Annals of the American Thoracic Society

In many parts of the world, the prevalence of both chronic obstructive pulmonary disease (COPD) and obesity is increasing at an alarming rate. Such patients tend to have greater respiratory symptoms, more severe restriction of daily activities, poorer health-related quality of life, and greater health care use than their nonobese counterparts. Physiologically, increasing weight gain is associated with lung volume reduction effects in both health and disease, and this should be considered when interpreting common pulmonary function tests where lung volume is the denominator, such as FEV1/FVC and the ratio of diffusing capacity of carbon monoxide to alveolar volume, or indeed when evaluating the physiological consequences of emphysema in obese individuals. Contrary to expectation, the presence of mild to moderate obesity in COPD appears to have little deleterious effect on respiratory mechanics and muscle function, exertional dyspnea, and peak symptom-limited oxygen uptake during cardiopulmonary exercise testing. Thus, in evaluating obese patients with COPD reporting activity restriction, additional nonpulmonary factors, such as increased metabolic loading, cardiocirculatory impairment, and musculoskeletal abnormalities, should be considered. Care should be taken to recognize the presence of obstructive sleep apnea in obese patients with COPD, as effective treatment of the former condition likely conveys an important survival advantage. Finally, morbid obesity in COPD presents significant challenges to effective management, given the combined effects of erosion of the ventilatory reserve and serious metabolic and cardiovascular comorbidities that collectively predispose to an increased risk of death from respiratory failure.

The prevalence of obesity and chronic obstructive pulmonary disease (COPD) is increasing at a remarkable rate in the Western world, and this has major negative health and economic ramifications (1, 2). Predictably, the prevalence of combined COPD and obesity will also increase. A number of studies have reported a higher prevalence of obesity among individuals with COPD compared with individuals without COPD (35). Estimates of obesity in patients with COPD in Canada (25%) (6) and South America (23%) (7) were similar; they were higher than that reported in the Dutch population (18%) (4) and much lower than that reported in a small population sample in northern California (54%) (5). Early population studies have proposed a possible protective health effect of mild to moderate obesity in COPD (“the obesity paradox”) in terms of survival (810). However, recent population-level data have also shown significantly increased respiratory-related mortality among individuals with COPD with morbid obesity (body mass index [BMI] > 40 kg/m2) (11). Interestingly, a number of studies report that the presence of obesity in patients hospitalized for exacerbations of COPD was associated with improved in-hospital mortality and reduced 30-day readmission rates in retrospective population studies (12, 13). Despite this, there is evidence of increased health care use (including hospitalization) among obese individuals with COPD compared with nonobese patients (6).

The clinical consequences of obesity in COPD are diverse and are broadly outlined in Table 1. Obesity in COPD is known to be associated with reduced self-reported daily activity levels (14), and this, in turn, may predispose to increased risk for comorbidities, which include skeletal muscle deconditioning, insulin resistance, osteoporosis, and cardiovascular disease. The mechanisms of activity limitation in obese COPD have only recently become the focus of systematic study (1517).

Table 1. Obesity in chronic obstructive pulmonary disease: clinical associations

 Effect of Obesity
Perceived activity related dyspnea (6)
Reported restriction of daily activities (6)
Oxygen uptake at peak exercise (15, 16)⇔ or ⇑
Risk of comorbidities (i.e., chronic heart failure) (97)
Hospitalizations and health care use (6)
Sleep disorders (91)
Respiratory failure (11)
Depression (97)
Quality of life (97)
Mortality following COPD exacerbation (12, 13)

Definition of abbreviation: COPD = chronic obstructive pulmonary disease.

⇔ = no effect, ⇓ = decrease, ⇑ = increase.

