Dyspnea in Obese Healthy Men* Hamid Sahebjami, MD, FCCP

Dyspnea in Obese Healthy Men* Hamid Sahebjami, MD, FCCP Study objectives: To determine whether obese, apparently healthy individuals experience dyspnea at rest and, if so, whether their pulmonary function test (PFT) profile and maximal respiratory pressures are different from obese, healthy subjects without dyspnea. Design: Prospective, open. Setting: Pulmonary function test laboratory, Veterans Administration Medical Center. Patients: Twenty-three obese male subjects (each with a body mass index [BMI] of> 28 kglm 2 ) with an FEV 1 level and an FEV 1 /FVC ratio ~ Fifteen complained of dyspnea, where eight denied having it, at rest. 80% of predicted and no coexisting conditions. Measurements and results: Standard PFT parameters and maximum static inspiratory (Pimax) and expiratory (PEmax) mouth pressures were determined. Subjects with dyspnea had similar age and height but larger body weight (113.9 ± 5.0 vs 97.4 ± 2.6 kg, p = 0.03) and BMI (37.4 ± 1.6 vs 31.8 ± 0.7 kglm 2, p = 0.02) than subjects without dyspnea, and a greater number of them were current or previous smokers. Forced expiratory flow at 75% vital capacity (54.9 ± 6 vs 75.5 ± 7% predicted, p = 0.05), maximum voluntary ventilation (MVV; 90.2 ± 3.8 vs 107.8 ± 9.3% predicted, p = 0.05), and PEmax (77 ± 2 vs 97.8% predicted, p = 0.007) were significantly reduced in the group of subjects with dyspnea. Large airway function (FVC, FEV 1, and FEV 1 /FVC ratio), lung volumes, and gas exchange parameters were similar between the two groups. Conclusions: Some obese, but otherwise healthy, individuals experience dyspnea at rest. Reduced PEmax and MVV combined with greater body mass and peripheral airway disease are most likely responsible for the sensation of dyspnea in these individuals. (CHEST 1998; 114:1373-1377) Key words: chest wall mechanics; peripheral ailways; respiratory muscles Abbreviations: BMI =body mass index; BSDI =Borg scale dyspnea index; DLCO =carbon monoxide diffusing capacity o f the lung; ERV = expiratmy reserve volume; FEF 75 = forced expiratory flow at 75% vital capacity; FRC = function residual capacity; IC = inspiratory capacity; MW = maximum voluntary ventilation; PEmax = maximum static expiratory mouth pressure; PFT = pulmona1y function test; PTmax = maximum static inspiratory mouth pressure; RMS = respiratory muscle strength; RV = residual volume; SVC = slow vital capacity; TLC = total lung capacity D o some obese individuals experience dyspnea at rest in the absence of significant coexisting disorders known to lead to the sensation of dyspnea? This question has not been answered in the medical literature. Historically, in most major textbooks of medicine and respiratory disease, obesity is not included as a cause of dyspnea. Obese subjects experience exertional dyspnea, in the absence of pulmonary abnormalities, due to increased work of breathing and the metabolic load placed on their gas transport system when performing external work. 1 It is also well known *From the Pulmonary Section, Department of Veterans, Affairs Medical Center; and Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH. Manuscript received January 6, 1998; revision accepted May 13, 1998. Correspondence to: Hamid Sahebjami, MD, Pulmonary Section (lllf), Veterans Administration Medical Center, 3200 Vine Street, Cincinnati, OH 45220 that obesity alone affects respiratory function in humans. The effects of obesity include reduced expiratory reserve volume (ERV) and functional residual capacity (FRC) due to alterations in chest wall mechanics 2-8 ; decreased total respiratory compliance 3-8 ; reduced flow rates at low lung volumes and increased residual volume (RV) and its ratio to total lung capacity (TLC) suggestive of peripheral airway disease 9 10 ; diminished maximum voluntary ventilation 2 3 5 6 10 11 ; and increased total respiratory resistance and work.1 2 Despite the information gleaned from these effects, it is not clear whether obesity alone can cause dyspnea in subjects at rest. The purpose of the present study was to determine whether baseline dyspnea is present among obese individuals without coexisting disorders known to cause dyspnea, and to assess whether the pulmonary function test (PFT) profile and the maximal CHEST I 114 I 5 I NOVEMBER, 1998 1373

