Eur J Clin Pharmacol (1992) 42:561-562
© Springer-Verlag 1992
Inhibition of gustatory rhinorrhoea by intranasal ipratropium bromide N. B. Choudry 1, A. J. Harrison 2, and R. W. Fuller s
1Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, and 2Boehringer Ingelheim Limited, Bracknell, Berkshire, UK Received: June 11, 1991/Accepted in revised form: October 29, 1991
Key words: Rhinorrhoea, Ipratropium bromide
Nasal symptoms in the general population commonly arise from infection, allergy, or exposure to inhaled irritants. There are two mechanism by which the symptoms occur: first, vasodilatation leading to mucosal swelling and plasma exudation into the nose; second, glandular secretion [1, 2]. These effects can follow either direct stimulation of the blood vessel or glands by either inflammatory mediators [1] or irritants, or stimulation of nasal or extranasal sensory nerves leading to reflex activation of the glands and blood vessels [3]. Gustatory rhinorrhoea has been reported after eating spicy food and is a common and sometimes embarrassing symptom. It could occur through direct irritation by vapours arising from the food during swallowing, through local absorption of the spices, or through stimulation of neural reflexes within the nose or the oropharynx. We have investigated the hypothesis that the symptoms of gustatory rhinorrhoea are due to the stimulation of neural reflexes by giving the antimuscarinic agent ipratropium bromide intranasally to healthy volunteers who all ate the same spicy curry. We studied 43 volunteers aged 27 (SEM 1) y (26 m and 15 f). The volunteers marked visual analogue scales from 0-100 m m documenting their current perception of runny nose, sneezing, cough, blocked nose, itchy nose, sweating, flushing, and use of paper tissues. They then tool either ipratropium bromide 400 ~tg per nostril or a matched placebo from a metered dose inhaler in double-blind random order. After 30 rain they then ate the same quantity of mutton nahari (a strong curry) served with plain boiled rice over 10 min. Then 20 rain later they again marked the visual analogue scales and noted the number of tissues that they had used. The number of tissues and the change in distance from zero in m m on the visual analogue scales were analysed by non-parametric analysis of variance and the Mann-Whitney U test. A summary of the results is shown in Table 1. The volunteers who took placebo reported a significant
(P < 0.003) increase in the symptoms of runny nose and flushing and in the use of tissues. Those treated with ipratropium bromide had a similar increase in flushing, but had significantly fewer symptoms of runny nose (P < 0.05). T h e y also used fewer tissues, but this was not statistically significantly different from placebo. This study confirms the results of two earlier studies in small numbers of volunteers [5, 6], and shows that gustatory rhinorrhoea is due to stimulation of a neural reflex, probably arising outside the nose. Treatment with the antimuscarinic agent ipratropium bromide significantly reduced the symptoms of runny nose and reduced the use of tissues, although the latter did not reach statistical significance, probably due to the small number of tissues used in the placebo group. However, the symptom of facial flushing was not reduced, suggesting that ipratropium was exerting its effect locally in the nose. Gustatory rhinorrhoea is therefore probably due to a neural reflex rather than to the direct action of the spices on the glands and blood vessels of the nose itself. This study also confirms the effectiveness of anticholinergic agents in reducing rhinorrhoea, as has been reported in patients suffering from rhinorrhoea due to other causes, such as allergy [7] and vasomotor rhinitis [4]. This implies that maj or control of the volume of nasal secretion Table 1. The median VAS in mm for the symptoms and the number of tissues used
Symptoms
Before placebo
Runny nose Sneezing Cough Blocked nose Itchy nose Sweating Flushing Tissues
2 0 1 20 1 1 1 0
Curry plus placebo 16a 0 3 18 1 5 13a ia
Before Curry ipratropium plus ipratropium 7 9b 0 0 1 1.5 12 10 1.5 2 0 4 1 13° 0 0.5
"P < 0.003 compared with pre-treatment b p < 0.05 compared with placebo
562 is t h r o u g h the n e u r o g e n i c supply to the glands, rather than due to plasma exudation f r o m the b l o o d vessels,
Acknowledgements. We should like to thank the chef at Chutney's Drummond Street, London for preparing the curry.