This review focuses on the physiological rather than the biological (reviewed elsewhere [18, 19]) consequences of obesity in patients with COPD. We examine the effect of mild to moderate obesity on respiratory system function during rest and exercise in healthy individuals and in patients with preexisting COPD and review current concepts of exercise limitation in the latter. We review how the presence of obesity can affect the clinical interpretation of pulmonary function abnormalities across the range of COPD severities. Considering that the physiological derangements of increased weight gain become exaggerated in patients with morbid obesity, special care is taken to highlight the specific features where a differential effect of morbid obesity can be anticipated. Finally, we briefly address the physiological consequences of obesity in the respiratory adjustments to sleep in patients with COPD. The physiological consequences of obesity during rest and exercise in health and in COPD were the subject of a recent review by some of the same authors (20). These sections have been expanded in the current review, which additionally includes sections on the effect of obesity on pulmonary function test interpretation, ventilatory insufficiency, and sleep-disordered breathing in patients with COPD.

Lung Mechanics

Most studies that have examined the potential deleterious consequences of obesity have used BMI as a frame of reference. Although such classifications are widely accepted, studies that exclusively rely on BMI to define obesity often preclude definitive conclusions regarding physiological effects (2125). Thus, it is possible that adipose distribution patterns (e.g., central versus peripheral) may have differential effects on respiratory mechanics (2126). To accurately describe distribution patterns of lean and adipose mass, imaging techniques (i.e., bone mineral density, computed tomography, and magnetic resonance imaging) are recommended and in turn provide useful insight to these deleterious physiological effects.

The mass loading effects of excess adipose tissue on the chest wall and abdomen result in reduced compliance (increased stiffness) of the relaxed respiratory system (2730). Although early physiological studies emphasized the contribution of reduced chest wall compliance (27), recent studies in anesthetized subjects highlight the significant contribution of reduced lung compliance (29, 31). Thus, excessive bibasal airway closure and pulmonary gas trapping (32), diffuse microatelectasis, and relatively increased intrathoracic blood volume (33) collectively increase static lung elastic recoil pressure (30). The net effect of these obesity-related changes on lung and chest wall compliance is a resetting of the respiratory system’s relaxation volume (functional residual capacity [FRC], used interchangeably with resting end-expiratory lung volume [EELV] for the purpose of this review) to a lower volume than predicted in normal-weight individuals (31, 34, 35). Because resting EELV is lower in obesity, tidal volume (Vt) becomes positioned closer to the lower nonlinear and less-compliant extreme of the respiratory system’s sigmoid-shaped pressure–volume relation. Reduced respiratory system compliance contributes to increased work and oxygen cost of breathing, particularly in patients with morbid obesity (36).

The impact of these abnormalities on lung volumes across the stages of obesity has been well characterized. Jones and Nzekwu, for instance, demonstrated an inverse relationship between increasing BMI and decreasing EELV and expiratory reserve volume (ERV) in a healthy population (35). The relationship between increasing BMI and decreasing EELV (or ERV) was exponential, with the greatest decline in these lung volumes being evident in the overweight to obese (BMI > 30 kg/m2) range and little further change as BMI reached the morbid obesity range. Thus, the progressive decrease in ERV with obesity stabilizes after a BMI of approximately 35 kg/m2 (35). This probably reflects the reaching of a “minimal operational ERV,” which is limited by the volume at which the small airways close (32). In fact, there is some evidence that in moderate to severe obesity, individuals become prone to expiratory flow limitation and regional gas trapping during resting tidal breathing (34).

TLC declines modestly with mild to moderate obesity (35, 3739). Consequently, inspiratory capacity (IC) increases with increasing BMI, reflecting the relative preservation of TLC in the presence of decreased EELV (35, 40). In morbidly obese subjects, however, decreases in EELV taper off and TLC starts to decrease as BMI further increases (3537, 41). It follows that IC tends to diminish within the morbid obesity range. Of note, FVC is commonly reduced to a greater extent than the “slow” VC due to airways compression during the forced maneuver (42).

The reduced EELV in obesity also means that airways resistance (Raw)—particularly in the noncartilaginous small airways—is increased, and expiratory flow limitation may exist during resting breathing (4345). Body habitus has an important influence on the relationship between Raw and dyspnea in these subjects. For instance, expiratory flow limitation and breathlessness are more common in the supine than in the seated position (45). Common pulmonary function abnormalities of obesity are listed in Table 2.

