- Email: [email protected]
Respiratory physiology and pulmonary complications in obesity
Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 157–161
Contents lists available at SciVerse ScienceDirect
Best Practice & Research Clinical Endocrinology & Metabolism journal homepage: www.elsevier.com/locate/beem
6
Respiratory physiology and pulmonary complications in obesity Justin C. Sebastian, MD, FRCP(C), FCCP, Dip. ABIM, Assistant Clinical Professor, Consultant Respirologist a, b, * a b
University of Alberta, Edmonton, Alberta, Canada Royal Alexandra Hospital, Edmonton, Alberta, Canada
Keywords: pulmonary function tests dyspnea asthma COPD sleep apnea
Obesity is generally accepted as a global epidemic and the most common metabolic disorder in the world. Obesity affects every organ system but the consequences on the respiratory system are often underappreciated. While the respiratory consequences of being overweight are predominantly mechanical, an inflammatory element has also been proposed. For this discussion, the components of the respiratory system can be divided into the airways, pulmonary parenchyma, pulmonary vasculature, and the upper respiratory tract. This section will discuss respiratory physiology and the mechanisms leading to breathing difficulties in obesity followed by the impact of obesity on commonly occurring pulmonary disorders. Ó 2013 Elsevier Ltd. All rights reserved.
Discussion Body mass index (BMI) is a widely accepted measure of obesity which is considered the most common metabolic disorder in the world.1 BMI measurements lack the ability to describe the distribution of fat. Consequently, a higher BMI may not predict the physiological changes on the respiratory system universally.2 Studies have shown that dual energy X-ray absorptiometry (DEXA) had significantly better correlation with lung function impairment than anthropometric measurements.3 At a glance, the physiological changes in obesity could be comparable to the effects of a “bear hug”. Adiposity on the thoracic cage and abdomen can have an effect on chest wall movement, airway size, respiratory muscle function, and lung perfusion.
* Royal Alexandra Hospital, 1370, 10665 Jasper Avenue, Edmonton, Alberta T5J 3S9, Canada. Tel.: þ1 780 702 3866. E-mail address: [email protected]. 1521-690X/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.beem.2013.04.014
158
J.C. Sebastian / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 157–161
The ability to move the chest wall diminishes with the accumulation of fat, leading to stiffness and decreased lung compliance. Measuring compliance is difficult but reductions seem to be exponentially related to increases in BMI.4 Respiratory muscle strength can be measured by maximum inspiratory and expiratory pressures. While respiratory muscle strength remains preserved in obesity, the reduction in chest wall compliance can lead to heightened demands on the diaphragm reducing endurance.5,6 Respiratory muscle endurance can be measured with pulmonary function tests (PFTs) by performing a maneuver known as maximal voluntary ventilation (MVV). Respiratory muscle endurance may be reduced as much as 45% in obese individuals.6 This may explain the common occurrence of breathlessness among obese individuals and their susceptibility to respiratory failure after abdominal surgery, sepsis and metabolic derangement.7 Ventilation and perfusion is the greatest in the dependent portions of the lung. This would represent the bases in a seated and non-obese individual. In obesity, weight gain promotes a rapid, shallow breathing pattern. For such individuals, as functional residual capacity (FRC) declines, there is a reversal in ventilation with a larger proportion of tidal breathing being distributed to the upper lung zones, while perfusion remains at the bottom.8 As FRC drops, airway closure may occur within tidal breathing, promoting alveolar collapse, and atelectasis at the lung bases. This ventilation and perfusion mismatch correlates to reduction in expiratory reserve volume (ERV). These changes can influence arterial PO2 and may account for the vulnerability to hypoxia amongst obese individuals. Resistance describes the caliber of the airway, which is a major mechanical property of the lungs. As with obstructive lung disease, obesity causes airway caliber to narrow leading to increased resistance. For this reason obesity can mimics or worsen the severity of asthma symptoms. Airway resistance in obesity is closely related to reduction in lung volumes and FRC.9 PFTs are a valuable clinical tool that correlates with increases in BMI. The most frequent anomaly is the reduction in FRC and ERV. ERV accounts for the