Effects of Postural Drainage, Exercise, and Cough on Mucus Clearance in Chronic Bronchitis 3 F. A. OLDENBURG, JR.,4 M. B. DOLOVICH, J. M. MONTGOMERY, and M. T. NEWHOUSE
SUMMARY The effects of postural drainage, exercise, and cough on mucus clearance were compared in 8 patients with chronic bronchitis. A bolus of 90mTc albumin aerosol was inhaled at a high inspiratory flow rate to enhance proximal deposition. Retention of deposited aerosol in the lung, as a function of time, was quantified using a gamma camera and subsequent computer analysis. Coughing greatly accelerated total lung (p < 0.005) and peripheral (p < 0.005) mucus clearance. Exercise resulted in much smaller changes than did cough, but significantly increased total lung clearance (p < 0.005). Postural drainage in which coughing was prohibited did not alter clearance. These results have therapeutic implications and stress the importance of controlling cough when evaluating therapeutic interventions by these techniques.
Introduction Hilding (1) suggested that mucociliary dysfunction may be one of the earliest abnormalities in chronic bronchitis. The epithelial damage, mucous gland hypertrophy, mucus hypersecretion, and bacterial colonization in the lower respiratory tract may reflect or result in impaired lung defense mechanisms (1). Studies to determine clearance rates in patients with chronic bronchitis have produced conflicting data (2-5), but most investigators conclude that clearance is impaired. Adjunct therapy for patients with chronic bronchitis has often included postural
(Received in original form November 3, 1978 and in revised form May 18,1979) i From the Chest and Allergy Unit, St. Joseph's Hospital, Department of Medicine, McMaster University, Hamilton, Ontario L8N 1Y4, Canada. 2 Requests for reprints should be addressed to Dr. M. T. Newhouse, Chest and Allergy Unit, St. Joseph's Hospital, 50 Charlton East, Hamilton, Ontario L8N 1Y4, Canada. 3 Supported by the Ontario Thoracic Society. 4 American Lung Association Training Fellow. Present Address: Pulmonary Function Department, Eastern Maine Medical Center, Bangor, Me.
drainage, percussion, and coughing in an attempt to improve mucus clearance and, as a consequence, lung function. Despite long-standing application of these treatment measures, there are few data to substantiate their efficicacy (6). Vibration, percussion, and postural drainage all increase expectoration of sputum (7). The effect of cough alone, however, has not been well documented. Exercise is also believed to be beneficial in patients with chronic bronchitis, one benefit being an increase in the total amount of work that a patient can perform (8). However, there is no evidence that exercise changes lung function significantly (8), and the improvement documented by various investigators has been explained by Haas and Cardon (9) as being due to improved muscular efficiency occurring after exercise training. Wolff and associates (10) have shown that exercise increases mucociliary transport in normal subjects. Accelerated mucus transport due to exercise in patients with chronic bronchitis would be an additional reason for advocating exercise programs. This study compared bronchial mucus clearance during quiet breathing, postural drainage, cough, and exercise in a group of clinically stable patients with chronic bronchitis.
AMERICAN REVIEW OF RESPIRATORY DISEASE, VOLUME 120, 1979
739
740
OLDENBURG, DOLOVICH, MONTGOMERY, AND NEWHOUSE
TABLE 1 CLINICAL AND PHYSICAL CHARACTERISTICS OF SUBJECTS FEV,
Deposition
FVC
Subject No.
Age (yr)
(L, BTPS)
(L, BTPS)
Inner Zone
Sex
(% pred.)
(% pred.)
(%r
Outer Zone
(%r
1
63
M
20.3(2.8)
70
M
65.3(3.4)
10.2(1.6)
3
62
M
53.1 (2.8)
19.6(1.7)
4
55
F
66.3(1.7)
9.2(0.6)
5
62
M
65.9(2.9)
10.9(1.9)
6
58
M
67.3(2.5)
16.3(1.0)
7
64
M
72.5(5.2)
11.4(2.3)
8
63
M
3.0 (68.0) 2.9 (92.9) 2.3 (61.1) 2.5 (82.0) 4.0 (87.7) 2.5 (67.6) 2.4 (64.1) 3.1 (86.0)
50.9(1.8)
2
1.6 (66.6) 1.6 (64.0) 1.1 (40.7) 1.4 (58.3) 2.6 (76.5) 0.9 (29.0) 1.1 (39.3) 2.6 (92.9)
64.5(3.6)
14.0(1.5)
Definitions of abbreviations: FEV, = forced expiratory volume in one second; FVC = forced vital capacity. * Results are mean values ( ± SD) for 5 days.
Methods Subjects. Eight patients with simple and obstructive chronic bronchitis (table 1) participated in the study after informed consent had been obtained. All had been cigarette smokers, but only one (Subject 8) smoked at the time of the study and he refrained from smoking for at least 1 h before and during each clearance study. All patients were stable throughout the experimental period. Daily sputum production by history was quite variable, ranging from 10 to 120 ml. Baseline forced expiratory volumes in one second (FEV ) were within ± 15 % for all study days. Other than antihypertensive drugs, the only medications taken by this group of patients were bronchodilators, which were discontinued 12 h before each study. Preselection requirements were that the subjects (1) had chronic bronchitis (cough and sputum production for 3 months during 3 consecutive yr), (2) could exercise to 70-75 % of maximal predicted heart rate, and (3) refrained from coughing during the 2.5-h study period unless instructed to cough. Clearance techniques. Mucociliary transport and mucus clearance associated with cough were measured by quantifying the removal of an inhaled radiolabeled aerosol deposited on the bronchial mucosa. Because of the difficulty in controlling deposition in untrained subjects with varying degrees of airflow obstruction, an aerosol delivery system (figure 1) was developed to simplify subject participation and to eliminate the need for carefully controlled inspiratory air flow. The radio-aerosol (mass median diameter, 3.2 /um; geometric SD, 3.56) was generated by a compressed air driven nebulizer (Bunn no. 810) from a 0.025 % solution of 99mTc-
albumin in normal saline. When operated at 7.51 L/min, the output of the nebulizer was 0.327 ml/ min. The same aerosol was generated for each inhalation. All tubing except the calibrated Plexiglas® piston was standard black ABS plastic plumbing pipe, covered with lead shielding. T h e apparatus was ready for use when the aerosol filled the holding tower and the calibrated piston. T o perform an inhalation, the subject inserted the mouthpiece, and the cross clamp was released from the rubber tubing. A maximal inspiratory effort was immediately made from functional residual capacity (FRC), with the volume of aerosol inhaled limited by the One-Way Valve Calibrated Syringe :to Collection Bag
Holding Tower
2 inches Cross Clamp
Nebulizer
Mouth Piece Lead Shield Compressed Air
Fig. 1. System to deliver a bolus of radioaerosol reproducibly and preferentially to the large airways (see text for description).
