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PHYS THER
Vol. 79, No. 11, November 1999, pp. 1026-1031
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Research Reports

Cough Threshold in People With Spinal Cord Injuries

Kwan-Hwa Lin, Yih-Loong Lai, Huey-Dong Wu, Tyng-Quey Wang and Yen-Ho Wang

KH Lin, PhD, RPT, is Associate Professor, School of Physical Therapy, College of Medicine, National Taiwan University, No. 7, Chung-Shan S Rd, Taipei, Taiwan, Republic of China (lkh{at}ha.mc.ntu.edu.tw). Address all correspondence to Dr Lin
YL Lai is with the Department of Physiology, College of Medicine, National Taiwan University
HD Wu is with the Department of Integrated Diagno-therapeutics, National Taiwan University Hospital
TQ Wang is with the Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital
YH Wang is with the Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital


Submitted March 25, 1998; Accepted July 23, 1999


   Abstract
 
Background and Purpose. The purpose of this study was to compare the cough threshold between people with and without spinal cord injury (SCI). The effect of smoking on cough threshold was also investigated. Subjects. The participants were 26 people with SCI (15 smokers, 11 nonsmokers) and 18 people without SCI (9 smokers, 9 nonsmokers). Methods. Aerosols of citric acid were delivered with incremental doubling concentration from 62.5 mmol to 2 mol. Cough threshold was defined as the first concentration of citric acid that induced at least 2 coughs, which is associated with large chest excursion and concurrently acoustic response. Results. The mean cough thresholds of smokers and nonsmokers with SCI (209 and 417 mmol, respectively) were lower than those of smokers and nonsmokers without SCI (467 and 1,072 mmol, respectively). The mean citric acid cough thresholds decreased in smokers with and without SCI when compared with nonsmokers with and without SCI. Conclusion and Discussion. The cough sensitivity increased in subjects with SCI, and smoking could also increase the cough sensitivity. Training about the frequency and technique of cough in patients with SCI should be carefully monitored.

Key Words: Citric acid • Cough • Smoking • Spinal cord injury


   Introduction
Top
 Abstract
 Introduction
Method
 Results
 Discussion and Conclusion
 References
 
Coughing is an important mechanism to clear mucus or sputum from the conducting airways.1 People with spinal cord injury (SCI) have impaired coughing ability due to factors such as the paralysis or weakness of expiratory muscles.2,3 Several methods have been proposed to improve the coughing ability of people with SCI.4,5 There is a lack of studies, however, concerning the sensory and autonomic components (vagal afferent and efferent) of the cough reflex in people with SCI.

The cough reflex arises from the rapidly adapting receptors located in the airways and is mediated by vagal afferents to the cough center in the brain stem.1,6 The central output then sends information via vagal efferents to airway smooth muscles and via spinal nerves to the expiratory muscles to produce coughs.1,3 With power spectral analysis of parasympathetic vagal tone, transient bradycardia was observed in patients with acute7 and chronic8 tetraplegia. Dicpinigaitis et al9 further demonstrated bronchial hyperresponsiveness to methacholine (acetylcholine agonist) in patients with cervical spinal cord injury. Transection of the cervical or thoracic spine interrupts the sympathetic innervation, but the vagal nuclei of the brain stem remain intact.7–9 Such unopposed vagal tone might be expected to cause enhanced vagal activity to the heart and airways.7–9 Therefore, we hypothesized that the interruption of sympathetic outflow in people with SCI results in an increase in cough sensitivity (ie, a decrease in the cough threshold). The change in cough sensitivity may affect the chest care given by physical therapists and the administration of cough medicine.

