Background: Studies on the diffusing capacity of the lung for carbon monoxide (DLCO) in obese patients are conflicting, some studies showing increased DLCO and others unaltered or reduced values in these subjects. Objectives: To compare obese patients to controls, examine the contribution of alveolar volume (VA) and CO transfer coefficient (KCO) to DLCO, and calculate DLCO values adjusted for VA. Methods: We measured body mass index (BMI), waist circumference (WC), spirometry and DLCO in 98 adult obese patients without cardiopulmonary or smoking history and 48 healthy subjects. All tests were performed in the same laboratory. Results: Using conventional reference values, mean DLCO and VA were lower (–6%, p < 0.05, and –13%, p < 0.001, respectively), and KCO was higher (+9%, p < 0.05) in obese patients than in controls. VA decreased whereas KCO increased with increasing BMI and WC in the obese group. Patients with lower DLCO had low KCO in addition to decreased VA. In contrast, some obese patients maintained normal VA, which, coupled with high KCO, resulted in higher DLCO. The main result is that diffusion capacity differences between obese patients and controls disappeared using reference equations adjusting DLCO for VA. Conclusions: Using conventional reference equations, our obese patients show slightly lower mean DLCO, lower mean VA and higher mean KCO than controls, but with a large range of DLCO values and patterns. Adjusting DLCO for VA suggests that low lung volumes are the main cause of low DLCO and high KCO values in obese patients.

The impairment of the respiratory function in obesity has long been recognized [1]. However, while the effects of obesity on spirometric variables are well established, studies on the diffusing capacity of the lung for carbon monoxide (DLCO) in obese patients are conflicting. Some studies found increased DLCO values [2,3,4]. In contrast, others found that DLCO was unaltered or reduced in obese subjects [5,6,7,8,9,10]. The earliest study concluded that, in the case of low-normal DLCO, loss of the pulmonary capillary bed should be suspected in obese patients [3]. Part of these discrepancies may be explained by the lack of control subjects in some of these series, the measured DLCO being compared to predicted values. In addition, medical history, especially smoking history, was not taken into account in all studies.

The calculation of single-breath DLCO requires measurement of two variables, the permeability factor (kCO, Krogh factor) and the alveolar volume (VA). kCO is measured as the exponential decay in fractional concentration of CO over the breath-holding period. VA is measured using the gas dilution method. The kCO converts to KCO or DLCO/VA by dividing by the STPD to BTPS conversion and by the barometric pressure term, and DLCO is the product of KCO and VA [11]. Consequently, low DLCO results from low KCO and/or low VA. Only a few studies on obesity reported KCO and/or VA values [2,4,5,10]. Interpreting these variables in obese patients should contribute to understanding the discrepancies between the published studies, and identifying the role of low lung volumes [6] or increased KCO [2,3] in DLCO variations. Furthermore, the low VA values observed in some series can also explain at least part of the high KCO reported in some obese patients. In normal subjects, KCO increases when VA decreases. Consequently, DLCO is lower and KCO is higher at lower lung volumes compared with reference values estimated at total lung capacity [12,13]. Reference equations have been published to adjust DLCO and KCO for lung volume [12,13,14,15,16]. Obtaining normal DLCO values with these equations would support that DLCO changes in obese patients result mainly from altered lung volumes.

Considering the above, the aims of this study were: (i) to compare the DLCO of obese patients to those of controls obtained in the same laboratory; (ii) to examine the contribution of VA and KCO to DLCO values, especially in obese patients with higher DLCO or lower DLCO, and (iii) to compare the DLCO values of obese patients to reference values adjusted for VA.

We retrospectively reviewed the medical records of adult patients (>18 years) who were referred to our department for pulmonary function tests before weight reduction surgery between January 2003 and June 2008. Patients were reassessed in our department. Patients with smoking history, diabetes, obesity hypoventilation syndrome, cardiopulmonary and chest wall abnormalities, revealed by a complete medical history, physical examination and chest radiograph, were excluded.

Control subjects were technicians, nurses, physicians or students from our department, and healthy subjects referred for assessment before exercise training protocols. All of them denied cardiopulmonary history or symptoms and smoking history, and allowed us verbally to put their data in our database in an anonymous manner. This study has been approved by the Institutional Review Board of the French Learned Society for Respiratory Medicine – Société de Pneumologie de Langue Française (CEPRO 2008–022).