volume of air that can be forcefully expired from the end of normal expiration while FRC equals ERV plus reserve volume. Although they are closely related, ERV reduces early on, even with a modest increase in weight. ERV can decline further in the supine position as the diaphragm assumes a higher position in the chest.2 The reductions in FRC and ERV, caused by weight gain, occur exponentially and can be encountered with BMI values <30 kg/m2.10 Vital capacity and total lung capacity are often preserved unless obesity is extreme. Reduction in these lung volumes, even in enormous individuals, should raise the possibility of intrinsic lung disease.2 Spirometry seldom changes in mild obesity but simultaneous reduction in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) can be encountered as BMI increases. The FEV1 to FVC ratio, a marker of airway obstruction, is usually maintained unless there is coexistent airway disease.2 Concurrent decline in FEV1 and FVC can be predictive of a low MVV, indicating the presence of diaphragmatic dysfunction, as discussed earlier.7 The upper airway is a complex anatomical structure that is subject to the neuromuscular and mechanical effects of obesity. Obstructive sleep apnea (OSA) is a common disorder caused by recurrent episodes of upper airway obstruction during sleep. This obstruction occurs due to pharyngeal collapse from the mechanical load of adiposity around the pharynx. In addition, the diminished neuromuscular activity occurring during sleep promotes further pharyngeal collapsibility.11 Leptin, an adipose tissue hormone, promotes visceral fat deposition which includes the upper body.12 TNF alpha, along with other inflammatory cytokines, promotes pharyngeal neuromuscular dysfunction, thereby inhibiting the compensatory response to protect the airway from closure during sleep.11 Investigators have found this diminished neuromuscular control independently increases an individual’s susceptibility to OSA.13 Obesity, sleep deprivation and OSA are associated with elevation in leptin and inflammatory cytokines. However, the administration of continuous positive airway pressure (CPAP) is associated with reduction in these levels.14,15 Dyspnea is a common complaint amongst obese individuals, even in the absence of respiratory disease and related illnesses. Determinates of breathlessness are difficult to predict. One study compared asymptomatic obese and normal weight women during exercise and found that breathlessness, oxygen consumption, and minute ventilation were no different between them. This would suggest that mechanical factors related to obesity did not contribute to breathlessness.16 On the other hand, it has been shown when exertional dyspnea is present there was an increase in the oxygen cost of
J.C. Sebastian / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 157–161
159
breathing compared to overweight individuals without exertional dyspnea.17 Obese people with breathing difficulties at rest were found to have lower MVV and increased oxygen cost of breathing suggesting respiratory muscle weakness and fatigue.7 While the exact mechanism and cause of dyspnea remains disputed, the presences of comorbidities such as diastolic dysfunction, coronary artery disease, pulmonary hypertension, and obstructive airways disease can serve to further aggravate and potentiate dyspnea. Respiratory disorders are arguably as prevalent yet undeniably interrelated to obesity. The following section will discuss the impact of obesity on commonly occurring respiratory disorders such as asthma, chronic obstructive pulmonary disease (COPD), and OSA. The frequency of asthma and obesity has increased concurrently over the past two decades.18 Several trends have been established between both conditions but the nature of this association remains unsettled. There is a notable relationship between BMI and asthma to the extent that it has been shown that weight gain 5 kg during a four-year span increased the risk of asthma in a dosedependent manner.19 Airway hyperreactivity (AHR) and atopy were found to be more prevalent in women with increasing BMI.20,21 The risk of developing asthma was noted to be greater in obese women than in obese men, implicating sex hormones and body fat distribution as risk factors for asthma.22 Obesity is known to increase the risk of gastroesophageal reflux (GERD) which can mimic asthma-like symptoms.23,24 Obese individuals were also found to be more symptomatic and required twice as much bronchodilators than the non-obese.25 From a clinical standpoint, it is a difficult task to determine whether respiratory symptoms in overweight individuals are due to the mechanical