Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (12)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prudon, B.
Right arrow Articles by Pavord, I. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prudon, B.
Right arrow Articles by Pavord, I. D.
(Chest. 2005;127:550-557.)
© 2005 American College of Chest Physicians

Cough and Glottic-Stop Reflex Sensitivity in Health and Disease*

Benjamin Prudon, BSc; Surinder S. Birring, MB ChB, MD; Dhiraj D. Vara, ARTP; Andrew P. Hall, MB BChir; Jonathan P. Thompson, MB ChB, MD and Ian D. Pavord, DM

* From the Institute for Lung Health (Mr. Prudon, Drs. Birring and Pavord, and Mr. Vara), Department of Respiratory Medicine, Glenfield Hospital, Leicester; and the University Department of Anaesthesia (Drs. Hall and Thompson), Leicester Royal Infirmary, Leicester, UK.

Correspondence to: Surinder Birring, MB ChB, MD, Institute for Lung Health, Department of Respiratory Medicine, Glenfield Hospital, Leicester, LE3 9QP UK; e-mail: sb134{at}le.ac.uk


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: Little is known about the normal ranges and repeatability of cough reflex sensitivity measurements, or the relationship of cough reflex sensitivity to other upper airway reflexes in subjects with chronic dry cough. We set out to define the normal range of cough reflex sensitivity and its repeatability in health and disease, and to assess its relationship to the glottic-stop reflex.

Design: Prospective, cross-sectional study.

Subjects and methods: We measured capsaicin cough reflex sensitivity in 134 healthy subjects and 88 patients with respiratory disease, and assessed the repeatability over 2 weeks in a subgroup of individuals (healthy subjects, 15; chronic cough patients, 15). In another subgroup (healthy patients, 16; chronic cough patients, 14), we measured the sensitivity of the glottic-stop reflex (using inhaled ammonia).

Results: Capsaicin cough sensitivity varied widely in the population of healthy subjects, and there was considerable overlap of cough reflex sensitivity between healthy control subjects and patients with cough. The intraclass correlation coefficients for repeatability of cough sensitivity (concentration of capsaicin that causes two coughs, and concentration of capsaicin that causes five coughs) were 0.89 and 0.88, respectively. Patients with chronic cough had a significantly more sensitive glottic-stop reflex than healthy subjects (glottic-stop sensitivity threshold, 483 ppm vs 1,029 ppm, respectively; p = 0.01), and there was a significant positive correlation between glottic-stop and cough reflex sensitivity (r = 0.5; p < 0.01).

Conclusions: We have shown a wide variation of cough reflex sensitivity in healthy subjects, although the measurement does have good 2-week repeatability. There was a reasonably close relationship between cough sensitivity and glottic-stop reflex sensitivity, indicating either that the cough reflex and the glottic-stop reflex share a common pathway or that subjects who have a chronic cough have a global abnormality of upper airway reflexes.

Key Words: capsaicin • chronic cough • cough sensitivity • glottic-stop reflex • repeatability


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Assessment of cough reflex sensitivity is widely performed in the research setting, and many studies have established that patients with a chronic dry cough have a heightened cough reflex compared to that in healthy subjects,1234 and that cough sensitivity decreases after successful treatment of the cough.56 However, little is known about normal ranges from larger populations of subjects, and the repeatability of these measurements has not been studied in adults with chronic cough. Furthermore, many of the available studies are potentially flawed as they have not standardized the inspiratory flow rate, which has previously been shown to be an important determinant of the cough response in children,7 and may also be important in adults.

