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Baclofen-induced cough suppression in cervical spinal cord injury
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Baclofen-Induced Cough Suppression in Cervical Spinal Cord Injury Peter V. Dicpinigaitis, MD, David R. Grimm, EdD, Marvin Lesser, MD ABSTRACT. Dicpinigaitis PV, Grimm DR, Lesser M. Baclofen-induced cough suppression in cervical spinal cord injury. Arch Phys Med Rehabil 2000;81:921-3. Objective: To determine the effect of the GABA-agonist baclofen on cough reflex sensitivity in subjects with cervical spinal cord injury (C-SCI). Baclofen has been shown to inhibit the cough reflex in able-bodied volunteers. Design: Prospective, nonrandomized control trial. Setting: Veterans Affairs medical center with large outpatient SCI population. Participants: Twelve adult males (11 outpatients) with C-SCI chronically maintained on oral baclofen for the treatment of muscle spasm. Intervention: Subjects underwent cough challenge testing with inhaled capsaicin. The concentrations (µM) of capsaicin inducing 2 or more (C2 ) and 5 or more (C5 ) coughs were determined. Mean values for log C2 and log C5 were compared with a control group of outpatients with C-SCI not receiving baclofen. Results: Subjects treated with baclofen had a significantly higher cough threshold (diminished cough reflex sensitivity) than control subjects. Mean (⫾ standard error of the mean) values for log C2 in study subjects and controls were 1.28 ⫾ .16 and .65 ⫾ .15, respectively ( p ⫽ .009). Mean values for log C5 in subjects receiving baclofen and in control subjects were 2.20 ⫾ .22 and 1.43 ⫾ .23, respectively ( p ⫽ .024). Subjects and controls did not differ in terms of age, spirometric parameters, or duration of injury. Conclusions: The results suggest that chronic therapy with baclofen diminishes cough reflex sensitivity in subjects with C-SCI. The clinical significance of this finding remains to be elucidated. Key Words: Cough; Baclofen; Capsaicin; Spinal cord injuries; Tetraplegia; Rehabilitation. 娀 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
T
HE COUGH REFLEX serves a protective function by preventing foreign material from entering the respiratory tract and by facilitating the expulsion of mucus from the airways. Cough is triggered by stimulation of sensory receptors within the respiratory tract, whose afferent impulses activate a
From the Department of Medicine, Albert Einstein College of Medicine (Dicpinigaitis), and the Spinal Cord Pulmonary Research Center, Veterans Affairs Medical Center (Grimm, Lesser), Bronx, NY; and the Department of Medicine, Mount Sinai School of Medicine, New York, NY (Grimm, Lesser). Submitted June 22, 1999. Accepted November 10, 1999. Supported by the Eastern Paralyzed Veterans Association. Presented in part at the Annual Conference of the American Paraplegia Society, September 9, 1999, Los Vegas, NV. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Reprint requests to Peter Dicpinigaitis, MD, Albert Einstein Hospital, 1825 Eastchester Rd, Bronx, NY 10461. 0003-9993/00/8107-5700$3.00/0 doi:10.1053/apmr.2000.5612
brainstem cough center.1 The expiratory muscles, by generating elevated intrathoracic pressures, produce an effective cough. Since cervical spinal cord injury (C-SCI) causes the loss of innervation of the expiratory muscles, the ability to generate an adequate cough is severely compromised, resulting in the common occurrence of mucus plugging, atelectasis, and recurrent respiratory infections. The deleterious effects of C-SCI on respiratory muscle strength and pulmonary function have been thoroughly studied.2,3 We have recently demonstrated, however, that the sensitivity of the cough reflex remains intact in persons with C-SCI.4 Gamma-aminobutyric acid (GABA), an inhibitory transmitter of the central nervous system, is also found in peripheral tissues, including the lungs.5 