effects of obesity or a comorbid state such as asthma. In addition to history and physical examination, physiological testing with complete PFTs and bronchoprovocation testing are essential in confirming the presence of asthma and to provide direction of therapy. COPD can affect up to one-quarter of smokers above the age of 40, and many are unaware or undiagnosed.26 The prevalence of obesity is notably higher amongst COPD patients in comparison to the general population but this can vary depending on geographic location.27,28 The occurrence of obesity may also vary amongst clinical phenotypes of COPD. In classical terms the “pink puffers” represent those who are underweight and dyspneic while “blue bloaters” are those who are overweight and bronchitic. There is recognizable change in body composition among all COPD patients leading to reduction of fat-free mass (FFM). Selective wasting of FFM results in relative or absolute increase in fat mass.29 Low BMI is associated with an increase in all-cause mortality in COPD that is unrelated to COPD severity.30 The relative risk of mortality seems to decrease in overweight and obese patients with COPD.30 This phenomenon is referred to as a “reverse epidemiology of obesity” or “obesity paradox”, which is shared amongst other chronic diseases such as end-stage renal disease, chronic heart failure, and rheumatoid arthritis.31 Loss of FFM contributes to muscle weakness and reduced exercise capacity.32,33 Obesity is a well-established risk factor for developing OSA. The mechanisms leading to OSA were discussed earlier. While the prevalence of OSA in the general population ranges from 9 to 24%, it is felt to be the greater and as high as 71% in the bariatric surgical population.34,35 Even with adequate health care, up to 80% of OSA has gone undiagnosed.36 The inflammatory state associated with OSA and the impact of CPAP was reviewed earlier. A patient’s risk of having OSA can be determined using one of several validated prediction rules or questionnaires, such as Adjusted Neck Circumference (ANC)37 or STOP-Bang (snoring, tiredness, observed apnea, elevated BP, and BMI, age, neck circumference, and male gender) Questionnaire.38 Patients found to be at risk of having OSA should undergo a polysomnogram to confirm the diagnosis and determine severity. CPAP is a proven therapy for all severities of OSA. Obesity hypoventilation syndrome (OHS) refers to a variety of sleep-disordered breathing, characterized by alveolar hypoventilation in an obese individual which leads to hypercapnia accompanied by hypoxia. The incidence of OHS may be as high as 31% in adults with a BMI >35 kg/m2 and 48% in individuals with BMI >50 kg/m2.39,40 Individuals with OHS experience greater morbidity from complications such as pulmonary hypertension, cor-pulmonale, cardiac failure, polycythemia, and pulmonary embolism, compared to obesity subjects without OHS.39,40 Overlap syndrome describes individuals having both COPD and OSA. Patients with overlap syndrome are at risk of the similar dangers as those with OHS. The mainstay of treatment would be noninvasive intermittent positive pressure ventilation, such as CPAP or bi-level positive airway pressure therapy.
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J.C. Sebastian / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 157–161
In closing, obesity appears to impose various effects on the respiratory system through mechanical, biochemical, and structural changes. These can promote or intensify respiratory symptoms or preexisting respiratory conditions.
Practice Points PFTs correlate with increases in body mass index. Reduction in FRC and ERV is the most frequent change seen in obesity. Dyspnea is a common manifestation in obesity. Causes include the individual or concurrent effects of increased weight and other comorbidities. Obesity increases the risk of asthma and may mimic or aggravate asthma-like symptoms. History, physical examination, complete PFTs, and bronchoprovocation testing are essential to confirm the presence of true asthma and evaluating dyspnea in obese individuals. COPD may promote selective reduction in fat-free mass. A lower BMI is associated with increased morbidity and mortality in those with COPD. This phenomenon is referred to as “obesity paradox” and may be encountered in other chronic diseases. Obesity increases the risk of obstructive sleep apnea through mechanical and biochemical changes. The risk of having sleep apnea can be determined by validated questionnaires and confirmed with a polysomnogram. Treatment with CPAP has been associated with a reduction in circulating inflammatory markers as well as morbidity and mortality.
