Orthopnea and Tidal Expiratory Flow Limitation in Chronic Heart Failure*

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1 CHEST Orthopnea and Tidal Expiratory Flow Limitation in Chronic Heart Failure* Roberto Torchio, MD; Carlo Gulotta, MD; Pietro Greco-Lucchina, MD; Alberto Perboni, MD; Luigina Avonto, MD; Heberto Ghezzo, MD; and Joseph Milic-Emili, MD Original Research HEART FAILURE Background: Tidal expiratory flow limitation (FL) is common in patients with acute left heart failure and contributes significantly to orthopnea. Whether tidal FL exists in patients with chronic heart failure (CHF) remains to be determined. Purpose: To measure tidal FL and respiratory function in CHF patients and their relationships to orthopnea. Methods: In 20 CHF patients (mean [ SD] ejection fraction, 23 8%; mean systolic pulmonary artery pressure [spap], mm Hg; mean age, years) and 20 control subjects who were matched for age and gender, we assessed FL, Borg score, spirometry, maximal inspiratory pressure (PImax), mouth occlusion pressure 100 ms after the onset of inspiratory effort (P 0.1 ), and breathing pattern in both the sitting and supine positions. The Medical Research Council score and orthopnea score were also determined. Results: In the sitting position, tidal FL was absent in all patients and healthy subjects. In CHF patients, PImax was reduced, and ventilation and P 0.1 /PImax ratio was increased relative to those of control subjects. In the supine position, 12 CHF patients had FL and 18 CHF patients claimed orthopnea with a mean Borg score increasing from in the sitting position to in the supine position in CHF patients. In contrast, orthopnea was absent in all control subjects. The FL patients were older than the non-fl patients (mean age, 63 8 vs years, respectively; p < 0.03). In shifting from the seated to the supine position, the P 0.1 /PImax ratio and the effective inspiratory impedance increased more in CHF patients than in control subjects. The best predictors of orthopnea in CHF patients were spap, supine PImax, and the percentage change in inspiratory capacity (IC) from the seated to the supine position (r ; p < 0.001). Conclusions: In sitting CHF patients, tidal FL is absent but is common supine. Supine FL, together with increased respiratory impedance and decreased inspiratory muscle force, can elicit orthopnea, whom independent indicators are spap, supine PImax and change in IC percentage. (CHEST 2006; 130: ) Key words: chronic heart failure; expiratory tidal flow limitation; orthopnea Abbreviations: AHF acute heart failure; CHF chronic heart failure; Dlco diffusing capacity of the lung for carbon monoxide; ERV expiratory reserve volume; FEF 75 forced expiratory flow when 75% of FVC has been exhaled; FL flow limitation; FRC functional residual capacity; IC inspiratory capacity; MRC Medical Research Council; NEP negative expiratory pressure; P(A-a)O 2 alveolar-arterial oxygen pressure difference; PCWP pulmonary capillary wedge pressure; PEEPi intrinsic positive end-expiratory pressure; Pimax maximal inspiratory pressure; Pimus pressure generated from inspiratory muscles; P 0.1 mouth occlusion pressure 100 ms after onset of inspiratory effort; Prs relaxation pressure; Raw airway resistance; RV residual volume; spap systolic pulmonary artery pressure; TLC total lung capacity; V o 2 max maximal oxygen uptake; Vr relaxation volume; Vt tidal volume Orthopnea is a major complaint of patients with acute heart failure (AHF). Although its nature is multifactorial, recent studies 1,2 have shown that tidal expiratory flow limitation (FL) is common in supine patients with acute AHF in whom, by imposing an inspiratory threshold load due to dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi), contributes significantly to orthopnea. While in the sitting patients with chronic heart failure (CHF) tidal FL is absent, 3 its prevalence in patient in the supine position has not as yet been assessed. 472 Original Research

