doi:10.1152/japplphysiol.00694.2009 108:206-211, 2010. First published 29 October 2009;J Appl Physiol

Cheryl M. Salome, Gregory G. King and Norbert BerendPhysiology of obesity and effects on lung function

You might find this additional info useful...

67 articles, 27 of which can be accessed free at:This article cites /content/108/1/206.full.html#ref-list-1

9 other HighWire hosted articles, the first 5 are:This article has been cited by

  [PDF] [Full Text] [Abstract]

, January 1, 2012; 112 (1): 118-126.J Appl PhysiolR. A. Watson, N. B. Pride, E. Louise Thomas, P. W. Ind and J. D. BellRelation between trunk fat volume and reduction of total lung capacity in obese men 

[PDF] [Full Text] [Abstract], June , 2012; 39 (6): 1449-1457.Eur Respir J

Troy J. Cross, Surendan Sabapathy, Kenneth C. Beck, Norman R. Morris and Bruce D. JohnsonfailureThe resistive and elastic work of breathing during exercise in patients with chronic heart 

[PDF] [Full Text] [Abstract], March , 2013; 22 (127): 44-52.Eur Respir Rev

Selma B. de Nijs, Lisette N. Venekamp and Elisabeth H. BelAdult-onset asthma: is it really different? 

[PDF] [Abstract], March 6, 2013; 1 (1): 80-92.COPD and Comorbidity

Erica P.A. Rutten, Emiel F.M. Wouters and Frits M.E. FranssenMalnutrition and obesity in COPD 

[PDF] [Full Text] [Abstract], July , 2013; 98 (1): 174-179.Am J Clin Nutr

Sara Khan, Xiao-Mei Mai and Yue Chenexcess adiposityPlasma 25-hydroxyvitamin D associated with pulmonary function in Canadian adults with

including high resolution figures, can be found at:Updated information and services /content/108/1/206.full.html

can be found at:Journal of Applied Physiologyabout Additional material and information http://www.the-aps.org/publications/jappl

This information is current as of August 20, 2014. 

ISSN: 0363-6143, ESSN: 1522-1563. Visit our website at http://www.the-aps.org/.Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2010 by the American Physiological Society.those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a year (monthly) by the American

publishes original papers that deal with diverse areas of research in applied physiology, especiallyJournal of Applied Physiology

on August 20, 2014

Dow

nloaded from on A

ugust 20, 2014D

ownloaded from

HIGHLIGHTED TOPIC Pulmonary Physiology and Pathophysiology in Obesity

Physiology of obesity and effects on lung function

Cheryl M. Salome,1,2 Gregory G. King,1,2,3 and Norbert Berend1,2

1Woolcock Institute of Medical Research, Glebe; 2University of Sydney, Sydney; and 3Department of Respiratory Medicine,Royal North Shore Hospital, St. Leonards, New South Wales, Australia

Submitted 30 June 2009; accepted in final form 27 October 2009

Salome CM, King GG, Berend N. Physiology of obesity and effects on lungfunction. J Appl Physiol 108: 206–211, 2010. First published October 29, 2009;doi:10.1152/japplphysiol.00694.2009.—In obese people, the presence of adiposetissue around the rib cage and abdomen and in the visceral cavity loads the chestwall and reduces functional residual capacity (FRC). The reduction in FRC and inexpiratory reserve volume is detectable, even at a modest increase in weight.However, obesity has little direct effect on airway caliber. Spirometric variablesdecrease in proportion to lung volumes, but are rarely below the normal range, evenin the extremely obese, while reductions in expiratory flows and increases in airwayresistance are largely normalized by adjusting for lung volumes. Nevertheless, thereduction in FRC has consequences for other aspects of lung function. A low FRCincreases the risk of both expiratory flow limitation and airway closure. Markedreductions in expiratory reserve volume may lead to abnormalities in ventilationdistribution, with closure of airways in the dependent zones of the lung andventilation perfusion inequalities. Greater airway closure during tidal breathing isassociated with lower arterial oxygen saturation in some subjects, even though lungCO-diffusing capacity is normal or increased in the obese. Bronchoconstriction hasthe potential to enhance the effects of obesity on airway closure and thus onventilation distribution. Thus obesity has effects on lung function that can reducerespiratory well-being, even in the absence of specific respiratory disease, and mayalso 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,such as breathlessness, particularly during exercise, even ifthey have no obvious respiratory illness (4, 45). Obesity has aclear potential to have a direct effect on respiratory well-being,since it increases oxygen consumption and carbon dioxideproduction, while at the same time it stiffens the respiratorysystem and increases the mechanical work needed for breath-ing. The association between obesity and asthma has alsoraised new concerns about whether the mechanical effects ofobesity on the respiratory system contribute to airway dysfunc-tion that could induce or worsen asthma. This review willexplore the effects of obesity [body mass index (BMI) � 30kg/m2] on “normal” pulmonary physiology. The more substan-tial derangements associated with the obesity-hypoventilationsyndrome are the subject of another review in this series.