References 1. Formiguera X & Canton A. Obesity: epidemiology in clinical aspects. Best Practice and Research Clinical Gastroenterology 2004; 18: 1125–1146. *2. Parameswaran K, Todd DC & Soth M. Altered respiratory physiology in obesity. Canadian Respiratory Journal 2006; 13: 203–210. 3. Sutherland TJ, Goulding A, Grant AM et al. The effect of adiposity measured by dual-energy X-ray absorptiometry on lung function. European Respiratory Journal 2008; 32(1): 85–91. 4. Pelosi P, Croci M, Ravagnam I et al. The effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia. Anesthesia and Analgesia 1998; 87: 654–660. 5. Kelly TM, Jensen RL, Elliott CG et al. Maximum respiratory pressure in morbidly obese subjects. Respiration 1988; 54: 73– 77. 6. Koenig SM. Pulmonary complications of obesity. American Journal of the Medical Sciences 2001; 321: 249–279. 7. Sahebjami H & Gartside PS. Pulmonary function in obese subjects with normal FEV1/FVC ratio. Chest 1996; 110: 1425–1429. 8. Holly HS, Milic-Emili J, Becklake MR et al. Regional distribution of pulmonary ventilation and perfusion in obesity. Journal of Clinical Investigation 1967; 46: 475–481. 9. Yap JC, Watson RA, Gilbey S et al. Effects of posture on respiratory mechanics in obesity. Journal of Applied Physiology 1995 Oct; 79(4): 119–205. *10. Jones RL & Nzekwu MM. The effects of body mass index on lung volumes. Chest 2006; 130: 827–833. 11. Schwartz AR, Patil SP, Squier S et al. Obesity and upper airway control during sleep. Journal of Applied Physiology 2010 Feb; 108: 430–435. 12. Kennedy A, Gettys TW, Watson P et al. The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity and energy expenditure. Journal of Clinical Endocrinology and Metabolism 1997; 82: 1293–1300. *13. Patil SP, Schneider H, Marx JJ et al. Neuromechanical control of the upper airway patency during sleep. Journal of Applied Physiology 2007; 102: 547–556. 14. Sánchez-de-la-Torre M, Mediano O, Barceló A et al. The influence of obesity and obstructive sleep apnea on metabolic hormones. Sleep Breath 2012; 16: 649–656. *15. Arias MA, García-Río F, Alonso-Fernández A et al. CPAP decreases plasma levels of soluble tumour necrosis factor-alpha receptor 1 in obstructive sleep apnoea. European Respiratory Journal 2008; 32: 1009–1015. 16. Ofir D, Laveneziana P, Webb KA et al. Ventilatory and perceptual responses to cycle exercise in obese women. Journal of Applied Physiology 2007; 102: 2217–2226. 17. Babb TG, Ranasinghe KG, Comeau LA et al. Dyspnea on exertion in obese women: association with an increased oxygen cost of breathing. American Journal of Respiratory and Critical Care Medicine 2008; 178(2): 116–123. 18. Mannino DM, Homa DM, Akinbami LJ et al. Surveillance for asthma – United states. 1980–1999. MMWR Surveillance Summaries 2002; 51: 1–13. 19. Camargo Jr. CA, Woiss ST, Zhang S et al. Prospective study of body mass index, weight change, and risk of adult-onset asthma in women. Archives of Internal Medicine 1999; 159: 2582–2588.
