Distal airway dysfunction in obese subjects corrects after bariatric surgery

Distal airway dysfunction in obese subjects corrects after bariatric surgery

Surgery for Obesity and Related Diseases 8 (2012) 582–589 Original article Distal airway dysfunction in obese subjects corrects after bariatric surg...

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Surgery for Obesity and Related Diseases 8 (2012) 582–589

Original article

Distal airway dysfunction in obese subjects corrects after bariatric surgery Beno W. Oppenheimer, M.D.a,*, Ryan Macht, B.S.b, Roberta M. Goldring, M.D.a, Alexandra Stabile, M.P.H.a, Kenneth I. Berger, M.D.a, Manish Parikh, M.D.b a

André Cournand Pulmonary Physiology Laboratory, Division of Pulmonary, Critical Care and Sleep, Department of Medicine, Bellevue Hospital/New York University School of Medicine, New York, New York b Department of Surgery, Bellevue Hospital Bariatric Center, New York University School of Medicine, New York, New York Received April 29, 2011; accepted August 5, 2011


Background: Obesity is frequently associated with respiratory symptoms despite normal large airway function as assessed by spirometry. However, reduced functional residual capacity and expiratory reserve volume are common and might reflect distal airway dysfunction. Impulse oscillometry (IOS) might identify distal airway abnormalities not detected using routine spirometry screening. Our objective was to test the hypothesis that excess body weight will result in distal airway dysfunction detected by IOS that reverses after bariatric surgery. The setting was a university hospital. Methods: A total of 342 subjects underwent spirometry, plethysmography, and IOS before bariatric surgery. Of these patients, 75 repeated the testing after the loss of 20% of the total body weight. The data from 47 subjects with normal baseline spirometry and complete pre- and postoperative data were analyzed. Results: IOS detected preoperative distal airway dysfunction despite normal spirometry findings by an abnormal airway resistance at an oscillation frequency of 20 Hz (4.75 ⫾ 1.2 cm H2O/L/s), frequency dependence of resistance from 5 to 20 Hz (2.20 ⫾ 1.6 cm H2O/L/s), and reactance at 5 Hz (⫺3.47 ⫾ 2.1 cm H2O/L/s). Postoperatively, the subjects demonstrated 57% ⫾ 15% excess weight loss. The body mass index decreased (from 44 ⫾ 6 to 32 ⫾ 5 kg/m2, P ⬍ .001). Improvements in functional residual capacity (from 59% ⫾ 11% to 75% ⫾ 20% predicted, P ⬍ .001) and expiratory reserve volume (from 41% ⫾ 20% to 75% ⫾ 20% predicted, P ⬍ .001) were demonstrated. Distal airway function also improved: airway resistance at an oscillation frequency of 20 Hz (3.91 ⫾ .9, P ⬍ .001), frequency dependence of resistance from 5 to 20 Hz (1.17 ⫾ .9, P ⬍ .001), and reactance at 5 Hz (⫺1.85 ⫾ .9, P ⬍ .001). Conclusion: The present study detected significant distal airway dysfunction despite normal preoperative spirometry findings. The effect of increased body weight was likely the main mechanism for these abnormalities. However, the inflammatory state of obesity or associated respiratory disease could also be invoked. These abnormalities improved significantly toward normal after weight loss. The results of the present study highlight the importance of bariatric surgery as an effective intervention in reversing these respiratory abnormalities. (Surg Obes Relat Dis 2012;8:582–589.) Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.