Table 2. Effects of obesity on pulmonary function

 Effect of Obesity
Respiratory compliance (lung, chest wall, respiratory system)
FEV1⇔ or ⇓
RV and TLC⇔ or slight ⇓
Airway resistance⇑ (specific resistance ⇔)
Respiratory muscle strength⇔ or ⇓
Work of breathing at rest
PaO2⇔ or ⇓
P(A-a)O2⇔ or ⇑

Definition of abbreviations: DlCO = diffusing capacity of the lung for carbon monoxide; ERV = expiratory reserve volume; IC = inspiratory capacity; P(A-a)O2 = alveolar-arterial oxygen pressure difference; PaO2 = partial pressure of arterial oxygen; RV = residual volume.

⇔ = normal; ⇑ = increase; ⇓ = decrease.

Respiratory Muscles

There are conflicting data on the consequences of obesity on respiratory muscle strength and endurance (as reviewed in Reference 46). Increased elastic work and variable reduction in the maximal force-generating capacity of the respiratory muscles indicate that they are likely to be chronically overloaded as obesity progresses (28, 29). In fact, the metabolic cost of breathing is substantially increased in morbidly obese subjects (47). Respiratory muscle unloading at rest (using positive pressure ventilation) decreased the oxygen cost of breathing by 16% in morbidly obese subjects but by less than 1% in normal-weight control subjects (47). However, whether intrinsic mechanical loading has a “training” effect, or a fatiguing effect, on the respiratory muscles is disputable. Nevertheless, in some studies, static maximum inspiratory muscle strength and respiratory muscle endurance have been shown to improve in association with loss of BMI after bariatric surgery (48). The diaphragm may be overstretched in individuals with abdominal obesity, at least in the supine position, thereby placing it at a mechanical disadvantage, which may contribute to dyspnea (45).

Gas Exchange

Ventilation/perfusion (V./Q.) mismatch and microatelectasis worsen with increasing BMI, and their impact becomes physiologically relevant (i.e., partial pressure of oxygen [PaO2] within the range of 60–70 mm Hg and enlarged alveolar–arterial oxygen gradient) in the morbidly obese group (30, 49). The effect of obesity on lung diffusing capacity for carbon monoxide (DlCO) is controversial, with most studies indicating that absolute DlCO is normal but increased after alveolar volume correction (50, 51). However, some studies suggest absolute DlCO may be increased in extremely obese subjects, probably as a result of the increase in lung blood volume (35, 39, 49, 52). Partial pressure of carbon dioxide (PaCO2) may be elevated in some morbidly obese subjects in whom the ventilatory drive is not sufficiently increased to counterbalance the higher work of breathing and lower ventilatory efficiency (5355).

Lung Mechanics

In COPD, as in health, EELV and ERV decrease exponentially with increasing BMI, with the main decrease being evident in the range of 20 to 35 kg/m2. TLC and residual volume (RV) remain relatively stable or only slightly reduced over this range of increasing BMI (15, 56). Importantly, the resting IC increases linearly in response to increasing BMI across all COPD severity stages, reflecting the greater reduction in EELV relative to TLC (Figure 1). We have argued that recruitment of IC and reduction in absolute operating lung volumes is potentially advantageous from a mechanical standpoint in the obese patients with COPD (15). In morbidly obese patients, however, decreases in EELV taper off, and TLC may be reduced by up to 20% (56). Consequently, the mechanical advantages of recruiting IC in mild to moderate obesity in COPD are likely negated in extreme obesity (15). Collectively, these data indicate that the functional reserves of the respiratory system in adapting to weight gain are severely compromised in patients with COPD with morbid obesity.

