The Effect of Inhalation Therapy on Ventilatory Function and Expectoration* Chang Shim, Af.D.;** Surinda Bajwa, M.D.;f M. Henry Williams, Jr., M.D., F.C.C.P.J
and
Fifteen outpatients with stable chronic obstructive pulmonary disease were treated on separate days in random sequence with the following four regimens: (1) intermittent positive-pressure breathing (IPPB) with 2.5 mg of aerosol isoproterenol hydrochloride; (2) aerosol isoproterenol from a cartridge nebulizer (two puffs every ten minutes for three times); (3) aerosol placebo (two puffs every ten minutes for three times); and (4) aerosol isoproterenol as in treatment 2, plus a slow maneuver for vital capacity eveiy ten minutes for five times. The forced vital capacity and arterial blood gas levels were determined before and 60 minutes after the start of therapy. Sputum was collected over a 60-minute period from the start of therapy. The total volume of sputum was measured, and the volume of bronchial mucus was estimated by subtracting the volume of saliva
as calculated from the concentration of amvlase. Therapy with aerosol isoproterenol was no better than the placebo in promoting expectoration of sputum. Therapy with IPPB did increase the volume of sputum expectorated, compared to the other modes of therapy, but this was not statistically significant Increased expectoration was not associated with an increased rate of expiratory flow. Therapy with aerosol isoproterenol, however delivered, produced a greater increase in the forced expiratory flow in one second, compared to placebo. Levels of arterial blood gases showed no consistent change, except for a faD in the arterial oxygen pressure which occurred most frequently after therapy with IPPB. These studies failed to reveal a therapeutic benefit from this type of inhalation therapy.
Tntermittent positive-pressure breathing (IPPB) is a form of therapy widely used for patients with chronic obstructive pulmonary disease (COPD). It can be lifesaving for the patient with respiratory failure by assisting or controlling ventilation. Treatment with IPPB is also used for many other therapeutic reasons in patients with COPD. These in-
mote expectoration of sputum when used in association with aerosol isoproterenol? If so, does this result in a decrease of obstruction of the airways?
For editorial comment, see page 782 elude delivery of aerosol medications, promotion of expectoration of sputum, and reduction of work of breathing. Since treatment with IPPB is expensive, time-consuming, and potentially hazardous as a source of nosocomial infections, its beneficial effects should be clearly demonstrated if IPPB is to be used in patients with stable COPD. The present study was designed primarily to answer the following two questions about therapy with IPPB. Does it pro•From the Pulmonary Division, Department of Medicine, Albert Einstein College of Medicine, and the Chest Service, Department of Medicine, Bronx Municipal Hospital Center, Bronx, NY. Supported by National Institutes of Health grant HL 18434. ••Associate Professor of Medicine. Resident
J
Professor of Medicine. Manuscript received September 1; revision accepted October 10. Reprint requests: Dr. Williams, Medicine, Van Etten, 612, Albert Einstein College of Medicine, Bronx 10461
798 SHIM, BAJWA, WILLIAMS
MATERIALS AND METHODS
Eighteen outpatients with COPD who gave a history of daily expectoration of sputum consented to participate in the study to evaluate the short-term effects of inhalation therapy. All of the patients were already familiar with testing of pulmonary function. None had been receiving longterm therapy with IPPB. The patients reported to the laboratory in the morning without taking medication for at least 15 hours. After a 30-minute rest a sample of arterial blood was obtained for gas analysis. Then forced vital capacity ( F V C ) was measured. Immediately thereafter inhalation therapy was begun using one of the following four 60-minute regimens in random sequence. The first regimen consisted of IPPB with 0.5 ml (2.5 mg) of a 1:200 solution of isoproterenol hydrochloride diluted with 2.0 ml of physiologic saline solution, administered until all of the medication was used (usually 15 minutes). The pressure limit of the respirator (Bennett AP-5) was adjusted so that the tidal volume was 1,000 to 1,600 ml. The patient was encouraged to expectorate sputum every ten minutes during the 60-minute period. The second regimen consisted of inhalation of aerosol isoproterenol from a cartridge nebulizer (Isuprel Mistometer; two puffs at the start and again ten minutes and 20 minutes later). The patient was encouraged to expectorate sputum every ten minutes during the 60-minute period.