2 Accordingly, in seated and supine CHF patients and in age-matched and sex-matched control subjects we have assessed the following: the prevalence of tidal FL and its association to dyspnea and orthopnea. In addition, we have measured the maximal inspiratory pressure (Pimax), blood gas levels at rest, and the control of breathing. Patients Materials and Methods The study was carried out on 20 stable ambulatory patients (18 men) with congestive heart failure due to cardiomyopathy (6 postischemic patients) without pleural effusions. No patients had been hospitalized within the 20 days preceding the study. No patients were current smokers, but nine patients were exsmokers. All patients received therapy with diuretics. Within a month prior to our study, the Weber class was determined by cardiopulmonary exercise testing as follows 4 : Weber class B, 7 patients (maximal oxygen uptake [V o 2 max], between 16.0 and 19.8 ml/kg/min); Weber class C, 10 patients (V o 2 max, between 11.7 and 15.5 ml/kg/min); and Weber class D, 3 patients (V o 2 max, between 7.1 and 9.8 ml/kg/min). Heart failure was defined as symptomatic left ventricular dysfunction, with a left ejection fraction of 0.45 documented by bidimensional echocardiography. Patients were excluded from the study if they had primary pulmonary, neurologic, or myopathic disease. Echocardiographic ejection fraction, systolic pulmonary artery pressure (spap), and heart diameters were measured within the 2 weeks preceding our study. Twenty healthy subjects (ie, control subjects) matched for sex and age were also studied. All control subjects were nonsmokers, but nine patients were ex-smokers (Table 1). The study was approved by the local ethics committee, and informed consent was obtained from each subject. In the subjects in the present study, the closing capacity and gas exchange were assessed in the sitting position, as previously described. 3 Chronic dyspnea was scored using the modified Medical Research Council (MRC) scale based on six increasing grades (0 to 5). 5 Seated and supine dyspnea were measured by a modified Borg scale, ranking the magnitude from 0 (none) to 10 (maximal). 6 Twenty minutes of positioning in the decubitus position was required before assessing the supine Borg score. Orthopnea was defined as a worsening of the Borg score with the patient in the supine position. 7 Twelve months after this study, it was possible to retrieve the clinical data of 13 of the 20 patients. Three patients had died, and 10 patients were still alive. *From Fisiopatologia Respiratoria (Drs. Torchio, Gulotta, and Perboni) and Cardiology (Drs. Greco-Lucchina and Avonto), Ospedale San Luigi Gonzaga, Orbassano, Turin, Italy; and Meakins-Christies Laboratories (Drs. Ghezzo and Milic-Emili), McGill University, Montreal, QC, Canada. The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Manuscript received December 23, 2005; revision accepted February 13, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: Roberto Torchio, MD, Fisiopatologia Respiratoria, Ospedale S Luigi Gonzaga, I Orbassano, Torino, Italy; r.torchio@inrete.it DOI: /chest Table 1 Anthropometric Characteristics and Baseline Respiratory Data for Control Subjects and CHF Patients Measured in the Seated Position* Variables Control Subjects (n 20) CHF Patients (n 20) Each patient underwent a spirometric, plethysmographic, and diffusing capacity of the lung for carbon monoxide (Dlco) study that was performed in the sitting position. Using a plethysmograph (Autobox 2800; SensorMedics; Yorba Linda, CA), airway resistance (Raw) was measured at a panting frequency of 1 Hz. Spirometric and plethysmographic volumes were assessed according to European Respiratory Society (ERS). 8 Dlco was measured with a water-sealed spirometer (Biomedin; Padua, Italy) using helium for alveolar volume measurement. 8 Predicted values for Raw were from Peslin et al, 9 and those for Dlco from the ERS. 8 Breathing pattern, mouth occlusion pressure 100 ms after the onset of inspiratory effort (P 0.1 ), and Pimax were measured (VMAX 229; SensorMedics) as previously described. 10 The Pimax was measured at residual volume (RV) according to American Thoracic Society/ERS 11 with predicted values from Black and Hyatt. 12 Tidal FL was assessed with the negative expiratory pressure (NEP) technique. 13 A NEP of 5 cmh 2 O was applied (Direc/ NEP System 200A; Raytech Instruments; Vancouver, BC, Canada) 0.2 s after the onset of expiration. Flow-volume curves obtained without and with NEP were superimposed as follows: patients in whom the expiratory flow with NEP was the same as the reference flow during part of the whole expiration were considered to have FL. 13 Pao 2 and Paco 2 were also measured with a blood gas analyzer (ABL 735; Radiometer; Copenhagen, Denmark); the PAo 2 that was used to compute the alveolar-arterial oxygen pressure difference (P[A-a]O 2 ) was estimated with the following equation: PAo 2 [(P B 47) Fio 2 )] Paco 2 /R p Value Sex, No. Male Female 2 2 Age, yr NS BMI, kg/m NS Nonsmokers, No Ex-smokers, No. 9 9 Ejection fraction, % 23 8 spap, mm Hg LVTDV, ml FEV 1, % predicted FVC, % predicted FEV 1 /FVC, % predicted NS FEF 75, % predicted TLC, % predicted FRC, % predicted IC, % predicted ERV, % predicted RV, % predicted NS Dlco, % predicted P(A-a)O 2, kpa MRC score Borg score *Values are given as the mean SD, unless otherwise indicated. BMI body mass index; LVTDV left ventricular telediastolic volume; NS not significant. CHEST / 130 / 2/ AUGUST,