respiratory pressure are different in these individuals with and without dyspnea. Study Design and Population MATERIALS AND METHODS During a 3-month period, all male patients referred to the PFT Laboratmy at the Cincinnati Veterans Affairs Medical Center who had a body mass index (BMI) ~ phase of this investigation. Subjects were asked to rest in a chair 28 kglm 2 entered the initial for approximately 10 min after arriving at the laboratory. They were then instructed to complete a written questionnaire, which asked them whether they did or did not have any trouble breathing at rest (while at home or in the PFT laboratory), and to record the severity of the breathing difficulty by making a mark on a modified Borg category scale, ranging from 0 to 10 and including verbal descriptors 13 14 The number marked by the subject was referred to as the Borg Scale Dyspnea Index (BSDI). Physiologic parameters were then measured and recorded. Of all subjects tested during the period of investigation, those who were able to complete the questionnaire, the Borg category scale, and the physiologic measurement in whom the FEV 1 and FEV/ FVC ratio were > 80% predicted w ere screened. Clinical records of these subjects, including electrocardiograms and chest radiographs, were reviewed. The final selection was based on the absence of the exclusion criteria among the individuals, which were: (l ) cardiopulmonary disease; (2) neuromuscular disorders; (3) malignancies; (4) pre- or postoperative states; and (5) serious systemic illnesses (chronic renal failure, complicated diabetes mellitus, malnutrition, etc). The above conditions may, independent of obesity, be associated with the sensation of dyspnea. Therefore, the group selected for this report consisted of obese individuals who, to the best of our knowledge, were free of coexisting conditions that could have influenced the presence and severity of dyspnea. The study was approved by our Institutional Review Board. Measurements Body weight and height were measured with subjects wearing indoor clothing and shoes with 2.5-cm heels, and the BMI was calculated as body weighuheight (kg!m 2 ). 2 Flow rates, lung volumes, and single-breath carbon monoxide diffusing capacity of the lung (DLCO) were determined using automated equipment (model GS/Pius; Warren E. Collins; Braintree, MA). Forced inspiratory and expiratmy maneuvers were performed three times, and the best values obtained from the maximum inspiratory and expiratory flow-volume curves w ere used for comparison. FRC was measured b y the nitrogenwashout technique, and RV was obtained as FRC minus ERV. TLC was calculated as RV plus vital capacity (VC). DLCO was performed in duplicate, and the larger value was reported. Recommendations for standardized procedures for various lung function test measurements were followed. 1 5-17 Maximum voluntary ventilation (MW) was determined after instructing each subject to breathe as fast and as deeply as possible for a p eriod of 12 s. If the frequency of breathing was less than 60/min and the tidal volume was less than 40% ofvc on the first maneuver, the patient was instructed to breathe faster and deeper on the next maneuver; the greater frequency and volume data of the two efforts were used for comparison 18 Predicted values from the following reports were used as a reference to assess various PFTs: Knudson and associates 19 for spirometry, Goldman and Becklake 20 for lung volumes, Baldwin and associates 2 1 for MVV, and Gaensler and Smith 22 for DLCO. Maximum static inspiratmy (Pimax) and expiratory (PEmax) mouth pressures w ere measured at HV and TLC, respectively, using the method of Black and Hyatt. 23 An index of respiratory muscle strength (RMS) was calculated from (Pimax + PEmax) :2 according to Aldrich et aj.2 4 Arterial blood samples were drawn from the radial artery with the patient in a sitting position while breathing room air. Arterial blood-gas analysis was performed using the ABG-520 analyzer (Radiometer America; Westlake, OH). Statistical Analysis For each parameter measured or calculated, the values for individual patients were averaged per group, and the SEM was calculated. Differences between groups were tested by an unpaired t test; p values of :S 0.05 were considered significant. RESULTS Sixty male individuals with a BMI of ;::::: 28 kglm 2 were tested during the observation period; of these, only 23 met the inclusion criteria for