The increased cough sensitivity in patients with chronic cough may be due to increased concentrations of inflammatory mediators within the airway wall, and to the subsequent sensitization of nerve endings.89 Whether other upper airway reflexes are abnormal is unclear. One such reflex is the glottic-stop reflex to inhaled ammonia. The reflex closure of the glottis in response to irritant stimuli can be detected by a pneumotachograph. Assessed in this way, the glottic-stop reflex has been shown to be valid and repeatable, and has been advocated as a valuable tool in preanesthetic assessment.10111213 We measured capsaicin cough reflex sensitivity in a large number of healthy subjects and patients with chronic cough, and assessed the repeatability after 2 weeks using a breath-activated dosimeter with an inspiratory flow limit. We also compared cough reflex sensitivity to glottic-stop reflex sensitivity in healthy subjects and patients with chronic cough.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Subjects
One hundred thirty-four healthy volunteers were recruited from those responding to a local media advertisement. The volunteers completed a standardized questionnaire that asked about diagnoses of respiratory problems, gastroesophageal reflux (GER), rhinitis, and smoking history. Exclusion criteria were a diagnosis of respiratory disease or current respiratory symptoms, GER, upper airways symptoms, and current smoking, or a > 10 pack-year smoking history. All healthy subjects had normal spirometric values, with 29% defined as being atopic by the appearance of a > 2 mm wheal reaction to grass pollen, house dust mite, or cat fur compared to control solution. Eighty-eight subjects with respiratory conditions were recruited from adult respiratory outpatient clinics. The criteria used to diagnose cough-variant asthma, eosinophilic bronchitis, GER-associated cough, and other conditions were as previously described.14 Because of concerns about stopping therapy, some patients with asthma and COPD received therapy with inhaled corticosteroids and ß2-agonists at the time of the tests but were studied when symptomatic. Otherwise, patients were untreated and symptomatic. Both patients and control subjects were excluded from the study if they had experienced an upper respiratory tract infection within the last 2 months. Fifteen healthy subjects and 15 stable patients with a chronic cough (idiopathic chronic cough [ICC], 12 patients; cough-variant asthma, 1 patient; rhinitis-associated cough, 1 patient; and both rhinitis and GER-associated cough, 1 patient) participated in cough sensitivity repeatability. Thirty-four subjects were randomly selected for comparison with glottic-stop reflex sensitivity (healthy, 17 subjects; and chronic dry cough, 17 patients [ICC, 12 patients; cough-variant asthma, 2 patients; rhinitis-associated cough, 1 patient; GER-related cough, 1 patient; and rhinitis and GER cough, 1 patient]). The study was approved by the Leicestershire Research Ethics Committee, and all subjects gave full informed consent to participate in the study.

Cough Reflex Sensitivity Measurements
Serial dilutions of capsaicin (Sigma-Aldrich; St. Louis, MO) were used to produce doubling concentrations from 0.49 to 500 µmol/L. Subjects inhaled single vital capacity breaths of capsaicin solution via an air-powered dosimeter (KoKo Digidoser; Pulmonary Data Services Instrumentation Inc; Louisville, CO). The inspiration flow was standardized at 0.5 L/s with an inspiratory flow regulator valve, and the dosimeter output was set at 10 µL. Subjects inhaled 10 µL 0.9% saline solution followed by doubling-dose increases of capsaicin solution from 0.49 to 500 µmol/L every minute. Cough counting, facilitated by tape recording, was done for 30 s after exposure to each dose, and the investigation ended when the subject coughed five or more times in response to one dose, or received a dose of the highest concentration. To assess repeatability, subjects had a second cough reflex sensitivity measurement 2 weeks after the first, at the same time of day in order to avoid possible bias from diurnal variations.15

Glottic-Stop Reflex Sensitivity Measurements
Measurements of glottic-stop reflex sensitivity were made as previously described.1617 Briefly, subjects were asked to take several tidal breaths of room air (limb A), followed by a single tidal breath of dilute ammonia vapor unknowingly (limb B), which was controlled by the switching of the balloon valves by the operator, and then back to room air (Fig 1 ). The ammonia in limb B passed through a calibrated flowmeter, which allowed the concentration of ammonia vapor to be varied from 0 to 3,500 ppm. The investigation started with no ammonia in limb B, after which the concentration was increased in a standardized manner. The mouthpiece was connected to a pneumotachograph, which allowed real-time flow/time monitoring for the glottic-stop during each concentration of ammonia administered (Fig 2 ). The glottic stop was defined as a rapid decline in the inspiratory flow rate followed by a recovery, and the test completed when the threshold concentration of ammonia causing a glottic-stop reflex was recorded.



View larger version (28K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Diagram of the equipment used to measure the sensitivity of the glottic-stop reflex. A = room air limb; B = ammonia and air limb.

 


View larger version (17K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2. An example of a typical glottic stop. A = controller opens the ammonia limb; B = glottic stop, a rapid reduction in the inspiratory flow rate, followed by a recovery.