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20. Jeng AS, Lee JH, Park SW et al. Severe airway hyperresponsiveness in school-aged boys with high body mass index. Korean Journal of Internal Medicine 2006; 21: 10–14. 21. Huang S, Shiao G & Chou P. Association between body mass index and allergy in teenage girls in Taiwan. Clinical Experimental Allergy 1999; 29: 323–329. 22. Chinn S, Downs SH, Anto JM et al. Incidence of asthma and not change in symptoms in relation to changes in obesity. European Respiratory Journal 2006; 28: 763–771. 23. Jacobsen BC, Somers Sx, Fuchs CS et al. Body mass index and symptoms of gastroesophageal reflux in women. New England Journal of Medicine 2006; 354: 2340–2348. 24. Gunnbjornsdottir MI, Omenaas E, Gislason T et al. Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms. European Respiratory Journal 2004; 24: 116–121. *25. Sin DD, Jones RL & Man SF. Obesity is a risk factor for dyspnea but not for airflow obstruction. Archives of Internal Medicine 2002; 162: 1477–1481. *26. Schirnhofer L, Lamprecht B, Vollmer WM et al. COPD prevalence in Salzburg, Austria: results from the burden of obstructive lung disease [bold] study. Chest 2007; 131: 29–36. 27. Schokker DF, Visacher TL, Nooynes AC et al. Prevalence of overweight and obesity in the Netherlands. Obesity Reviews 2007; 8: 101–108. 28. Eisner MD, Blanc PD, Sidney S et al. Body composition and functional limitation in COPD. Respiratory Research 2007; 8: 7. 29. Engelen MP, Schols AM, Lamers RJ et al. Different patterns of chronic tissue wasting among patients with chronic obstructive pulmonary disease. Clinical Nutrition 1999; 18: 275–280. *30. Landbe C, Prescott E, Lange P et al. Prognostic value of nutritional status in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 1999; 160: 1856–1861. 31. Kalantar-Zudeh K, Horwich Tb, Oreopoulos A et al. Risk factor paradox in wasting diseases. Current Opinion in Clinical Nutrition and Metabolic Care 2007; 10: 433–442. 32. Engelan MP, Schols AM, Does JD et al. Skeletal muscle weakness is associated with wasting of extremity fat-free mass but not with airflow obstruction in patients with chronic obstructive pulmonary disease. American Journal of Clinical Nutrition 2000; 71: 733–738. 33. Baarends EM, Schols AM, Mostert R et al. Peak exercise response in relation to tissue depletion in patients with chronic obstructive pulmonary disease. European Respiratory Journal 1997; 10: 2807–2813. 34. Young T, Palta M, Dempsey J et al. The occurrence of sleep-disordered breathing among middle-aged adults. New England Journal of Medicine 1993; 328: 1230–1235. *35. Frey WC & Pilcher J. Obstructive sleep-related breathing disorders in patients evaluated for bariatric surgery. Obesity Surgery 2003; 13: 676–683. 36. Kapur V, Strohl KP, Redline S et al. Under diagnosis of sleep apnea syndrome in U.S. communities. Sleep Breath 2002; 6: 49–54. 37. Flemons WW. Clinical practice. Obstructive sleep apnea. New England Journal of Medicine 2002; 347: 498–504. *38. Chung F, Yegneswaran B, Liao P et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology 2008; 108: 812–821. 39. Sugerman HJ, Fairman RP, Sood RK et al. Long-term effects of gastric surgery for treating respiratory insufficiency of obesity. American Journal of Clinical Nutrition 1992; 55: 597S–601S. *40. Nowbar S, Burkart KM, Gonzales R et al. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome [comment]. American Journal of Medicine 2004; 116: 1–7.