this study and are reported. Eight subjects denied having dyspnea (nondyspneic group), and 15 complained of dyspnea (dyspneic group). Age and height were similar in the two groups, whereas BSDI, weight, and BMI were significantly greater in the dyspneic group (Table 1). A larger percentage of subjects with dyspnea were current or previous smokers (86.6% combined) compared with the nondyspneic group (62.5% combined) as shown in Table 1. As presented in Table 2, measures reflecting large airway function (FVC, FEVv and FEV/FVC ratio) were equally within normal limits in both groups. forced expiratory flow rates over mid and low volume ranges tended to be smaller in the dyspneic group, but only forced expiratory flow at 75% VC (FEF 75 ) reached borderline significance (p = 0.050). Simi- Table!-Characteristics of Obese Subjects* Characteristic BSDI Age, yr Height, em Weight, kg BMI, kglm 2 Smoking history, n Current Previous Never tp < 0.0001. tr = o.0332. p = 0.0285. out n =8 0.12 ::':: 0.08t 52.2 ::':: 3.5 175.5 ::':: 2.2 97.4 ::':: 2.6 t 31.8 ::':: 0.7 4 (50.0%) 1 (12.5%) 3 (37.5%) 3.1 ::':: 0.3 52.3 ::':: 3.0 174.0::'::1.1 113.9 ::':: 5.0 37.4 ::':: 1.6 9 (60.0%) 4 (26.7%) 2 (13.3%) 1374 Clinical Investigations

Table 2-Spirometric Parameters in Obese Subjects* out Parameter n = 8 p Value FVC, % predicted 96.1 ::':: 4.8 93.4 ::':: 2.4 NS FEV 1, % predicted 96.3 ::':: 5.4 89.4 ::':: 2.1 NS FEV/ FVC, % predicted 99.5 ::':: 1.5 95.3 ::':: 1.7 NS FEF 50, % predicted 88.2 ::':: 7.7 82.2 ::':: 5.2 NS FEF 7,s, % predicted 75.7 ::':: 7.5 54.9 ::':: 6.0 0.05 FEF ;z_ 75, % predicted 87.3 ::':: 6.3 73.0 ::':: 5.2 NS PIFR,t Us 5.5 ::':: 0.6 5.6 ::':: 0.3 NS MVV, % predicted 107.8 ::':: 9.3 90.2 ::':: 3.8 0.05 t PIFR = peak inspiratory flow rate. larly, the percent MVV was lower in the dyspneic group with a borderline significance (p = 0.050). No differences in lung volume (Table 3) or in gas-exchange parameters (Table 4) were present between the two groups. Individuals who were obese and had dyspnea had significantly smaller PEmax and RMS levels, both as absolute measures and as the percent predicted (Table 5). DISCUSSION Results of this study show that obesity alone, in the absence of other known causes, can be associated with the sensation of dyspnea at rest. Based on BSDI, the dyspnea experienced by obese individuals is mild in intensity (BSDI = 3.1 ± 0.3 on a scale of 0 to 10). The clinical profile of an obese person with dyspnea consists of greater body weight and BMI and more likelihood of being a current or a previous smoker. The physiologic profile of an obese individual with dyspnea is characterized by a reduction in flow rates at low lung volumes, diminished MVV, and significantly reduced PEmax. Based on the selection criteria, large airway function represented by FVC, FEV 1, and the FEV/FVC Table 4-Gas-Exchange Parameters in Obese Subjects* Parameter Pao 2, mm Hg Paco 2, mm Hg ph DLCO, % predicted out 11 = 8 83.0 ::':: 4.5 41.0 ::':: 1.5 7.40 ::':: 0.01 93.6 ::':: 5.3 76.8 ::':: 3.2 40.6 ::':: 0.7 7.40 ::':: 0.004 88.6 ::':: 3.4 ratio was not significantly abnormal in both groups of obese patients in the present study. However, FEF 75 was lower in the dyspneic group. Indeed, 5 (62.5%) of the subjects without dyspnea but 13 (86.6%) of the subjects with dyspnea had FEF 75 < 80% predicted. The percentage of subjects with abnormal FEF 75 values in each group reflected exactly the percentage of combined current and previous smokers in the same groups (Table 1). To determine whether smoking (both current and previous) had an impact on RMS and MVV in obese subjects, these parameters were compared between smokers and nonsmokers in each group. In the obese, dyspneic group, RMS and MVV were > 80% predicted in all nonsmokers. Among smokers, RMS and MVV were < 80% predicted in 46 and 25% of subjects, respectively. In the nondyspneic group, RMS and MVV were of > 80% predicted in all nonsmokers. Among smokers, 20% of subjects had low RMS and MVV. Irrespective of smoking history, peripheral airway abnormalities have been reported even in nonsmoking obese individuals. Rubinstein and associates 9 reported significant abnormalities in flow rates over both high and low lung volumes, increased RV, RVffLC ratio, and airway resistance in markedly obese, nonsmoking men and women. The mechanism(s) underlying these abnormalities in nonsmoking, morbidly