The presence of diffuse small airways disease in COPD is likely to further amplify the aforementioned association of increasing BMI and increasing Raw in obesity (4447). The relationship between lung volume and Raw, however, is complex and probably nonlinear. Consequently, volume-corrected (specific) Raw may actually decrease as BMI increases in patients with COPD (56). Although this can be interpreted as evidence that the small airways are not intrinsically dysfunctional in these patients, this might reflect an inadequate linear correction (i.e., Raw × volume−1). There is also new evidence relating morbid obesity to increased tracheal collapsibility in patients with COPD (57). This phenomenon might be linked to atrophy of elastic fibers in the posterior membranous portion and/or more negative airway transmural pressure in the central airways. Whether increased tracheal collapsibility contributes to patients’ symptoms and sleep-disordered breathing (see below) remains unclear.

Respiratory Muscles

Although much is known about the respiratory muscles in COPD (58), there has been no large systematic evaluation of respiratory muscle structure and function in obese patients with COPD. In the physiological study of Ora and coworkers of patients with COPD and mild to moderate obesity, there was no difference in respiratory muscle strength during rest and exercise in the obese group compared with the normal-weight group (15). The former had greater static lung recoil and intraabdominal pressures despite similar lung function impairment by FEV1 criteria (15). The factors that predispose to hypercapnic ventilatory failure in patients in whom COPD and morbid obesity coexist have not been systematically studied.

Gas Exchange

The impact of obesity on arterial oxygenation in subjects with COPD will vary with the extent of disease-induced V./Q. mismatch and emphysematous destruction (59). Increases in EELV may partially counterbalance the tendency to small airway closure in dependent lung regions, but the net effect on V./Q. balance is difficult to predict in individual patients. PaCO2 is usually in the normal range or slightly elevated in mild to moderate obesity (8). Hypercapnic patients with advanced COPD who become morbidly obese are expected to present with the highest PaCO2 values, but objective data in this regard are still lacking. Obesity hypoventilation syndrome is at the end of the spectrum of obesity-related hypercapnia (PaCO2 > 45 mm Hg), affecting up to 50% of patients with a BMI of 50 kg/m2 or greater (60). However, COPD is an exclusion criterion for obesity hypoventilation syndrome.

Clinical Interpretation of Pulmonary Function Testing in Patients with COPD and Obesity

The significant relationship found between increasing BMI and lung volumes/capacities in patients with COPD has several implications for interpretation of common pulmonary function tests. Due to the reducing effects of a high BMI on indices of lung hyperinflation (i.e., FRC, RV), interpretation of these measurements should ideally take into account the influence of increased body weight (56). A practical implication of the potential reduction in slow VC and FVC with increasing obesity is the potential decrease in the sensitivity of spirometry to detect airflow obstruction using fixed ratio criteria (post-bronchodilator FEV1/FVC < 0.7), such as in smokers at risk for COPD (e.g., underdiagnosis) (42). Obesity-associated reduction in Va should also be considered when interpreting diffusing capacity for carbon monoxide (DlCO/Va) measurements (or transfer factor) and specific airway resistance in patients with COPD. Similarly, physiological assessments of emphysema using lung hyperinflation and reduced DlCO criteria may be less reliable in patients with concomitant obesity.

Healthy Subjects

Most studies expressing peak symptom-limited oxygen uptake in absolute terms or as % predicted have concluded that, contrary to expectations, cardiorespiratory fitness is generally in the normal range in individuals with mild to moderate obesity (34, 38, 44, 61, 62). Peak work rate measured during incremental cycle exercise may be diminished or fall within the lower range of normal (44, 63, 64). The corollary is that the determinants of peak oxygen uptake (i.e., cardiac output and the arteriovenous oxygen difference) are also generally preserved in moderate obesity.

Ventilatory requirements are increased during exercise, reflecting the higher metabolic cost (increased oxygen uptake and carbon dioxide production) of external work (38, 44, 6473). The upward parallel shift in the oxygen uptake/work rate slope in obesity is explained by the increased metabolic requirements of lifting heavy limbs during cycling (67, 68). Because EELV is lower at rest and throughout exercise in the obese, there is a propensity for increased expiratory flow limitation and increased gas trapping during the increased ventilation of exercise (44). However, this dynamic increase in EELV (“pseudonormalization”) may actually convey a mechanical advantage: as Vt increases it becomes positioned on a more compliant portion of the respiratory system’s pressure–volume relation, thus avoiding the lower nonlinear extreme (44). Breathing pattern responses to incremental cycle exercise are usually more shallow and rapid in obese compared with normal-weight individuals (38, 44, 73). The larger resting IC and inspiratory reserve volume (IRV) means that obese subjects can accommodate increases in EELV without end-inspiratory lung volume prematurely encroaching on the TLC (Figure 2).