741
POSTURAL DRAINAGE, EXERCISE, COUGH, AND BRONCHIAL CLEARANCE
volume to which the adjustable calibrated piston had been set (65 to 96 ml, depending on the patient's size). T h e duration of inspiration was less than 1 s and was immediately followed by a forced expiration to residual volume, back into the circuit. Excess volume passed through the apparatus via the one-way valve at the top into a collection bag. T h e cross clamp was reapplied, and the subject resumed breathing of room air. The piston was then reset for the next inspiration. T h e number of breaths required for good imaging varied between subjects. Eight to 12 breaths were usually necessary when the initial burden in the nebulizer was 10 mCi of 99mTc-albumin in 5 ml of saline. Each subject received a lung radiation dose of approximately 160 millirads and a whole-body radiation dose of 5 millirads for the entire 5-day study (11). Radioactivity was measured with an Anger scintillation camera interfaced to a data storage and retrieval system that permitted off-line computer handling of data from 3 areas of the right lung (12). These areas consisted of a region 5 by 12 cm centered over the large bronchi, denned as the inner zone, and two 2.5-cm zones, concentric about the inner zone in an onion peel fashion, denned as middle and outer zones. Studies in our laboratory have shown that the proximal boundary of the outer zone corresponded approximately to 2-4 mm airways, from examination of sagittal sections of fixed human lungs and labeling peripheral airways with radioisotopes. Because of radiation from swallowed secretions in the esophagus, the trachea and more proximal part of the right mainstem bronchus were excluded from analysis. Subject positioning in front of the gamma camera was kept constant for each study by means of light markers and restraints. All measurements of chest radioactivity were made with the subjects in the upright position, from the posteroanterior position. Initial or baseline whole lung counts averaged 25,000 cpm. T h e baseline deposition pattern for each study day was determined by calculating the ratio of the percentage of radioactivity in the outer to inner zones. Retention, calculated as a percentage of baseline deposited radioactivity, was plotted for the whole lung and for each of the 3 zones. Only the total lung and outer zone were analyzed for the purposes of this study, because interpretation of inner zone clearance was difficult owing to transport of distal radioactivity into this region. Experimental design. There were 5 study days for each subject. T h e order of the experiments was randomized. All experiments on an individual subject were performed within 7 days, at the same time of day, except for Subject 8, who completed the experiment within 10 days. Each subject served as his or her own control. Control. A quiet breathing experiment during which the subject rested upright throughout the 2.5-h study. Exercise. T h e subject rested for the first 0.5 h.
Then, from 0.5 to 1.16 h, exercise was performed on a cycle ergometer (Monarch) for five 4-min periods with 4-min periods between each exercise period for rest and monitoring of lung radioactivity. Subjects rested again from 1.16 to 2.5 h. Work loads were adjusted for each subject so that the heart rate was maintained at 70 to 75 % of the predicted maximum. Postural drainage. T h e subject rested for the first 0.5 h, then from 0.5 to 1.16 h, the subject lay quietly on a tilt table in the left lateral decubitus position in a 15-degree head-down position for five 6-min periods with a 1-min period between each maneuver to monitor lung radioactivity. Cough. The subject rested for the first 0.5 h. Then, from 0.5 to 1.16 h, the subject coughed once each minute for 5 min, with 3 min for rest and monitoring of lung radioactivity. For each experiment, 1-min measurements of lung radioactivity were made at specified times throughout the 2.5 h: every 6 min from 0 to 0.5 h, every 8 min from 0.5 to 1.16 h, and every 16 min from 1.16 to 2.5 h. Spontaneous cough was not a problem. All patients were monitored carefully and were encouraged to suppress the tendency to cough during the control, postural drainage, and exercise studies. Sputum was not collected during the study days. Retention curves were drawn for each subject for each study day. Statistical comparisons were made by paired t-test analysis at every 0.2-h point. T h e 2 rest days were averaged for comparison with the other therapeutic maneuvers. Standard deviations were used where indicated. Results T h e m e a n percentage ( ± SD) of i n n e r a n d outer zone deposition for each subject for t h e 5 exp e r i m e n t days showed a large intersubject variation, b u t little intrasubject variation (table 1). T h e r e was n o significant difference in baseline deposition by 2-way analysis of variance between any of the study days. T h e reproducibility of the m e t h o d comparing total l u n g clearance for the control days in 7 subjects is shown in figure 2. Subject 1 h a d only o n e control day because of technical difficulties with the d a t a retrieval system. T h e r e was n o significant difference by paired t-test analysis 100 I"
2j H u] c
I 70 h I I 601L__J 0
^^iT
• control 1 ,„ o control 2 1 0.5
tn=
7)
1 1.0 TIME (hrs)
I 1.5
1 2.0
,
1 2.5
Fig. 2. Comparison of total lung clearance between 2 control days for 7 subjects (mean ± 1 SD).