Coughing can be induced voluntarily or reflexively.1 Bickerman and Barach10 were the first researchers to use citric acid aerosol (C6 H8 O7 · H2 O) to provoke the cough reflex in humans. The lowest concentration of a chemical irritant that elicits one to several coughs is known as the cough threshold.11 Previous studies12,13 have shown a wide interindividual and intraindividual response to citric acid. Cough threshold to citric acid, however, was reproducible with careful control of the time of the day the stimulus is introduced, the inspiratory flow rate, and the mode of inhalation.12–14 In general, the citric acid stimulus to cough has been shown to be reliable, reproducible, and consistent for quantifying the "sensitivity" of the cough reflex in people with and without SCI.12–14

Some of our patients with SCI are smokers. Taylor et al15 reported that smoking is associated with an increase in cough sensitivity. Therefore, the purpose of our study was to compare the cough threshold in smokers and nonsmokers with and without SCI.


   Method
Top
 Abstract
 Introduction
 Method
Results
 Discussion and Conclusion
 References
 
Subjects

The participants were 26 people with cervical and thoracic spinal cord (C4-T12) lesions and 18 people without spinal injury. Only male subjects were recruited because males have a high incidence of spinal injury compared with females.16 All subjects had neither systemic medical problems nor respiratory tract inflammation recently. The subjects with ASIA class A SCIs17 had complete lesions for least 1 year (range=1–20 years). The smokers were identified as having smoked at least 2 cigarettes a day for more than 1 year. Therefore, the subjects were divided into 4 groups: (1) smokers with SCI (7 with tetraplegia and 8 with paraplegia), (2) nonsmokers with SCI (6 with tetraplegia and 5 with paraplegia), (3) smokers without SCI (n=9), and (4) nonsmokers without SCI (n=9). All subjects gave informed consent for this study.

The characteristics of the subjects are presented in Table 1. There were no differences in age, height, or weight among the 4 groups. There also was no difference in duration of injury between the smokers and nonsmokers with SCI and no difference in the amount (pack-years) of cigarette smoking between subjects with and without SCI.


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  		Table 1. Basic Data of Smoking and Nonsmoking Subjects With and Without Spinal Cord Injury (SCI)

 
Citric Acid Cough Threshold

The citric acid aerosol was generated by a disposable jet nebulizer,* which was driven by a DeVilbiss Pulmi-Aide compressor/nebulizer (model 5650D){dagger} at the maximum output of 0.35 mL/min. The particle size of the aerosol was 0.5 to 5 µm, as stated by the manufacturer. Aerosols of citric acid were delivered with an incremental doubling concentration from 62.5 mmol to 2 mol (ie, 62.5 mmol, 125 mmol, 250 mmol, 500 mmol, 1 mol, and 2 mol).14 Citric acid aerosols were delivered until cough responses were observed. Five minutes was allowed to elapse between any 2 applications of the aerosol. At any one concentration, sterilized citric acid aerosol was administered by 6 successive deep inhalations. The first concentration of citric acid that induced at least 2 coughs within 3 minutes was defined as the citric acid cough threshold. The cough threshold was also expressed as the logarithmic concentration of citric acid for statistical analysis.14 The force of the cough was not monitored, but the cough was identified by the chest-wall movement and the acoustic response due to the sudden opening of the vocal cords.

Measurement of Cough Response

The cough response was recorded by a phonemeter (model TR-21A{ddagger}) attached to the side of the subject's Adam's apple to detect the sudden change in waveform of the sound. The chest excursion during a cough was detected by a pneumobelt (Pneumotrace Respiration Transducer, model 1130§) around the lower ribs. Both the sound wave and the chest excursion signals were recorded by a polygraph,|| as shown in Figure 1. The acoustic characteristics of cough were consistently observed in association with pneumobelt traces, which was considered valid for chest motion.18


Figure 1
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  		Figure 1. Example of cough responses after citric acid aerosol inhalation. The top panel shows the alteration of chest movement during coughing ({downarrow}); the lower panel shows the correspondent alteration of sound wave during coughing.