CHEST, 73: 6, JUNE, 1978
For the third regimen the protocol was identical to regimen 2, except that an aerosol placebo was used instead of isoproterenol, unknown to the patient. For the fourth regimen, the protocol was identical to regimen 2. In addition, the patient was asked to do a slow maneuver for vital capacity ( V C ) every ten minutes during the 60-minute period. This was included because patients with COPD often cough vigorously when they perform such a maneuver for VC in the pulmonary function laboratory. To evaluate expectoration, each patient was issued two containers and asked to collect all of the sputum in one container and all of the saliva in the other for 60 minutes from the start of treatment. At the end of this period, another sample of arterial blood was obtained, and the maneuver for FVC was repeated. Bronchial mucus, herein defined as the mucous secretion from the tracheobronchial tree below the larnyx, is contaminated with saliva in the mouth in the process of expectoration (this mixture is defined as sputum). Therefore, in a sample of sputum, we do not know die exact amount contributed by the bronchial mucus. Since bronchial mucus does not contain the amylase that is highly concentrated in saliva, we used the level of amylase in the sputum as an indicator of the degree of contamination of bronchial mucus with saliva. (Mucus obtained from a dog's tracheal pouch 1 had an amylase level of 100 units/ml, a negligible value compared to the average salivary level of amylase of 435,000 units/ml). The volume of sputum was measured. The activity of amylase in the sputum and the simultaneously collected saliva was determined by a photometric technique after incubating an aliquot with a dyed amylose (Amylochrome). 2 ' 3 On the basis of the amylase activity of the saliva and sputum, assuming the amylase activity of the bronchial secretion to be negligible, the bronchial mucous volume was determined
T a b l e 1 — V o l u m e s of Sputum and Bronchial Four Regimens
No. of Patients
Regimen
t
Mucus
after
Volume, ml*
Sputum**
Bronchial Mucus t
Aerosol placebo
14
8.39 ± 7 . 4 3
4.24 ± 4 . 3 3
Aerosol isoproterenol
15
8.36 ± 5 . 9 9
3.70 ± 2 . 9 7
I P P B and isoproterenol
15
Slow maneuver for VC and isoproterenol
15
13.33 ± 1 2 . 6 0 7.02 ± 8 . 5 0 9.36 ± 6 . 4 4
3.66 ± 3 . 3 3
*Mean ± SD. There was no significant difference among volumes of sputum and volumes of bronchial mucus. * ^Bronchial secretion mixed with saliva. fEstimated. by subtracting the salivary volume from the volume of sputum, according to the following equation: volume of bronchial mucus = volume of sputum ( 1 — [amylase activity of sputum/am ylase activity of saliva]), where amylase activity is measured in units per milliliter. The VC, the forced expiratory volume in one second ( F E V i ) , and the maximum midexpiratory flow of all of the patients were compared before and after each treatment. The volume of sputum and the volume of bronchial mucus were also compared after the different treatments. RESULTS
Fifteen patients finished the study. Three patients dropped out after finishing only one or two treat-
401-
30
2
20
9
10
5
10
PLACEBO CHEST, 73: 6, JUNE, 1978
15
I
5
10
15
ISOPROTERENOL
5
10
15
IPPB WITH ISOPRO
5
10
VC WITH ISOPRO
15
FIGURE 1. Volume of sputum (thin ban) and volume of bronchial mucus ( thick bars) in 15 patients after four regimens. Numbers below bars represent specific patients. Isopro, isoproterenol.