 
Statistical Analysis
The concentration of capsaicin that causes two coughs (C2) and the concentration of capsaicin that causes five coughs (C5) were calculated by the linear interpolation of the log dose-response curves, and were described as the geometric mean (logSD). A value of 500 µmol/L was assigned if interpolated values were > 500 µmol/L. All data were normally distributed after appropriate transformation, and independent-sample t tests and analysis of variance were used for across group comparisons. Factorial analysis of variance with the Tukey least significant difference for post hoc analysis was used to analyze capsaicin cough sensitivity data from patients with chronic cough to correct for gender differences. Correlations between variables were analyzed using the Pearson correlation coefficient (r). Repeatability data were assessed as the 95% confidence intervals (CIs) for repeat observations (two times the within-subject SD) and as the intraclass correlation coefficients.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Demographic details of healthy subjects and cough patients are shown in Table 1 . Measurements of cough reflex sensitivity were obtained in all 134 healthy subjects (Fig 3 ). We found a wide variation in cough sensitivity within the whole group. The geometric mean for C2 was 12.6 µmol/L (logSD, 0.5 µmol/L), and that for C5 was 158.5 µmol/L (logSD, 0.6 µmol/L). Men had a significantly less sensitive reflex compared to women for both C2 (mean difference, 0.9 doubling doses; 95% CI 0.3 to 1.5 doubling doses; p = 0.003) and C5 (mean difference, 0.9 doubling doses; 95% CI 0.3 to 1.5; p = 0.006). There was no relationship between age and logC2 within the whole group (r = –0.15; p = 0.08), but there was a weak negative correlation between age and logC5 (r = –0.18; p = 0.04; Fig 3). There were no differences in the geometric mean C2 or C5 in healthy women aged < 50 years compared to age > 50 years (Fig 3) and no effect of atopy.


View this table:
[in this window]
[in a new window]

  		Table 1. Clinical Characteristics*

 


View larger version (20K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3. Capsaicin cough reflex sensitivity of healthy subjects. Top, a: logC2; bottom, b: logC5. {triangleup} = women; {blacktriangleup} = men.

 
Measurements of cough reflex sensitivity in 88 patients with respiratory disease are shown in Table 2 . There were significant differences in the geometric means of C2 and C5 between healthy subjects and patients with cough-variant asthma, GER disease, and ICC, but there were not differences with patients with non-cough-variant asthma, COPD, and sarcoidosis (Table 2). There was no significant difference between the geometric means of C2 and C5 in patients with chronic productive cough and chronic dry cough (C2: 4.8 vs 2.9 µmol/L, respectively; mean difference, 0.7 doubling dose; 95% CI, –0.4 to 1.8 doubling doses; p = 0.22; and C5: 45 vs 18 µmol/L, respectively; mean difference, 1.4 doubling doses; 95% CI, –1.2 to 3.9; p = 0.3).


View this table:
[in this window]
[in a new window]

  		Table 2. Capsaicin Cough Reflex Sensitivity*

 
In the whole population, the intraclass correlation coefficient for logC2 was 0.89, and for logC5 it was 0.88 (Fig 4 ). The 95% CI for the doubling-dose change of C2 and C5 for the whole group was 1.5 and 3.3, respectively. There was a significant negative correlation between within-subject differences in C2 and C5 and the mean C2 and C5 in patients with chronic cough (r = –0.86 and –0.84, respectively; p < 0.001) [Fig 4].



View larger version (18K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4. Bland-Altman plot of (top, a) logC2 and (bottom, b) logC5 repeated over 2 weeks in patients with chronic cough and in healthy subjects. {triangleup}, healthy subjects; {blacktriangleup}, chronic cough patients; solid line, mean difference; dashed lines, 95% limit of agreement for C2 and C5.

 
We were unable to make a measurement of glottic-stop sensitivity in three of the chronic cough subjects and in one healthy subject because of coughing in response to inhaling ammonia (otherwise, there were no adverse events reported with capsaicin or ammonia inhalation). Cough subjects had a significantly more sensitive glottic-stop reflex than the healthy subjects (483 ppm vs 1,029 ppm; mean difference, 546 ppm; 95% CI, 137 to 954 ppm; p = 0.01) [Fig 5 ], as well having a significantly heightened cough reflex for both C2 (2.2 µmol/L vs 11.7 µmol/L; mean difference, 2.4 doubling doses; 95% CI, 1.3 to 3.5; p < 0.001) and C5 (10.8 µmol/L vs 172.6 µmol/L; mean difference, 4.0 doubling doses; 95% CI, 2.5 to 5.5 doubling doses; p < 0.001). There was a significant correlation between cough reflex sensitivity and glottic-stop reflex sensitivity (r = 0.5; p = 0.006).