LUNG VOLUMES

The most consistently reported effect of obesity on lungfunction is a reduction in the functional residual capacity(FRC) (28, 40). This effect reflects a shift in the balance ofinflationary and deflationary pressures on the lung due to the

mass load of adipose tissue around the rib cage and abdomenand in the visceral cavity (52). There is an exponential rela-tionship between BMI and FRC (28, 40), with a reduction inFRC detectable even in overweight individuals (28). In obesity,the reduction in FRC may become so marked that the FRCapproaches residual volume (RV).

However, the effects of obesity on the extremes of lungvolumes, at total lung capacity (TLC) and RV, are modest.Many studies report an association between increasing bodyweight and decreasing TLC (11, 28, 42); however, the changesare small, and TLC is usually maintained above the lower limitof normal, even in severe obesity (11, 28, 63). The RV isusually well preserved (5, 11, 48, 63, 67), and the RV-to-TLCratio remains normal or slightly increased (5, 28). In thepresence of a modest reduction in TLC and a well-preservedRV, the reduction in FRC is manifested by an increase ininspiratory capacity and a very marked decrease in the expi-ratory reserve volume (ERV) (28).

The reasons for the reduction in TLC are not known, but itis probably due to a mechanical effect of the adipose tissue,since TLC is increased by weight loss in both mild (64) andmorbidly obese (60) subjects. A reduction in the downwardmovement of the diaphragm, due to increased abdominal mass,is likely to decrease TLC by limiting the room for lungexpansion on inflation. Alternatively, deposition of fat in sub-

Address for reprint requests and other correspondence: C. Salome, Wool-cock Institute of Medical Research, P.O. Box M77, Missenden Rd. NSW 2050,Australia (e-mail: cms@woolcock.org.au).

J Appl Physiol 108: 206–211, 2010.First published October 29, 2009; doi:10.1152/japplphysiol.00694.2009.Review

8750-7587/10 $8.00 Copyright © 2010 the American Physiological Society http://www.jap.org206

on August 20, 2014

Dow

nloaded from

pleural spaces (49) might directly reduce lung volume byreducing the volume of the chest cavity, although there is nodirect evidence of any association between subpleural fat andeither body fat or lung volumes. Evidence that respiratorymuscle strength and maximum inspiratory and expiratory pres-sures are similar in obese and normal weight subjects (29, 48,65) suggests that stiffening of the chest wall is probably not amajor determinant of TLC.

FAT DISTRIBUTION AND BODY COMPOSITION

BMI is a global measure of body mass that includes both fatand lean mass and takes no account of differences in fatdistribution. If the reduction of lung volumes in obesity is dueto a direct mechanical effect on lung volumes, then the distri-bution of body fat should modify the relationship between BMIand lung volumes. Abdominal and thoracic fat are likely tohave direct effects on the downward movement of the dia-phragm and on chest wall properties, while fat on the hips andthighs would be unlikely to have any direct mechanical effecton the lungs. Both abdominal fat, measured by waist circum-ference (10), waist-to-hip ratio (7), or abdominal height (37),and thoracic or upper body fat, measured by subscapular skinfold thickness (31) or biceps skin fold thickness (11), areassociated with reductions in lung volumes. Several studieshave used dual-energy X-ray absorptiometry (DXA) to quan-tify fat and lean mass in different regions of the body and relatethese findings to lung function (12, 58). Sutherland et al. (58)used a wide range of body fat variables to determine the effectof fat distribution on lung volumes in healthy adults. Lungvolumes were only loosely associated with BMI, but bothDXA and non-DXA-derived variables reflecting upper body fathad highly significant negative correlations with FRC and ERVin both men and women. There were no differences in thestrength of these associations between the markers of abdom-inal obesity (waist circumference, waist-to-hip ratio, DXAwaist fat, DXA abdominal fat) or thoracic fat (DXA trunk fat,DXA thoracic fat). These findings confirm the important effectof upper body fat on the lung, but the inability to differentiatethe effects of abdominal and thoracic fat suggests that they maybe interdependent.

LUNG AND RESPIRATORY SYSTEM MECHANICS

Obesity is characterized by a stiffening of the total respira-tory system (35), which is presumed to be due to a combinationof effects on lung and chest wall compliance (41). Most studieshave demonstrated a reduction in lung compliance in obeseindividuals (21, 40, 41, 53) that appears to be exponentiallyrelated to BMI (40). Reductions in lung compliance may be theresult of increased pulmonary blood volume, closure of depen-dent airways, resulting in small areas of atelectasis (21), orincreased alveolar surface tension due to the reduction in FRC.