3 where PB is barometric pressure, Fio 2 is the fraction of inspired O 2, and R is the respiratory quotient, which was assumed to be 0.8. Statistical Analysis The data are presented as the mean SD. Correlation coefficients were obtained with the Spearman ( value) nonparametric test for MRC score and the Pearson test (r value) for all other parameters. Where appropriate, paired and unpaired Student t tests were used. Statistical analysis was performed using a statistical software package (SPSS; SPSS Inc; Chicago, IL). Seated Results Table 1 shows the anthropometric characteristics and baseline respiratory data of CHF patients and control subjects. In control subjects, all respiratory data were within normal limits, the MRC and resting Borg scores were zero, and tidal FL was absent. In the CHF patients, the total lung capacity and its subdivisions were reduced relative to control subjects, while the FEV 1 /FVC ratio was within normal limits. In CHF patients, the functional residual capacity (FRC) percent predicted correlated negatively with the telediastolic volume of the left ventricle (r 0.52; p 0.02) [Fig 1]. None of the CHF patient experienced FL in the seated position. In the CHF patients, the mean MRC score amounted to (moderate breathlessness) and the mean Borg score was , with the two scores being weakly correlated (p 0.05). In CHF patients, resting ventilation and P 0.1 were Figure 1. Relationship between left ventricular telediastolic volume and FRC. % pred percent predicted. high with respect to control subjects (Table 2). Since Pimax was reduced in CHF patients, the mean P 0.1 /Pimax ratio was very high relative to that in control subjects ( % vs %, respectively; p 0.01). The Pao 2 and Paco 2 were lower in CHF patients than in control subjects, while the P(A-a)o 2 was higher (Table 1). The MRC score was significantly higher in the CHF patients than in control subjects. This score was correlated with P 0.1 /Pimax ratio and respiratory rate. The mean MRC score and P 0.1 /Pimax ratio were the only significantly different parameters among CHF patients who died within 12 months and survivors ( vs [p 0.02]; and 4 2vs11 8, respectively [p 0.02]). Supine None of the control subjects experienced FL while in the supine position. In contrast, 12 CHF patients experienced FL while in the supine position, reflecting the decrease in supine expiratory reserve volume (ERV) with consequent decrease in expiratory flow reserve. None of the variables studied varied significantly among the 12 CHF patients who experienced FL while in the supine position and in the other 8 patients who did not experience FL while in the supine position. In contrast, there was a significant difference in mean age between these two groups (63 8 years vs years, respectively; p 0.03) but not in Weber class. The percentage of the tidal volume that entailed FL also correlated with age (r 0.527; p 0.02). It should be noted, however, that among the 12 FL patients 58% were ex-smokers, whereas in the non-fl group only 2 of 8 patients (25%) were ex-smokers. In the supine position, the Borg score increased markedly in CHF patients (ie, orthopnea 7 ), while in the control subjects it remained zero (Table 2). This was associated with increased P 0.1 and especially increased P 0.1 /Pimax ratio, with the latter reflecting in part the concurrent decrease in Pimax. The mean effective inspiratory impedance 14 also increased from to cm H 2 O/L/s (p 0.001), whereas the slight increase observed in control subjects was not significant. Supine Pimax was significantly reduced in both CHF patients (p 0.001) and control subjects (p 0.05). Moreover, in CHF patients with FL the mean Pimax reduction was highly significant (70 30 to cm H 2 O; p 0.001). The supine Borg score correlated with the change in inspiratory capacity ( IC) [r 0.59; p 0.01] (Fig 2), supine Pimax (r 0.58; p 0.01), spap (r 0.53; p 0.02) [ Fig 3], P 0.1 /Pimax ratio 474 Original Research