Pulmonary Function Tests

Lung volumes, flow-volume curves and single-breath DLCO tests were measured using a MS-PFT device (Jaeger USA Masterscreen Diffusion TP, VIASYS Healthcare, Yorba Linda, Calif., USA), and following the ATS/ERS recommendations [17,18,19,20]. Functional residual capacity was determined using the helium dilution technique. For DLCO measurement, we paid particular attention to equipment quality control and test acceptability [18]. Equipment and protocols were unchanged during the 5.5-year period and tests were performed by experienced technicians. Reference equations for spirometry and DLCO used in our laboratory are those published by the European Respiratory Society in 1993 [17,21]. Predicted VA is predicted total lung capacity – anatomic dead space (150 ml) [17,18]. Reference values used to adjust DLCO or KCO for VA are those published by Chinn et al. [14], Frans et al. [12], Johnson [16], Stam et al. [13] and Filley et al. [15]. DLCO values of patients were corrected for hemoglobin (Hb) [18]. Results are expressed as absolute values and percentage of predicted values.

Height and weight were measured and body mass index (BMI) was calculated. Waist circumference (WC) was quantified by placing a measuring tape around the waist at the midpoint between the lowest rib margin and the upper point of the iliac crest at the end of expiration. WC was measured by experienced personnel from the Internal Medicine and Nutrition Department.

Analysis

Student’s t test was used to compare the variables of patients and controls. One-way analysis of variance (ANOVA) was performed to compare DLCO%, KCO% or VA% of controls and obese patients grouped by DLCO% (>mean DLCO% of the control group or <90% mean DLCO% of the control group). When the F value indicated significant differences, a Student-Neuman-Keuls test for multiple comparisons was performed. Linear regression between DLCO%, KCO% or VA% and either BMI or WC were assessed, and the Pearson correlation coefficients were calculated. Data are given as mean ± standard deviation. Statistical significance required a p <0.05.

Subject Characteristics

A total of 98 of 265 obese patients (37%) referred to our department met the inclusion criteria. Data from 48 controls were also analyzed. The demographic and anthropometric characteristics are presented in table 1. The mean age of control males was lower than that of obese males (32 ± 11 vs. 40 ± 11 years, p < 0.05), the range of values being not very different (21–60 years in controls, and 21–65 years in obese patients). Since DLCO was expressed in percent of predicted values based on age and height, this did not preclude comparisons between obese and control males. The Hb values of obese patients were 14.7 ± 1.3 in males and 13.4 ± 1.1 g·dl–1 in females. Therefore, there was no difference between the corrected and the uncorrected DLCO values, which are calculated by the device with default Hb values of 14.6 in males and 13.5 in females.

Table 1

Baseline characteristics and pulmonary function results

Baseline characteristics and pulmonary function results
Baseline characteristics and pulmonary function results

DLCO, VA and KCO in Obese Patients and Controls Using Conventional Reference Values

Mean DLCO% and VA% were significantly lower in obese patients than in controls (–6%, p < 0.05 and –13%, p < 0.001, respectively). In contrast, KCO% was higher in the obese group (+9%, p < 0.05; table 1). The 23 obese patients with higher DLCO% (>mean DLCO% of the control group) had VA% of 97 ± 9% of predicted values, not different from that of controls, and KCO% of 112 ± 15% of predicted values, higher than that of controls (p < 0.01). The 33 obese patients with lower DLCO% (<90% mean DLCO% of the control group) had VA% of 81 ± 12% of predicted values, lower than that of controls (p < 0.01) and KCO% of 95 ± 15% of predicted values, not different from that of controls.

Relationship between DLCO, KCO or VA and BMI or WC

In the obese group, VA% was inversely correlated with BMI (r = –0.38, p < 0.001; fig. 1). KCO% was correlated with BMI (r = 0.32, p < 0.005). There was no correlation between DLCO% and BMI. In obese men, VA% was inversely correlated with BMI (r = –0.60, p < 0.005), KCO% was not correlated with BMI, and DLCO% tended to be inversely correlated with BMI (r = –0.38, p = 0.06). In obese women, VA% was inversely correlated with BMI (r = –0.28, p < 0.05). KCO% was correlated with BMI (r = 0.38, p < 0.05), and there was no correlation between DLCO% and BMI. In the control group, there was no correlation between BMI and either DLCO%, KCO% or VA%.