Distal airway function; Oscillometry; Bariatric surgery; Pulmonary function

*Correspondence: Beno W. Oppenheimer, M.D., André Cournand Pulmonary Physiology Laboratory, Division of Pulmonary, Critical Care and Sleep, Department of Medicine, Bellevue Hospital, 462 First Avenue, Room 7W54, New York, NY 10016. E-mail: [email protected]

Obesity is a chronic disease associated with physiologic impairments and co-morbidities in nearly every organ system [1–3]. Previous studies have shown that a reduction in vital capacity and forced expiratory volume in 1 second (FEV1) are associated with increased morbidity and mortality in both obese and nonobese subjects [4 –7]. Because self-reported respiratory symptoms are common in obese patients, even in the absence of clinically evident pulmonary disease [8], the eval-

1550-7289/12/$ – see front matter Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery. doi:10.1016/j.soard.2011.08.004

Distal Airway Dysfunction in Obese Subjects / Surgery for Obesity and Related Diseases 8 (2012) 582–589

uation of lung function and its potential correction after weight loss is of clinical importance. Lung function abnormalities in obesity include a reduction in selected lung volumes, including functional residual capacity (FRC) and expiratory reserve volume (ERV) [4,9 – 13]. The decrease in FRC presumably results from a combination of an increase in abdominal pressure and alteration in the recoil properties of the chest wall, and the decrease in ERV is presumably due to airway closure as a manifestation of airway/lung compression [12,14 –16]. The spirometric evaluation of airflow is usually normal. Although spirometry is an effective tool to evaluate large airway function, it is unable to fully assess abnormalities in the distal airways. The distal airways represent a “silent zone” of the lung that has a large aggregate cross-sectional area and, therefore, contributes minimally to total resistance [17–19]. Thus, significant physiologic and structural pathologic features can be missed using standard spirometry, and distal airway disease could be masked. Newer techniques, such as impulse oscillometry (IOS), have been developed that might detect functional abnormalities of the airways more distally than those evaluated using spirometry [18,20 –24]. This noninvasive method applies pressure oscillations to the airways and analyzes the resulting alteration in airflow. By analysis of the data over a range of oscillation frequencies, IOS is able to identify abnormalities in airway resistance not apparent on spirometry and, in addition, assess distal airway mechanics [18,21,25–29]. Oscillometry has demonstrated abnormalities in obese subjects despite normal spirometry findings, suggesting that distal airway dysfunction is a critical component of the obese phenotype [30]. Bariatric surgery has been shown to improve or resolve respiratory symptoms; however, studies comparing pre- and postoperative respiratory physiology have used only spirometry to assess airway function [31,32]. Because distal airway abnormalities can be missed by spirometry, the goal of the present study was to further define the respiratory profile of obesity by including an assessment of distal airway function; and evaluating the effect of surgically induced weight loss on the respiratory profile. Methods Subjects The present study retrospectively reviewed the data from a cohort of obese subjects undergoing bariatric surgery. The goal of the present study was to evaluate distal airway function. Thus, only subjects with normal large airway function as determined by spirometry were included, because disease of the larger airways could preclude identification of a distal abnormality. A total of 342 subjects were referred to the Bellevue Hospital Pulmonary Physiology Laboratory for preoperative evalua-


tion during an 18-month period as a part of the Bellevue Hospital Bariatric Center standard clinical protocol. Testing included spirometry, plethysmography, and IOS. Postoperatively, 121 of the 342 patients lost ⬎20% of their total body weight and were referred for repeat pulmonary function testing. A 20% weight loss was selected according to the findings from a previous study demonstrating near normalization of lung volumes with this degree of weight loss [33]. Of these 121 patients, 46 were lost to follow-up and 75 underwent repeat testing. Because normal airway function by spirometry was required in the present study, data are presented for 47 of the 75 patients who met these criteria and who were able to complete all aspects of the preoperative and postoperative testing. Normal airway function was defined as a ratio between a FEV1 to forced vital capacity (FVC) of ⱖ77%. This high cutoff value for FEV1/FVC was specifically chosen to ensure that subjects with mild large airway disease were excluded from the present study. Data pertaining to patient symptoms were obtained from patient records and confirmed by telephone interview for 39 of the patients. The percentage of excess weight loss was calculated using the body weight measured on the day of repeat pulmonary function testing. The percentage of excess weight loss was determined as follows: 100 ⫻ (preoperative weight ⫺ current weight)/(preoperative weight ⫺ ideal body weight). Ideal body weight was obtained from the 1983 Metropolitan Life Insurance height weight tables. Spirometry and lung volumes Spirometry was performed in accordance with the American Thoracic Society/European Respiratory Society standards (Vmax Encore, SensorMedics, Yorba Linda, CA) [34,35]. The data collected included FEV1, FVC, FEV1/FVC, ERV, and inspiratory capacity (IC). Specific criteria were used to ensure maximal effort for the spirometric measurements of vital capacity, IC, and ERV: (1) an exhalation time of ⱖ6 seconds; (2) a plateau of the exhaled volume versus the time tracing; and (3) ⱖ2 trials with reproducible data. The FRC was determined by plethysmography in all subjects. ERV was measured as the slow exhaled volume from the end-tidal position. The residual volume and total lung capacity were calculated from these measurements. Assessment of respiratory mechanics: IOS IOS is a noninvasive method that uses pressure and airflow oscillations over a range of oscillation frequencies to assess the properties of the proximal and distal airways [18,21,25–29]. IOS was performed using the Jaeger Impulse Oscillation System (Jaeger USA, Yorba Linda, CA) [36]. The IOS system applies pressure impulses to the airway every .2 second while the subject breathes quietly through