Baclofen, a GABA-B agonist, is a commonly used agent for the relief of muscle spasm, especially in patients with SCI or multiple sclerosis. Baclofen has been shown, in animal studies, to inhibit cough through a central site of action.6 Recently, the antitussive effect of baclofen has been confirmed in healthy, human volunteers.7 The aim of the present study was to investigate the effect of baclofen on cough reflex sensitivity in subjects with C-SCI. Cough sensitivity was measured by cough challenge testing with capsaicin, the pungent extract of red peppers that induces cough in a reproducible and dose-dependent manner.8 METHODS Subjects Twelve male subjects (11 outpatients) with mid-to-lower C-SCI, chronically maintained on baclofen for the relief of muscle spasm, were recruited for study, which was approved by the Institutional Review Board of the Veterans Affairs Medical Center, Bronx, New York. Subjects were without history of pulmonary disease or recent (within 1 month) symptoms of respiratory tract infection, seasonal allergies, postnasal drip, or gastroesophageal reflux. All subjects underwent annual, complete physical examinations at our institution’s Spinal Cord Damage Research Center, but were not examined immediately before the study. Of the 12 subjects, 3 were cigarette smokers. Data including subjects’ age, level and duration of injury, baseline forced vital capacity (FVC), and dosage and duration of baclofen therapy are provided (table 1). Capsaicin Cough Challenge Cough challenge testing was performed as previously described.4 Solutions of capsaicina were prepared and further diluted with physiologic saline solution to make serial doubling concentrations ranging from .98 to 1,000µM. After performing baseline spirometry, subjects inhaled single breaths of capsaicin aerosol from a compressed air-driven nebulizerb controlled by a dosimeter.c Single breaths of capsaicin were administered in ascending order, with inhalations of saline randomly interspersed to increase challenge blindness, until the concentrations inducing two or more coughs (C2 ) and five or more coughs (C5 ) were reached. Breaths were delivered at 1-minute intervals. The number of coughs in response to each concentration of capsaicin immediately after each inhalation was recorded by a Arch Phys Med Rehabil Vol 81, July 2000
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BACLOFEN-INDUCED COUGH SUPPRESSION, Dicpinigaitis Table 1: Subject Data
Table 2: Comparison of Baclofen and Control Groups
Subject
Age (yrs)
Injury Level
Injury Duration (yrs)
FVC(L) (%Predicted)
Baclofen Dose (mg/d)
Therapy Duration (yrs)
1 2 3 4 5 6 7 8 9 10 11 12
33 27 37 52 48 27 50 38 32 59 41 26
C6 C5 C6 C6 C7 C6 C6 C7 C6-C7 C4-C5 C7 C5
19 7 12 32 20 6 29 21 9 23 24 3
2.98 (56) 2.18 (34) 3.61 (67) 4.02 (73) 3.26 (65) 2.80 (53) 3.70 (67) 3.32 (60) 3.12 (54) 3.16 (59) 2.50 (49) 2.82 (49)
120 80 40 160 60 120 60 80 40 120 80 20
19 7 12 ⬎10 15 6 4 1 9 10 24 3
blinded observer. Subjects were unaware that the end point of the study was the number of coughs induced. Data Analysis Mean ⫾ standard error of the mean (SEM) values for log C2 and log C5 were calculated and compared, by an unpaired Student’s t test for independent samples, to a control group of 12 nonsmoking men with C-SCI, not receiving baclofen, who underwent identical cough challenge testing.4 RESULTS All subjects were able to perform baseline spirometry and capsaicin challenge studies adequately. The induction of 5 or more coughs was achieved in all subjects. Mean (⫾ SEM) log C2 and log C5 values for study subjects and controls (fig 1) showed that subjects maintained on baclofen had significantly higher cough thresholds (decreased cough reflex sensitivity)
Fig 1. Capsaicin cough challenge data in subjects treated with baclofen and control subjects: 䊊, mean log C5; 䊉, mean log C2. Error bars represent ⴞ standard error of the mean. * p ⴝ .024; ** p ⴝ .009.