Fig. 1

Relationship between VA, KCO or DLCO (expressed in percentage of ERS predicted values [17]), and body mass index (BMI) in 98 obese patients.

Fig. 1

Relationship between VA, KCO or DLCO (expressed in percentage of ERS predicted values [17]), and body mass index (BMI) in 98 obese patients.

Close modal

VA% was inversely correlated with WC (r = –0.45, p < 0.01). KCO% was correlated with WC (r = 0.60, p < 0.0001). There was no correlation between DLCO% and WC.

DLCO Values Adjusted for VA

Results are presented in table 2. There was no difference between obese patients and controls using these reference equations. Using the equations of Chinn et al. [14], 10% of obese women and 16% of obese men had DLCO adjusted for VA of <80%, and 4% of women and 8% of men had DLCO adjusted for VA of >110%. Using the equations of Stam et al. [13], 18% of obese women and 20% of obese men had KCO adjusted for VA of <80%, and 2% of women and 4% of men had KCOadjusted for VA of >110%.

Table 2

DLCO values adjusted for alveolar volumes

DLCO values adjusted for alveolar volumes
DLCO values adjusted for alveolar volumes

DLCO, KCO and VA in Obese Patients and Controls Using Conventional Reference Values

In our group of 98 obese patients, mean DLCO% was slightly but significantly lower (–6%) than that in the control group. A low VA% (–13% compared to controls) likely explains the lower DLCO% in our obese patients. This hypothesis is supported by several studies in which DLCO and VA were measured in obese patients at rest [22], during exercise [23] or after weight loss [10]. Although VA was inversely correlated with BMI (fig. 1), we found no correlation between DLCO and BMI. This is likely the result of the positive correlation between KCO and BMI and the inverse correlation between VA and BMI (fig. 1). The impact of VA on DLCO could be identified as this series included a large proportion of very obese patients who demonstrate the largest loss of VA. Indeed, 77 of 98 patients (79%) had a BMI of >40. Interestingly, obese patients presented with a large range of DLCO% values, from 65 to 114%. Our 33 patients with lower DLCO% had low VA%, and these low VA% were not, as was expected, coupled with high KCO%. On the other hand, the 23 obese patients with higher DLCO showed a high KCO% together with VA% very close to our control VA%. Whether the preservation of normal lung volume in obese patients is associated with specific fat distribution deserves to be investigated. Taken as a whole, these results illustrate that, using conventional reference equations, obese patients can present with a variety of DLCO values and patterns.

DLCO and KCO in Obese Patients and Controls Using Reference Values Adjusted for VA

Several reference equations have been established to adjust DLCO and KCO for lung volume. We used some of these equations [12,13,14,15,16] in our series and found that mean adjusted DLCO values were similar in the obese and control groups. This suggests that altered lung volumes explain most of DLCO variations in obese patients. This conclusion, however, is based on the assumption that the KCO–VA relationship does not differ significantly in normal subjects and in obese patients, since the VA effects on DLCO were derived from studies in normal subjects with submaximal inspiratory volumes. Increased abdominal pressure and mechanical constraint placed on the chest wall by fat accumulation are the main mechanisms leading to low lung volumes in obesity [23]. No structural pulmonary abnormalities have been described, and normalization of lung function after weight loss has been reported. Therefore, one may hypothesize that the KCO–VA relationship is not significantly modified in obesity. To further investigate this hypothesis, studying the contribution to lung diffusion capacity of the distribution of gas and perfusion in the lungs of obese patients, especially in basal lung areas [24], should be of interest. In this view, comparing Krogh factors and lung volumes measured with the re-breathing and single breath methods at the same inspired volume should allow correcting diffusion for the effects of unequal ventilation in obese subjects [25,26].

After adjustment of DLCO or KCO for lung volume, 10–20% of obese patients, according to the chosen equation, had values of <80% of predicted. This may suggest that, in addition to low lung volumes, obesity-associated disorders may contribute to decrease diffusing capacity in some patients. In a recent study, 40% of obese patients with reduced DLCO presented with moderate or severe diastolic dysfunction, which may trigger disruption of the alveolar-capillary barrier [9]. Type 2 diabetes, which reduces alveolar microvascular reserves and lung volumes, may also impair diffusing capacity in obese patients [27].