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the apparatus. Using this pressure and the resulting alteration in airflow, fast Fourier transformation yields data for respiratory system mechanics (airway resistance and reactance) within a range of oscillation frequencies (5–35 Hz). The parameters obtained included (1) airway resistance at an oscillation frequency of 20 Hz (R20); (2) frequency dependence of resistance from 5 to 20 Hz (R5–20); and (3) reactance at 5 Hz (X5). The interpretation of these parameters was according to the studies by DuBois et al., Otis et al., and Mead, where R20 reflects airway resistance, R5–20 reflects the heterogeneity of distal airway mechanics, and X5 reflects dynamic elastance [37–39]. Previous observations from our laboratory have demonstrated that R20 correlates with measurements of airway resistance obtained with esophageal manometry, R5–20 correlates with the frequency dependence of compliance an accepted measure of distal airway heterogeneity, and X5 correlates with dynamic lung compliance [25]. The measurements were obtained at FRC during tidal breathing with patients in the seated position with a nose clip while firmly supporting the cheeks. At the end of the measurement, the patients were instructed to perform an IC maneuver to confirm that the measurements were performed at FRC by comparison with the IC determined by spirometry. Only trials with constant tidal volume and a coherence ⬎.85 at oscillation frequencies of ⱖ10 Hz were considered for analysis. Reproducibility between trials (variability ⬍10%) was required for all parameters. To evaluate the effects of lung volume on airway resistance, R20 was referenced to FRC for calculation of specific conductance. Specific conductance (SGrs) was calculated for R20 by dividing 1/R20 by the measured FRC (SGrs at 20 Hz). The IOS data are presented as raw data and compared with an upper limit of normal selected from previous publications. Although a single value for an upper limit of normal was selected for all parameters, these values represent a conservative estimate, because they approximate 150% of the previously published mean values in normal subjects [21,36,40 – 44]. Data for specific conductance were compared with the lower limit of normal calculated from normative data for IOS resistance obtained in our laboratory from 46 asymptomatic nonsmoking subjects without lung disease and for whom the spirometry, lung volume, and IOS findings were within normal limits. Statistical analysis The data are summarized as the mean ⫾ standard deviation or standard error. Differences between groups were assessed using Student’s paired t test or Mann-Whitney U test. Analyses were performed using the Statistical Package for Social Sciences for Windows, version 17.0 (SPSS, Chicago, IL). The institutional review boards of the New York University School of Medicine and Bellevue Hospital approved the present study.