4 Table 2 Cardiac and Respiratory Data for 20 Control Subjects and 20 CHF Patients Measured in the Seated and Supine Positions* Control Subjects (n 20) CHF Patients (n 20) Variables Seated Supine Seated Supine IC, L ERV, L FVC, L FEV 1,L FEV 1 /FVC ratio, % FEF 75, L/s V e, L/min Vt, L Respiratory rate, breaths/min Pimax, % predicted P 0.1 /Pimax, % P 0.1 /(Vt/tI), cm H 2 O/L/s MRC score FL/NFL 0/20 0/20 0/20 12/8 Borg score *Values are given as the mean SD, unless otherwise indicated. P 0.1 /(VT/tI) pulmonary impedance. V e minute ventilation; NFL negative flow limitation. p (sitting vs supine position; paired t test). p 0.05 (CHF patients vs control subjects; unpaired t test). p (sitting vs supine position; paired t test). p (CHF patients vs control subjects; unpaired t test). p 0.05 (sitting vs supine position; paired t test). (r 0.48; p 0.003), inspiratory time/total breath cycle time ratio (r 0.50; p 0.024), and supine ERV (r 0.461; p 0.04). Stepwise multivariate regression analysis selected all of the above parameters as significant independent contributors to Borg score, reflecting its multifactorial nature. However, the best predictors were supine Pimax (cm H 2 O), spap (mm Hg), and IC, as follows: Borg score spap Pimax IC (1) where r 0.80, r , and p In FL patients, the supine Borg score was correlated with the IC (r 0.67; p 0.017), whereas in non-fl patients this was not the case. Figure 2. Relationship between supine Borg score and IC from the seated to the supine position. Figure 3. Relationship between supine Borg score and spap. CHEST / 130 / 2/ AUGUST,

5 Discussion The new findings of this study are as follows: (1) in CHF patients, tidal FL is absent while sitting but is common while in the supine position; (2) the patients who experienced FL in the supine position were significantly older than those who did not; (3) in the supine position, almost all patients (18 of 20 patients) exhibited orthopnea, the nature of which appears to be multifactorial; but its best predictors, selected by multiple regression analysis, were spap, supine Pimax, and IC from the seated to the supine position. Sitting In line with most previous reports, 3,15,16 our CHF patients exhibited a reduction of total lung capacity, FRC, and RV but had a normal FEV 1 /FVC ratio. The FRC reduction was correlated with cardiomegaly, since there was a significant correlation of left end-diastolic volume to FRC (Fig 1). This finding could partially explain the difference between our data and those of Yap et al 17 and Hart et al, 18 who found no reduction of FRC in their CHF patients. Eight of 10 patients in the study by Yap et al 17 and 5 of 10 patients in the study by Hart et al 18 had CHF due to coronary artery disease or hypertension, whereas most of our patients had idiopathic cardiomyopathy. As previously reported, 3,16,19 21 Pimax was also reduced. The nature of the inspiratory muscle weakness is multifactorial, including the reduction of respiratory muscle blood flow, hypoxia, oxidative stress, disuse, medication, systemic inflammation, and nutritional depletion. The enlarged chest wall due to cardiomegaly and increased intrathoracic blood volume should also contribute to reduced Pimax because the pressure generated from inspiratory muscles (Pimus) should decrease due to length tension and geometric factors. 22 This uncoupling of the lung and chest wall with a concurrent decrease in the relaxation volume (Vr) of the respiratory system, as reflected by the decreased FRC, should also decrease the Pimax measured at RV because of the decreased contribution of the relaxation pressure (Prs) of the respiratory system to Pimax. In fact, as in the following equation: Pimax Pimus Prs (2) it follows that at RV Pimax decreases as a result of both decreased Pimus and Prs. Altered diaphragmatic position can also modify its length-tension relationships and contribute to reduced Pimax. 23 Ventilation and Neuromuscular Inspiratory Drive: Resting ventilation in CHF patients was high relative to control subjects, resulting in reduced mean Paco 2 ( mm Hg vs mm Hg, respectively; p 0.03). In patients with reduced Pimax, P 0.1 underestimates the inspiratory neural drive. Accordingly, the P 0.1 /Pimax ratio is used instead as an index of neuromuscular inspiratory drive normalized for muscle strength. In agreement with most previous studies, 3,16,19,20 but not all, 21 we found an increase in P 0.1 /Pimax ratio in CHF patients relative to control subjects ( vs , respectively; p 0.01). Bruschi et al 24 found increased P 0.1 /Pimax ratio in CHF patients who are at risk for nocturnal Cheynes-Stokes respiration and showed that this parameter, together with respiratory frequency, is a useful predictor of Cheynes-Stokes respiration. Reduced levels of Paco 2 and increased ph were previously found in patients with high pulmonary capillary wedge pressure (PCWP) because the stimulation of pulmonary receptors, as a result of raised PCWP, heightens the central neural drive. 