Patients with COPD

A comparison of differential responses to incremental cycle ergometry in obese and normal-weight patients with COPD, matched for FEV1, is summarized in Table 3. As in health, metabolic and ventilatory requirements are increased for a given external power output during cycle exercise in obese compared with normal-weight patients with COPD (15). Peak oxygen uptake (corrected for ideal body weight) during incremental cycle exercise in obese patients with COPD was similar or even greater compared with normal-weight patients matched for FEV1 (15, 16). Thus, surprisingly, the presence of obesity could not be shown to be a disadvantage with respect to dyspnea and exercise intolerance during laboratory exercise testing in COPD (15, 16).

Table 3. Effects of obesity on responses to incremental cycle exercise in chronic obstructive pulmonary disease

Preserved exercise capacity (i.e., no reduction in peak work rate or Vo2).
Increased metabolic load (Vo2 and Vco2) for a given work rate (i.e., an upward parallel shift in the Vo2/work rate relation).
No difference in the anaerobic threshold when Vo2 is expressed relative to peak Vo2.
No difference in heart rate at rest or at peak exercise.
No difference in oxygen saturation at rest or at peak exercise.
Increased ventilation for a given work rate, as a result of the increased metabolic load.
Ve/Vco2 similar or decreased at a given work rate during exercise.
Breathing pattern similar for a given ventilation. Increases in ventilation may be accomplished by increases in breathing frequency with no change in Vt.
Reduced dynamic EELV and EILV at rest and throughout exercise.
IC at rest and during exercise either increased or unchanged. The change in IC from rest to peak exercise is similar.
No difference in symptom intensity ratings of dyspnea or leg discomfort at a given work rate.
No difference in the reasons for stopping exercise.

Definition of abbreviations: EELV = end-expiratory lung volume; EILV = end-inspiratory lung volume; IC = inspiratory capacity; Vco2 = carbon dioxide production; Ve/Vco2 = ventilatory equivalent for carbon dioxide; Vo2 = oxygen consumption; VT = tidal volume.

In COPD, the resting IC is an important predictor of peak ventilation during symptom-limited exercise (7476). In the presence of expiratory flow limitation, the IC represents the operating limits for Vt expansion during physical activity. The lower the IC (due to lung hyperinflation), the lower the ventilation at which Vt reaches its plateau (or maximal value), having encroached on the minimal dynamic IRV (77). After reaching the Vt/ventilation plateau (or critically reduced IRV), dyspnea intensity rises sharply to intolerable levels and “unsatisfied inspiration” displaces “increased breathing work/effort” as the dominant qualitative descriptor (78). In the obese patient with COPD, an increased resting IC (and IRV) means that he or she can exercise to a higher ventilation before the Vt plateau occurs: the onset of intolerable dyspnea is, therefore, delayed.

In obese COPD, dyspnea intensity ratings were found to be lower or similar at any given oxygen uptake or ventilation, compared with FEV1-matched normal-weight patients with COPD (Figure 3) (15, 16). We have postulated that a number of factors mitigate the expected increase in dyspnea intensity for a given ventilation in obese patients with COPD (15, 16). These potential contributory factors include: (1) increased static elastic lung recoil pressure, which increases driving pressure for tidal expiratory flows during rest and exercise in obese COPD; (2) increased resting IC and IRV and the lower operating lung volumes during exercise, which convey mechanical advantages for the respiratory muscles; (3) increased intraabdominal pressures, which improves diaphragmatic function by forcing a more cephalad position of this muscle at the onset of inspiration; (4) recruitment of regional lung volume (and hitherto closed airways) during dynamic increases in EELV, which attenuates the increased resistance as respired flow rates increase during exercise; and (5) increased dynamic EELV, which improves pulmonary gas exchange (as indicated by lower ventilation/carbon dioxide production ratios) to a greater extent than in normal-weight patients with COPD.

