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Salome Et Al 2010 Physiology of Obesity and Effects On Lung Function
Salome Et Al 2010 Physiology of Obesity and Effects On Lung Function
Salome CM, King GG, Berend N. Physiology of obesity and effects on lung
function. J Appl Physiol 108: 206 –211, 2010. First published October 29, 2009;
doi:10.1152/japplphysiol.00694.2009.—In obese people, the presence of adipose
tissue around the rib cage and abdomen and in the visceral cavity loads the chest
wall and reduces functional residual capacity (FRC). The reduction in FRC and in
expiratory reserve volume is detectable, even at a modest increase in weight.
However, obesity has little direct effect on airway caliber. Spirometric variables
decrease in proportion to lung volumes, but are rarely below the normal range, even
in the extremely obese, while reductions in expiratory flows and increases in airway
resistance are largely normalized by adjusting for lung volumes. Nevertheless, the
reduction in FRC has consequences for other aspects of lung function. A low FRC
increases the risk of both expiratory flow limitation and airway closure. Marked
reductions in expiratory reserve volume may lead to abnormalities in ventilation
distribution, with closure of airways in the dependent zones of the lung and
ventilation perfusion inequalities. Greater airway closure during tidal breathing is
associated with lower arterial oxygen saturation in some subjects, even though lung
CO-diffusing capacity is normal or increased in the obese. Bronchoconstriction has
the potential to enhance the effects of obesity on airway closure and thus on
ventilation distribution. Thus obesity has effects on lung function that can reduce
respiratory well-being, even in the absence of specific respiratory disease, and may
also exaggerate the effects of existing airway disease.
spirometry; lung volumes lung mechanics; airway closure; ventilation distribution
OBESE PEOPLE ARE AT INCREASED risk of respiratory symptoms, mass load of adipose tissue around the rib cage and abdomen
such as breathlessness, particularly during exercise, even if and in the visceral cavity (52). There is an exponential rela-
they have no obvious respiratory illness (4, 45). Obesity has a tionship between BMI and FRC (28, 40), with a reduction in
clear potential to have a direct effect on respiratory well-being, FRC detectable even in overweight individuals (28). In obesity,
since it increases oxygen consumption and carbon dioxide the reduction in FRC may become so marked that the FRC
production, while at the same time it stiffens the respiratory approaches residual volume (RV).
system and increases the mechanical work needed for breath- However, the effects of obesity on the extremes of lung
ing. The association between obesity and asthma has also volumes, at total lung capacity (TLC) and RV, are modest.
raised new concerns about whether the mechanical effects of Many studies report an association between increasing body
obesity on the respiratory system contribute to airway dysfunc- weight and decreasing TLC (11, 28, 42); however, the changes
tion that could induce or worsen asthma. This review will are small, and TLC is usually maintained above the lower limit
explore the effects of obesity [body mass index (BMI) ⱖ 30 of normal, even in severe obesity (11, 28, 63). The RV is
kg/m2] on “normal” pulmonary physiology. The more substan- usually well preserved (5, 11, 48, 63, 67), and the RV-to-TLC
tial derangements associated with the obesity-hypoventilation ratio remains normal or slightly increased (5, 28). In the
syndrome are the subject of another review in this series. presence of a modest reduction in TLC and a well-preserved
LUNG VOLUMES RV, the reduction in FRC is manifested by an increase in
inspiratory capacity and a very marked decrease in the expi-
The most consistently reported effect of obesity on lung ratory reserve volume (ERV) (28).
function is a reduction in the functional residual capacity The reasons for the reduction in TLC are not known, but it
(FRC) (28, 40). This effect reflects a shift in the balance of is probably due to a mechanical effect of the adipose tissue,
inflationary and deflationary pressures on the lung due to the since TLC is increased by weight loss in both mild (64) and
morbidly obese (60) subjects. A reduction in the downward
Address for reprint requests and other correspondence: C. Salome, Wool-
movement of the diaphragm, due to increased abdominal mass,
cock Institute of Medical Research, P.O. Box M77, Missenden Rd. NSW 2050, is likely to decrease TLC by limiting the room for lung
Australia (e-mail: cms@woolcock.org.au). expansion on inflation. Alternatively, deposition of fat in sub-
206 8750-7587/10 $8.00 Copyright © 2010 the American Physiological Society http://www.jap.org
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Review
PHYSIOLOGY OF OBESITY AND EFFECTS ON LUNG FUNCTION 207
pleural spaces (49) might directly reduce lung volume by obesity, as well as in studies of conscious subjects using
reducing the volume of the chest cavity, although there is no different measurement techniques (53, 55). Sharp et al. (52)
direct evidence of any association between subpleural fat and found that mass loading of the thorax in normal weight con-
either body fat or lung volumes. Evidence that respiratory scious or anesthetized/paralyzed subjects produces a parallel
muscle strength and maximum inspiratory and expiratory pres- rightward shift of the chest wall pressure-volume curve without
sures are similar in obese and normal weight subjects (29, 48, affecting compliance. The chest wall pressure-volume curve of
65) suggests that stiffening of the chest wall is probably not a obese subjects resembled that of normal subjects with mass
major determinant of TLC. loading of the thorax. Excess body mass in simple obesity may
act as an inspiratory threshold load, and, once the threshold is
FAT DISTRIBUTION AND BODY COMPOSITION overcome, the chest wall behaves normally.