References 1. Davies RJ, Ollier S, Cundell DR (1989) Drug treatment for nasal allergy. Clin Exp Allergy 19:559-568 2. Raphael GD, Meredith SD, Baraniuk JN, Kaliner MA (1988) Nasal reflexes. Am J Rhinol 2:109-116 3. Konno A, Togawa K, Fujiwara T (1983) The mechanisms involved in onset of allergic manifestations in the nose. Eur J Resp Dis 64: 155-166
4. Borum R Mygind N, Schultz Larsen F (1979) Intranasal ipratropium: a new treatment for perennial rhinitis. Clin Otolaryngol 4: 407-411 5. Raphael G, Hauptschein Raphael M, Kaliner M (1989) Gustatory rhinitis: a syndrome of food-induced rhinorrhoea. J Allergy Clin Immuno183:110-115 6. Onsberg B, Winter B, Mygind N (1987) Cold air-induced rhinorrhea and high-dose ipratropium. Arch Otolaryngol Head Neck Surg 113:160-162 7. Borum R Mygind N, Schultz Larsen F (1983) Ipratropium treatment for rhinorrhoea in patients with perennial rhinitis. An open follow-up study of efficacy and safety. Clin Otolaryngol 8:267-272 Dr. R. W. Fuller Department of Respiratory Medicine Glaxo Group Research Ltd Greenford Road Greenford Middlesex UB6 0HE, UK
© Springer-Verlag 1992
Inhibition of gustatory rhinorrhoea by intranasal ipratropium bromide N. B. Choudry 1, A. J. Harrison 2, and R. W. Fuller s
1Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, and 2Boehringer Ingelheim Limited, Bracknell, Berkshire, UK Received: June 11, 1991/Accepted in revised form: October 29, 1991
Key words: Rhinorrhoea, Ipratropium bromide
Nasal symptoms in the general population commonly arise from infection, allergy, or exposure to inhaled irritants. There are two mechanism by which the symptoms occur: first, vasodilatation leading to mucosal swelling and plasma exudation into the nose; second, glandular secretion [1, 2]. These effects can follow either direct stimulation of the blood vessel or glands by either inflammatory mediators [1] or irritants, or stimulation of nasal or extranasal sensory nerves leading to reflex activation of the glands and blood vessels [3]. Gustatory rhinorrhoea has been reported after eating spicy food and is a common and sometimes embarrassing symptom. It could occur through direct irritation by vapours arising from the food during swallowing, through local absorption of the spices, or through stimulation of neural reflexes within the nose or the oropharynx. We have investigated the hypothesis that the symptoms of gustatory rhinorrhoea are due to the stimulation of neural reflexes by giving the antimuscarinic agent ipratropium bromide intranasally to healthy volunteers who all ate the same spicy curry. We studied 43 volunteers aged 27 (SEM 1) y (26 m and 15 f). The volunteers marked visual analogue scales from 0-100 m m documenting their current perception of runny nose, sneezing, cough, blocked nose, itchy nose, sweating, flushing, and use of paper tissues. They then tool either ipratropium bromide 400 ~tg per nostril or a matched placebo from a metered dose inhaler in double-blind random order. After 30 rain they then ate the same quantity of mutton nahari (a strong curry) served with plain boiled rice over 10 min. Then 20 rain later they again marked the visual analogue scales and noted the number of tissues that they had used. The number of tissues and the change in distance from zero in m m on the visual analogue scales were analysed by non-parametric analysis of variance and the Mann-Whitney U test. A summary of the results is shown in Table 1. The volunteers who took placebo reported a significant
(P < 0.003) increase in the symptoms of runny nose and flushing and in the use of tissues. Those treated with ipratropium bromide had a similar increase in flushing, but had significantly fewer symptoms of runny nose (P < 0.05). T h e y also used fewer tissues, but this was not statistically significantly different from placebo. This study confirms the results of two earlier studies in small numbers of volunteers [5, 6], and shows that gustatory rhinorrhoea is due to stimulation of a neural reflex, probably arising outside the nose. Treatment with the antimuscarinic agent ipratropium bromide significantly reduced the symptoms of runny nose and reduced the use of tissues, although the latter did not reach statistical significance, probably due to the small number of tissues used in the placebo group. However, the symptom of facial flushing was not reduced, suggesting that ipratropium was exerting its effect locally in the nose. Gustatory rhinorrhoea is therefore probably due to a neural reflex rather than to the direct action of the spices on the glands and blood vessels of the nose itself. This study also confirms the effectiveness of anticholinergic agents in reducing rhinorrhoea, as has been reported in patients suffering from rhinorrhoea due to other causes, such as allergy [7] and vasomotor rhinitis [4]. This implies that maj or control of the volume of nasal secretion Table 1. The median VAS in mm for the symptoms and the number of tissues used
Symptoms
Before placebo
Runny nose Sneezing Cough Blocked nose Itchy nose Sweating Flushing Tissues
2 0 1 20 1 1 1 0
Curry plus placebo 16a 0 3 18 1 5 13a ia
Before Curry ipratropium plus ipratropium 7 9b 0 0 1 1.5 12 10 1.5 2 0 4 1 13° 0 0.5
"P < 0.003 compared with pre-treatment b p < 0.05 compared with placebo
562 is t h r o u g h the n e u r o g e n i c supply to the glands, rather than due to plasma exudation f r o m the b l o o d vessels,
Acknowledgements. We should like to thank the chef at Chutney's Drummond Street, London for preparing the curry.
References 1. Davies RJ, Ollier S, Cundell DR (1989) Drug treatment for nasal allergy. Clin Exp Allergy 19:559-568 2. Raphael GD, Meredith SD, Baraniuk JN, Kaliner MA (1988) Nasal reflexes. Am J Rhinol 2:109-116 3. Konno A, Togawa K, Fujiwara T (1983) The mechanisms involved in onset of allergic manifestations in the nose. Eur J Resp Dis 64: 155-166
4. Borum R Mygind N, Schultz Larsen F (1979) Intranasal ipratropium: a new treatment for perennial rhinitis. Clin Otolaryngol 4: 407-411 5. Raphael G, Hauptschein Raphael M, Kaliner M (1989) Gustatory rhinitis: a syndrome of food-induced rhinorrhoea. J Allergy Clin Immuno183:110-115 6. Onsberg B, Winter B, Mygind N (1987) Cold air-induced rhinorrhea and high-dose ipratropium. Arch Otolaryngol Head Neck Surg 113:160-162 7. Borum R Mygind N, Schultz Larsen F (1983) Ipratropium treatment for rhinorrhoea in patients with perennial rhinitis. An open follow-up study of efficacy and safety. Clin Otolaryngol 8:267-272 Dr. R. W. Fuller Department of Respiratory Medicine Glaxo Group Research Ltd Greenford Road Greenford Middlesex UB6 0HE, UK
