Eight patients (2 women and 6 men) with stable mild-to-severe COPD participated in the study (Table 1). Subjects with known cardiovascular disease, neurologic or psychiatric illness, or impaired lower extremity function or those requiring supplemental oxygen were excluded from the study. All patients received their regular treatment of inhaled bronchodilators, and none received oral steroid therapy. Four of the patients were receiving inhaled steroid therapy, and one patient was receiving oral theophylline therapy. No change in the medications was made for the purpose of the study. Patients were asked to abstain from smoking on the day of the study and to avoid eating for at least 2 h prior to undergoing testing. The study was approved by the ethics committee of the hospital, and all subjects gave written informed consent.
Protocols and Instrumentation
One week prior to the actual study, subjects underwent pulmonary function testing (system 1085; Medical Graphics Corp; St. Paul, MN) and performed an incremental exercise test on a bicycle ergometer (model 400L; Medical Fitness Equipment; Maarn, the Netherlands) to determine their maximum exercise workload (WLmax). Subjects maintained a mean (± SD) pedaling rate of 60 ± 5 revolutions per minute, and workload was increased by 10 W every minute until subjects could no longer continue. During this initial session, a physiotherapist instructed subjects on how to perform the PLB technique (ie, nasal inspiration followed by expiratory blowing against partially closed lips avoiding forceful expiration), and subjects also practiced the technique while pedaling and wearing a tight-fitting facemask in order to familiarize them with the study protocol. None of the subjects had difficulty in learning the breathing technique.
On the day of the study, while seated on the bicycle ergometer, each subject first performed maximal inspiratory maneuvers (ie, the Mueller maneuver) and combined maneuvers consisting of a Mueller maneuver and abdominal expulsive maneuvers with the glottis open to determine their maximum static inspiratory pleural pressure (Pplmax) and maximum inspiratory transdia-phragmatic pressure (Pdimax), respectively. Pdimax was measured at functional residual capacity (FRC), and the highest value obtained from three or more attempts was used in the subsequent analysis. For Pplmax, subjects performed the maximal inspiratory maneuvers at several lung volumes ranging from FRC to total lung capacity (TLC). While still seated on the bicycle, patients then breathed for 8 min using PLB and 8 min without using PLB (ie, control breathing). This was followed by 8-min periods of control breathing and PLB during constant-work-rate exercise at 60% of WLmax. The order of control breathing and PLB were alternated among subjects, whereas exercise always followed the resting condition. Subjects were allowed to rest for at least 10 to 15 min between the two exercise runs.
The breathing circuit consisted of a tight-fitting facemask (dead space, 90 mL) that was connected to a heated pneumotachograph (model No. 3; Fleisch; Lausanne, Switzerland), which permitted the measurement of inspiratory and expiratory airflow (V). Vt was obtained by integrating the flow signal. The facemask was transparent, enabling investigators to verify that subjects were performing the PLB maneuver appropriately and when requested. Pleural pressure (Ppl) and gastric pressure (Pga) were measured using two balloon-tipped catheters that were passed transnasally, and transdiaphragmatic pressure (Pdi) was obtained by subtracting Ppl from the Pga.
EELV was estimated by having subjects perform inspiratory capacity maneuvers every minute during the last 4 min of each experimental condition. EELV was obtained by subtracting the inspiratory capacity values from measures of TLC that had been previously obtained with whole-body plethysmography.
Subjects were asked to rate the sensation of “breathlessness” that they perceived every minute during each of the conditions studied using a visual analog scale (VAS). The VAS was displayed on a 10-cm oscilloscope screen with the verbal anchors “no breathlessness” and “maximal breathlessness” corresponding to the numerical values of 0 and 10, respectively, positioned at the bottom and top of the scale. Subjects were able to control the position of the line representing their breathlessness by means of a variable potentiometer attached to the bicycle handlebar.
All signals were acquired online at a sampling rate of 100 Hz. Offline breath-by-breath analysis was performed on the last 4 min of each 8-min data segment. Timing parameters including inspiratory time (Ti), expiratory time (Te), total breathing cycle time (Ttot), and duty cycle were determined from the flow signal.
Mean pressure swings were calculated between points of end-expiratory and end-inspiratory zero flow. The tension-time index of the diaphragm (TTdi) was calculated as the product of the ratio of the delta mean inspiratory Pdi to the Pdimax and the inspiratory duty cycle.
Resistive work of breathing was determined by measuring the area enclosed by plots of Ppl vs Vt (see A panels in Fig 2) and was partitioned into inspiratory resistive work of breathing (Wires) and expiratory resistive work of breathing (WEres) components. The individual average loops presented for each subject were obtained by combining ensemble averaged inspiratory and expiratory data sections, with each normalized to mean Ti and Te values, respectively.
The maximum static inspiratory pressure-generating capacity (Pcapl) was determined first by plotting the Pplmax values along with their corresponding lung volumes, normalized to TLC, on a pressure-volume diagram and fitting a polynomial curve through these data points. For each subject, individual Ppl vs lung volume (Vl) loops were then positioned on this pressure-volume diagram, using the EELV values obtained under each of the experimental conditions and normalized to TLC. For every data point comprising the inspiratory portion of the individual Ppl-VL loops, the corresponding Pplmax values were then adjusted for flow by applying a correction that reduced Pplmax by 5% for every liter per second increase in inspiratory V according to the following equation:
Pcapl = Pplmax — [Pplmax X 0.05 V (L/s)].
For each data point in the inspiratory Ppl-VL loop, Ppl was then expressed as a percentage of Pcapl, and an average value for inspiration was calculated. The ratio of Ppl to Pcapl (percent) was also determined at the point at which Ppl was at the peak value during inspiration.
Statistical analysis for the comparison of variables between control breathing and PLB during rest and exercise was performed using the Student t test for paired data. Associations between the changes in the dyspnea scores and the changes promoted to breathing pattern variables, operational lung volumes, FEV1 (percent predicted), and the ratio of the mean Ppl to Pcapl, were assessed by computing the Pearson product moment correlation coefficient. Significance for all tests was considered to be p < 0.05.
Table 1—Anthropometric and Lung Function Data on Patients Studied
|Subject/Sex/Age, yr||Ht, m||Wt, kg||FEVj, l||fvc, l||fev/fvc, %||rv, l||TLC, L||FRC, L|
|Mean ± SD||1.67 ± 0.09||66.6 ± 14.7||1.34 ± 0.44||2.77 ± 0.48||49 ± 14||4.15 ± 1.61||7.30 ± 1.56||5.12 ± 1.77|
|(50 ± 21)||(72 ± 19)||(207 ± 66)||(120 ± 17)||(160 ± 40)|