742
OLDENBURG, DOLOVICH, MONTGOMERY, AND NEWHOUSE
control * postural drainage exercise cough
duration of drainage, cough or exercise
o Average of two control days
Fig. 3. Comparison of the effects on total lung clearance of the control, postural drainage, exercise, and coughing maneuvers. Curves represent m e a n data for the group for each maneuver.
for any of the measured points. The maximal difference in retention between the 2 control days at any point in time for an individual subject was 12 %. Similar variations were noted for outer lung zone clearance on the control days. Total lung clearance varied widely as a result
of the various experimental maneuvers- (figure 3). The individual data for both total lung and peripheral lung clearance at the beginning (0.4 h) and end (1.2 h) of each maneuver are given in table 2. Compared to the control days, which were averaged to give a single curve, postural drainage had no significant effect on clearance (p > 0.5) (figure 3). Exercise (figure 4) increased mucus clearance by 7.5 % over resting values at 1.2 h (p < 0.025) but much less than cough (figure 5), which accelerated clearance by 40.8 % at 1.2 h (p < 0.001). Peripheral zone lung clearance curves (figure 6) were similar to those for the whole lung. However, exercise did not significantly accelerate peripheral clearance (p = 0.9). The failure of exercise to increase peripheral clearance significantly can probably be explained by the results of Subject 8, who had considerably slower clearance with exercise. Review of his initial inner zone deposition rate revealed that 10.7 % less radioactivity was deposited in this zone during the exercise days as compared to either control day. When this subject was excluded from the study, exercise significantly improved peripheral zone clearance (7.6 % at 1.4 h, p < 0.05) as compared to the control days.
TABLE 2 TOTAL LUNG AND PERIPHERAL LUNG RETENTION DATA Control Patient Retention, total lung, % 1 2 3 4 5 6 7 8
Exercise
Postural Drainage
Cough
0.4 h
1.2 h
0.4 h
1.2 h
0.4 h
1.2 h
0.4 h
1.2 h
96.0 94.7 93.8 93.8 95.8 97.3 94.5 93.8
86.0 85.0 90.6 87.8 90.3 96.3 86.3 87.0
97.0 93.0 93.0 98.0 90.0 92.0 95.0 94.0
82.0 75.5 84.0 83.0 72.0 83.5 86.0 83.0
100.0 97.0 98.5 93.0 93.0 93.0 97.5 95.0
88.0 88.0 97.5 87.2 82.5 88.0 93.5 91.5
95.0 100.0 99.0 97.0 98.0 94.0 95.0 97.0
69.0 49.0 87.5 47.0 40.0 34.0 23.3 40.0
Mean ± 1 SD Retention, peripheral lung, % 1 2 3 4 5 6 7 8
95.0 1.3
88.7 3.7
94.0 2.6
81.1 4.8
95.9 2.8
96.9 2.1
89.5 4.6
48.7 20.5
97.3 94.0 92.0 94.8 94.8 92.5 98.5 94.0
79.0 92.0 88.3 85.0 90.3 86.3 96.3 96.5
94.0 93.5 91.0 96.5 92.5 92.5 93.0 100.0
73.0 89.5 80.0 89.0 73.0 86.0 77.5 95.0
93.0 97.0 98.5 96.0 93.5 90.0 92.0 93.5
76.5 75.1 96.0 93.0 82.0 87.5 80.5 93.0
92.0 96.5 94.5 97.0 97.0 97.5 98.0
66.5 59.5 85.0 70.0 47.5 65.0 42.5
Mean ± 1 SD
94.8 2.2
89.2 5.9
94.1 2.9
82.9 8.2
94.2 2.79
85.5 8.05
96.1 2.11
-
62.3 14.3
POSTURAL DRAINAGE, EXERCISE, COUGH, AND BRONCHIAL CLEARANCE
• Mean (n=8) ± S.D.
Ui
743 control* (n=8) postural drainage (n=8) exercise (n=8) cough (n=7)
duration of drainage, cough or exercise
O
O 2 -15
3 if 0.1
0.1
0.01 0.001
p values
1.0 TIME (hrs)
Fig. 4. T h e time course of total lung clearance d u r i n g the exercise maneuvers expressed as a m e a n percentage change from control ± 1 SD.
There was no significant difference between FEVj and FVC before and after any of the experimental maneuvers in any of the 8 subjects. Discussion
To compare the removal of labeled mucus from the lung during various maneuvers, care must be taken to achieve a reproducible initial deposition pattern of labeled aerosol in the lung for each maneuver. The deposition of particles in the lung depends on particle size and shape, density, electrical charge, and hygroscopic properties, as well as inspiratory flow rate, initial lung volume, inspired volume, and degree of airflow obstruction (13-15). These factors were maintained relatively constant throughout the study. We have developed a system for depositing aerosol mainly in proximal airways (63.3 ± 7.7 % of total right lung burden). The apparatus is simple to build and simple for untrained subjects to use. The reproducibility of our method is substantiated by the small SD
1.0
1.5
TIME (hrs)
Fig. 5. T h e time course of total lung clearance during the coughing maneuver expressed as a m e a n percentage change from control ± 1 SD.
1.0
1.5
TIME (hrs) * Average of two control days
Fig. 6. Comparison of the effects on peripheral lung clearance of the control, postural drainage, exercise, and coughing maneuvers. Curves represent m e a n d a t a for the group for each maneuver.
in intrasubject deposition (table 1) and mean clearance rates for the 2 control days (figure 2). Coughing maneuvers produced the greatest increase in total lung (40.8 ± 19.2 %) and peripheral lung (29.6 ±17.6 %) clearance. Leith (16) reviewed the possible effects of cough on mucus clearance. He concluded that in larger airways up to the sixth or seventh generation, mucus can be "pumped" up the tracheobronchial tree using energy transferred from the expired air. Dynamic collapse that occurred in conjunction with the coughing maneuver increased clearance by increasing gas velocities that could reach three-quarters of the speed of sound (16). Macklem and Wilson (17) showed that at 25 % of vital capacity dynamic collapse does not occur beyond the third-generation bronchi, although at lower lung volumes dynamic collapse occurs in more peripheral bronchi where airflow velocity is greatly decreased. These studies have suggested to other investigators (18) that cough would have little effect on more peripheral mucus clearance. At least one group of investigators (18) has used this as an argument to suggest that physiotherapy (postural drainage, percussion, and vibration) was effective in accelerating clearance despite the fact that coughing was not controlled. Yet our results indicate that cough is quite effective in improving peripheral clearance Coughing may result in a ''milking" effect on secretions in the small airways. Faridy (19) has observed the effect of lung movement on acceleration of surfactant transport up the bronchia] tree, and one might expect a similar effect on mucus. Because cough is effective in increasing clear-
744
OLDENBURG, DOLOVICH, MONTGOMERY, AND NEWHOUSE
ance in all lung zones, investigators should realize that cough alone may account for changes in mucus transport observed during various therapeutic interventions. As the quality of a given cough conceivably varies depending on the patient's effort and expiratory flow, it is not adequate simply to control the number of coughs in experiments. Nor can the expectorated sputum simply be collected and corrections made for the expectorated radioactivity, because there may be contamination from pharyngeal radioactivity due to mucociliary transport and possibly initial pharyngeal radioactivity not cleared by gargling. Postural drainage maneuvers in our subjects did not improve total lung or peripheral lung clearance over resting values (figure 2). Postural drainage is commonly prescribed for patients with hypersecretion; however, data are lacking with regard to its efficacy because most studies have not been controlled for cough. In animal experiments, Chopra and co-workers (20) showed that in anaesthetised dogs postural drainage increased tracheal transport by 39.7 %. Wong and associates (21) showed that postural drainage (25° head-down position) accelerated tracheal mucus transport in patients with cystic fibrosis but not in normal subjects. Cough was not controlled, although corrections were made for obvious bolus displacement. On theoretical grounds, Blake (22) suggested that gravity would increase mucociliary clearance especially if the depth of the serous layer was significantly increased. The more abundant secretions with different rheologic properties found in cystic fibrosis may account for the difference in results between our patients with chronic bronchitis and those with cystic fibrosis. Another possible explanation for the discrepancy in findings is that our subjects were upright for clearance measurements for one-sixth of the postural drainage maneuvers. In patients with chronic obstructive pulmonary disease, Clarke and coworkers (7) showed that postural drainage, vibration, percussion, and assisted cough increased sputum production. Subsequently, Bateman and associates (18), using a radioaerosol technique, studied whole lung and peripheral lung clearance after physiotherapy in patients with chronic irreversible airway obstruction. Mucus clearance was increased by 33 and 28 %, respectively; however, the relative importance of postural drainage and cough was not measured. Using a vibrating pad, Pavia and co-workers (23) were unable to show a significant increase in mucociliary transport in patients with chron-
ic bronchitis. We were unable to demonstrate any improvement in mucus clearance due to postural drainage alone, suggesting that vibration and percussion or cough may be responsible for most of the increase in sputum clearance reported by other investigators. Because the increase in clearance rates that we observed for cough alone was equivalent to or greater than that reported by Bateman and associates (18), it is possible that cough alone accounted for the observed acceleration in clearance during combined chest physiotherapy. The use of postural drainage alone in stable chronic bronchitis does not appear to be justified. Studies comparing spontaneous cough, assisted cough, postural drainage, and vibration and percussion in the same subjects may be able to clarify this issue. Exercise increased total lung clearance by 7.5 % (p < 0.05), as compared to control days (figure 4). Wolff and co-workers (10) reported a similar acceleration of clearance in 10 normal subjects, although they noted a delay in the onset of increased clearance after the beginning of exercise that was not observed in the present study. There have been few reports in the literature concerning exercise and mucus clearance. Anderson and associates (24) observed no significant change in nasal clearance after vigorous exercise; however, several individual subjects were noted to have greatly accelerated clearance. Our finding of slightly improved clearance rates with exercise in some patients may have therapeutic implications. Most investigators believe that the effects of exercise in patients with chronic bronchitis are indirect because most lung function parameters do not improve with exercise (8). If, however, the trend toward increased mucus transport can be maintained on a longterm basis, then common complications such as mucus plugging and lower respiratory tract infections may be decreased. This study has demonstrated that in patients with stable chronic bronchitis: (2) cough greatly accelerates the bronchial clearance of mucus and must be controlled in studies of this nature, (2) exercise improves mucus clearance much less than does cough, and (3) postural drainage does not appear to improve mucus clearance.
Acknowledgment The writers thank G. Obminski, B.Sc, for technical assistance and Mrs. M. Owens for assistance with the preparation of the manuscript.
POSTURAL DRAINAGE, EXERCISE, COUGH, AND BRONCHIAL CLEARANCE
References 1. Hilding AC. Mucociliary insufficiency and its possible relation to chronic bronchitis and emphysema. Med Thorac 1965; 22:329-45. 2. Santa Cruz R, Landa J, Hirsh J, Sackner MD. Tracheal mucus velocity in normal man and patients with obstructive lung disease: effects of terbutaline. Am Rev Respir Dis 1974; 109: 458-63. 3. Goodman RM, Vergin BM, Landa JF, Golinvaux MH, Sackner MA. Tracheal mucus velocity in nonsmokers, smokers, and patients with obstructive lung disease (abstract). Fed Proc 1977; 36:607. 4. Luchsinger PC, La Garde B, Kilfeather JE. Particle clearance from the human tracheobronchial tree. Am Rev Respir Dis 1968; 97:1046-50. 5. Lourenco RV. Distribution and clearance of aerosols. Am Rev Respir Dis 1970; 101:460-1. 6. Jones NL. Physical therapy. Am Rev Respir Dis 1974; 110(Suppl: 137). 7. Clarke SW, Cochrane GM, Webber B. Effects of sputum on pulmonary function. Thorax 1973; 28:262. 8. Chester EH, Belman MJ, Bahler RC, Baum L, Schey G, Buch P. T h e effect of physical training on cardiopulmonary performance in patients with chronic obstructive pulmonary disease. Chest 1977; 72:695-702. 9. Haas A, Cardon H. Rehabilitation in chronic obstructive pulmonary disease. Med Clin North Am 1961; 53:593-606. 10. Wolff RK, Dolovich MB, Obminski G, Newhouse MT. Effects of exercise and eucapnic hyperventilation on bronchial clearance in man. J Appl Physiol: Respir Environ Exercise Physiol 1977; 43:46-50. 11. Ellett W H , Callahan AB, Brownell GL. Gammaray dosimetry of internal emitters. II. Monte Carlo calculations of absorbed dose from uniform sources. Br J Radiol 1965; 38:541-4. 12. Sanchis J, Dolovich MB, Chalmers R, Newhouse
13. 14.