obese subjects is(are) not clear. Sahebjami and Gartside 10 reported similar findings in a Table 3-Lung Volumes in Obese Subjects* Table 5-Respiratory Muscle Strength in Obese Subjects* Parameter out 11 = 8 out Parameter n = 8 p Value TLC, % predicted FRC, % predicted RV, % predicted VC, % predicted IC, % predicted ERV, % predicted RVffLC,% predicted 97.5 ::':: 3.4 90.1 ::':: 5.5 94.2 ::':: 4.1 96.5 ::':: 4.5 104.6 ::':: 7.6 81.1 ::':: 17 92.8 ::':: 3.0 99.4 ::':: 3.1 96.2 ::':: 5.2 105.1 ::':: 6.5 91.8 ::':: 2.6 100.6 ::':: 3.6 67.2 ::':: 8.3 100.7 ::':: 3.6 Pimax, em H 2 0 124 ::':: 8 106 ::':: 7 NS % predicted 108 ::':: 7 92 ::':: 5 NS PEmax, e m H 2 0 206 ::':: 15 164 ::':: 6 0.0054 % predicted 97 ::':: 8 77 ::':: 2 0.0078 RMS,t em H 2 0 165 ::':: 9 135 ::':: 5 0.0066 % predicted 101 ::':: 6 82 ::':: 3 0.0049 frms = respiratory muscle strength ([Pimax + P Emax] :2). CHEST I 114 I 5 I NOVEMBER, 1998 1375

group of obese individuals in whom the FEV /FVC ratio was > 80%. Neither report addressed the question of dyspnea and its relationship with physiologic parameters. The most significant physiologic difference in the present study between the obese, otherwise healthy individuals with or without dyspnea was the level of RMS. Note that PEmax, RMS, and MVV were reduced in subjects with dyspnea. This study also showed that Pimax, PEmax, and RMS were within the predicted range in obese individuals without dyspnea who were free from other underlying diseases. RMS has been reported to be preserved in obese subjects with eucapnea 25-27 but reduced in some patients vvith obesity-hypoventilation syndrome.ll 28 In a previous report from our laboratmy on PFT profile of apparently healthy obese subjects with a FEV /FVC ratio of > 80%, 10 PI max, PEmax, and RMS were found to be within the predicted range in those in whom MW was also > 80%; others with lower MWs had also diminished muscle strength. Twenty-five percent of the subjects in the latter group had hypercapnia. Correlation between MW and various measures of RMS have been previously observed. 29 3 0 In the present study, individuals without dyspnea had significantly greater RMS and MW values than those of the dyspneic group. The sensation of dyspnea results from a complex interaction of signals arising from a variety of receptors in the upper airways, the lung parenchyma, and the chest wall and from within the CNS. These signals represent a complex interplay of mechanic, physiologic, metabolic, and neurologic factors in addition to others. 31 32 The psychological profile of obese individuals who participated in the present study were not assessed and, therefore, cannot be addressed. Judged by the results of gas-exchange parameters (Table 4), differences in the state of chemoreceptor activity cannot be invoked as the cause of dyspnea. Furthermore, static measures of lung function (as judged by lung volumes) and large ai1way dynamics (as assessed by spirometric examination) exclude significant parenchymal or airflow abnormalities as being responsible for the perception of dyspnea. Massive obesity (BMI > 50 kglm 2 ) has been shown to be associated with a hypervolemic, hyperdynamic state due to increased total blood volume and cardiac output leading to pulmona1y congestion, dyspnea, and massive edema. 33,: 34 None of the subjects in this study were massively obese nor did they manifest this clinical syndrome. The compliance of the total respiratmy system is reduced in normal obese subjects. 12 Some of the reduction is due to a fall in lung compliance and some to reduced chest wall compliance. 12 The re- duction in compliance of the total respiratory system, however, is principally due to diminished chest wall compliance as the result of increased elastic resistance to distention and reduced distensibility of extra pulmonary structures. 3 In the present study, the obese subjects with dyspnea had greater body weight, which suggests the presence of peripheral airway abnormalities, and diminished PEmax and MW compared with the nondyspneic group. The increased incidence of peripheral airway abnormalities in these subjects reflected the larger number of smokers in the group. The reduced PEmax could have resulted from the larger body mass that must be lifted, the stiffness of the chest wall that must be overcome, and the RMS. 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