Evidence for an effect of obesity on chest wall compliancevaries between studies, possibly as a result of methodologicaldifferences. Measurement of chest wall compliance is difficult,since the respiratory muscles must be relaxed and inactive toallow an accurate measurement. Studies of conscious, sponta-neously breathing subjects have suggested that there is areduction in chest wall compliance in obesity (35). However,normal chest wall compliance has been reported in studies ofanesthetized, paralyzed subjects in mild (40) or severe (21)

obesity, as well as in studies of conscious subjects usingdifferent measurement techniques (53, 55). Sharp et al. (52)found that mass loading of the thorax in normal weight con-scious or anesthetized/paralyzed subjects produces a parallelrightward shift of the chest wall pressure-volume curve withoutaffecting compliance. The chest wall pressure-volume curve ofobese subjects resembled that of normal subjects with massloading of the thorax. Excess body mass in simple obesity mayact as an inspiratory threshold load, and, once the threshold isovercome, the chest wall behaves normally.

AIRWAY FUNCTION

Spirometric variables, such as forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC), tend to decreasewith increasing BMI (51, 54, 67). However, the effect is small,and both FEV1 and FVC are usually within the normal range inhealthy, obese adults (51, 54) and children (50). The FEV1-to-FVC ratio is usually well preserved or increased (31, 44, 51,54, 67), even in morbid obesity (5), indicating that both FEV1

and FVC are affected to the same extent. This finding impliesthat the major effect of obesity is on lung volumes, with nodirect effect on airway obstruction.

Similarly, expiratory flows decrease with increasing weight(5, 44), in proportion to the lung volumes (67). A decrease inexpiratory flows in an obese individual is unlikely to indicatebronchial obstruction, unless the flow measurements have beennormalized for the reduction in vital capacity. Figure 1 showsflow volume loops from a healthy obese woman with signifi-cant reduction in lung volumes, but very well preserved expi-ratory flows. However, the expiratory flow at 50% of thereduced vital capacity is low compared with the predictedvalue, based on the predicted vital capacity. In a large sampleof obese and normal weight nonsmokers, Rubenstein et al. (44)found significant reductions in expiratory flows in obese men,but not in obese women. The difference between obese and

Fig. 1. Flow-volume loops from healthy obese female, aged 35 yr, BMI � 43kg/m2, with reduced total lung capacity (TLC), functional residual capacity(FRC), and vital capacity, but well-preserved expiratory flows. The dashed lineshows the predicted flow-volume loop; the solid line is the actual loop. Thepredicted lung volumes are shown on the bar, vertical arrow shows predictedflow at 50% vital capacity, and horizontal arrow shows the actual value. RV,residual volume.

Review

207PHYSIOLOGY OF OBESITY AND EFFECTS ON LUNG FUNCTION

J Appl Physiol • VOL 108 • JANUARY 2010 • www.jap.org

on August 20, 2014

Dow

nloaded from

normal weight men in expiratory flow at 50% of the reducedvital capacity disappeared after normalization for vital capac-ity. However, significant differences in expiratory flow at 25%of the reduced vital capacity persisted after normalization,suggesting the possibility of peripheral airway obstruction inobese men.

Mechanical properties of the airway, such as resistance andreactance, are highly dependent on lung volume and are,therefore, affected by any reduction in FRC. Respiratory re-sistance is increased in the obese (65), indicating that airwaycaliber is reduced throughout the tidal breathing cycle. How-ever, specific airway resistance, calculated by adjusting for thelung volume at which the measurements were made, is in thenormal range (36, 44, 65, 67), so that the apparent reduction inairway caliber in the obese is attributable to the reduction inlung volumes rather than to airway obstruction. However,some studies have suggested that the increase in resistance maynot be due entirely to the reduced lung volume, since differ-ences between obese and nonobese may persist after adjust-ment for lung volumes (30, 63). The cause of the additionalresistance is unknown, and it is unclear whether there are anystructural changes in the airways of the obese. It is possible thatairway structures could be remodeled by exposure to proin-flammatory adipokines, or damaged by the continual openingand closing of small airways throughout the breathing cycle(34). It is not known whether fat is present in the airways ofobese people or has any direct effect on airway structure, butstudies of diet-induced obesity in rats have reported changes inlipid deposition in the lungs (26), which may affect surfactantfunction (25). There is some evidence that peripheral airwayobstruction may be increased in the obese, since the frequencydependence of resistance increases with increasing obesity(67). Furthermore, frequency dependence of compliance wasincreased in a group of morbidly obese subjects who hadnormal lung compliance, but very low ERV (16). Longitudinalstudies of the effects of weight loss might be enlightening,since improvements in lung volumes after weight loss that arenot accompanied by improvements in volume-adjusted airwaycaliber could suggest that there is a persistent remodeling of theairways, rather than a direct mechanical effect on airwaycaliber.