View larger version (14K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 5. Measurements of glottic reflex sensitivity and cough reflex sensitivity in chronic cough patients and healthy subjects. {triangleup} = healthy subjects; {blacktriangleup} = chronic cough; glottic threshold = concentration of ammonia.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
We set out to investigate the validity of a single-breath inspiratory flow-regulated dosimeter technique for measuring capsaicin cough reflex sensitivity, in a relatively large population of control subjects and patients with respiratory disease with and without cough. We found that capsaicin cough sensitivity, whether expressed as C2 or C5, was significantly increased in healthy women compared to men. There was no marked effect of age. We confirmed that capsaicin cough sensitivity is significantly increased in respiratory conditions associated with cough, and have shown for the first time in an adult population with chronic cough that it can be measured in a repeatable way. Also, we have made the novel observation that patients with chronic cough have heightened glottic-stop reflex, and that glottic-stop reflex sensitivity correlates with capsaicin cough reflex.

This is the largest series of healthy control subjects subjected to cough reflex sensitivity testing in a standardized manner and, as such, represents a valuable resource for researchers in this field. The large numbers have allowed us to thoroughly investigate the effects of potential confounding factors such as gender, age, and atopic status. Ours is the first study to address the within-subject repeatability of cough reflex sensitivity testing in healthy adults and patients with chronic cough. This information is fundamentally important for the interpretation of serial test results and for planning of interventional studies.

Our findings on the sex differences in capsaicin cough reflex sensitivity are consistent with those of Dicpinigaitis and Rauf18 and Fujimura et al.19 Our findings are also consistent with those from a chronic cough population in which C2 and C5 were 1.5 and 2.6 doubling doses lower, respectively, in women than in men.20 The heightened capsaicin cough sensitivity seen in women offers a possible explanation for the female predominance in most cough syndromes.20 We were unable to confirm previous findings, in a population of similar size, showing that there is increased cough reflex sensitivity following menopause in healthy women,19 suggesting that the frequent clinical observation of cough onset around the time of menopause is not due to a group shift in cough reflex sensitivity at this age.

Our findings about patients with disease are largely consistent with previous findings. Cough reflex sensitivity was enhanced in patients with cough-variant asthma, GER-associated cough and ICC, but not in those with asthma without cough.12321 Our findings in COPD patients contrast with those of Doherty et al,2 who found a small but significant increase in cough sensitivity. We also found no evidence of heightened cough reflex sensitivity in unselected patients with sarcoidosis, a group that has not previously been studied. It is important to emphasize that our primary focus in studying patients with respiratory disease, with and without cough, was to validate our technique for assessing capsaicin cough reflex sensitivity measurement and not to explore minor differences between disease categories or disease-specific gender differences. We accept that the numbers studied in some categories were small and that there were differences in gender distribution, which, although corrected for by our analysis, might increase the chance of a type 2 error. It is important that larger, carefully controlled studies are performed before our findings can be regarded as definitive. Nevertheless, it is clear there was considerable overlap of measurements between health and disease suggesting that, in contrast to tests of airway hyperresponsiveness in asthma patients,22 the measurement of cough sensitivity has limited value in validating a clinical diagnosis of chronic cough. However, we have found the test to be repeatable. Our findings in healthy control subjects and patients with chronic cough are in keeping with those of Dicpinigaitis23 and others2425 who have found broadly similar repeatability in a cohort of healthy volunteers. The good repeatability of the test, together with the earlier demonstration that the measure improves significantly with the successful treatment of cough, suggests that capsaicin cough reflex sensitivity may be more useful in monitoring the response to intervention.26 There was a relationship between the mean values for C2 and C5 and the difference between repeat measures in patients with chronic cough. This finding was not an a priori hypothesis and could have arisen by chance or could be a function of regression toward the mean. Larger studies are required to determine whether this effect is real and to investigate the mechanism. We have not investigated the relationship between capsaicin cough sensitivity and other objective and subjective markers of cough severity. However, the recent development of well-validated measures272829 has made this feasible, and future studies should investigate this.