15. 16. 17.
18.
19.
20.
21.
22. 23.
24.
745
MT. Quantitation of regional aerosol deposition and clearance in normal human lungs. J Appl Physiol 1972; 33:757-62. Newhouse MT, Ruffin RE. Deposition and fate of inhaled aerosols. Chest 1978; 735:936S-42S. Pavia D, Thomson ML, Clarke SW, Shannon HS. The effect of lung function and mode of inhalation on penetration of aerosol into the human lung. Thorax 1977; 32:194-7. Morrow PE. Alveolar clearance of aerosols. Arch Intern Med 1973; 131:101-8. Leith DE. Cough. Phys Ther 1968; 48:439-47. Macklem P T , Wilson NJ. Measurement of intratracheal pressure in man. J Appl Physiol 1965; 20:653-66. Bateman JRM, Newman SP, Daunt KM, Clarke SW, Pavia D. The effect of physiotherapy on regional lung clearance in patients with chronic irreversible airways obstruction. Clin Sci Mol Med 1978; 54:IP. Faridy EE. Effect of ventilation on movement of surfactant in airways (abstract). Fed Proc 1976; 35:528. Chopra SK, Taplin GV, Simmons DH, Robinson GD, Elan D, Coulson A. Effects of hydration and physical therapy on tracheal transport velocity. Am Rev Respir Dis 1977; 115:1009-14. Wong J, Keens T, Wannamaker E, Crozier D, Levison H, Aspin N. The effects of gravity on tracheal mucus transport rates in normal subjects and patients with cystic fibrosis. Paediatrics 1977;60:146-52. Blake Jr.: On the movement of mucus in the lung. J Biomechanic 1975; 8:179Pavia D, Thomson M, Phillipakos D. A preliminary study of the effect of a vibrating pad on bronchial clearance. Am Rev Respir Dis 1976; 113:92-6. Anderson J, Lundgvist GR, Jensen DL, Proctor DF. Human response to 78-hour exposure to dry air. Arch Environ Health 1974; 29:319-24.
SUMMARY The effects of postural drainage, exercise, and cough on mucus clearance were compared in 8 patients with chronic bronchitis. A bolus of 90mTc albumin aerosol was inhaled at a high inspiratory flow rate to enhance proximal deposition. Retention of deposited aerosol in the lung, as a function of time, was quantified using a gamma camera and subsequent computer analysis. Coughing greatly accelerated total lung (p < 0.005) and peripheral (p < 0.005) mucus clearance. Exercise resulted in much smaller changes than did cough, but significantly increased total lung clearance (p < 0.005). Postural drainage in which coughing was prohibited did not alter clearance. These results have therapeutic implications and stress the importance of controlling cough when evaluating therapeutic interventions by these techniques.
Introduction Hilding (1) suggested that mucociliary dysfunction may be one of the earliest abnormalities in chronic bronchitis. The epithelial damage, mucous gland hypertrophy, mucus hypersecretion, and bacterial colonization in the lower respiratory tract may reflect or result in impaired lung defense mechanisms (1). Studies to determine clearance rates in patients with chronic bronchitis have produced conflicting data (2-5), but most investigators conclude that clearance is impaired. Adjunct therapy for patients with chronic bronchitis has often included postural
(Received in original form November 3, 1978 and in revised form May 18,1979) i From the Chest and Allergy Unit, St. Joseph's Hospital, Department of Medicine, McMaster University, Hamilton, Ontario L8N 1Y4, Canada. 2 Requests for reprints should be addressed to Dr. M. T. Newhouse, Chest and Allergy Unit, St. Joseph's Hospital, 50 Charlton East, Hamilton, Ontario L8N 1Y4, Canada. 3 Supported by the Ontario Thoracic Society. 4 American Lung Association Training Fellow. Present Address: Pulmonary Function Department, Eastern Maine Medical Center, Bangor, Me.
drainage, percussion, and coughing in an attempt to improve mucus clearance and, as a consequence, lung function. Despite long-standing application of these treatment measures, there are few data to substantiate their efficicacy (6). Vibration, percussion, and postural drainage all increase expectoration of sputum (7). The effect of cough alone, however, has not been well documented. Exercise is also believed to be beneficial in patients with chronic bronchitis, one benefit being an increase in the total amount of work that a patient can perform (8). However, there is no evidence that exercise changes lung function significantly (8), and the improvement documented by various investigators has been explained by Haas and Cardon (9) as being due to improved muscular efficiency occurring after exercise training. Wolff and associates (10) have shown that exercise increases mucociliary transport in normal subjects. Accelerated mucus transport due to exercise in patients with chronic bronchitis would be an additional reason for advocating exercise programs. This study compared bronchial mucus clearance during quiet breathing, postural drainage, cough, and exercise in a group of clinically stable patients with chronic bronchitis.
AMERICAN REVIEW OF RESPIRATORY DISEASE, VOLUME 120, 1979
739
740
OLDENBURG, DOLOVICH, MONTGOMERY, AND NEWHOUSE
TABLE 1 CLINICAL AND PHYSICAL CHARACTERISTICS OF SUBJECTS FEV,
Deposition
FVC
Subject No.
Age (yr)
(L, BTPS)
(L, BTPS)
Inner Zone
Sex
(% pred.)
(% pred.)
(%r
Outer Zone
(%r
1
63
M
20.3(2.8)
70
M
65.3(3.4)
10.2(1.6)
3
62
M
53.1 (2.8)
19.6(1.7)
4
55
F
66.3(1.7)
9.2(0.6)
5
62
M
65.9(2.9)
10.9(1.9)
6
58
M
67.3(2.5)
16.3(1.0)
7
64
M
72.5(5.2)
11.4(2.3)
8
63
M
3.0 (68.0) 2.9 (92.9) 2.3 (61.1) 2.5 (82.0) 4.0 (87.7) 2.5 (67.6) 2.4 (64.1) 3.1 (86.0)
50.9(1.8)
2
1.6 (66.6) 1.6 (64.0) 1.1 (40.7) 1.4 (58.3) 2.6 (76.5) 0.9 (29.0) 1.1 (39.3) 2.6 (92.9)
64.5(3.6)
14.0(1.5)
Definitions of abbreviations: FEV, = forced expiratory volume in one second; FVC = forced vital capacity. * Results are mean values ( ± SD) for 5 days.