Breathing at low lung volume places the tidal flow volumeloop in a region where it may encroach on the maximal flowvolume envelope (Fig. 1) and thus increase the risk of expira-tory flow limitation in the obese individual. However, it is notclear whether expiratory flow limitation is a common occur-rence in the obese. Two studies (18, 39), using the negativeexpiratory pressure technique, have found that expiratory flowlimitation only occurred in �20% of severely obese subjectswhen upright, but both expiratory flow limitation and breath-lessness increase substantially when the subjects are supine.However, the negative expiratory pressure technique uses aforced expiration and may not be able to detect expiratory flowlimitation that occurs during tidal breathing at low lung vol-umes. Ofir et al. (38) quantified expiratory flow limitation fromthe flow-volume loop, as the percentage of the tidal volumethat encroached on the maximal flow envelope, and foundhighly significant differences between obese and normalweight women seated at rest. New techniques are available formeasuring expiratory flow limitation during tidal breathing,based on the forced oscillation technique (13), that would

allow larger studies to determine the extent of expiratory flowlimitation in obese populations.

TIDAL VOLUMES

Tidal volumes are often reduced in severe obesity, andbreathing follows a rapid, shallow pattern (48). This pattern islikely to be a response to the increased stiffness of the respi-ratory system, since a rapid, shallow breathing pattern is atypical response to an elastic load (1), which can be induced innormal weight subjects with elastic strapping of the chest (8).During exercise, obese subjects preferentially increase theirbreathing frequency more, and tidal volumes less, than nono-bese subjects (15, 38). Similar changes occur during broncho-constriction in association with increasing elastic loads, repre-sented by increasing respiratory system elastance (47). How-ever, in mild-moderate obesity, tidal volumes at rest are oftenin the normal range (6, 38, 47, 62), and the frequency andmagnitude of regular sighs and deep inspirations appear similarto those in normal weight subjects (6, 62). This suggests thatthe modulation of airway smooth muscle contractility by reg-ular tidal stretching and deep inspirations (19) may be unim-paired in mild-moderate obesity.

AIRWAY CLOSURE, VENTILATION DISTRIBUTION,AND GAS EXCHANGE

As FRC is reduced to the extent that it approaches RV, theobese individual is at increased risk of airway closure andabnormalities of ventilation distribution. Indicators of gas trap-ping and airway closure, such as RV (48, 63) and closingcapacity (22), are not usually increased in the obese at rest.However, there is consistent evidence that, because the FRC isso low, closing capacity exceeds the FRC, and airway closurecan occur within the tidal breaths (17, 20, 22, 34). Closingcapacity, and particularly the extent to which closure occurswithin the range of tidal breathing, has been correlated witharterial PO2 (17, 22), raising the possibility that airway closureduring tidal breathing is associated with underventilation ofsome regions of the lung.

Physiological studies using single breath or multibreathwashout tests suggest that heterogeneity of ventilation is nor-mal or close to normal, even in extreme obesity. Heterogeneityof ventilation distribution, measured by slope of phase III fromsingle-breath washouts or by lung clearance index, is normal inthe obese (22). However, studies using imaging techniquesreveal abnormalities of regional ventilation in some obeseindividuals. In an upright nonobese individual, the distributionof regional ventilation is greatest in the lower, dependent lungzones and decreases toward the upper zones. In obese individ-uals, this distribution may be reversed (14, 23, 24). Holleyet al. (23) found that, in obese subjects with marked reductionsin ERV to �20% predicted, ventilation was preferentiallydistributed to the upper zones of the lung, leaving the lower,dependent zones relatively underventilated. Demedts (14)found reduced regional ventilation in the lower zones in obesesubjects, consistent with relative air trapping in the bases.While the mechanism for this underventilation and air trappingin the bases is not clear, Demedts suggests that it is unlikely,due to intrinsic changes in the airways that cause them to closeat higher transpulmonary pressure. Instead, he suggests thatlimitations in chest wall and diaphragm movements alter the

Review

208 PHYSIOLOGY OF OBESITY AND EFFECTS ON LUNG FUNCTION

J Appl Physiol • VOL 108 • JANUARY 2010 • www.jap.org

on August 20, 2014

Dow

nloaded from

configuration of the lungs and enhance basal air trapping at lowlung volumes. The distribution of perfusion is predominantlyto the lower zones, so those obese individuals with a reversalof the normal distribution of ventilation are at risk of regionalventilation-perfusion mismatch in the dependent zones of thelung (23).

Mild hypoxemia and increased alveolar-arterial oxygen dif-ference are frequently reported, even in eucapnic obese indi-viduals (21, 22, 27, 40, 60), and have been associated withabdominal obesity in the morbidly obese (66). However, theeffect of weight loss on gas exchange is variable, since somestudies show improvements in arterial oxygen tensions (43,60), while others report no change (20, 64), despite a concur-rent reduction in closing capacity (20). Most studies suggestthat lung CO-diffusing capacity is normal (15, 42, 53, 57), evenin morbid obesity (5). However, some studies suggest it may beincreased in extremely obese subjects (42, 44), probably as aresult of the increase in blood volume (42).