BMI is a global measure of body mass that includes both fat AIRWAY FUNCTION
and lean mass and takes no account of differences in fat
distribution. If the reduction of lung volumes in obesity is due Spirometric variables, such as forced expiratory volume in 1
to a direct mechanical effect on lung volumes, then the distri- s (FEV1) and forced vital capacity (FVC), tend to decrease
bution of body fat should modify the relationship between BMI with increasing BMI (51, 54, 67). However, the effect is small,
and lung volumes. Abdominal and thoracic fat are likely to and both FEV1 and FVC are usually within the normal range in
have direct effects on the downward movement of the dia- healthy, obese adults (51, 54) and children (50). The FEV1-to-
phragm and on chest wall properties, while fat on the hips and FVC ratio is usually well preserved or increased (31, 44, 51,
thighs would be unlikely to have any direct mechanical effect 54, 67), even in morbid obesity (5), indicating that both FEV1
on the lungs. Both abdominal fat, measured by waist circum- and FVC are affected to the same extent. This finding implies
ference (10), waist-to-hip ratio (7), or abdominal height (37), that the major effect of obesity is on lung volumes, with no
and thoracic or upper body fat, measured by subscapular skin direct effect on airway obstruction.
fold thickness (31) or biceps skin fold thickness (11), are Similarly, expiratory flows decrease with increasing weight
associated with reductions in lung volumes. Several studies (5, 44), in proportion to the lung volumes (67). A decrease in
have used dual-energy X-ray absorptiometry (DXA) to quan- expiratory flows in an obese individual is unlikely to indicate
tify fat and lean mass in different regions of the body and relate bronchial obstruction, unless the flow measurements have been
these findings to lung function (12, 58). Sutherland et al. (58) normalized for the reduction in vital capacity. Figure 1 shows
used a wide range of body fat variables to determine the effect flow volume loops from a healthy obese woman with signifi-
of fat distribution on lung volumes in healthy adults. Lung cant reduction in lung volumes, but very well preserved expi-
volumes were only loosely associated with BMI, but both ratory flows. However, the expiratory flow at 50% of the
DXA and non-DXA-derived variables reflecting upper body fat reduced vital capacity is low compared with the predicted
had highly significant negative correlations with FRC and ERV value, based on the predicted vital capacity. In a large sample
in both men and women. There were no differences in the of obese and normal weight nonsmokers, Rubenstein et al. (44)
strength of these associations between the markers of abdom- found significant reductions in expiratory flows in obese men,
inal obesity (waist circumference, waist-to-hip ratio, DXA but not in obese women. The difference between obese and
waist fat, DXA abdominal fat) or thoracic fat (DXA trunk fat,
DXA thoracic fat). These findings confirm the important effect
of upper body fat on the lung, but the inability to differentiate
the effects of abdominal and thoracic fat suggests that they may
be interdependent.
normal weight men in expiratory flow at 50% of the reduced allow larger studies to determine the extent of expiratory flow
vital capacity disappeared after normalization for vital capac- limitation in obese populations.
ity. However, significant differences in expiratory flow at 25%
of the reduced vital capacity persisted after normalization, TIDAL VOLUMES
suggesting the possibility of peripheral airway obstruction in
Tidal volumes are often reduced in severe obesity, and
obese men.
breathing follows a rapid, shallow pattern (48). This pattern is
Mechanical properties of the airway, such as resistance and
likely to be a response to the increased stiffness of the respi-
reactance, are highly dependent on lung volume and are,
ratory system, since a rapid, shallow breathing pattern is a
therefore, affected by any reduction in FRC. Respiratory re-
typical response to an elastic load (1), which can be induced in
sistance is increased in the obese (65), indicating that airway
normal weight subjects with elastic strapping of the chest (8).