25 However, we found no significant correlation of spap to P 0.1 or P 0.1 /Pimax ratio. This may be due to the fact that most of our patients had elevated levels of spap, which may mask any correlation between spap and other variables. Recently, Meyer et al 26 found respiratory muscle weakness in patients with idiopathic pulmonary hypertension and found P 0.1 to be significantly higher than in those patients than in control subjects. In their patients, the P 0.1 /Pimax ratio showed significant correlation with the total ventilation-carbon dioxide slope during exercise. This observation confirms that increased ventilation and increased respiratory drive are hallmarks of heart failure. Hyperventilation during exercise, whether or not it was associated with periodic breathing, is now considered to be an independent risk factor for mortality and morbidity in CHF patients. 27 Supine Tidal Flow Limitation: In the study by Duguet et al, 1 9 of 12 patients with acute left ventricular failure exhibited tidal expiratory FL when in the supine position, and all of these 9 patients claimed to have orthopnea. By contrast, only one of the three subjects who denied having orthopnea exhibited tidal FL while in the supine position. Recently, Boni et al 2 showed that in patients with both AHF and CHF supine FL is relatively common and that it can be reversed by therapy with diuretics. Age is a major factor promoting FL, because with increasing age the maximal expiratory flows at low lung volume decrease progressively due to gas trapping. 28 De Bischopp et al 29 recently studied apparently healthy subjects aged from 66 to 88 years and found that 476 Original Research

6 30% had FL even in the seated position. The patients studied by Duguet et al 1 and Boni et al 2 were quite old (mean age, years and 77 7 years, respectively). A reduction in expiratory flow reserve plays a pivotal role in determining tidal flow limitation. Similarly, a reduction of the ERV plays an important role. In fact, when a subject breathes tidally at low volumes (ie, with a low ERV), the tidal volume changes occur over a portion of the maximal flowvolume curve with low maximal flows. Since the ERV is normally reduced while in the supine position, 22 the prevalence of tidal FL in the supine position is generally higher than that in the sitting position. 1,2 Orthopnea: Tidal FL in the supine position is associated with orthopnea in COPD patients, 7 obese patients, 30 and goiter patients. 31 Almost all of our CHF patients (18 of 20 patients) claimed to have orthopnea, 7 the critical trigger for which is commonly attributed to increased pulmonary venous return while in the supine position. This is supported by the significant correlation between PCWP and orthopnea. 32 We found a significant correlation between supine Borg score and spap (r 0.53; p 0.02) [Fig 3]. Furthermore, the two CHF patients who denied orthopnea were younger (48 and 57 years) and had relatively low values of spap (25 mm Hg and 35 mm Hg). The several following mechanisms 25,33,34 have been suggested to link the increase in central blood volume in CHF patients to orthopnea: (1) stimulation of the juxtacapillary receptors and increased vagal afferentation due to congestion and edema; (2) increased inspiratory loading; and (3) impaired Pimax. Increased vagal afferentation may lead to hyperventilation and cause breathlessness. Minute ventilation was higher than that in control subjects, both in the sitting and supine position, and the P 0.1 /Pimax ratio increased significantly in the supine position in both CHF patients and control subjects (p 0.001), but in CHF patients the mean increase was much more pronounced (62 50% vs 44 28%, respectively). The postural increase in respiratory impedance (45 33% vs 20 35%, respectively; p 0.03) was also higher in CHF patients. This implies increased inspiratory loading and could be due in part to the increased Raw and respiratory system elastance caused by the reduction in FRC. In our 12 patients who had FL while in the supine position, the FEV 1 /FVC ratio (p 0.001), forced expiratory flow when 75% of FVC has been exhaled (FEF 75 ) [p 0.05], and Pimax (p 0.001) decreased significantly when shifting from the sitting to the supine position, while such changes were not significant in the 8 non-fl patients. The increase in mean Borg score with posture was higher in these subjects with respect to non-fl patients (from to vs to , respectively), and the supine Borg score was negatively correlated with the IC, as previously described. 