BREATHLESSNESS DURING EXERCISE AND AT REST

Breathlessness during exercise is a common complaintamong obese individuals, but the mechanisms that drive thesesymptoms are not well defined. In severely obese subjects,Dempsey et al. (15) found that, even during maximal exerciseon a cycle ergometer, these subjects were able to increase theirventilation sufficiently to avoid hypercapnia. Furthermore, theventilatory response to inhaled CO2 in these obese subjects wasnot different from that in a normal weight control group (15).Peak exercise capacity, in terms of both peak work rate andoxygen consumption, is normal in healthy obese subjects (2, 3,38). Ofir et al. (38) compared obese and normal weight womenduring cycle exercise and found that, although oxygen con-sumption and minute ventilation were greater in the obesesubjects at all work rates, the relationships between breathless-ness scores and both oxygen consumption and minute ventila-tion were no different in the obese and normal weight subjects.The implication of this finding is that the determinants ofbreathlessness were similar in obese and normal weight sub-jects, and that respiratory mechanical factors related to obesitydid not contribute to breathlessness in the obese subjects. Babbet al. (3) found there was no difference in peak exercisecapacity between obese women with and without exertionalbreathlessness; however, breathlessness was associated with agreater increase in the oxygen cost of breathing during exer-cise.

Breathlessness at rest may also be reported by obese indi-viduals (4, 45), but it is unclear if this is due entirely to obesity.Sahebjami and Gartside (45, 46) found that, among 23 healthyobese men, the 15 who reported breathing difficulties at resthad lower maximum voluntary ventilation and lower maximalexpiratory flows at low lung volumes. The dyspneic group alsoincluded a greater proportion of smokers, which may accountfor some of the symptoms and differences in lung function.However, the link between breathlessness and poor perfor-mance on a test of maximum voluntary ventilation may beassociated with an increase in the oxygen cost of breathing,since the oxygen cost of breathing increases parabolically withbreathing frequency (33).

EFFECTS OF BRONCHOCONSTRICTION ON LUNG FUNCTIONIN THE OBESE

Recent interest in the association between obesity andasthma raises the question of whether the physiological effectsof obesity modulate the pathophysiology of asthma. Nicola-cakis et al. (36) suggest that obesity and asthma have additive,rather than synergistic effects, on outcomes such as spirometryand lung volumes, implying that asthma and obesity affect therespiratory system through different processes. It remains un-clear whether there is any association between obesity andairway hyperresponsiveness, a characteristic feature of thepathophysiology of asthma. However, the reduction in operat-ing lung volume in the obese has the potential to modify theeffects of bronchoconstriction and increase the occurrence ofexpiratory flow limitation. Bronchoconstriction in the obese isassociated with increased airway closure compared with nono-bese controls (9) and thus could increase gas trapping and alterventilation distribution, but there are no published data aboutthe effect of bronchoconstriction on ventilation distribution inthe obese. Bronchoconstriction causes greater hyperinflation inobese asthmatic (56) and nonasthmatic (47) subjects, whichmay increase the severity of dyspnea (32). The occurrence ofadditional elastic loads during bronchoconstriction, reflectedby greater changes in respiratory system reactance in obesethan nonobese subjects (47, 62), which are not well reflected byspirometry, may explain why some obese asthmatic subjectshave more severe symptoms than their lean counterparts,despite similar spirometry (61). In patients with moderatechronic obstructive pulmonary disease, a simulated increase inbody weight of 10 kg resulted in a marked reduction in exerciseperformance (59), suggesting that the combination of increasedweight and airway obstruction could have a substantial effecton respiratory well-being.

IMPLICATIONS FOR FUTURE RESEARCH

Although the physiology of obesity and its effects on lungfunction have been the subject of intense investigation over thelast 50 years, the recent observation of the association betweenasthma and obesity has raised new questions about the me-chanical effects of obesity on the lungs, and the mechanismsthat drive breathlessness in the obese are still not well under-stood.

It is still unknown whether obesity has any effect on thestructure of the airways, either by altered lipid deposition or byremodeling. Although these questions may be best answeredby direct studies of airway pathology, physiological studies ofthe effects of weight loss on volume-adjusted flow and resis-tance would also be useful.

Expiratory flow limitation is a potentially important deter-minant of breathlessness in the obese, although studies usingnegative expiratory pressure suggest that flow limitation is nota common feature of obesity. However, the negative expiratorypressure technique may be an inappropriate method to detectflow limitation during tidal breathing at low FRC in the obese.Studies using a measurement based on tidal breathing (13)would be useful to determine the prevalence of flow limitationin obese populations and its relationship to lung volume and tobreathlessness.