Table 1 Clinical characteristics and airway function (n ⫽ 47) Variable


Age (yr) Women (n) Anthropometric data Height (m) Weight (kg) BMI (kg/m2) Waist circumference (in.) (n ⫽ 39) Men (n ⫽ 1) Women (n ⫽ 38) Surgical data EWL (%) Laparoscopic surgery Roux-en-Y gastric bypass Adjustable gastric banding Sleeve gastrectomy Follow-up (d) Co-morbidities Asthma Hypercholesterolemia Hypertension Sleep apnea Thyroid disease GERD Diabetes Spirometry FVC (% predicted) FEV1 (% predicted) FEV1/FVC (%)

39 ⫾ 10.4 46 (98)


1.6 ⫾ .1 112 ⫾ 17.2 44 ⫾ 6.2

82 ⫾ 13.6* 32 ⫾ 4.7*

54 49 ⫾ 5.4

48* 40 ⫾ 4.6* 57 ⫾ 15

28 (60) 10 (21) 9 (19) 263 ⫾ 188 12 (26) 15 (32) 22 (47) 8 (17) 5 (11) 12 (26) 15 (32) 90 ⫾ 13.6 89 ⫾ 14.3 83 ⫾ 3.3

96 ⫾ 13.3* 95 ⫾ 14.2* 84 ⫾ 4.2

BMI ⫽ body mass index; EWL ⫽ excess weight loss [calculated as 100 ⫻ (preoperative weight ⫺ current weight)/(preoperative weight ⫺ ideal body weight)]; GERD ⫽ gastroesophageal reflux disease; FVC ⫽ forced vital capacity; FEV1 ⫽ forced expiratory volume in 1 second. * Statistically significant difference between pre- and postoperative values (P ⬍ .001).

Results The clinical characteristics of the 47 subjects analyzed are listed in Table 1. The subjects analyzed in the present study were representative of the population seen at the Bellevue Hospital Bariatric Center with respect to gender, age, body mass index (BMI), and co-morbidities. Most patients were female (98%), with a mean age of 39 ⫾ 10.4 years and mean BMI of 44 ⫾ 6.2 kg/m2. The most common weight loss procedure received by the subjects was Rouxen-Y gastric bypass (60%); however, laparoscopic adjustable gastric banding (21%) and laparoscopic sleeve gastrectomy (19%) were also performed. Of these 47 patients, 26% reported a history of asthma; no subject reported current cigarette use. Also, 25 subjects reported having chronic respiratory symptoms, with dyspnea the most common (24 subjects). All subjects had normal baseline spirometry findings, consistent with the inclusion criteria. After weight loss, an increase in FEV1 was noted and attributed to the increase in FVC, because the FEV1/FVC ratio remained unchanged.

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Fig. 1 illustrates the pre- and postoperative weight, BMI, and waist circumference. Preoperatively, the increased weight and BMI were associated with predominant central obesity (waist circumference 50 ⫾ 5.4 in.). Postoperatively, the subjects lost weight with an average of 57% ⫾ 15% of the excess weight at baseline. This resulted in a significant reduction in the mean BMI from 44 ⫾ 6.2 kg/m2 to 32 ⫾ 4.7 kg/m2, mean weight from 112 ⫾ 17.2 kg to 82 ⫾ 13.6

Fig. 2. Pre- and postoperative respiratory symptoms. Symptoms were present in 25 (53%) of 47 subjects. Dyspnea was most commonly reported respiratory symptom (51% of subjects). After weight loss, the prevalence of respiratory symptoms greatly reduced. Black bars indicate preoperative; white bars, postoperative.

kg, and waist circumference (39 subjects) from 50 ⫾ 5.4 in. to 40 ⫾ 4.7 in. Fig. 2 illustrates the prevalence of pre- and postoperative respiratory symptoms. Respiratory symptoms were present in 25 (53%) of the 47 subjects. The demographic characteristics, spirometry, plethysmography, and IOS values did not differ significantly between those reporting any respiratory symptoms and those who did not report respiratory symptoms. Dyspnea was the most commonly reported respiratory symptom (24 of 47, 51%), followed by cough (11 of 47, 23%), and wheeze (5 of 47, 10%). After weight loss, only 3 patients reported the persistence of dyspnea (88% reduction). Wheezing and coughing were persistent in 2 and 5 subjects, respectively, after surgery. The pre- and postoperative lung volumes and capacities are illustrated in Fig. 3. Preoperatively, the mean value for the total lung capacity and vital capacity were within the normal range (84% ⫾ 10.7% and 91% ⫾

Fig. 1. Mean values for BMI (kg/m2), weight (lb), and waist circumference (in.) values. For waist circumference, n ⫽ 39. Dotted line represents upper limit of normal for each relevant parameter. All parameters improved significantly after weight reduction surgery. Black symbols indicate preoperative; white symbols, postoperative.