Methods Subjects. Eight patients with simple and obstructive chronic bronchitis (table 1) participated in the study after informed consent had been obtained. All had been cigarette smokers, but only one (Subject 8) smoked at the time of the study and he refrained from smoking for at least 1 h before and during each clearance study. All patients were stable throughout the experimental period. Daily sputum production by history was quite variable, ranging from 10 to 120 ml. Baseline forced expiratory volumes in one second (FEV ) were within ± 15 % for all study days. Other than antihypertensive drugs, the only medications taken by this group of patients were bronchodilators, which were discontinued 12 h before each study. Preselection requirements were that the subjects (1) had chronic bronchitis (cough and sputum production for 3 months during 3 consecutive yr), (2) could exercise to 70-75 % of maximal predicted heart rate, and (3) refrained from coughing during the 2.5-h study period unless instructed to cough. Clearance techniques. Mucociliary transport and mucus clearance associated with cough were measured by quantifying the removal of an inhaled radiolabeled aerosol deposited on the bronchial mucosa. Because of the difficulty in controlling deposition in untrained subjects with varying degrees of airflow obstruction, an aerosol delivery system (figure 1) was developed to simplify subject participation and to eliminate the need for carefully controlled inspiratory air flow. The radio-aerosol (mass median diameter, 3.2 /um; geometric SD, 3.56) was generated by a compressed air driven nebulizer (Bunn no. 810) from a 0.025 % solution of 99mTc-
albumin in normal saline. When operated at 7.51 L/min, the output of the nebulizer was 0.327 ml/ min. The same aerosol was generated for each inhalation. All tubing except the calibrated Plexiglas® piston was standard black ABS plastic plumbing pipe, covered with lead shielding. T h e apparatus was ready for use when the aerosol filled the holding tower and the calibrated piston. T o perform an inhalation, the subject inserted the mouthpiece, and the cross clamp was released from the rubber tubing. A maximal inspiratory effort was immediately made from functional residual capacity (FRC), with the volume of aerosol inhaled limited by the One-Way Valve Calibrated Syringe :to Collection Bag
Holding Tower
2 inches Cross Clamp
Nebulizer
Mouth Piece Lead Shield Compressed Air
Fig. 1. System to deliver a bolus of radioaerosol reproducibly and preferentially to the large airways (see text for description).
741
POSTURAL DRAINAGE, EXERCISE, COUGH, AND BRONCHIAL CLEARANCE
volume to which the adjustable calibrated piston had been set (65 to 96 ml, depending on the patient's size). T h e duration of inspiration was less than 1 s and was immediately followed by a forced expiration to residual volume, back into the circuit. Excess volume passed through the apparatus via the one-way valve at the top into a collection bag. T h e cross clamp was reapplied, and the subject resumed breathing of room air. The piston was then reset for the next inspiration. T h e number of breaths required for good imaging varied between subjects. Eight to 12 breaths were usually necessary when the initial burden in the nebulizer was 10 mCi of 99mTc-albumin in 5 ml of saline. Each subject received a lung radiation dose of approximately 160 millirads and a whole-body radiation dose of 5 millirads for the entire 5-day study (11). Radioactivity was measured with an Anger scintillation camera interfaced to a data storage and retrieval system that permitted off-line computer handling of data from 3 areas of the right lung (12). These areas consisted of a region 5 by 12 cm centered over the large bronchi, denned as the inner zone, and two 2.5-cm zones, concentric about the inner zone in an onion peel fashion, denned as middle and outer zones. Studies in our laboratory have shown that the proximal boundary of the outer zone corresponded approximately to 2-4 mm airways, from examination of sagittal sections of fixed human lungs and labeling peripheral airways with radioisotopes. Because of radiation from swallowed secretions in the esophagus, the trachea and more proximal part of the right mainstem bronchus were excluded from analysis. Subject positioning in front of the gamma camera was kept constant for each study by means of light markers and restraints. All measurements of chest radioactivity were made with the subjects in the upright position, from the posteroanterior position. Initial or baseline whole lung counts averaged 25,000 cpm. T h e baseline deposition pattern for each study day was determined by calculating the ratio of the percentage of radioactivity in the outer to inner zones. Retention, calculated as a percentage of baseline deposited radioactivity, was plotted for the whole lung and for each of the 3 zones. Only the total lung and outer zone were analyzed for the purposes of this study, because interpretation of inner zone clearance was difficult owing to transport of distal radioactivity into this region. Experimental design. There were 5 study days for each subject. T h e order of the experiments was randomized. All experiments on an individual subject were performed within 7 days, at the same time of day, except for Subject 8, who completed the experiment within 10 days. Each subject served as his or her own control. Control. A quiet breathing experiment during which the subject rested upright throughout the 2.5-h study. Exercise. T h e subject rested for the first 0.5 h.