Bronchoconstriction has the potential to enhance some of theeffects of obesity, such as airway closure, which may then

Review

209PHYSIOLOGY OF OBESITY AND EFFECTS ON LUNG FUNCTION

J Appl Physiol • VOL 108 • JANUARY 2010 • www.jap.org

on August 20, 2014

Dow

nloaded from

affect ventilation distribution. A better understanding of theextent to which obesity modifies the physiological effects ofbronchoconstriction may improve our understanding of therelationship between asthma and obesity.

REFERENCES

1. Axen K, Haas SS, Haas F, Gaudino D, Haas A. Ventilatory adjustmentsduring sustained mechanical loading in conscious humans. J Appl Physiol55: 1211–1218, 1983.

2. Babb TG, DeLorey DS, Wyrick BL, Gardner PP. Mild obesity does notlimit change in end-expiratory lung volume during cyling in youngwomen. J Appl Physiol 92: 2483–2490, 2002.

3. Babb TG, Ranasinghe KG, Comeau LA, Semon TL, Schwartz B.Dyspnea on exertion in obese women. Association with increased oxygencost of beathing. Am J Respir Crit Care Med 178: 116–123, 2008.

4. Bai J, Peat JK, Berry G, Marks GB, Woolcock AJ. Questionnaire itemsthat predict asthma and other respiratory conditions in adults. Chest 114:1342–1348, 1998.

5. Biring M, Lewis M, Liu JT, Mohsenifar Z. Pulmonary physiologicchanges of morbid obesity. Am J Med Sci 318: 293–297, 1999.

6. Boulet LP, Turcotte H, Boulet G, Simard B, Robichaud P. Deepinspiration avoidance and airway response to methacholine: influence ofbody mass index. Can Respir J 12: 371–376, 2005.

7. Canoy D, Luben R, Welch A, Bingham S, Wareham N, Day N, KhawKT. Abdominal obesity and respiratory function in men and women in theEPIC-Norfolk Study, United Kingdom. Am J Epidemiol 159: 1140–1149,2004.

8. Caro CG, Butler J, DuBois AB. Some effects of restriction of chest cageexpansion on pulmonary function man: an experimental study. J ClinInvest 39: 573–583, 1960.

9. Chapman DG, Berend N, King GG, Salome CM. Increased airwayclosure is a determinant of airway hyperresponsiveness. Eur Respir J 32:1563–1569, 2008.

10. Chen Y, Rennie D, Cormier YF, Dosman JA. Waist circumference isassociated with pulmonary function in normal-weight, overweight, andobese subjects. Am J Clin Nutr 85: 35–39, 2007.

11. Collins LC, Hoberty PD, Walker JF, Fletcher EC, Peiris AN. Theeffect of body fat distribution on pulmonary function tests. Chest 107:1298–1302, 1995.

12. De Lorenzo A, Maiolo C, Mohamed EI, Andreoli A, Petrone-De LucaP, Rossi P. Body composition analysis and changes in airways function inobese adults after hypocaloric diet. Chest 119: 1409–1415, 2001.

13. Dellaca RL, Santus P, Aliverti A, Stevenson N, Centanni S, MacklemPT, Pedotti A, Calverley PMA. Detection of expiratory flow limitation inCOPD using the forced oscillation technique. Eur Respir J 23: 232–240,2004.

14. Demedts M. Regional distribution of lung volumes and of gas inspired atresidual volume: influence of age, body weight and posture. Bull EurPhysiopath Respir 16: 271–285, 1980.

15. Dempsey JA, Reddan W, Rankin J, Balke B. Alveolar-arterial gasexchange during muscular work in obesity. J Appl Physiol 21: 1807–1814,1966.

16. Douglas FG, Chong PY. Influence of obesity on peripheral airwayspatency. J Appl Physiol 33: 559–563, 1972.

17. Farebrother MJB, McHardy GJR, Munro JF. Relation between pul-monary gas exchange and closing volume before and after substantialweight loss in obese subjects. Br Med J 3: 391–393, 1974.

18. Ferretti A, Giampiccolo P, Cavalli A, Milic-Emili J, Tantucci C.Expiratory flow limitation and orthopnea in massively obese subjects.Chest 119: 1401–1408, 2001.

19. Fredberg J, Inouye D, Mijailovich M, Butler J. Perturbed equilibriumof myosin binding in airway smooth muscle and its implications inbronchospasm. Am J Respir Crit Care Med 159: 959–967, 1999.

20. Hakala K, Mustajoki P, Aittomaki J, Sovijarvi AR. Effect of weightloss and body position on pulmonary function and gas exchange abnor-malities in morbid obesity. Int J Obes 19: 343–346, 1995.

21. Hedenstierna G, Santesson J. Breathing mechanics, dead space and gasexchange in the extremely obese, breathing spontaneously and duringanaesthesia with intermittent positive pressure ventilation. Acta Anaesthe-siol Scand 20: 284–254, 1976.