Some studies have shown that 6-minute-walk distance is reduced in obese compared with normal-weight patients with COPD (79, 80). The question arises whether the respiratory mechanical advantages of mild to moderate obesity are also applicable to weight-bearing exercise (e.g., walking). In a recent comparison of linearized treadmill and cycle exercise (matched for rise in external work), moderately obese patients with COPD showed greater arterial oxygen desaturation and a higher oxygen uptake for a given work rate during the former (17). However, selective stress on the quadriceps muscle during cycling forced an earlier metabolic acidosis with accompanying increased ventilatory stimulation, which improved alveolar ventilation at a given oxygen uptake relative to treadmill exercise (81). Despite these between-test differences in metabolic loading and pulmonary gas exchange, relationships between ventilation and carbon dioxide production and between dyspnea intensity (Borg ratings) and ventilation were similar and therefore independent of exercise modality (17). It follows that the respiratory mechanical advantages of obesity in COPD also likely apply during walking.

There is a lack of exercise studies in morbidly obese COPD, as the few available investigations focused on mild to moderate obesity (1517). Of particular interest for patients with COPD, ventilation/carbon dioxide production values were in the normal range, if not slightly reduced. These data suggest that exercise may induce further increases in PaCO2 in morbidly obese patients with advanced COPD. Moreover, the oxygen cost of exercise ventilation is likely to represent an even greater fraction of total body oxygen uptake in these patients (15, 16, 80). In association with the reduction of resting IC in morbid obesity and COPD, the respiratory system is more likely to reach its physiological limits at relatively low exercise levels.

Multifactorial nature of exercise limitation in obese patients with COPD

In a population-based sample, obese patients with COPD self-reported greater exercise intolerance and activity restriction than normal-weight patients with COPD and obese individuals without COPD (6). A few studies have reported that patients with combined obesity and COPD have reduced exercise capacity as measured by 6-minute-walk distance compared with nonobese patients with COPD (79, 80). The general assumption has been that respiratory factors (a mixed obstructive–restrictive ventilatory deficit) are a proximate cause of exercise limitation in obese patients with COPD. Although this might well be the case in patients with COPD with morbid obesity, detailed physiological studies during cycle and treadmill exercise in patients with mild to moderate obesity (without comorbidities) indicate that respiratory mechanical factors and associated dyspnea are not more important in contributing to exercise limitation than in normal-weight individuals with similar COPD severity (1517). It is therefore reasonable to postulate that reduced exercise tolerance in obese patients with COPD is multifactorial and that additional (and partially reversible) factors, such as increased metabolic loading, musculoskeletal abnormalities, and cardiocirculatory impairment, may all contribute in highly variable combinations. These considerations are important when individualizing exercise training protocols for obese patients with COPD for the purpose of weight reduction.

Obesity, particularly if severe, is a well-established risk factor for sleep-disordered breathing in patients with COPD (82, 83) and in the general population. These combined abnormalities are characterized by further deterioration in lung mechanics with attendant negative consequences for pulmonary gas exchange (hypoxemia and hypercapnia) (84). Of particular relevance, during sleep there is a further reduction in EELV due to the combined effects of lower tonic skeletal muscle activity (particularly during rapid eye movement [REM] sleep), increased Raw, upward diaphragmatic displacement, and posture-related decrements in lung compliance (82, 85). As a consequence of breathing at lower lung volumes during sleep compared with the awake condition, the small airways in the dependent lung zones close earlier during exhalation. This has dual negative effects on worsening V./Q. mismatch and reducing intrapulmonary oxygen and carbon dioxide reserves. These effects would easily aggravate any resting hypoxemia, as decreases in PaO2 would occur in the steep part of the oxygen dissociation curve (82). Changes in the carbon dioxide set-point secondary to long-term hypoventilation in some obese hypercapnic patients may also be contributory—a phenomenon particularly deleterious when ventilation responsiveness to chemical stimuli is blunted and the wakefulness drive is reduced (e.g., REM sleep) (85). Decrease in accessory respiratory muscle activity during REM sleep (86) places additional burden on the diaphragm, which is already under mechanical disadvantage. In summary, higher dead space (Vd/Vt), lower awake PaO2, lower EELV and “functional” respiratory muscle weakness, and V./Q. mismatch conspire against breathing stability during sleep in morbidly obese patients with COPD (Figure 4) (8289). Moreover, the excessive mechanical (elastic) loading of the respiratory muscles and impaired pulmonary gas exchange that characterize morbid obesity may collectively predispose to respiratory and cardiocirculatory failure in patients already mechanically compromised by COPD.