Then, from 0.5 to 1.16 h, exercise was performed on a cycle ergometer (Monarch) for five 4-min periods with 4-min periods between each exercise period for rest and monitoring of lung radioactivity. Subjects rested again from 1.16 to 2.5 h. Work loads were adjusted for each subject so that the heart rate was maintained at 70 to 75 % of the predicted maximum. Postural drainage. T h e subject rested for the first 0.5 h, then from 0.5 to 1.16 h, the subject lay quietly on a tilt table in the left lateral decubitus position in a 15-degree head-down position for five 6-min periods with a 1-min period between each maneuver to monitor lung radioactivity. Cough. The subject rested for the first 0.5 h. Then, from 0.5 to 1.16 h, the subject coughed once each minute for 5 min, with 3 min for rest and monitoring of lung radioactivity. For each experiment, 1-min measurements of lung radioactivity were made at specified times throughout the 2.5 h: every 6 min from 0 to 0.5 h, every 8 min from 0.5 to 1.16 h, and every 16 min from 1.16 to 2.5 h. Spontaneous cough was not a problem. All patients were monitored carefully and were encouraged to suppress the tendency to cough during the control, postural drainage, and exercise studies. Sputum was not collected during the study days. Retention curves were drawn for each subject for each study day. Statistical comparisons were made by paired t-test analysis at every 0.2-h point. T h e 2 rest days were averaged for comparison with the other therapeutic maneuvers. Standard deviations were used where indicated. Results T h e m e a n percentage ( ± SD) of i n n e r a n d outer zone deposition for each subject for t h e 5 exp e r i m e n t days showed a large intersubject variation, b u t little intrasubject variation (table 1). T h e r e was n o significant difference in baseline deposition by 2-way analysis of variance between any of the study days. T h e reproducibility of the m e t h o d comparing total l u n g clearance for the control days in 7 subjects is shown in figure 2. Subject 1 h a d only o n e control day because of technical difficulties with the d a t a retrieval system. T h e r e was n o significant difference by paired t-test analysis 100 I"
2j H u] c
I 70 h I I 601L__J 0
^^iT
• control 1 ,„ o control 2 1 0.5
tn=
7)
1 1.0 TIME (hrs)
I 1.5
1 2.0
,
1 2.5
Fig. 2. Comparison of total lung clearance between 2 control days for 7 subjects (mean ± 1 SD).
742
OLDENBURG, DOLOVICH, MONTGOMERY, AND NEWHOUSE
control * postural drainage exercise cough
duration of drainage, cough or exercise
o Average of two control days
Fig. 3. Comparison of the effects on total lung clearance of the control, postural drainage, exercise, and coughing maneuvers. Curves represent m e a n data for the group for each maneuver.
for any of the measured points. The maximal difference in retention between the 2 control days at any point in time for an individual subject was 12 %. Similar variations were noted for outer lung zone clearance on the control days. Total lung clearance varied widely as a result
of the various experimental maneuvers- (figure 3). The individual data for both total lung and peripheral lung clearance at the beginning (0.4 h) and end (1.2 h) of each maneuver are given in table 2. Compared to the control days, which were averaged to give a single curve, postural drainage had no significant effect on clearance (p > 0.5) (figure 3). Exercise (figure 4) increased mucus clearance by 7.5 % over resting values at 1.2 h (p < 0.025) but much less than cough (figure 5), which accelerated clearance by 40.8 % at 1.2 h (p < 0.001). Peripheral zone lung clearance curves (figure 6) were similar to those for the whole lung. However, exercise did not significantly accelerate peripheral clearance (p = 0.9). The failure of exercise to increase peripheral clearance significantly can probably be explained by the results of Subject 8, who had considerably slower clearance with exercise. Review of his initial inner zone deposition rate revealed that 10.7 % less radioactivity was deposited in this zone during the exercise days as compared to either control day. When this subject was excluded from the study, exercise significantly improved peripheral zone clearance (7.6 % at 1.4 h, p < 0.05) as compared to the control days.
TABLE 2 TOTAL LUNG AND PERIPHERAL LUNG RETENTION DATA Control Patient Retention, total lung, % 1 2 3 4 5 6 7 8
Exercise
Postural Drainage
Cough
0.4 h
1.2 h
0.4 h
1.2 h
0.4 h
1.2 h
0.4 h
1.2 h
96.0 94.7 93.8 93.8 95.8 97.3 94.5 93.8
86.0 85.0 90.6 87.8 90.3 96.3 86.3 87.0
97.0 93.0 93.0 98.0 90.0 92.0 95.0 94.0
82.0 75.5 84.0 83.0 72.0 83.5 86.0 83.0
100.0 97.0 98.5 93.0 93.0 93.0 97.5 95.0
88.0 88.0 97.5 87.2 82.5 88.0 93.5 91.5
95.0 100.0 99.0 97.0 98.0 94.0 95.0 97.0
69.0 49.0 87.5 47.0 40.0 34.0 23.3 40.0
Mean ± 1 SD Retention, peripheral lung, % 1 2 3 4 5 6 7 8
95.0 1.3
88.7 3.7
94.0 2.6
81.1 4.8
95.9 2.8
96.9 2.1
89.5 4.6
48.7 20.5
97.3 94.0 92.0 94.8 94.8 92.5 98.5 94.0
79.0 92.0 88.3 85.0 90.3 86.3 96.3 96.5
94.0 93.5 91.0 96.5 92.5 92.5 93.0 100.0
73.0 89.5 80.0 89.0 73.0 86.0 77.5 95.0
93.0 97.0 98.5 96.0 93.5 90.0 92.0 93.5
76.5 75.1 96.0 93.0 82.0 87.5 80.5 93.0
92.0 96.5 94.5 97.0 97.0 97.5 98.0
66.5 59.5 85.0 70.0 47.5 65.0 42.5
Mean ± 1 SD
94.8 2.2
89.2 5.9
94.1 2.9
82.9 8.2
94.2 2.79
85.5 8.05
96.1 2.11
-
62.3 14.3
POSTURAL DRAINAGE, EXERCISE, COUGH, AND BRONCHIAL CLEARANCE
• Mean (n=8) ± S.D.
Ui
743 control* (n=8) postural drainage (n=8) exercise (n=8) cough (n=7)
duration of drainage, cough or exercise
O
O 2 -15
3 if 0.1
0.1
0.01 0.001
p values
1.0 TIME (hrs)
Fig. 4. T h e time course of total lung clearance d u r i n g the exercise maneuvers expressed as a m e a n percentage change from control ± 1 SD.
There was no significant difference between FEVj and FVC before and after any of the experimental maneuvers in any of the 8 subjects. Discussion
To compare the removal of labeled mucus from the lung during various maneuvers, care must be taken to achieve a reproducible initial deposition pattern of labeled aerosol in the lung for each maneuver. The deposition of particles in the lung depends on particle size and shape, density, electrical charge, and hygroscopic properties, as well as inspiratory flow rate, initial lung volume, inspired volume, and degree of airflow obstruction (13-15). These factors were maintained relatively constant throughout the study. We have developed a system for depositing aerosol mainly in proximal airways (63.3 ± 7.7 % of total right lung burden). The apparatus is simple to build and simple for untrained subjects to use. The reproducibility of our method is substantiated by the small SD
1.0
1.5
TIME (hrs)
Fig. 5. T h e time course of total lung clearance during the coughing maneuver expressed as a m e a n percentage change from control ± 1 SD.