Contents lists available at SciVerse ScienceDirect
Best Practice & Research Clinical Endocrinology & Metabolism journal homepage: www.elsevier.com/locate/beem
6
Respiratory physiology and pulmonary complications in obesity Justin C. Sebastian, MD, FRCP(C), FCCP, Dip. ABIM, Assistant Clinical Professor, Consultant Respirologist a, b, * a b
University of Alberta, Edmonton, Alberta, Canada Royal Alexandra Hospital, Edmonton, Alberta, Canada
Keywords: pulmonary function tests dyspnea asthma COPD sleep apnea
Obesity is generally accepted as a global epidemic and the most common metabolic disorder in the world. Obesity affects every organ system but the consequences on the respiratory system are often underappreciated. While the respiratory consequences of being overweight are predominantly mechanical, an inflammatory element has also been proposed. For this discussion, the components of the respiratory system can be divided into the airways, pulmonary parenchyma, pulmonary vasculature, and the upper respiratory tract. This section will discuss respiratory physiology and the mechanisms leading to breathing difficulties in obesity followed by the impact of obesity on commonly occurring pulmonary disorders. Ó 2013 Elsevier Ltd. All rights reserved.
Discussion Body mass index (BMI) is a widely accepted measure of obesity which is considered the most common metabolic disorder in the world.1 BMI measurements lack the ability to describe the distribution of fat. Consequently, a higher BMI may not predict the physiological changes on the respiratory system universally.2 Studies have shown that dual energy X-ray absorptiometry (DEXA) had significantly better correlation with lung function impairment than anthropometric measurements.3 At a glance, the physiological changes in obesity could be comparable to the effects of a “bear hug”. Adiposity on the thoracic cage and abdomen can have an effect on chest wall movement, airway size, respiratory muscle function, and lung perfusion.
* Royal Alexandra Hospital, 1370, 10665 Jasper Avenue, Edmonton, Alberta T5J 3S9, Canada. Tel.: þ1 780 702 3866. E-mail address: [email protected]. 1521-690X/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.beem.2013.04.014
158
J.C. Sebastian / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 157–161
The ability to move the chest wall diminishes with the accumulation of fat, leading to stiffness and decreased lung compliance. Measuring compliance is difficult but reductions seem to be exponentially related to increases in BMI.4 Respiratory muscle strength can be measured by maximum inspiratory and expiratory pressures. While respiratory muscle strength remains preserved in obesity, the reduction in chest wall compliance can lead to heightened demands on the diaphragm reducing endurance.5,6 Respiratory muscle endurance can be measured with pulmonary function tests (PFTs) by performing a maneuver known as maximal voluntary ventilation (MVV). Respiratory muscle endurance may be reduced as much as 45% in obese individuals.6 This may explain the common occurrence of breathlessness among obese individuals and their susceptibility to respiratory failure after abdominal surgery, sepsis and metabolic derangement.7 Ventilation and perfusion is the greatest in the dependent portions of the lung. This would represent the bases in a seated and non-obese individual. In obesity, weight gain promotes a rapid, shallow breathing pattern. For such individuals, as functional residual capacity (FRC) declines, there is a reversal in ventilation with a larger proportion of tidal breathing being distributed to the upper lung zones, while perfusion remains at the bottom.8 As FRC drops, airway closure may occur within tidal breathing, promoting alveolar collapse, and atelectasis at the lung bases. This ventilation and perfusion mismatch correlates to reduction in expiratory reserve volume (ERV). These changes can influence arterial PO2 and may account for the vulnerability to hypoxia amongst obese individuals. Resistance describes the caliber of the airway, which is a major mechanical property of the lungs. As with obstructive lung disease, obesity causes airway caliber to narrow leading to increased resistance. For this reason obesity can mimics or worsen the severity of asthma symptoms. Airway resistance in obesity is closely related to reduction in lung volumes and FRC.9 PFTs are a valuable clinical tool that correlates with increases in BMI. The most frequent anomaly is the reduction in FRC and ERV. ERV accounts for the volume of air that can be forcefully expired from the end of normal expiration while FRC equals ERV plus