 
Measurement of Lung Function

Lung function was measured by a spirometer (Microspiro HI-601#), which was valid and accurate.19 Because citric acid may cause bronchoconstriction, both the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were measured immediately before and 3 minutes after the inhalation of citric acid aerosol to ensure that there was no change in expiratory flow volume. The decrease in FEV1/FVC (%) indicated bronchoconstriction.9,14

Data Analysis

All data were stored in a computer. The statistical analysis was performed using SPSS for Windows.** A 2-way ANOVA was used to analyze the effects of spinal injury and smoking on cough sensitivity. A Newman-Keuls test was used to differentiate differences between any 2 groups. If there was no interaction between spinal injury and smoking, the main effect was compared by an independent t test. The lung function before and after use of the citric acid aerosol was compared by a paired t test. All data were expressed as means and standard deviations. The level of significance was set at P<.05.


   Results
Top
 Abstract
 Introduction
 Method
 Results
Discussion and Conclusion
 References
 
Citric Acid Cough Threshold

The 2-way ANOVA indicated that there were main effects of spinal injury and smoking, although the interaction between SCI and smoking was not statistically significant (Tab. 2). As shown in Fig. 2, the mean cough thresholds of the subjects with SCI (both smokers and nonsmokers) were lower than those of the subjects without SCI (both smokers and nonsmokers). Furthermore, the mean effective citric acid cough threshold in the subjects with SCI patients who smoked was 209 mmol (range=102–427), which was lower than that of the subjects with SCI who did not smoke (x=417 mmol, range=224–776). The mean citric acid cough threshold for the subjects without SCI who smoked (x=467 mmol, range=224–977) was lower than that of the subjects without SCI who did not smoke (x=1,072 mmol, range=562–2,041).


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  		Table 2. Results of Two-Way Analysis of Variance for Effects of Injury and Smoking on Cough Threshold (N = 44)

 

Figure 2
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  		Figure 2. Comparison of citric acid (CA) concentration for inducing at least 2 coughs between subjects with spinal cord injury (SCI) and subjects without SCI who were smokers (S) and nonsmokers (NS). Asterisk (*) indicates difference at P<.05.

 
Pulmonary Lung Function Parameters

The FVC and FEV1 were less in the smokers and nonsmokers with SCI than in the smokers and nonsmokers without SCI (Tab. 3). There was no difference, however, in the ratio of FEV1 /FVC (%) among the 4 groups. After citric aerosol inhalation, there was no change in lung function in any group.


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  		Table 3. Lung Function Measures Before and After Citric Acid Aerosol Inhalationa

 

   Discussion and Conclusion
Top
 Abstract
 Introduction
 Method
 Results
 Discussion and Conclusion
References
 
This study demonstrated that the cough threshold was reduced in subjects with SCI compared with subjects without SCI. We also showed that subjects with SCI who smoked had lower cough thresholds than did subjects with SCI who did not smoke. The results indicate, therefore, that both spinal injury and smoking can reduce cough threshold in people with SCI.

The results support our hypothesis that spinal injury is a contributing factor for reducing the cough threshold. The unopposed vagal efferents in the subjects with SCI increased their discharge to augment cough sensitivity.20,21 The influence for lower thoracic injuries would be less. People with chronic SCI (ie, of more than 1 year's duration) may have morphological or osmolarity changes in the airway epithelium to increase the exposure of the receptor to chemical irritant,22 thus increasing the vagal afferent or efferent activities. Because there was no change in pulmonary function following application of citric acid aerosol in either the subjects with SCI or the subjects without SCI (Tab. 3), the observed changes of citric acid cough threshold in the subjects with SCI would not be due to the effect of bronchoconstriction. This view agrees with the finding of Dicpinigaitis et al.9

Our findings suggest that the ability to sense irritants in the airways is increased in people with SCI. The advantage of increased cough sensitivity is to detect chemical irritants or sputum easily and possibly help the clearance of the airways by coughing. The disadvantages of increased sensitivity are associated with frequent coughing and throat discomfort. Because huffing (known as "forced expiration") produces less discomfort in the throat than does coughing,23 people with SCI may try huffing. Huffing creates forced expiratory flows at different lung volumes through an open glottis (with their mouth open) and produces intrapulmonary pressures much lower than those produced by coughing.23 Less compression and narrowing of the airway during a huff may increase airflow and the efficiency of bronchial clearance.