Fig. 3. Lung volumes and capacities. Data expressed as mean ⫾ standard deviation. Shaded area represents normal values for total lung capacity. Black symbols indicate preoperative; white symbols, postoperative.


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Fig. 4 illustrates the mean values ⫾ SE for IOS parameters before and after surgically induced weight loss. Preoperatively, 87% of subjects showed abnormalities in all IOS values. After the weight reduction, a statistically significant improvement was noted in all IOS parameters to or toward normal. The R20 decreased from 4.75 ⫾ 1.2 to 3.91 ⫾ .9 cm H2O/L/s, indicating improvement in airway resistance; R5–20 decreased from 2.20 ⫾ 1.6 to 1.17 ⫾ .9 cm H2O/L/s, indicating improvement in distal airway heterogeneity; X5 increased from ⫺3.47 ⫾ 2.1 to ⫺1.85 ⫾ .9 cm H2O/L/s, indicating improvement in respiratory system elastance. Fig. 5 illustrates resistance at 20 Hz related to lung volume at FRC, expressed as specific conductance (SGrs at 20 Hz). Preoperatively, the specific conductance was within normal limits, indicating that the increased resistance was predominantly from the decrease in FRC. After weight loss, SGrs at 20 Hz remained within normal limits and was unchanged from preoperative values, indicating that the improvement in resistance occurred in proportion to the improvement in lung volume seen with weight reduction. Discussion The present study examined a specially selected group of morbidly obese subjects with normal large airway function on spirometry. The respiratory physiologic profile was evaluated using spirometry, plethysmography, and IOS before and after bariatric surgery. Preoperatively, despite normal large airway function as assessed by spirometry, abnormal IOS parameters were seen in nearly all patients in this cohort, indicating that obese patients have significant respiratory dysfunction that might not be detected by conventional techniques. Dysfunction in distal airways is clinically

Fig. 4. Pre- and postoperative IOS data for R20, R5–20, and X5. Data presented as mean ⫾ standard error. Dotted line represents upper limit of normal. Significant improvement in IOS parameters noted after surgery. Black symbols indicate preoperative; white symbols, postoperative.

13.6% predicted), respectively. However, a marked reduction in the ERV, FRC, and residual volume was observed (41% ⫾ 21.4%, 59% ⫾ 11.5%, and 69% ⫾ 21.4% predicted), compatible with airway compression without air trapping (low residual volume/total lung capacity, .28 ⫾ .1). After weight loss, a significant improvement in ERV and FRC was noted to or toward normal (80% ⫾ 33.8% and 75% ⫾ 20.0% predicted).

Fig. 5. Pre- and postoperative resistance at 20 Hz related to lung volume and expressed as specific conductance (SGrs at 20 Hz). Data presented as mean ⫾ standard error. Dotted line represents lower limit of normal. Black symbols indicate preoperative; white symbols, postoperative.