1.0
1.5
TIME (hrs) * Average of two control days
Fig. 6. Comparison of the effects on peripheral lung clearance of the control, postural drainage, exercise, and coughing maneuvers. Curves represent m e a n d a t a for the group for each maneuver.
in intrasubject deposition (table 1) and mean clearance rates for the 2 control days (figure 2). Coughing maneuvers produced the greatest increase in total lung (40.8 ± 19.2 %) and peripheral lung (29.6 ±17.6 %) clearance. Leith (16) reviewed the possible effects of cough on mucus clearance. He concluded that in larger airways up to the sixth or seventh generation, mucus can be "pumped" up the tracheobronchial tree using energy transferred from the expired air. Dynamic collapse that occurred in conjunction with the coughing maneuver increased clearance by increasing gas velocities that could reach three-quarters of the speed of sound (16). Macklem and Wilson (17) showed that at 25 % of vital capacity dynamic collapse does not occur beyond the third-generation bronchi, although at lower lung volumes dynamic collapse occurs in more peripheral bronchi where airflow velocity is greatly decreased. These studies have suggested to other investigators (18) that cough would have little effect on more peripheral mucus clearance. At least one group of investigators (18) has used this as an argument to suggest that physiotherapy (postural drainage, percussion, and vibration) was effective in accelerating clearance despite the fact that coughing was not controlled. Yet our results indicate that cough is quite effective in improving peripheral clearance Coughing may result in a ''milking" effect on secretions in the small airways. Faridy (19) has observed the effect of lung movement on acceleration of surfactant transport up the bronchia] tree, and one might expect a similar effect on mucus. Because cough is effective in increasing clear-
744
OLDENBURG, DOLOVICH, MONTGOMERY, AND NEWHOUSE
ance in all lung zones, investigators should realize that cough alone may account for changes in mucus transport observed during various therapeutic interventions. As the quality of a given cough conceivably varies depending on the patient's effort and expiratory flow, it is not adequate simply to control the number of coughs in experiments. Nor can the expectorated sputum simply be collected and corrections made for the expectorated radioactivity, because there may be contamination from pharyngeal radioactivity due to mucociliary transport and possibly initial pharyngeal radioactivity not cleared by gargling. Postural drainage maneuvers in our subjects did not improve total lung or peripheral lung clearance over resting values (figure 2). Postural drainage is commonly prescribed for patients with hypersecretion; however, data are lacking with regard to its efficacy because most studies have not been controlled for cough. In animal experiments, Chopra and co-workers (20) showed that in anaesthetised dogs postural drainage increased tracheal transport by 39.7 %. Wong and associates (21) showed that postural drainage (25° head-down position) accelerated tracheal mucus transport in patients with cystic fibrosis but not in normal subjects. Cough was not controlled, although corrections were made for obvious bolus displacement. On theoretical grounds, Blake (22) suggested that gravity would increase mucociliary clearance especially if the depth of the serous layer was significantly increased. The more abundant secretions with different rheologic properties found in cystic fibrosis may account for the difference in results between our patients with chronic bronchitis and those with cystic fibrosis. Another possible explanation for the discrepancy in findings is that our subjects were upright for clearance measurements for one-sixth of the postural drainage maneuvers. In patients with chronic obstructive pulmonary disease, Clarke and coworkers (7) showed that postural drainage, vibration, percussion, and assisted cough increased sputum production. Subsequently, Bateman and associates (18), using a radioaerosol technique, studied whole lung and peripheral lung clearance after physiotherapy in patients with chronic irreversible airway obstruction. Mucus clearance was increased by 33 and 28 %, respectively; however, the relative importance of postural drainage and cough was not measured. Using a vibrating pad, Pavia and co-workers (23) were unable to show a significant increase in mucociliary transport in patients with chron-
ic bronchitis. We were unable to demonstrate any improvement in mucus clearance due to postural drainage alone, suggesting that vibration and percussion or cough may be responsible for most of the increase in sputum clearance reported by other investigators. Because the increase in clearance rates that we observed for cough alone was equivalent to or greater than that reported by Bateman and associates (18), it is possible that cough alone accounted for the observed acceleration in clearance during combined chest physiotherapy. The use of postural drainage alone in stable chronic bronchitis does not appear to be justified. Studies comparing spontaneous cough, assisted cough, postural drainage, and vibration and percussion in the same subjects may be able to clarify this issue. Exercise increased total lung clearance by 7.5 % (p < 0.05), as compared to control days (figure 4). Wolff and co-workers (10) reported a similar acceleration of clearance in 10 normal subjects, although they noted a delay in the onset of increased clearance after the beginning of exercise that was not observed in the present study. There have been few reports in the literature concerning exercise and mucus clearance. Anderson and associates (24) observed no significant change in nasal clearance after vigorous exercise; however, several individual subjects were noted to have greatly accelerated clearance. Our finding of slightly improved clearance rates with exercise in some patients may have therapeutic implications. Most investigators believe that the effects of exercise in patients with chronic bronchitis are indirect because most lung function parameters do not improve with exercise (8). If, however, the trend toward increased mucus transport can be maintained on a longterm basis, then common complications such as mucus plugging and lower respiratory tract infections may be decreased. This study has demonstrated that in patients with stable chronic bronchitis: (2) cough greatly accelerates the bronchial clearance of mucus and must be controlled in studies of this nature, (2) exercise improves mucus clearance much less than does cough, and (3) postural drainage does not appear to improve mucus clearance.
Acknowledgment The writers thank G. Obminski, B.Sc, for technical assistance and Mrs. M. Owens for assistance with the preparation of the manuscript.
POSTURAL DRAINAGE, EXERCISE, COUGH, AND BRONCHIAL CLEARANCE
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