caliber is reduced throughout the tidal breathing cycle. How-
During exercise, obese subjects preferentially increase their
ever, specific airway resistance, calculated by adjusting for the
breathing frequency more, and tidal volumes less, than nono-
lung volume at which the measurements were made, is in the
bese subjects (15, 38). Similar changes occur during broncho-
normal range (36, 44, 65, 67), so that the apparent reduction in
constriction in association with increasing elastic loads, repre-
airway caliber in the obese is attributable to the reduction in
sented by increasing respiratory system elastance (47). How-
lung volumes rather than to airway obstruction. However,
ever, in mild-moderate obesity, tidal volumes at rest are often
some studies have suggested that the increase in resistance may
in the normal range (6, 38, 47, 62), and the frequency and
not be due entirely to the reduced lung volume, since differ-
magnitude of regular sighs and deep inspirations appear similar
ences between obese and nonobese may persist after adjust-
to those in normal weight subjects (6, 62). This suggests that
ment for lung volumes (30, 63). The cause of the additional
the modulation of airway smooth muscle contractility by reg-
resistance is unknown, and it is unclear whether there are any
ular tidal stretching and deep inspirations (19) may be unim-
structural changes in the airways of the obese. It is possible that
paired in mild-moderate obesity.
airway structures could be remodeled by exposure to proin-
flammatory adipokines, or damaged by the continual opening AIRWAY CLOSURE, VENTILATION DISTRIBUTION,
and closing of small airways throughout the breathing cycle AND GAS EXCHANGE
(34). It is not known whether fat is present in the airways of
obese people or has any direct effect on airway structure, but As FRC is reduced to the extent that it approaches RV, the
studies of diet-induced obesity in rats have reported changes in obese individual is at increased risk of airway closure and
lipid deposition in the lungs (26), which may affect surfactant abnormalities of ventilation distribution. Indicators of gas trap-
function (25). There is some evidence that peripheral airway ping and airway closure, such as RV (48, 63) and closing
obstruction may be increased in the obese, since the frequency capacity (22), are not usually increased in the obese at rest.
dependence of resistance increases with increasing obesity However, there is consistent evidence that, because the FRC is
(67). Furthermore, frequency dependence of compliance was so low, closing capacity exceeds the FRC, and airway closure
increased in a group of morbidly obese subjects who had can occur within the tidal breaths (17, 20, 22, 34). Closing
normal lung compliance, but very low ERV (16). Longitudinal capacity, and particularly the extent to which closure occurs
studies of the effects of weight loss might be enlightening, within the range of tidal breathing, has been correlated with
since improvements in lung volumes after weight loss that are arterial PO2 (17, 22), raising the possibility that airway closure
not accompanied by improvements in volume-adjusted airway during tidal breathing is associated with underventilation of
caliber could suggest that there is a persistent remodeling of the some regions of the lung.
airways, rather than a direct mechanical effect on airway Physiological studies using single breath or multibreath
caliber. washout tests suggest that heterogeneity of ventilation is nor-
Breathing at low lung volume places the tidal flow volume mal or close to normal, even in extreme obesity. Heterogeneity
loop in a region where it may encroach on the maximal flow of ventilation distribution, measured by slope of phase III from
volume envelope (Fig. 1) and thus increase the risk of expira- single-breath washouts or by lung clearance index, is normal in
tory flow limitation in the obese individual. However, it is not the obese (22). However, studies using imaging techniques
clear whether expiratory flow limitation is a common occur- reveal abnormalities of regional ventilation in some obese
rence in the obese. Two studies (18, 39), using the negative individuals. In an upright nonobese individual, the distribution
expiratory pressure technique, have found that expiratory flow of regional ventilation is greatest in the lower, dependent lung
limitation only occurred in ⬃20% of severely obese subjects zones and decreases toward the upper zones. In obese individ-
when upright, but both expiratory flow limitation and breath- uals, this distribution may be reversed (14, 23, 24). Holley
lessness increase substantially when the subjects are supine. et al. (23) found that, in obese subjects with marked reductions
However, the negative expiratory pressure technique uses a in ERV to ⬃20% predicted, ventilation was preferentially
forced expiration and may not be able to detect expiratory flow distributed to the upper zones of the lung, leaving the lower,
limitation that occurs during tidal breathing at low lung vol- dependent zones relatively underventilated. Demedts (14)
umes. Ofir et al. (38) quantified expiratory flow limitation from found reduced regional ventilation in the lower zones in obese
the flow-volume loop, as the percentage of the tidal volume subjects, consistent with relative air trapping in the bases.
that encroached on the maximal flow envelope, and found While the mechanism for this underventilation and air trapping
highly significant differences between obese and normal in the bases is not clear, Demedts suggests that it is unlikely,
weight women seated at rest. New techniques are available for due to intrinsic changes in the airways that cause them to close
measuring expiratory flow limitation during tidal breathing, at higher transpulmonary pressure. Instead, he suggests that
based on the forced oscillation technique (13), that would limitations in chest wall and diaphragm movements alter the
affect ventilation distribution. A better understanding of the during anaesthesia with intermittent positive pressure ventilation. Acta
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