Arch Phys Med Rehabil Vol 81, July 2000
Subjects (n) Age (yrs) Duration of injury (yrs) FVC (L) FVC (% predicted) FEV1 (L) FEV1 (% predicted) log C2 log C5
Baclofen
Control
p
12 39.2 ⫾ 3.2 17.1 ⫾ 2.7 3.12 ⫾ .15 57.2 ⫾ 3.0 2.44 ⫾ .16 55.3 ⫾ 3.8 1.28 ⫾ .16 2.20 ⫾ .22
12 43.2 ⫾ 3.7 15.6 ⫾ 2.9 3.11 ⫾ .21 57.5 ⫾ 3.1 2.54 ⫾ .16 58.1 ⫾ 2.8 .65 ⫾ .15 1.43 ⫾ .23
NS NS NS NS NS NS .009 .024
Values expressed as mean (standard error of the mean). Abbreviation: NS, not significant.
than control subjects. Subjects and controls did not differ in terms of age, level of injury, duration of injury, or baseline spirometric parameters (table 2), including FVC and forced expiratory volume in 1 second (FEV1 ). DISCUSSION Our finding that chronic therapy with the GABA-B agonist baclofen inhibits the sensitivity of the cough reflex in subjects with C-SCI is consistent with findings of previous studies on the antitussive effect of baclofen in healthy volunteers,7 in patients with idiopathic cough,9 and in patients with cough from angiotensin-converting enzyme (ACE) inhibitors.10 Because few subjects were available, our study group of 12 subjects included 3 smokers, whereas the control group consisted entirely of nonsmokers. It appears unlikely that the inclusion of three smokers among the subjects weakens the validity of our results, since cough threshold values did not significantly differ between smoking and nonsmoking subjects. The few, small studies previously performed in smokers have yielded contrasting data regarding the effect, if any, of cigarette smoking on cough reflex sensitivity.11-13 An effective cough requires an intact cough reflex as well as functional muscles of expiration to create elevated intrathoracic pressures. Subjects with C-SCI have a severely impaired cough because of loss of innervation of the expiratory muscles, despite the preservation of normal cough reflex sensitivity.4 Inhibition of the cough reflex by chronic baclofen therapy may further compromise the generation of an effective cough in subjects with C-SCI, thus rendering them at even greater risk for respiratory complications such as atelectasis and aspiration pneumonia. Although the clinical significance of our results is unknown at this time, previous studies in other populations suggest that suppression of the cough reflex may indeed have important clinical ramifications. For example, a diminished cough reflex has been associated with increased risk of developing aspiration pneumonia in stroke patients14 and in the elderly.15 Conversely, stroke patients whose hypertension is treated with ACE inhibitors, drugs which enhance cough reflex sensitivity, have a reduced incidence of pneumonia compared with stroke patients treated with other antihypertensive agents.16 The effect, if any, of baclofen on respiratory complications in subjects with C-SCI awaits further elucidation in prospective clinical trials. References 1. Widdicombe JG. Neurophysiology of the cough reflex. Eur Respir J 1995;8:1193-202. 2. Mansel JK, Norman JR. Respiratory complications and management of spinal cord injuries. Chest 1990;97:1446-52.
BACLOFEN-INDUCED COUGH SUPPRESSION, Dicpinigaitis
3. Wang AY, Jaeger RJ, Yarkony GM, Turba RM. Cough in spinal cord injured patients: the relationship between motor level and peak expiratory flow. Spinal Cord 1997;35:299-302. 4. Dicpinigaitis PV, Grimm DR, Lesser M. Cough reflex sensitivity in subjects with cervical spinal cord injury. Am J Respir Crit Care Med 1999;159:1660-2. 5. Ong J, Kerr DIB. GABA-receptors in peripheral tissues. Life Sci 1990;46:1489-501. 6. Bolser DC, DeGennaro FC, O’Reilly S, Chapman RW, Kreutner W, Egan RW, et al. Peripheral and central sites of action of GABA-B agonists to inhibit the cough reflex in the cat and guinea pig. Br J Pharmacol 1994;113:1344-8. 7. Dicpinigaitis PV, Dobkin JB. Antitussive effect of the GABAagonist baclofen. Chest 1997;111:996-9. 8. Midgren B, Hansson L, Karlsson J-A, Simonsson BG, Persson CGA. Capsaicin-induced cough in humans. Am Rev Respir Dis 1992;146:347-51. 9. Dicpinigaitis PV, Rauf K. Treatment of chronic, refractory cough with baclofen. Respiration 1998;65:86-8. 10. Dicpinigaitis PV. Use of baclofen to suppress cough induced by angiotensin-converting enzyme inhibitors. Ann Pharmacother 1996; 30:1242-5. 11. Auffarth B, de Monchy JGR, van der Mark TW, Postma DS, Koeter GH. Citric acid cough threshold and airway responsiveness
12. 13. 14. 15. 16.