Using adjusted DLCO% or KCO% values for VA, we found very few obese patients (2–8% according to the reference equation) with high DLCO% or KCO% values. High KCO in obesity has been attributed to larger total circulating blood volume that increases pulmonary vascular recruitment [28]. The last assumption has received particular attention and was supported by the finding of an increased capillary volume in severely obese patients using the Roughton and Forster method [8]. Another author achieved similar conclusions using the diffusing capacity for nitric oxide [10]. However, both authors found diminished membrane diffusion that counterbalanced the high capillary volume and lead to normal DLCO values in their obese patients.

Limitations of the Study and Perspectives

Larger series of obese patients are needed to study the role of fat distribution on VA and DLCO. In this view, WC may be a better predictor of DLCO than BMI since it reflects central adiposity [29,30]. In addition, the small sex-related differences we observed (tendency of DLCO to decrease with BMI and lack of correlation between KCO and BMI in men, in contrast to women) suggest that there may be a larger loss of lung function in obese men compared to women which deserves to be confirmed [31,32]. In further series, particular attention should also be paid to patients >60 years, since VA dependence of DLCO has been found to be larger in younger subjects [13].

In conclusion, using conventional reference equations, our series of very obese patients shows slightly lower DLCO, lower VA and higher KCO than controls, with subtle gender differences. However, the range of DLCO values is large, from low DLCO characterized by low VA and KCO, to high-normal DLCO characterized by normal VA and high KCO. Using reference equations adjusting DLCO for VA, the differences between the obese and the control groups disappear, suggesting that low lung volumes are the main cause of low DLCO and high KCO values in obese patients. These results may help to better understand lung function in very obese patients in clinical situations of increasing frequency, such as pre-bariatric surgery assessment.