The mechanism of increased cough reflex sensitivity in patients with chronic cough is unclear but may involve the release of inflammatory mediators and the sensitization of sensory nerve endings. The inhalation of inflammatory mediators, such as prostaglandin F2{alpha} or E2, increases the cough response to inhaled capsaicin, which would be consistent with this mechanism.89 Whether other upper airway reflexes are abnormal in patients with chronic cough has not been established. We have studied the glottic-stop reflex since there is a well-validated and repeatable method to assess this.1011121330 The mechanism of glottic-stop reflex is unclear but may involve similar afferent pathways to cough. We found increased glottic-stop reflex sensitivity in patients with chronic cough and that the glottic-stop threshold correlated with capsaicin cough reflex sensitivity. Our population of cough patients had largely unexplained chronic cough, and we cannot exclude the possibility that increased glottic-stop reflex sensitivity is confined to this group. Glottic-stop reflex sensitivity is increased in smokers and following upper respiratory tract infections,1331 neither of which was present in the population of chronic cough patients that we studied. Our finding would be consistent with a common abnormal pathway in chronic cough patients, although a global abnormality of upper airway protective reflexes cannot be excluded. Further work is required to investigate this possibility.


   Acknowledgements
 
The authors thank all the volunteers who participated in this project, and all the staff of the Department of Respiratory Medicine, Glenfield Hospital.


   Footnotes
 
Abbreviations: CI = confidence interval; C2 = concentration of capsaicin that causes two coughs; C5 = concentration of capsaicin that causes five coughs; GER = gastroesophageal reflux; ICC = idiopathic chronic cough

This study was funded by The British Lung Foundation, University Hospitals of the Leicester NHS Trust, and PPP Foundation. Surinder Birring is a British Lung Foundation Clinical Research Fellow.