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relevant and might be a manifestation of airway compression, because of excess body weight, the inflammatory state of obesity, or an early manifestation of associated respiratory disease. These abnormalities improved significantly to or toward normal after weight loss. Therefore, the present study highlights the importance of bariatric surgery as an effective intervention in reversing these respiratory functional abnormalities. The metabolic syndrome has been associated with reductions in lung function independent of other risk factors. This association has been attributed to the metabolic effects of adipose tissue and/or the mechanical effects of abdominal obesity per se [4,45,46]. The latter association might result from altered mechanics of the diaphragm and chest wall and might also relate to closure of distal lung units (lung base). This effect on distal airway dysfunction has been previously recognized [12,30,47]. Several studies have demonstrated the importance of disease in the distal airways in diseases, such as asthma, bronchitis, and exposure to inhaled toxins. In each of these diseases, inflammation and remodeling in the peripheral airways plays a critical role in the disease pathophysiology and degree of airflow limitation [48 –53]. Previous studies have also demonstrated that the extent of distal airway dysfunction is predictive of progression of airflow obstruction in chronic obstructive pulmonary disease and has a direct relationship to mortality [54 –56]. The findings of the present study support that obesity is an additional disease in which the distal airways are significantly compromised. Because the total cross-sectional area of the distal airways is large, it has previously been difficult to noninvasively evaluate narrowing and changes in resistance at the most peripheral areas of the lung. Therefore, identifying distal airway abnormalities early, before the disease has progressed, might be helpful in both prognosis and treatment. IOS has been previously shown to be an accurate tool for detecting functional abnormalities in distal airways not previously detected by spirometry [21,36,44,57–59]. The use of IOS in the present study uncovered abnormalities in airway function not detected by spirometry and completes the respiratory profile of obesity to include distal airway dysfunction. Oscillometry demonstrated abnormalities of resistance despite normal spirometry, frequency dependence of resistance, reflecting the heterogeneity of airway mechanics and abnormal elastance compatible with increased “stiffness” of the respiratory system. This suggests that either spirometry is not sensitive enough to detect abnormalities found in obesity or that these abnormalities are located more peripherally in the lungs in a spirometric “silent zone.” These results are in accordance with previous studies [30,60], further highlighting the importance of recognizing distal airway dysfunction as a potential source of morbidity in obese subjects.


With significant postoperative weight loss, normalization of the lung volumes (FRC and ERV), improvement in all IOS parameters, and less subjective dyspnea was observed. Airflow, as assessed by FEV1, improved in proportion to improvement in FVC and FEV1/FVC remained unchanged. The improvement in FRC and ERV indicated unloading of the respiratory system upon weight loss with reversal of airway compression, and is likely to be responsible for the improvement in distal airway dysfunction. This effect on airway function can be confirmed by referencing airway resistance to lung volume (specific conductance) [30]. In the present study, specific conductance was normal in the preoperative state. Furthermore, the specific conductance remained unchanged postoperatively, indicating that resistance improved in proportion to the increase in lung volume, affirming the effect of excess body weight and airway compression on distal airway function. In addition to the improvement in respiratory physiology, surgery improved the respiratory symptoms. Although distal airway dysfunction might be a potential mechanism of dyspnea in these subjects, distal airway dysfunction was equally abnormal in both symptomatic and asymptomatic subjects. However, although the mechanism for dyspnea might not be clear, weight reduction after bariatric surgery was effective in reducing respiratory symptoms in 88% of the symptomatic subjects of the present study. In the present study, confounding factors that might have influenced the results included the presence of self-reported asthma in some subjects. However, an analysis of data from these subjects was indistinguishable from the group as a whole. Additionally, IOS results did not fully normalize after weight loss because the average weight loss was 57% of excess weight, and the BMI remained ⬎30 kg/m2 in approximately 50% of the subjects. However, even in these subjects, the improvement in resistance by oscillometry tracked the improvement in lung volume. Conclusion The present study evaluated pulmonary function before and after weight loss from bariatric surgery. Despite normal large airway function seen with spirometry, obese patients were found to have significant distal airway dysfunction and abnormalities of all IOS parameters. The effect of increased body weight was likely a main contributor to these abnormalities, but other potential physiologic mechanisms might also be responsible. Additional studies are needed to elucidate the mechanism of pulmonary dysfunction in morbid obesity to more fully understand this disease process. Additionally, a greater understanding of the clinical relevance of these abnormalities might be important in the future for perioperative risk assessment and long-term postoperative follow-up.


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