EFFECT OF INHALATION THERAPY
709
5.01-
4.0
£ 3.0 LU
£ 2.0
1.0 0
L
PLACEBO
ISOPROTERENOL
SLOW VC WITH ISOPRO
IPPB+ISOPRO
FIGURE 2. Vital capacity before and after four regimens. Isopro, isoproterenol.
ments. The mean volume of sputum expectorated during the 60-minute period was 13.3 ml for IPPB with aerosol isoproterenol, 8.4 ml for aerosol isoproterenol alone, 8.4 ml for aerosol placebo alone, and 9.4 ml for aerosol isoproterenol plus slow maneuvers for VC (Table 1 and Fig 1). The differences are not statistically significant. The salivary amylase activity ranged from 45,000 to 1,200,000 units/ml, with a mean of 435,000 ± 732,000 units/ml (dt SD). Salivary contamination of sputum as determined by the amylase level of sputum ranged from 2 to 100 percent and had a mean of 53 percent. The mean volume of bronchial mucus was 7.0 ml for IPPB with isoproterenol, 3.7 ml for aerosol isoproterenol alone, 4.2 ml for aerosol placebo alone, and 3.7 ml for aerosol isoproterenol plus slow maneuvers for VC. The differences again are not statistically significant. Individual analysis revealed that three
patients (patients 8, 9, and 12 in Fig 1) did produce a greater amount of bronchial mucus while receiving therapy with IPPB with isoproterenol than while receiving isoproterenol alone. The VC and rates of flow improved significantly after all modes of therapy, including the aerosol placebo (Fig 2 and 3). The improvement in FEVi was greater after therapy with aerosol isoproterenol from the cartridge nebulizer than after the aerosol placebo. There was no significant difference in the improvement in rates of flow after different modes of delivery of aerosol isoproterenol, as shown by the following mean values ( ± SD) for FEVi: placebo, 14.7 ±: 25.7 percent; isoproterenol alone, 44.6 =t 30.7 percent; IPPB with isoproterenol, 49.9 ±. 46.1 percent (P < 0.05, compared to placebo); and slow maneuvers for VC with isoproterenol, 46.9 rb 19.5 percent (P < 0.01, compared to placebo). Studies of arterial blood gases were carried
3.0 to
2.0
1.0
0L PLACEBO
ISOPROTERENOL
SLOW V C WITH ISOPRO
IPPB+ISOPRO
FIGURE 3. FEVX before and after four regimens. Isopro, isoproterenol.
800 SHIM, BAJWA, WILLIAMS
CHEST, 73: 6, JUNE, 1978
out in the first ten patients. After therapy with IPPB with isoproterenol, seven out of ten patients had a drop in the arterial oxygen pressure of 5 mm Hg or greater, whereas after the other modes of therapy, only two or three did so (not significant). There was no consistent change in the arterial carbon dioxide tension or pH. DISCUSSION
Therapy with IPPB is undoubtedly useful for assisted or controlled ventilation of patients with COPD in respiratory failure; however, for those in a chronic stable state, the usefulness of this form of therapy is debated. Numerous studies have demonstrated that the bronchodilator drug delivered via IPPB produces no better result than that delivered by hand-held nebulizer.4"7 Our results are in keeping with these. Many advocate IPPB for its ability to promote expectoration of sputum.8'9 Patients often report some benefit from therapy with IPPB in expectorating sputum. Our results do not support such claims. A paired f-test failed to show a significant difference in bronchial mucus produced after IPPB with isoproterenol and after aerosol isoproterenol alone; however, three patients did produce a larger volume of bronchial mucus after therapy with IPPB (patients 8, 9, and 12 in Fig 1). Even in these patients the improvement in VC and FEVi was no greater after EPPB with isoproterenol than after aerosol isoproterenol alone. This implies either that the bronchial mucus expectorated did not play an important role in obstruction of the airways of these patients or that the mucus production was stimulated by IPPB itself. This is contrary to the commonly held notion that expectoration of bronchial mucus clears the bronchial tree of obstructing mucus. It was surprising that administration of isoproterenol had no effect on expectoration of bronchial mucus. It has been demonstrated that isoproterenol promotes mucociliary clearance in the tracheobronchial tree,10 but sympathomimetic drugs have failed to affect the secretion from the bronchial glands of cultured tracheal ring.11 It has been postulated that administration of catecholamines might promote removal of secretions in patients with COPD.12 Patients occasionally claim that inhalation of aerosol isoproterenol facilitates removal of secretions; however, our results showed that aerosol isoproterenol was no better than placebo in promoting expectoration of bronchial mucus. Most patients did cough vigorously after each slow maneuver for VC and expectorated some sputum; however, the bronchial mucus volume was no CHEST, 73: 6, JUNE, 1978
greater with these maneuvers than after administration of isoproterenol or placebo without these maneuvers. We found the salivary amylase activity to be a useful marker of salivary contamination of sputum. Sputum was indeed extensively contaminated with saliva. About half of the sputum was, in fact, saliva, despite careful instruction to the patient to separate bronchial mucus from saliva in separate containers. We could not estimate the extent of salivary contamination by appearance. Others have successfully used the salivary amylase activity to establish the diagnosis of aspiration pneumonia.18 One must take this into account when, evaluating the volume or viscosity of sputum. REFERENCES
1 Wardell Jr JR, Chakrin L W , Payne B J : The canine tracheal pouch: A model for use in respiratory research. Am Rev Respir Dis 101:741-754, 1970 2 Klein B, Foreman JA, Searcy R L : New chromogenic substrate for determination of serum amylase activity. Clin Chem 1 6 : 3 2 - 3 8 , 1 9 7 0 3 Dalai F R , Winsten S: Laboratory evaluation of a chromogenic amylase method. Clin Chim Acta 32:327-332, 1971 4 Fowler WS, Helmholz H F Jr, Miller R D : Treatment of pulmonary emphysema with aerosolized bronchodilator drugs and intermittent positive pressure breathing. Proc Staff Meetings Mayo Clin 2 8 : 7 4 3 - 7 5 1 , 1 9 5 3 5 Goldberg I, Cherniak RM: The effect of nebulized bronchodilator delivered with and without IPPB on ventilatory function in chronic obstructive emphysema. Am Rev Respir Dis 9 1 : 1 3 - 2 0 , 1 9 6 5 6 Taylor W F , Heimlich EM, Stride L, et al: Intermittent positive pressure breathing versus Freon-unit nebulized isoproterenol in asthmatic children. J Allergy 38:257-263, 1966 7 Froeb H F : On the relief of bronchospasm and die induction of alveolar hyperventilation: A comparative study of nebulized bronchodilators by deep breathing and intermittent positive pressure. Dis Chest 38:483-489, 1960 8 Motley HL, Tomashefski J F : Treatment of chronic pulmonary disease with intermittent positive pressure breathing. Arch Industr Hyg Occup Med 5:1-9, 1952 9 Wu N, Miller W F , Cade R, et al: Intermittent positive pressure breathing in patients with chronic bronchopulmonary disease. Am Rev Tuberc Respir Dis 71:693-703, 1955 10 Yeates DB, Aspin N, Levinson H, et al: Mucociliary tracheal transport rates in man. J Appl Physiol 39:487-495, 1975 11 Sturgess J, Reid L : An organ culture study of the effects of drugs on the secretory activity of die human bronchial submucosal gland. Clin Sci 43:533-543, 1972 12 Santa Cruz R, Landa J, Hirsch J , et al: Tracheal mucous velocity in normal man and patients with obstructive lung disease: Effects of terbutaline. Am Rev Respir Dis 109: 458-463, 1974 13 Smith DD, McNamara T J : Sputum amylase in the evaluation of aspiration. Read before the annual meeting of the American Thoracic Society, New Orleans, May 16-19, 1976
EFFECT OF INHALATION THERAPY 801
and
Fifteen outpatients with stable chronic obstructive pulmonary disease were treated on separate days in random sequence with the following four regimens: (1) intermittent positive-pressure breathing (IPPB) with 2.5 mg of aerosol isoproterenol hydrochloride; (2) aerosol isoproterenol from a cartridge nebulizer (two puffs every ten minutes for three times); (3) aerosol placebo (two puffs every ten minutes for three times); and (4) aerosol isoproterenol as in treatment 2, plus a slow maneuver for vital capacity eveiy ten minutes for five times. The forced vital capacity and arterial blood gas levels were determined before and 60 minutes after the start of therapy. Sputum was collected over a 60-minute period from the start of therapy. The total volume of sputum was measured, and the volume of bronchial mucus was estimated by subtracting the volume of saliva
as calculated from the concentration of amvlase. Therapy with aerosol isoproterenol was no better than the placebo in promoting expectoration of sputum. Therapy with IPPB did increase the volume of sputum expectorated, compared to the other modes of therapy, but this was not statistically significant Increased expectoration was not associated with an increased rate of expiratory flow. Therapy with aerosol isoproterenol, however delivered, produced a greater increase in the forced expiratory flow in one second, compared to placebo. Levels of arterial blood gases showed no consistent change, except for a faD in the arterial oxygen pressure which occurred most frequently after therapy with IPPB. These studies failed to reveal a therapeutic benefit from this type of inhalation therapy.
Tntermittent positive-pressure breathing (IPPB) is a form of therapy widely used for patients with chronic obstructive pulmonary disease (COPD). It can be lifesaving for the patient with respiratory failure by assisting or controlling ventilation. Treatment with IPPB is also used for many other therapeutic reasons in patients with COPD. These in-
mote expectoration of sputum when used in association with aerosol isoproterenol? If so, does this result in a decrease of obstruction of the airways?
For editorial comment, see page 782 elude delivery of aerosol medications, promotion of expectoration of sputum, and reduction of work of breathing. Since treatment with IPPB is expensive, time-consuming, and potentially hazardous as a source of nosocomial infections, its beneficial effects should be clearly demonstrated if IPPB is to be used in patients with stable COPD. The present study was designed primarily to answer the following two questions about therapy with IPPB. Does it pro•From the Pulmonary Division, Department of Medicine, Albert Einstein College of Medicine, and the Chest Service, Department of Medicine, Bronx Municipal Hospital Center, Bronx, NY. Supported by National Institutes of Health grant HL 18434. ••Associate Professor of Medicine. Resident
J
Professor of Medicine. Manuscript received September 1; revision accepted October 10. Reprint requests: Dr. Williams, Medicine, Van Etten, 612, Albert Einstein College of Medicine, Bronx 10461
798 SHIM, BAJWA, WILLIAMS
MATERIALS AND METHODS
Eighteen outpatients with COPD who gave a history of daily expectoration of sputum consented to participate in the study to evaluate the short-term effects of inhalation therapy. All of the patients were already familiar with testing of pulmonary function. None had been receiving longterm therapy with IPPB. The patients reported to the laboratory in the morning without taking medication for at least 15 hours. After a 30-minute rest a sample of arterial blood was obtained for gas analysis. Then forced vital capacity ( F V C ) was measured. Immediately thereafter inhalation therapy was begun using one of the following four 60-minute regimens in random sequence. The first regimen consisted of IPPB with 0.5 ml (2.5 mg) of a 1:200 solution of isoproterenol hydrochloride diluted with 2.0 ml of physiologic saline solution, administered until all of the medication was used (usually 15 minutes). The pressure limit of the respirator (Bennett AP-5) was adjusted so that the tidal volume was 1,000 to 1,600 ml. The patient was encouraged to expectorate sputum every ten minutes during the 60-minute period. The second regimen consisted of inhalation of aerosol isoproterenol from a cartridge nebulizer (Isuprel Mistometer; two puffs at the start and again ten minutes and 20 minutes later). The patient was encouraged to expectorate sputum every ten minutes during the 60-minute period.
CHEST, 73: 6, JUNE, 1978
For the third regimen the protocol was identical to regimen 2, except that an aerosol placebo was used instead of isoproterenol, unknown to the patient. For the fourth regimen, the protocol was identical to regimen 2. In addition, the patient was asked to do a slow maneuver for vital capacity ( V C ) every ten minutes during the 60-minute period. This was included because patients with COPD often cough vigorously when they perform such a maneuver for VC in the pulmonary function laboratory. To evaluate expectoration, each patient was issued two containers and asked to collect all of the sputum in one container and all of the saliva in the other for 60 minutes from the start of treatment. At the end of this period, another sample of arterial blood was obtained, and the maneuver for FVC was repeated. Bronchial mucus, herein defined as the mucous secretion from the tracheobronchial tree below the larnyx, is contaminated with saliva in the mouth in the process of expectoration (this mixture is defined as sputum). Therefore, in a sample of sputum, we do not know die exact amount contributed by the bronchial mucus. Since bronchial mucus does not contain the amylase that is highly concentrated in saliva, we used the level of amylase in the sputum as an indicator of the degree of contamination of bronchial mucus with saliva. (Mucus obtained from a dog's tracheal pouch 1 had an amylase level of 100 units/ml, a negligible value compared to the average salivary level of amylase of 435,000 units/ml). The volume of sputum was measured. The activity of amylase in the sputum and the simultaneously collected saliva was determined by a photometric technique after incubating an aliquot with a dyed amylose (Amylochrome). 2 ' 3 On the basis of the amylase activity of the saliva and sputum, assuming the amylase activity of the bronchial secretion to be negligible, the bronchial mucous volume was determined
T a b l e 1 — V o l u m e s of Sputum and Bronchial Four Regimens
No. of Patients
Regimen
t
Mucus
after
Volume, ml*
Sputum**
Bronchial Mucus t
Aerosol placebo
14
8.39 ± 7 . 4 3
4.24 ± 4 . 3 3
Aerosol isoproterenol
15
8.36 ± 5 . 9 9
3.70 ± 2 . 9 7
I P P B and isoproterenol
15
Slow maneuver for VC and isoproterenol
15
13.33 ± 1 2 . 6 0 7.02 ± 8 . 5 0 9.36 ± 6 . 4 4
3.66 ± 3 . 3 3
*Mean ± SD. There was no significant difference among volumes of sputum and volumes of bronchial mucus. * ^Bronchial secretion mixed with saliva. fEstimated. by subtracting the salivary volume from the volume of sputum, according to the following equation: volume of bronchial mucus = volume of sputum ( 1 — [amylase activity of sputum/am ylase activity of saliva]), where amylase activity is measured in units per milliliter. The VC, the forced expiratory volume in one second ( F E V i ) , and the maximum midexpiratory flow of all of the patients were compared before and after each treatment. The volume of sputum and the volume of bronchial mucus were also compared after the different treatments. RESULTS
Fifteen patients finished the study. Three patients dropped out after finishing only one or two treat-
401-
30
2
20
9
10
5
10
PLACEBO CHEST, 73: 6, JUNE, 1978
15
I
5
10
15
ISOPROTERENOL
5
10
15
IPPB WITH ISOPRO
5
10
VC WITH ISOPRO
15
FIGURE 1. Volume of sputum (thin ban) and volume of bronchial mucus ( thick bars) in 15 patients after four regimens. Numbers below bars represent specific patients. Isopro, isoproterenol.
EFFECT OF INHALATION THERAPY
709
5.01-
4.0
£ 3.0 LU
£ 2.0
1.0 0
L
PLACEBO
ISOPROTERENOL
SLOW VC WITH ISOPRO
IPPB+ISOPRO
FIGURE 2. Vital capacity before and after four regimens. Isopro, isoproterenol.
ments. The mean volume of sputum expectorated during the 60-minute period was 13.3 ml for IPPB with aerosol isoproterenol, 8.4 ml for aerosol isoproterenol alone, 8.4 ml for aerosol placebo alone, and 9.4 ml for aerosol isoproterenol plus slow maneuvers for VC (Table 1 and Fig 1). The differences are not statistically significant. The salivary amylase activity ranged from 45,000 to 1,200,000 units/ml, with a mean of 435,000 ± 732,000 units/ml (dt SD). Salivary contamination of sputum as determined by the amylase level of sputum ranged from 2 to 100 percent and had a mean of 53 percent. The mean volume of bronchial mucus was 7.0 ml for IPPB with isoproterenol, 3.7 ml for aerosol isoproterenol alone, 4.2 ml for aerosol placebo alone, and 3.7 ml for aerosol isoproterenol plus slow maneuvers for VC. The differences again are not statistically significant. Individual analysis revealed that three
patients (patients 8, 9, and 12 in Fig 1) did produce a greater amount of bronchial mucus while receiving therapy with IPPB with isoproterenol than while receiving isoproterenol alone. The VC and rates of flow improved significantly after all modes of therapy, including the aerosol placebo (Fig 2 and 3). The improvement in FEVi was greater after therapy with aerosol isoproterenol from the cartridge nebulizer than after the aerosol placebo. There was no significant difference in the improvement in rates of flow after different modes of delivery of aerosol isoproterenol, as shown by the following mean values ( ± SD) for FEVi: placebo, 14.7 ±: 25.7 percent; isoproterenol alone, 44.6 =t 30.7 percent; IPPB with isoproterenol, 49.9 ±. 46.1 percent (P < 0.05, compared to placebo); and slow maneuvers for VC with isoproterenol, 46.9 rb 19.5 percent (P < 0.01, compared to placebo). Studies of arterial blood gases were carried
3.0 to
2.0
1.0
0L PLACEBO
ISOPROTERENOL
SLOW V C WITH ISOPRO
IPPB+ISOPRO
FIGURE 3. FEVX before and after four regimens. Isopro, isoproterenol.
800 SHIM, BAJWA, WILLIAMS
CHEST, 73: 6, JUNE, 1978
out in the first ten patients. After therapy with IPPB with isoproterenol, seven out of ten patients had a drop in the arterial oxygen pressure of 5 mm Hg or greater, whereas after the other modes of therapy, only two or three did so (not significant). There was no consistent change in the arterial carbon dioxide tension or pH. DISCUSSION
Therapy with IPPB is undoubtedly useful for assisted or controlled ventilation of patients with COPD in respiratory failure; however, for those in a chronic stable state, the usefulness of this form of therapy is debated. Numerous studies have demonstrated that the bronchodilator drug delivered via IPPB produces no better result than that delivered by hand-held nebulizer.4"7 Our results are in keeping with these. Many advocate IPPB for its ability to promote expectoration of sputum.8'9 Patients often report some benefit from therapy with IPPB in expectorating sputum. Our results do not support such claims. A paired f-test failed to show a significant difference in bronchial mucus produced after IPPB with isoproterenol and after aerosol isoproterenol alone; however, three patients did produce a larger volume of bronchial mucus after therapy with IPPB (patients 8, 9, and 12 in Fig 1). Even in these patients the improvement in VC and FEVi was no greater after EPPB with isoproterenol than after aerosol isoproterenol alone. This implies either that the bronchial mucus expectorated did not play an important role in obstruction of the airways of these patients or that the mucus production was stimulated by IPPB itself. This is contrary to the commonly held notion that expectoration of bronchial mucus clears the bronchial tree of obstructing mucus. It was surprising that administration of isoproterenol had no effect on expectoration of bronchial mucus. It has been demonstrated that isoproterenol promotes mucociliary clearance in the tracheobronchial tree,10 but sympathomimetic drugs have failed to affect the secretion from the bronchial glands of cultured tracheal ring.11 It has been postulated that administration of catecholamines might promote removal of secretions in patients with COPD.12 Patients occasionally claim that inhalation of aerosol isoproterenol facilitates removal of secretions; however, our results showed that aerosol isoproterenol was no better than placebo in promoting expectoration of bronchial mucus. Most patients did cough vigorously after each slow maneuver for VC and expectorated some sputum; however, the bronchial mucus volume was no CHEST, 73: 6, JUNE, 1978
greater with these maneuvers than after administration of isoproterenol or placebo without these maneuvers. We found the salivary amylase activity to be a useful marker of salivary contamination of sputum. Sputum was indeed extensively contaminated with saliva. About half of the sputum was, in fact, saliva, despite careful instruction to the patient to separate bronchial mucus from saliva in separate containers. We could not estimate the extent of salivary contamination by appearance. Others have successfully used the salivary amylase activity to establish the diagnosis of aspiration pneumonia.18 One must take this into account when, evaluating the volume or viscosity of sputum. REFERENCES
1 Wardell Jr JR, Chakrin L W , Payne B J : The canine tracheal pouch: A model for use in respiratory research. Am Rev Respir Dis 101:741-754, 1970 2 Klein B, Foreman JA, Searcy R L : New chromogenic substrate for determination of serum amylase activity. Clin Chem 1 6 : 3 2 - 3 8 , 1 9 7 0 3 Dalai F R , Winsten S: Laboratory evaluation of a chromogenic amylase method. Clin Chim Acta 32:327-332, 1971 4 Fowler WS, Helmholz H F Jr, Miller R D : Treatment of pulmonary emphysema with aerosolized bronchodilator drugs and intermittent positive pressure breathing. Proc Staff Meetings Mayo Clin 2 8 : 7 4 3 - 7 5 1 , 1 9 5 3 5 Goldberg I, Cherniak RM: The effect of nebulized bronchodilator delivered with and without IPPB on ventilatory function in chronic obstructive emphysema. Am Rev Respir Dis 9 1 : 1 3 - 2 0 , 1 9 6 5 6 Taylor W F , Heimlich EM, Stride L, et al: Intermittent positive pressure breathing versus Freon-unit nebulized isoproterenol in asthmatic children. J Allergy 38:257-263, 1966 7 Froeb H F : On the relief of bronchospasm and die induction of alveolar hyperventilation: A comparative study of nebulized bronchodilators by deep breathing and intermittent positive pressure. Dis Chest 38:483-489, 1960 8 Motley HL, Tomashefski J F : Treatment of chronic pulmonary disease with intermittent positive pressure breathing. Arch Industr Hyg Occup Med 5:1-9, 1952 9 Wu N, Miller W F , Cade R, et al: Intermittent positive pressure breathing in patients with chronic bronchopulmonary disease. Am Rev Tuberc Respir Dis 71:693-703, 1955 10 Yeates DB, Aspin N, Levinson H, et al: Mucociliary tracheal transport rates in man. J Appl Physiol 39:487-495, 1975 11 Sturgess J, Reid L : An organ culture study of the effects of drugs on the secretory activity of die human bronchial submucosal gland. Clin Sci 43:533-543, 1972 12 Santa Cruz R, Landa J, Hirsch J , et al: Tracheal mucous velocity in normal man and patients with obstructive lung disease: Effects of terbutaline. Am Rev Respir Dis 109: 458-463, 1974 13 Smith DD, McNamara T J : Sputum amylase in the evaluation of aspiration. Read before the annual meeting of the American Thoracic Society, New Orleans, May 16-19, 1976
EFFECT OF INHALATION THERAPY 801