22. Hedenstierna G, Santesson J, Norlander O. Airway closure and distri-bution of inspired gas in the extremely obese, breathing spontaneously and

during anaesthesia with intermittent positive pressure ventilation. ActaAnaesthesiol Scand 20: 334–342, 1976.

23. Holley HS, Milic-Emili J, Becklake MR, Bates DV. Regional distribu-tion of pulmonary ventilation and perfusion in obesity. J Clin Invest 46:475–481, 1967.

24. Hurewitz A, Susskind H, Harold W. Obesity alters regional ventilationin lateral decubitus position. J Appl Physiol 59: 774–783, 1985.

25. Inselman LS, Chander A, Spitzer AR. Diminished lung compliance andelevated surfactant lipids and proteins in nutritionally obese young rats.Lung 182: 101–117, 2004.

26. Inselman LS, RAW, Spencer H. Obesity-induced hyperplastic lunggrowth. Am Rev Respir Dis 135: 613–616, 1987.

27. Jenkins SC, Moxham J. The effects of mild obesity on lung function.Respir Med 85: 309–311, 1991.

28. Jones RL, Nzekwu MMU. The effects of body mass index on lungvolumes. Chest 130: 827–833, 2006.

29. Kelly TM, Jensen RL, Elliott CG, Crapo RO. Maximum respiratorypressures in morbidly obese subjects. Respiration 54: 73–77, 1988.

30. King GG, Brown NJ, Diba C, Thorpe CW, Munoz P, Marks GB,Toelle B, Ng K, Berend N, Salome CM. The effects of body weight onairway calibre. Eur Respir J 25: 896–901, 2005.

31. Lazarus R, Sparrow D, Weiss ST. Effects of obesity and fat distributionon ventilatory function. Chest 111: 891–898, 1997.

32. Lougheed MD, Lam M, Forkert L, Webb KA, O’Donnell DE. Breath-lessness during acute bronchoconstriction in asthma. Am Rev Respir Dis148: 1452–1459, 1993.

33. Luce JM. Respiratory complications of obesity. Chest 78: 626–631, 1980.34. Milic-Emili J, Torchio R, D’Angelo E. Closing-volume: a reappraisal

(1967–2007). Eur J Appl Physiol 99: 567–583, 2007.35. Naimark A, Cherniack RM. Compliance of the respiratory system and

its components in health and obesity. J Appl Physiol 15: 377–382, 1960.36. Nicolacakis K, Skowronski ME, Coreno AJ, West E, Nader NZ, Smith

RL, McFadden ER Jr. Observations on the physiological interactionsbetween obesity and asthma. J Appl Physiol 105: 1533–1541, 2008.

37. Ochs-Balcom HM, Grant BJ, Muti P, Sempos CT, Freudenheim JL,Trevisan M, Cassano PA, Iacoviella L, Schunemann HJ. Pulmonaryfunction and abdominal obesity in the general population. Chest 129:853–862, 2006.

38. Ofir D, Laveneziana P, Webb KA, O’Donnell DE. Ventilatory andperceptual responses to cycle exercise in obese women. J Appl Physiol102: 2217–2226, 2007.

39. Pankow W, Podszus T, Gutheil T, Penzel T, Peter JH, Von Wichert P.Expiratory flow limitation and intrinsic positive end-expiratory pressure inobesity. J Appl Physiol 85: 1236–1243, 1998.

40. Pelosi P, Croci M, Ravagnan I, Tredici S, Pedoto A, Lissoni A,Gattinoni L. The effects of body mass on lung volumes, respiratorymechanics, and gas exchange during general anesthesia. Anesth Analg 87:654–660, 1998.

41. Pelosi P, Croci M, Ravagnan I, Vicardi P, Gattinoni L. Total respira-tory system, lung, and chest wall mechanics in sedated-paralyzed postop-erative morbidly obese patients. Chest 109: 144–151, 1996.

42. Ray CS, Sue DY, Bray G, Hansen JE, Wasserman K. Effects of obesityon respiratory function. Am Rev Respir Dis 128: 501–506, 1983.

43. Refsum HE, Holter PH, Lovig T, Stadaas JO. Pulmonary function andenergy expenditure after marked weight loss in obese women: observa-tions before and one year after gastric banding. Int J Obes 14: 175–183,1990.

44. Rubinstein I, Zamel N, DuBarry L, Hoffstein V. Airflow limitation inmorbidly obese, nonsmoking men. Ann Intern Med 112: 828–832, 1990.

45. Sahebjami H. Dyspnea in obese healthy men. Chest 114: 1373–1377,1998.

46. Sahebjami H, Gartside PS. Pulmonary function in obese subjects with anormal FEV1/FVC ratio. Chest 110: 1425–1429, 1996.