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in asthmatic patients and smokers with chronic airflow obstruction. Thorax 1991;46:638-42. Schmidt D, Jorres RA, Magnussen H. Citric acid-induced cough thresholds in normal subjects, patients with bronchial asthma, and smokers. Eur J Med Res 1997;2:384-8. Taylor DR, Reid WD, Par PD, Fleetham JA. Cigarette smoke inhalation patterns and bronchial reactivity. Thorax 1988;43: 65-70. Addington RW, Stephens RE, Gilliland K, Rodriguez M. Assessing the laryngeal cough reflex and the risk of developing pneumonia after stroke. Arch Phys Med Rehabil 1999;80:150-4. Sekizawa K, Ujiie Y, Itabashi S, Sasaki H, Takishima T. Lack of cough reflex in aspiration pneumonia [letter]. Lancet 1990;335: 1228-9. Sekizawa K, Matsui T, Nakagawa T, Nakayama K, Sasaki H. ACE inhibitors and pneumonia [letter]. Lancet 1998;352:1069.
Suppliers a. Sigma Chemical Corp, 3050 Spruce St, St. Louis, MO 63103. b. Model 646; DeVilbiss Health Care, Inc, Somerset, PA. c. Koko DigiDoser; Pulmonary Data Service Instrumentation, Inc., 908 Main St, Louisville, CO 80027.
Arch Phys Med Rehabil Vol 81, July 2000
Baclofen-Induced Cough Suppression in Cervical Spinal Cord Injury Peter V. Dicpinigaitis, MD, David R. Grimm, EdD, Marvin Lesser, MD ABSTRACT. Dicpinigaitis PV, Grimm DR, Lesser M. Baclofen-induced cough suppression in cervical spinal cord injury. Arch Phys Med Rehabil 2000;81:921-3. Objective: To determine the effect of the GABA-agonist baclofen on cough reflex sensitivity in subjects with cervical spinal cord injury (C-SCI). Baclofen has been shown to inhibit the cough reflex in able-bodied volunteers. Design: Prospective, nonrandomized control trial. Setting: Veterans Affairs medical center with large outpatient SCI population. Participants: Twelve adult males (11 outpatients) with C-SCI chronically maintained on oral baclofen for the treatment of muscle spasm. Intervention: Subjects underwent cough challenge testing with inhaled capsaicin. The concentrations (µM) of capsaicin inducing 2 or more (C2 ) and 5 or more (C5 ) coughs were determined. Mean values for log C2 and log C5 were compared with a control group of outpatients with C-SCI not receiving baclofen. Results: Subjects treated with baclofen had a significantly higher cough threshold (diminished cough reflex sensitivity) than control subjects. Mean (⫾ standard error of the mean) values for log C2 in study subjects and controls were 1.28 ⫾ .16 and .65 ⫾ .15, respectively ( p ⫽ .009). Mean values for log C5 in subjects receiving baclofen and in control subjects were 2.20 ⫾ .22 and 1.43 ⫾ .23, respectively ( p ⫽ .024). Subjects and controls did not differ in terms of age, spirometric parameters, or duration of injury. Conclusions: The results suggest that chronic therapy with baclofen diminishes cough reflex sensitivity in subjects with C-SCI. The clinical significance of this finding remains to be elucidated. Key Words: Cough; Baclofen; Capsaicin; Spinal cord injuries; Tetraplegia; Rehabilitation. 娀 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
T
HE COUGH REFLEX serves a protective function by preventing foreign material from entering the respiratory tract and by facilitating the expulsion of mucus from the airways. Cough is triggered by stimulation of sensory receptors within the respiratory tract, whose afferent impulses activate a
From the Department of Medicine, Albert Einstein College of Medicine (Dicpinigaitis), and the Spinal Cord Pulmonary Research Center, Veterans Affairs Medical Center (Grimm, Lesser), Bronx, NY; and the Department of Medicine, Mount Sinai School of Medicine, New York, NY (Grimm, Lesser). Submitted June 22, 1999. Accepted November 10, 1999. Supported by the Eastern Paralyzed Veterans Association. Presented in part at the Annual Conference of the American Paraplegia Society, September 9, 1999, Los Vegas, NV. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Reprint requests to Peter Dicpinigaitis, MD, Albert Einstein Hospital, 1825 Eastchester Rd, Bronx, NY 10461. 0003-9993/00/8107-5700$3.00/0 doi:10.1053/apmr.2000.5612
brainstem cough center.1 The expiratory muscles, by generating elevated intrathoracic pressures, produce an effective cough. Since cervical spinal cord injury (C-SCI) causes the loss of innervation of the expiratory muscles, the ability to generate an adequate cough is severely compromised, resulting in the common occurrence of mucus plugging, atelectasis, and recurrent respiratory infections. The deleterious effects of C-SCI on respiratory muscle strength and pulmonary function have been thoroughly studied.2,3 We have recently demonstrated, however, that the sensitivity of the cough reflex remains intact in persons with C-SCI.4 Gamma-aminobutyric acid (GABA), an inhibitory transmitter of the central nervous system, is also found in peripheral tissues, including the lungs.5 Baclofen, a GABA-B agonist, is a commonly used agent for the relief of muscle spasm, especially in patients with SCI or multiple sclerosis. Baclofen has been shown, in animal studies, to inhibit cough through a central site of action.6 Recently, the antitussive effect of baclofen has been confirmed in healthy, human volunteers.7 The aim of the present study was to investigate the effect of baclofen on cough reflex sensitivity in subjects with C-SCI. Cough sensitivity was measured by cough challenge testing with capsaicin, the pungent extract of red peppers that induces cough in a reproducible and dose-dependent manner.8 METHODS Subjects Twelve male subjects (11 outpatients) with mid-to-lower C-SCI, chronically maintained on baclofen for the relief of muscle spasm, were recruited for study, which was approved by the Institutional Review Board of the Veterans Affairs Medical Center, Bronx, New York. Subjects were without history of pulmonary disease or recent (within 1 month) symptoms of respiratory tract infection, seasonal allergies, postnasal drip, or gastroesophageal reflux. All subjects underwent annual, complete physical examinations at our institution’s Spinal Cord Damage Research Center, but were not examined immediately before the study. Of the 12 subjects, 3 were cigarette smokers. Data including subjects’ age, level and duration of injury, baseline forced vital capacity (FVC), and dosage and duration of baclofen therapy are provided (table 1). Capsaicin Cough Challenge Cough challenge testing was performed as previously described.4 Solutions of capsaicina were prepared and further diluted with physiologic saline solution to make serial doubling concentrations ranging from .98 to 1,000µM. After performing baseline spirometry, subjects inhaled single breaths of capsaicin aerosol from a compressed air-driven nebulizerb controlled by a dosimeter.c Single breaths of capsaicin were administered in ascending order, with inhalations of saline randomly interspersed to increase challenge blindness, until the concentrations inducing two or more coughs (C2 ) and five or more coughs (C5 ) were reached. Breaths were delivered at 1-minute intervals. The number of coughs in response to each concentration of capsaicin immediately after each inhalation was recorded by a Arch Phys Med Rehabil Vol 81, July 2000
922
BACLOFEN-INDUCED COUGH SUPPRESSION, Dicpinigaitis Table 1: Subject Data
Table 2: Comparison of Baclofen and Control Groups
Subject
Age (yrs)
Injury Level
Injury Duration (yrs)
FVC(L) (%Predicted)
Baclofen Dose (mg/d)
Therapy Duration (yrs)
1 2 3 4 5 6 7 8 9 10 11 12
33 27 37 52 48 27 50 38 32 59 41 26
C6 C5 C6 C6 C7 C6 C6 C7 C6-C7 C4-C5 C7 C5
19 7 12 32 20 6 29 21 9 23 24 3
2.98 (56) 2.18 (34) 3.61 (67) 4.02 (73) 3.26 (65) 2.80 (53) 3.70 (67) 3.32 (60) 3.12 (54) 3.16 (59) 2.50 (49) 2.82 (49)
120 80 40 160 60 120 60 80 40 120 80 20
19 7 12 ⬎10 15 6 4 1 9 10 24 3
blinded observer. Subjects were unaware that the end point of the study was the number of coughs induced. Data Analysis Mean ⫾ standard error of the mean (SEM) values for log C2 and log C5 were calculated and compared, by an unpaired Student’s t test for independent samples, to a control group of 12 nonsmoking men with C-SCI, not receiving baclofen, who underwent identical cough challenge testing.4 RESULTS All subjects were able to perform baseline spirometry and capsaicin challenge studies adequately. The induction of 5 or more coughs was achieved in all subjects. Mean (⫾ SEM) log C2 and log C5 values for study subjects and controls (fig 1) showed that subjects maintained on baclofen had significantly higher cough thresholds (decreased cough reflex sensitivity)
Fig 1. Capsaicin cough challenge data in subjects treated with baclofen and control subjects: 䊊, mean log C5; 䊉, mean log C2. Error bars represent ⴞ standard error of the mean. * p ⴝ .024; ** p ⴝ .009.
Arch Phys Med Rehabil Vol 81, July 2000
Subjects (n) Age (yrs) Duration of injury (yrs) FVC (L) FVC (% predicted) FEV1 (L) FEV1 (% predicted) log C2 log C5
Baclofen
Control
p
12 39.2 ⫾ 3.2 17.1 ⫾ 2.7 3.12 ⫾ .15 57.2 ⫾ 3.0 2.44 ⫾ .16 55.3 ⫾ 3.8 1.28 ⫾ .16 2.20 ⫾ .22
12 43.2 ⫾ 3.7 15.6 ⫾ 2.9 3.11 ⫾ .21 57.5 ⫾ 3.1 2.54 ⫾ .16 58.1 ⫾ 2.8 .65 ⫾ .15 1.43 ⫾ .23
NS NS NS NS NS NS .009 .024
Values expressed as mean (standard error of the mean). Abbreviation: NS, not significant.
than control subjects. Subjects and controls did not differ in terms of age, level of injury, duration of injury, or baseline spirometric parameters (table 2), including FVC and forced expiratory volume in 1 second (FEV1 ). DISCUSSION Our finding that chronic therapy with the GABA-B agonist baclofen inhibits the sensitivity of the cough reflex in subjects with C-SCI is consistent with findings of previous studies on the antitussive effect of baclofen in healthy volunteers,7 in patients with idiopathic cough,9 and in patients with cough from angiotensin-converting enzyme (ACE) inhibitors.10 Because few subjects were available, our study group of 12 subjects included 3 smokers, whereas the control group consisted entirely of nonsmokers. It appears unlikely that the inclusion of three smokers among the subjects weakens the validity of our results, since cough threshold values did not significantly differ between smoking and nonsmoking subjects. The few, small studies previously performed in smokers have yielded contrasting data regarding the effect, if any, of cigarette smoking on cough reflex sensitivity.11-13 An effective cough requires an intact cough reflex as well as functional muscles of expiration to create elevated intrathoracic pressures. Subjects with C-SCI have a severely impaired cough because of loss of innervation of the expiratory muscles, despite the preservation of normal cough reflex sensitivity.4 Inhibition of the cough reflex by chronic baclofen therapy may further compromise the generation of an effective cough in subjects with C-SCI, thus rendering them at even greater risk for respiratory complications such as atelectasis and aspiration pneumonia. Although the clinical significance of our results is unknown at this time, previous studies in other populations suggest that suppression of the cough reflex may indeed have important clinical ramifications. For example, a diminished cough reflex has been associated with increased risk of developing aspiration pneumonia in stroke patients14 and in the elderly.15 Conversely, stroke patients whose hypertension is treated with ACE inhibitors, drugs which enhance cough reflex sensitivity, have a reduced incidence of pneumonia compared with stroke patients treated with other antihypertensive agents.16 The effect, if any, of baclofen on respiratory complications in subjects with C-SCI awaits further elucidation in prospective clinical trials. References 1. Widdicombe JG. Neurophysiology of the cough reflex. Eur Respir J 1995;8:1193-202. 2. Mansel JK, Norman JR. Respiratory complications and management of spinal cord injuries. Chest 1990;97:1446-52.
BACLOFEN-INDUCED COUGH SUPPRESSION, Dicpinigaitis
3. Wang AY, Jaeger RJ, Yarkony GM, Turba RM. Cough in spinal cord injured patients: the relationship between motor level and peak expiratory flow. Spinal Cord 1997;35:299-302. 4. Dicpinigaitis PV, Grimm DR, Lesser M. Cough reflex sensitivity in subjects with cervical spinal cord injury. Am J Respir Crit Care Med 1999;159:1660-2. 5. Ong J, Kerr DIB. GABA-receptors in peripheral tissues. Life Sci 1990;46:1489-501. 6. Bolser DC, DeGennaro FC, O’Reilly S, Chapman RW, Kreutner W, Egan RW, et al. Peripheral and central sites of action of GABA-B agonists to inhibit the cough reflex in the cat and guinea pig. Br J Pharmacol 1994;113:1344-8. 7. Dicpinigaitis PV, Dobkin JB. Antitussive effect of the GABAagonist baclofen. Chest 1997;111:996-9. 8. Midgren B, Hansson L, Karlsson J-A, Simonsson BG, Persson CGA. Capsaicin-induced cough in humans. Am Rev Respir Dis 1992;146:347-51. 9. Dicpinigaitis PV, Rauf K. Treatment of chronic, refractory cough with baclofen. Respiration 1998;65:86-8. 10. Dicpinigaitis PV. Use of baclofen to suppress cough induced by angiotensin-converting enzyme inhibitors. Ann Pharmacother 1996; 30:1242-5. 11. Auffarth B, de Monchy JGR, van der Mark TW, Postma DS, Koeter GH. Citric acid cough threshold and airway responsiveness
12. 13. 14. 15. 16.
923
in asthmatic patients and smokers with chronic airflow obstruction. Thorax 1991;46:638-42. Schmidt D, Jorres RA, Magnussen H. Citric acid-induced cough thresholds in normal subjects, patients with bronchial asthma, and smokers. Eur J Med Res 1997;2:384-8. Taylor DR, Reid WD, Par PD, Fleetham JA. Cigarette smoke inhalation patterns and bronchial reactivity. Thorax 1988;43: 65-70. Addington RW, Stephens RE, Gilliland K, Rodriguez M. Assessing the laryngeal cough reflex and the risk of developing pneumonia after stroke. Arch Phys Med Rehabil 1999;80:150-4. Sekizawa K, Ujiie Y, Itabashi S, Sasaki H, Takishima T. Lack of cough reflex in aspiration pneumonia [letter]. Lancet 1990;335: 1228-9. Sekizawa K, Matsui T, Nakagawa T, Nakayama K, Sasaki H. ACE inhibitors and pneumonia [letter]. Lancet 1998;352:1069.
Suppliers a. Sigma Chemical Corp, 3050 Spruce St, St. Louis, MO 63103. b. Model 646; DeVilbiss Health Care, Inc, Somerset, PA. c. Koko DigiDoser; Pulmonary Data Service Instrumentation, Inc., 908 Main St, Louisville, CO 80027.
Arch Phys Med Rehabil Vol 81, July 2000