We showed that the mean value of citric acid cough threshold in the subjects without SCI who did not smoke was 1,072 mmol (ie, 225 mg/mL). Previous researchers14,24,25 reported mean values for citric acid cough threshold ranging from 59 to 724 mg/mL in subjects without pulmonary problems who did not smoke. Schmidt et al25 reported the mean value of cough threshold for current smokers to be 40 mg/mL (ie, 190 mmol), with a range of 20 to 80 mg/mL. The mean values of cough threshold in our subjects without SCI (both smokers and nonsmokers) were within the ranges of previous studies. We believed the high intersubject variability with application of citric acid aerosol to be partly due to an inborn trait.24 The reproducibility of citric acid cough thresholds, however, was high.14,24 Although the sample size in our study was small, the power (1–ß) for statistical analysis in this study was from 0.7 to 0.8 in the 4 groups, which was, in our opinion, within the acceptable range.26

The results of our study indicate that cigarette smoking decreased the mean cough thresholds in both subjects with SCI and subjects without SCI, as compared with the subjects with similar characteristics who did not smoke. Although the underlying mechanism of smoking effects on citric acid cough threshold is not clear, a study of guinea pigs indicated that smoking increases epithelial permeability and thus enhances cough sensitivity following exposure to cigarette smoke.27 The increase in cough sensitivity in our subjects with SCI who smoked would enhance their frequency of coughing.

Furthermore, cigarette smoking may cause airflow obstruction.23 Therefore, smoking should be discouraged, and a chest care program with huffing could be tried in people with SCI. The mechanism of huffing is to produce dynamic squeezing and vibratory action to mobilize the secretions from the airways.28 As secretions reach the upper airways, a huff at a high lung volume can be used to clear them.


   Footnotes
 
Concept and research design were provided by KH Lin and HD Wu; writing, by KH Lin, YL Lai, and Professor Yu Ru Kou (Department of Physiology, National Yang-Ming University); data collection, by KH Lin; and data analysis, by KH Lin, HD Wu, Professor Huei-Chen Huang (Department of Pharmacology, College of Medicine, National Taiwan University), Dr Jau-Yih Tsauo (School of Physical Therapy, National Taiwan University), and Shiao-Chi Wu (Institute of Public Health, National Yang-Ming University). Project management was provided by KH Lin and Professor Shang-Ming Yu (Institute of Anatomy, National Yang-Ming University); fund procurement, by KH Lin and YL Lai; subjects, by KH Lin, YH Wang, and TQ Wang; facilities and equipment, by KH Lin and HD Wu; institutional liaisons, by KH Lin and YL Lai; and clerical support, by Hui-Wen Yang. Consultation (including review of manuscript before submission) was provided by YL Lai, HD Wu, and Yu Ru Kou. Shang-Ming Yu provided technical assistance. Huei-Chen Huang made invaluable suggestions.

This study was approved by the National Science Council, Taipei, Taiwan, Republic of China and was supported by a grant (NSC 85-2331-B-002-151) from the National Science Council.

Manufacturer Information

* Salter Labs, W Sycamore Rd, Arvin, CA 93203. Back

{dagger} Sunrise Medical, Somerset, PA 15501. Back

{ddagger} Grass Instrument Co, 101 Old Colony Ave, PO Box 516, Quincy, MA 02169. Back

§ UFI, 545 Main St, Morro Bay, CA 93442. Back

|| Gould Inc, 3631 Perkins Ave, Cleveland, OH 44114. Back

# Chest MI Inc, 3-6-10, Hongo, Bunkyo-ku, Tokyo, 113 Japan. Back

** SPSS Inc, 444 N Michigan Ave, Chicago, IL 60611. Back


   References
Top
 Abstract
 Introduction
 Method
 Results
 Discussion and Conclusion
 References
 

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