reserve volume. Although they are closely related, ERV reduces early on, even with a modest increase in weight. ERV can decline further in the supine position as the diaphragm assumes a higher position in the chest.2 The reductions in FRC and ERV, caused by weight gain, occur exponentially and can be encountered with BMI values <30 kg/m2.10 Vital capacity and total lung capacity are often preserved unless obesity is extreme. Reduction in these lung volumes, even in enormous individuals, should raise the possibility of intrinsic lung disease.2 Spirometry seldom changes in mild obesity but simultaneous reduction in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) can be encountered as BMI increases. The FEV1 to FVC ratio, a marker of airway obstruction, is usually maintained unless there is coexistent airway disease.2 Concurrent decline in FEV1 and FVC can be predictive of a low MVV, indicating the presence of diaphragmatic dysfunction, as discussed earlier.7 The upper airway is a complex anatomical structure that is subject to the neuromuscular and mechanical effects of obesity. Obstructive sleep apnea (OSA) is a common disorder caused by recurrent episodes of upper airway obstruction during sleep. This obstruction occurs due to pharyngeal collapse from the mechanical load of adiposity around the pharynx. In addition, the diminished neuromuscular activity occurring during sleep promotes further pharyngeal collapsibility.11 Leptin, an adipose tissue hormone, promotes visceral fat deposition which includes the upper body.12 TNF alpha, along with other inflammatory cytokines, promotes pharyngeal neuromuscular dysfunction, thereby inhibiting the compensatory response to protect the airway from closure during sleep.11 Investigators have found this diminished neuromuscular control independently increases an individual’s susceptibility to OSA.13 Obesity, sleep deprivation and OSA are associated with elevation in leptin and inflammatory cytokines. However, the administration of continuous positive airway pressure (CPAP) is associated with reduction in these levels.14,15 Dyspnea is a common complaint amongst obese individuals, even in the absence of respiratory disease and related illnesses. Determinates of breathlessness are difficult to predict. One study compared asymptomatic obese and normal weight women during exercise and found that breathlessness, oxygen consumption, and minute ventilation were no different between them. This would suggest that mechanical factors related to obesity did not contribute to breathlessness.16 On the other hand, it has been shown when exertional dyspnea is present there was an increase in the oxygen cost of
J.C. Sebastian / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 157–161
159
breathing compared to overweight individuals without exertional dyspnea.17 Obese people with breathing difficulties at rest were found to have lower MVV and increased oxygen cost of breathing suggesting respiratory muscle weakness and fatigue.7 While the exact mechanism and cause of dyspnea remains disputed, the presences of comorbidities such as diastolic dysfunction, coronary artery disease, pulmonary hypertension, and obstructive airways disease can serve to further aggravate and potentiate dyspnea. Respiratory disorders are arguably as prevalent yet undeniably interrelated to obesity. The following section will discuss the impact of obesity on commonly occurring respiratory disorders such as asthma, chronic obstructive pulmonary disease (COPD), and OSA. The frequency of asthma and obesity has increased concurrently over the past two decades.18 Several trends have been established between both conditions but the nature of this association remains unsettled. There is a notable relationship between BMI and asthma to the extent that it has been shown that weight gain 5 kg during a four-year span increased the risk of asthma in a dosedependent manner.19 Airway hyperreactivity (AHR) and atopy were found to be more prevalent in women with increasing BMI.20,21 The risk of developing asthma was noted to be greater in obese women than in obese men, implicating sex hormones and body fat distribution as risk factors for asthma.22 Obesity is known to increase the risk of gastroesophageal reflux (GERD) which can mimic asthma-like symptoms.23,24 Obese individuals were also found to be more symptomatic and required twice as much bronchodilators than the non-obese.25 From a clinical standpoint, it is a difficult task to determine whether respiratory symptoms in overweight individuals are due to the mechanical effects of obesity or a comorbid state such as asthma. In addition