Received for publication September 25, 2003. Accepted for publication July 13, 2004.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Choudry, NB, Fuller, RW (1992) Sensitivity of the cough reflex in patients with chronic cough. Eur Respir J 5,296-300[Abstract]
  2. Doherty, MJ, Mister, R, Pearson, MG, et al Capsaicin responsiveness and cough in asthma and chronic obstructive pulmonary disease. Thorax 2000;55,643-649[Abstract/Free Full Text]
  3. Benini, L, Ferrari, M, Sembenini, C, et al Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage. Gut 2000;46,762-767[Abstract/Free Full Text]
  4. Fuller, RW, Choudry, NB Increased cough reflex associated with angiotensin converting enzyme inhibitor cough. BMJ (Clin Res Ed) 1987;295,1025-1026[ISI][Medline]
  5. O’Connell, F, Thomas, VE, Pride, NB, et al Capsaicin cough sensitivity decreases with successful treatment of chronic cough. Am J Respir Crit Care Med 1994;150,374-380[Abstract]
  6. Yeo, WW, Chadwick, IG, Kraskiewicz, M, et al Resolution of ACE inhibitor cough: changes in subjective cough and responses to inhaled capsaicin, intradermal bradykinin and substance-P. Br J Clin Pharmacol 1995;40,423-429[ISI][Medline]
  7. Chang, AB, Phelan, PD, Roberts, RG, et al Capsaicin cough receptor sensitivity test in children. Eur Respir J 1996;9,2220-2223[Abstract]
  8. Nichol, G, Nix, A, Barnes, PJ, et al Prostaglandin F2 alpha enhancement of capsaicin induced cough in man: modulation by beta 2 adrenergic and anticholinergic drugs. Thorax 1990;45,694-698[Abstract]
  9. Stone, R, Barnes, PJ, Fuller, RW Contrasting effects of prostaglandins E2 and F2 alpha on sensitivity of the human cough reflex. J Appl Physiol 1992;73,649-653[Abstract/Free Full Text]
  10. Murphy, PJ, Langton, JA, Barker, P, et al Effect of oral diazepam on the sensitivity of upper airway reflexes. Br J Anaesth 1993;70,131-134[Abstract/Free Full Text]
  11. Raphael, JH, Stanley, GD, Langton, JA Effects of topical benzocaine and lignocaine on upper airway reflex sensitivity. Anaesthesia 1996;51,114-118[ISI][Medline]
  12. Caranza, R, Nandwani, N, Tring, JP, et al Upper airway reflex sensitivity following general anaesthesia for day- case surgery. Anaesthesia 2000;55,367-370[CrossRef][ISI][Medline]
  13. Erskine, RJ, Murphy, PJ, Langton, JA Sensitivity of upper airway reflexes in cigarette smokers: effect of abstinence. Br J Anaesth 1994;73,298-302[Abstract/Free Full Text]
  14. Brightling, CE, Ward, R, Goh, KL, et al Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med 1999;160,406-410[Abstract/Free Full Text]
  15. Pounsford, JC, Saunders, KB Diurnal variation and adaptation of the cough response to citric acid in normal subjects. Thorax 1985;40,657-661[Abstract]
  16. Langton, JA, Murphy, PJ, Barker, P, et al Measurement of the sensitivity of upper airway reflexes. Br J Anaesth 1993;70,126-130[Abstract/Free Full Text]
  17. Hall, AP, Fox, AJ, Raphael, JH, et al Upper airway reactivity and upper respiratory tract infection: effect of nebulized lidocaine. Br J Anaesth 1999;82,857-860[Abstract/Free Full Text]
  18. Dicpinigaitis, PV, Rauf, K The influence of gender on cough reflex sensitivity. Chest 1998;113,1319-1321[Abstract/Free Full Text]
  19. Fujimura, M, Kasahara, K, Kamio, Y, et al Female gender as a determinant of cough threshold to inhaled capsaicin. Eur Respir J 1996;9,1624-1626[Abstract]
  20. Kastelik, JA, Thompson, RH, Aziz, I, et al Sex-related differences in cough reflex sensitivity in patients with chronic cough. Am J Respir Crit Care Med 2002;166,961-964[Abstract/Free Full Text]
  21. Wong, CH, Morice, AH Cough threshold in patients with chronic obstructive pulmonary disease. Thorax 1999;54,62-64[Abstract/Free Full Text]
  22. Hunter, CJ, Brightling, CE, Woltmann, G, et al A comparison of the validity of different diagnostic tests in adults with asthma. Chest 2002;121,1051-1057[Abstract/Free Full Text]
  23. Dicpinigaitis, PV Short- and long-term reproducibility of capsaicin cough challenge testing. Pulm Pharmacol Ther 2003;16,61-65[CrossRef][ISI][Medline]
  24. Fujimura, M, Sakamoto, S, Kamio, Y, et al Cough receptor sensitivity and bronchial responsiveness in normal and asthmatic subjects. Eur Respir J 1992;5,291-295[Abstract]
  25. Di Franco, A, Dente, FL, Giannini, D, et al Effects of inhaled corticosteroids on cough threshold in patients with bronchial asthma. Pulm Pharmacol Ther 2001;14,35-40[CrossRef][ISI][Medline]
  26. Brightling, CE, Ward, R, Wardlaw, AJ, et al Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis. Eur Respir J 2000;15,682-686[Abstract]
  27. Birring, SS, Prudon, B, Carr, AJ, et al Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax 2003;58,339-343[Abstract/Free Full Text]
  28. French, CT, Irwin, RS, Fletcher, KE, et al Evaluation of a cough-specific quality-of-life questionnaire. Chest 2002;121,1123-1131[Abstract/Free Full Text]
  29. Matos, S, Birring, SS, Patel, RB, et al Day time cough counts using the Leicester Cough Monitor (LCM) in patients with chronic cough and healthy controls. Thorax 2003;58,iii48
  30. Murphy, PJ, Erskine, R, Langton, JA The effect of intravenously administered diazepam, midazolam and flumazenil on the sensitivity of upper airway reflexes. Anaesthesia 1994;49,105-110[ISI][Medline]
  31. Nandwani, N, Raphael, JH, Langton, JA Effect of an upper respiratory tract infection on upper airway reactivity. Br J Anaesth 1997;78,352-355[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 ThoraxHome page
D Lasserson, K Mills, R Arunachalam, M Polkey, J Moxham, and L Kalra
Differences in motor activation of voluntary and reflex cough in humans
Thorax, August 1, 2006; 61(8): 699 - 705.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
J. Widdicombe and G. Fontana
Cough: what's in a name?
Eur. Respir. J., July 1, 2006; 28(1): 10 - 15.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (12)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prudon, B.
Right arrow Articles by Pavord, I. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prudon, B.
Right arrow Articles by Pavord, I. D.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS