.8x; n = 32; SD (from regression) ± 10‐8 mmHg). For key to symbols see Figure . Closed circles, sitting before fasting; open circles, sitting after fasting; closed triangles, supine before fasting; open triangles, supine after fasting.

Reproduced from Figure of Farebrother et al. with permission of the British Medical Association


Figure 12.

In vivo adipose tissue oxygen status. Body weight and adipose tissue po2 determined by a fluorometric tissue oxygen sensor for lean (control, C57BL/6J) and obese ob/ob mice as well as mice with diet‐induced obesity (DIO). (n = 4 per group; all data expressed as mean ± SEM).

Reproduced from Figure D of Rausch et al. with permission of the Nature Publishing Group


Figure 13.

Schematic diagram showing potential mechanisms whereby obesity may lead to visceral adipose tissue hypoxia, and subsequent adipocyte necrosis and macrophage recruitment. FRC, functional residual capacity; Pao2, arterial partial pressure for oxygen.



Figure 14.

Relationship between intensity of breathing and leg discomfort (assessed by the modified Borg scale) and work rate during symptom‐limited incremental cycle exercise in obese women (closed circles) and in normal weight women (open circles). Relationships between intensity of breathing discomfort and both Ve and Vo2 during exercise were similar in obese and normal weight women. Values are means ± SE. *P < 0.05 obese vs. normal weight at a standardized cycle work rate.

Reproduced from Figure of Ofir et al. with permission of the American Physiological Society
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Further Reading
Malhotra A, Hillman D.  Obesity and the lung: Obesity, respiration, and intensive care. Thorax 63: 925–931, 2008.  
Tilg H, Moschen AR.  Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nature Rev Immunol 10:772-83, 2006.
Paramesawaran K, Todd DC, Soth M.  Altered respiratory physiology in obesity. Can Respir J 13: 203-10, 2006.
Handbook of Obesity.  Etiology and Pathophysiology. 2nd edition.  New York:Marcel Dekker, Inc. 2004.
The Obesity Society website.


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Stephanie A. Shore. Environmental Perturbations: Obesity. Compr Physiol 2010, 1: 263-282. doi: 10.1002/cphy.c100017