47. Salome CM, Munoz PA, Berend N, Thorpe CW, Schachter LM, KingGG. Effect of obesity on breathlessness and airway responsiveness tomethacholine in non-asthmatic subjects. Int J Obes 32: 502–509, 2008.

48. Sampson MG, Grassino AE. Load compensation in obese patients duringquiet tidal breathing. J Appl Physiol 55: 1269–1276, 1983.

49. Sargent EN, Boswell WD Jr, Ralls PW, Markovitz A. Subpleural fatpads in patients exposed to asbestos: distinction from non-calcified pleuralplaques. Radiology 152: 273–277, 1984.

50. Schachter LM, Peat JK, Salome CM. Asthma and atopy in overweightchildren. Thorax 58: 1031–1035, 2003.

Review

210 PHYSIOLOGY OF OBESITY AND EFFECTS ON LUNG FUNCTION

J Appl Physiol • VOL 108 • JANUARY 2010 • www.jap.org

on August 20, 2014

Dow

nloaded from

51. Schachter LM, Salome CM, Peat JK, Woolcock AJ. Obesity is a risk forasthma and wheeze but not airway hyperresponsiveness. Thorax 56: 4–8,2001.

52. Sharp JT, Henry JP, Swaeny SK, Meadows WR, Pietras RJ. Effects ofmass loading the respiratory system in man. J Appl Physiol 19: 959–966,1964.

53. Sharp JT, Henry JP, Swaeny SK, Meadows WR, Pietras RJ. The totalwork of breathing in normal and obese men. J Clin Invest 43: 728–739,1964.

54. Sin DD, Jones RL, Man SF. Obesity is a risk factor for dyspnea but notfor airflow obstruction. Arch Intern Med 162: 1477–1481, 2002.

55. Suratt PM, Wilhoit SC, Hsiao HS, Atkinson RL, Rochester DF.Compliance of chest wall in obese subjects. J Appl Physiol 57: 403–407,1984.

56. Sutherland TJT, Cowan JO, Taylor DR. Dynamic hyperinflation withbronchoconstriction: differences between obese and nonobese womenwith asthma. Am J Respir Crit Care Med 177: 970–975, 2008.

57. Sutherland TJT, Cowan JO, Young S, Goulding A, Grant AM,Williamson A, Brassett K, Herbison GP, Taylor DR. The associationbetween obesity and asthma: interactions between systemic and airwayinflammation. Am J Respir Crit Care Med 178: 469–475, 2008.

58. Sutherland TJT, Goulding A, Grant AM, Cowan JO, Williamson A,Williams SM, Skinner MA, Taylor DR. The effect of adiposity mea-sured by dual-energy x-ray absorptiometry on lung function. Eur Respir J32: 85–91, 2008.

59. Swinburn CR, Cooper BG, Mould H, Corris PA, Gibson GJ.Adverse effect of additional weight on exercise against gravity in patientswith chronic obstructive airways disease. Thorax 44: 716–720, 1989.

60. Thomas PS, Milledge JS. Respiratory function in the morbidly obesebefore and after weight loss. Thorax 44: 382–386, 1989.

61. Thomson CC, Clark S, Camargo CA Jr. Body mass index and asthmaseverity among adults presenting to the emergency department. Chest 124:795–802, 2003.

62. Torchio R, Gobbi A, Gulotta C, Dellaca R, Tinivella M, Hyatt RE,Brusasco V, Pellegrino R. Mechanical effects of obesity on airwayresponsiveness in otherwise healthy humans. J Appl Physiol 107: 408–416, 2009.

63. Watson RA, Pride NB. Postural changes in lung volumes and respiratoryresistance in subjects with obesity. J Appl Physiol 98: 512–517, 2005.

64. Womack CJ, Harris DL, Katzel LI, Hagberg JM, Bleecker ER,Goldberg AP. Weight loss, not aerobic exercise, improves pulmonaryfunction in older obese men. Journal of Gerontology: Medical Sciences55A: M453–M457, 2000.

65. Yap JC, Watson RA, Gilbey S, Pride NB. Effects of posture onrespiratory mechanics in obesity. J Appl Physiol 79: 1199–1205, 1995.

66. Zavorsky GS, Murias JM, Kim DJ, Gow J, Sylvestre JL, Christou NV.Waist-to-hip ratio is associated with pulmonary gas exchange in themorbidly obese. Chest 131: 362–367, 2007.

67. Zerah F, Harf A, Perlemuter L, Lorino H, Lorino AM, Atlan G.Effects of obesity on respiratory resistance. Chest 103: 1470–1476, 1993.

Review

211PHYSIOLOGY OF OBESITY AND EFFECTS ON LUNG FUNCTION

J Appl Physiol • VOL 108 • JANUARY 2010 • www.jap.org

on August 20, 2014

Dow

nloaded from