Clinical Consequences of OSA in Obese Patients with COPD

The concomitant increases in prevalence of both obesity and obstructive sleep apnea (OSA) has meant that prevalence of the OSA–COPD overlap syndrome has increased in tandem (82). In fact, obesity is a key contributor for sleep-disordered breathing, pulmonary hypertension, and obesity hypoventilation syndrome regardless the COPD severity (8284). The bulk of the evidence indicates that although the prevalence of OSA is not increased in COPD, the overlap syndrome is a negative prognostic factor in these patients (8284, 90). Decreased survival might be explained by a greater frequency of exacerbations (91), more severe hypoxemia (92, 93) and hypercapnia, and pulmonary hypertension (94), thereby predisposing to potentially lethal arrhythmias (95) and cor pulmonale. Although some patients with overlap syndrome do hypoventilate, it should be noted that COPD should be excluded to confidently make a diagnosis of the obesity-hypoventilation syndrome. Regardless of the specific diagnosis (overlap syndrome or obesity-hypoventilation syndrome), chronic daytime hypercapnia may ensue if treatment (continuous positive airways pressure or bilevel pressure support) is not initiated, patients lose the ability to compensate transient nocturnal hypercapnia, or respiratory muscles failure finally develops (83). Of note, two nonrandomized studies did show survival benefits for patients with COPD and OSA overlap who were treated and adhered to continuous positive airways pressure, a finding that might be ascribed to fewer cardiovascular events and severe exacerbations (91, 96).

The expected increase in the number of patients presenting with combined obesity and COPD will have major implications for health care practitioners in the pulmonary community. Our understanding of the impact of excessive weight gain on respiratory system function in COPD continues to grow. The lung volume reduction effect of increasing weight gain should be considered when interpreting common pulmonary function tests such as FEV1/FVC ratio and DlCO/Va or when evaluating the physiological consequences of emphysema. Contrary to expectation, the presence of mild to moderate obesity in patients with COPD appears to have little deleterious effect on peak symptom-limited oxygen uptake. We have proposed that the relatively larger IC and lower operating lung volumes throughout rest and exercise in obese patients with COPD (compared with normal-weight FEV1-matched patients) convey a mechanical advantage for the respiratory muscles. This allows obese patients with COPD to accommodate the increased ventilatory requirements of a standardized physical task without experiencing greater respiratory discomfort. It would seem that rather than implicating respiratory impairment as the proximate limiting factor to exercise, other nonpulmonary factors, such as high metabolic demand, musculoskeletal abnormalities, and cardiocirculatory impairment, additionally need to be considered in patients with mild to moderate obesity who report increased dyspnea and exercise intolerance during daily activities. However, the putative advantages of milder obesity on respiratory system mechanics in COPD is lost in severe obesity where IC becomes eroded, pulmonary gas exchange becomes compromised, and the load/capacity imbalance of the respiratory muscles reaches a critical level predisposing to respiratory failure. Finally, clinicians should be vigilant to the fact that sleep-disordered breathing commonly occurs in obese patients with COPD and that effective treatment of the former might well convey an important survival advantage.

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Correspondence and requests for reprints should be addressed to Denis O’Donnell, M.D., 102 Stuart Street, Kingston, ON, K7L 2V6 Canada. E-mail:

Author disclosures are available with the text of this article at


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