to history and physical examination, physiological testing with complete PFTs and bronchoprovocation testing are essential in confirming the presence of asthma and to provide direction of therapy. COPD can affect up to one-quarter of smokers above the age of 40, and many are unaware or undiagnosed.26 The prevalence of obesity is notably higher amongst COPD patients in comparison to the general population but this can vary depending on geographic location.27,28 The occurrence of obesity may also vary amongst clinical phenotypes of COPD. In classical terms the “pink puffers” represent those who are underweight and dyspneic while “blue bloaters” are those who are overweight and bronchitic. There is recognizable change in body composition among all COPD patients leading to reduction of fat-free mass (FFM). Selective wasting of FFM results in relative or absolute increase in fat mass.29 Low BMI is associated with an increase in all-cause mortality in COPD that is unrelated to COPD severity.30 The relative risk of mortality seems to decrease in overweight and obese patients with COPD.30 This phenomenon is referred to as a “reverse epidemiology of obesity” or “obesity paradox”, which is shared amongst other chronic diseases such as end-stage renal disease, chronic heart failure, and rheumatoid arthritis.31 Loss of FFM contributes to muscle weakness and reduced exercise capacity.32,33 Obesity is a well-established risk factor for developing OSA. The mechanisms leading to OSA were discussed earlier. While the prevalence of OSA in the general population ranges from 9 to 24%, it is felt to be the greater and as high as 71% in the bariatric surgical population.34,35 Even with adequate health care, up to 80% of OSA has gone undiagnosed.36 The inflammatory state associated with OSA and the impact of CPAP was reviewed earlier. A patient’s risk of having OSA can be determined using one of several validated prediction rules or questionnaires, such as Adjusted Neck Circumference (ANC)37 or STOP-Bang (snoring, tiredness, observed apnea, elevated BP, and BMI, age, neck circumference, and male gender) Questionnaire.38 Patients found to be at risk of having OSA should undergo a polysomnogram to confirm the diagnosis and determine severity. CPAP is a proven therapy for all severities of OSA. Obesity hypoventilation syndrome (OHS) refers to a variety of sleep-disordered breathing, characterized by alveolar hypoventilation in an obese individual which leads to hypercapnia accompanied by hypoxia. The incidence of OHS may be as high as 31% in adults with a BMI >35 kg/m2 and 48% in individuals with BMI >50 kg/m2.39,40 Individuals with OHS experience greater morbidity from complications such as pulmonary hypertension, cor-pulmonale, cardiac failure, polycythemia, and pulmonary embolism, compared to obesity subjects without OHS.39,40 Overlap syndrome describes individuals having both COPD and OSA. Patients with overlap syndrome are at risk of the similar dangers as those with OHS. The mainstay of treatment would be noninvasive intermittent positive pressure ventilation, such as CPAP or bi-level positive airway pressure therapy.
160
J.C. Sebastian / Best Practice & Research Clinical Endocrinology & Metabolism 27 (2013) 157–161
In closing, obesity appears to impose various effects on the respiratory system through mechanical, biochemical, and structural changes. These can promote or intensify respiratory symptoms or preexisting respiratory conditions.
Practice Points PFTs correlate with increases in body mass index. Reduction in FRC and ERV is the most frequent change seen in obesity. Dyspnea is a common manifestation in obesity. Causes include the individual or concurrent effects of increased weight and other comorbidities. Obesity increases the risk of asthma and may mimic or aggravate asthma-like symptoms. History, physical examination, complete PFTs, and bronchoprovocation testing are essential to confirm the presence of true asthma and evaluating dyspnea in obese individuals. COPD may promote selective reduction in fat-free mass. A lower BMI is associated with increased morbidity and mortality in those with COPD. This phenomenon is referred to as “obesity paradox” and may be encountered in other chronic diseases. Obesity increases the risk of obstructive sleep apnea through mechanical and biochemical changes. The risk of having sleep apnea can be determined by validated questionnaires and confirmed with a polysomnogram. Treatment with CPAP has been associated with a reduction in circulating inflammatory markers as well as morbidity and mortality.
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