2 In our study, IC also correlated with left ventricular telediastolic volume (r 0.457; p 0.05). In adopting the supine position, there is normally little or no change in vital capacity, while ERV is substantially reduced with a concurrent increase of IC. 22 The latter is caused by a reduction of Vr due to gravity. 22 In our CHF patients, the supine ERV was very small (ie, close to RV), probably due to cardiomegaly and increased intrathoracic liquid volume. 31 In our patients, the supine Borg score correlated with supine ERV (r 0.46; p 0.04). Such an association is also found in patients with morbid obesity, 30 and it has been suggested that, in these patients, the supine Vr is located below RV. This implies the presence of PEEPi at RV. This phenomenon was probably also present in our FL subjects and may explain the paradoxical reduction of Pimax observed in these patients (see below). Tidal FL seems to be a factor contributing to orthopnea in CHF patients, but the finding that supine Borg score correlated also with spap and supine Pimax suggest a multifactorial origin for this symptom. In a previous work, 3 spap was correlated to P(A-a)O 2 and to the closing volume/vital capacity ratio. In most of the patients (13 of 20 patients), CC exceeded FRC (ie, during tidal breathing there was a cyclic opening and closing of peripheral airways with a concurrent maldistribution of ventilation, with decreased Pao 2 and increased P[A-a]O 2 ). Supine positioning that reduces FRC could enhance this phenomenon, contributing to the worsening of orthopnea. Inspiratory Load and Muscular Force: The overall increase in inspiratory load is reflected by the significant mean increase in effective inspiratory impedance with change in posture in CHF patients compared to that in control subjects ( vs , respectively; p 0.05) indicating that P 0.1 was sufficient not only to overcome the increased breathing load but also to induce hyperventilation. The decrease in Pimax in the supine position contributed to the disproportionate increase in P 0.1 / Pimax ratio, reflecting increased effort in the face of weakened muscles with a concurrent increase in Borg score (Table 2). In fact, Pimax in the supine position together with spap and IC were the most significant independent contributors to Borg score CHEST / 130 / 2/ AUGUST,

7 (equation 1). In FL patients, the decreases in Pimax and the increases in Borg score with change in posture were greater than in non-fl subjects. In stable CHF patients, Nava et al 35 found a strong correlation between orthopnea and increased diaphragmatic effort in the supine position. The reduction of diaphragmatic effort through assisted noninvasive ventilation correlated significantly with the reduction in orthopnea. Tidal FL was not assessed, but dynamic PEEPi was increased in the supine position with a concurrent increase in resistance and transdiaphragmatic pressure. The effect of posture on Pimax in healthy subjects is controversial. In two previous studies, 22,36 no differences between Pimax measured in the upright and supine position were found, while in another study 37 Pimax was significantly lower in the supine position. There is no study comparing Pimax inthe upright and supine positions in CHF patients. We found a slight reduction in Pimax in control subjects and in CHF patients. The percentage change in posture was similar in the two groups. The reduction in mean Pimax was significantly higher in the 12 FL subjects compare to non-fl subjects ( vs 6 18%, respectively). This was probably due to the fact that in the supine patient Vr was below RV, and hence PEEPi was present at RV. Since PEEPi corresponds to positive Prs (equation 2), Pimax should be less than Pimus in the supine position. In contrast, Prs is normally negative at RV, and hence Pimax is higher than Pimus. It should be noted that altered diaphragmatic position 23 and chest wall geometry 22 may also contribute to changes in Pimax with posture. In conclusion, the present data show that, as a result of a marked decrease in ERV in the supine position, most CHF patients also exhibit tidal FL when supine with concurrent inspiratory threshold loading. 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