1.
McClean KM, Kee F, Young IS, Elborn JS: Obesity and the lung: 1. Epidemiology. Thorax 2008;63:649–654.
2.
Collard P, Wilputte JY, Aubert G, Rodenstein DO, Frans A: The single-breath diffusing capacity for carbon monoxide in obstructive sleep apnea and obesity. Chest 1996;110:1189–1193.
3.
Ray CS, Sue DY, Bray G, Hansen JE, Wasserman K: Effects of obesity on respiratory function. Am Rev Respir Dis 1983;128:501–506.
4.
Saydain G, Beck KC, Decker PA, Cowl CT, Scanlon PD: Clinical significance of elevated diffusing capacity. Chest 2004;125:446–452.
5.
Biring MS, Lewis MI, Liu JT, Mohsenifar Z: Pulmonary physiologic changes of morbid obesity. Am J Med Sci 1999;318:293–297.
6.
Jones RL, Nzekwu MM: The effects of body mass index on lung volumes. Chest 2006;130:827–833.
7.
Hakala K, Stenius-Aarniala B, Sovijarvi A: Effects of weight loss on peak flow variability, airways obstruction, and lung volumes in obese patients with asthma. Chest 2000;118:1315–1321.
8.
Oppenheimer BW, Berger KI, Rennert DA, Pierson RN, Norman RG, Rapoport DM, Kral JG, Goldring RM: Effect of circulatory congestion on the components of pulmonary diffusing capacity in morbid obesity. Obesity (Silver Spring) 2006;14:1172–1180.
9.
Ravipati G, Aronow WS, Sidana J, Maguire GP, McClung JA, Belkin RN, Lehrman SG: Association of reduced carbon monoxide diffusing capacity with moderate or severe left ventricular diastolic dysfunction in obese persons. Chest 2005;128:1620–1622.
10.
Zavorsky GS, Kim do J, Sylvestre JL, Christou NV: Alveolar-membrane diffusing capacity improves in the morbidly obese after bariatric surgery. Obes Surg 2008;18:256–263.
11.
Hughes JM, Pride NB: In defence of the carbon monoxide transfer coefficient KCO (TL/VA). Eur Respir J 2001;17:168–174.
12.
Frans A, Nemery B, Veriter C, Lacquet L, Francis C: Effect of alveolar volume on the interpretation of single breath DLCO. Respir Med 1997;91:263–273.
13.
Stam H, Hrachovina V, Stijnen T, Versprille A: Diffusing capacity dependent on lung volume and age in normal subjects. J Appl Physiol 1994;76:2356–2363.
14.
Chinn DJ, Cotes JE, Flowers R, Marks AM, Reed JW: Transfer factor (diffusing capacity) standardized for alveolar volume: validation, reference values and applications of a new linear model to replace KCO (TL/VA). Eur Respir J 1996;9:1269–1277.
15.
Filley GF, Macintosh DJ, Wright GW: Carbon monoxide uptake and pulmonary diffusing capacity in normal subjects at rest and during exercise. J Clin Invest 1954;33:530–539.
16.
Johnson DC: Importance of adjusting carbon monoxide diffusing capacity (DLCO) and carbon monoxide transfer coefficient (KCO) for alveolar volume. Respir Med 2000;94:28–37.
17.
Cotes JE, Chinn DJ, Quanjer PH, Roca J, Yernault JC: Standardization of the measurement of transfer factor (diffusing capacity). Work Group on Standardization of Respiratory Function Tests. European Community for Coal and Steel. Official position of the European Respiratory Society (in French). Rev Mal Respir 1994;11(suppl 3):41–52.
18.
Macintyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CP, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, Gustafsson P, Hankinson J, Jensen R, McKay R, Miller MR, Navajas D, Pedersen OF, Pellegrino R, Wanger J: Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005;26:720–735.
19.
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J: Standardisation of spirometry. Eur Respir J 2005;26:319–338.
20.
Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G: Standardisation of the measurement of lung volumes. Eur Respir J 2005;26:511–522.
21.
Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC: Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J 1993;16:5–40.
22.
Zavorsky GS, Cao J, Murias JM: Reference values of pulmonary diffusing capacity for nitric oxide in an adult population. Nitric Oxide 2008;18:70–79.
23.
Zavorsky GS, Kim do J, McGregor ER, Starling JM, Gavard JA: Pulmonary diffusing capacity for nitric oxide during exercise in morbid obesity. Obesity (Silver Spring) 2008;16:2431–2438.
24.
Holley HS, Milic-Emili J, Becklake MR, Bates DV: Regional distribution of pulmonary ventilation and perfusion in obesity. J Clin Invest 1967;46:475–481.
25.
Jansons H, Fokkens JK, Tweel van der I, Lammers JW, Folgering H: Influence of unequal ventilation on the single breath K(CO) in COPD revealed by comparison with the rebreathing K(CO). Respir Physiol Neurobiol 2002;133:109–119.
26.
Jansons H, Fokkens JK, van der Tweel I, Kreukniet J: Rebreathing K(CO) and single breath K(CO) measured at the same mean alveolar volume reveal a physiological relationship between unequal diffusion and unequal ventilation in normal subjects. Respiration 2000;67:383–388.
27.
Chance WW, Rhee C, Yilmaz C, Dane DM, Pruneda ML, Raskin P, Hsia CC: Diminished alveolar microvascular reserves in type 2 diabetes reflect systemic microangiopathy. Diabetes Care 2008;31:1596–1601.
28.
Zavorsky GS: Pulmonary gas exchange and diffusing capacity at rest and during exercise in those with morbid obesity: pre- and post-surgical intervention; in Parsons WV, Taylor CM (eds): New Research on Morbid Obesity. New York, Nova Science, 2008, pp 117–150.
29.
Chen Y, Rennie D, Cormier YF, Dosman J: Waist circumference is associated with pulmonary function in normal-weight, overweight, and obese subjects. Am J Clin Nutr 2007;85:35–39.
30.
Ochs-Balcom HM, Grant BJ, Muti P, Sempos CT, Freudenheim JL, Trevisan M, Cassano PA, Iacoviello L, Schunemann HJ: Pulmonary function and abdominal adiposity in the general population. Chest 2006;129:853–862.
31.
Zavorsky GS, Christou NV, Kim do J, Carli F, Mayo NE: Preoperative gender differences in pulmonary gas exchange in morbidly obese subjects. Obes Surg 2008;18:1587–1598.
32.
Bottai M, Pistelli F, Di Pede F, Carrozzi L, Baldacci S, Matteelli G, Scognamiglio A, Viegi G: Longitudinal changes of body mass index, spirometry and diffusion in a general population. Eur Respir J 2002;20:665–673.
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