Pregnancy rhinitis : pathophysiological effects of oestrogen and treatment with oral decongestants
Author: Toll, Karin
Date: 2007-11-09
Location: Birkeaulan, Karolinska Universitetssjukhuset, Huddinge
Time: 09.00
Department: Institutionen för klinisk vetenskap / Department of Clinical Sciences
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thesis.pdf (1.099Mb)
Abstract
Pregnancy rhinitis, a common condition, is thought to affect about 20 %
of pregnant women. This type of rhinitis may develop at any time during
pregnancy and the nasal stuffiness usually disappears shortly after
delivery. This condition is troublesome and can interfere with sleep,
induce tiredness and dryness of the mouth. It is difficult to treat and
no specific treatment seems to be entirely satisfactory. The aetiology of
pregnancy rhinitis and the effect of oestrogen on the nasal mucosa remain
to be clarified.
For purposes of research, it is essential to evaluate subjective complaints of nasal obstruction. Several methods can be used to rate sensory intensities. The telephone scoring system combined with a numerical rating scale (NRS) uses a computer to check the time when the estimate is made. Comparison of the symptoms estimated with two methods, a visual analogue scale (VAS) and telephone scoring system combined with a NRS show a strong correlation and symptom scores are similar. However, the patients find the latter system easier to use.
Phenylpropanolamine (PPA), a nasal decongestant given orally in sustained-release preparations, is commonly prescribed to relieve nasal blockage in viral infections of the upper airways and in allergic rhinitis. PPA in double the recommended dose has an excellent decongestive effect on the nasal mucosa of healthy subjects, and it has the same decongestive effect as oxymetazoline nasal spray, but the systolic and diastolic blood pressures also increase temporarily. When PPA is given in the recommended dose, as assessed by the telephone scoring system , it relieves nasal stuffiness in women with pregnancy rhinitis and has no effect on blood pressure.
The increase in oestrogen levels in blood during in vitro fertilization (IVF) in a group of healthy women causes hyperreactivity of the nasal mucosa after histamine challenge. However, no increase in nasal mucosal swelling is noted with low and high oestrogen levels before histamine challenge although perfusion and velocity tend to increase at high oestrogen levels as measured with laser Doppler flowmetry. The increase in perfusion and velocity after histamine challenge is lower at high than low oestrogen levels.
In the human nasal mucosa of healthy subjects, immunocytochemistry showed distinct oestrogen receptor (ER) beta positive cells in all sections. These cells, located subepithelially and close to the basal membrane, had no relation to the vascular or glandular structures or to the epithelium. They were comparatively large with a centrally-located nucleus. Immunoreactive signals for ER beta proteins were seen in their nuclei. Weak signals of ER beta immunostaining in the cytoplasm were also detected, which may indicate the presence of ER beta proteins in the cytoplasm. However, subglandular, endothelial and epithelial cells showed no immunoreactivity for ER beta in the nasal mucosa. Double immunostaining showed co-expression of ER beta with the specific mast cell marker, anti-human mast cell tryptase, in the vast majority of ER beta positive cells.
In conclusion, PPA in double the recommended dose has an excellent decongestive effect on the nasal mucosa of healthy subjects, and it has the same decongestive effect as oxymetazoline nasal spray. PPA given in the recommended dose relieves nasal stuffiness in women with pregnancy rhinitis and has no effect on blood pressure. These data indicate that PPA may be useful in the treatment of pregnancy rhinitis. In the human nasal mucosa of healthy subjects, we found ER beta positive cells. The increase in oestrogen levels in blood during IVF in a group of healthy women causes hyperreactivity of the nasal mucosa after histamine challenge. These findings indicate that oestrogen may play a role in the development of pregnancy rhinitis.
For purposes of research, it is essential to evaluate subjective complaints of nasal obstruction. Several methods can be used to rate sensory intensities. The telephone scoring system combined with a numerical rating scale (NRS) uses a computer to check the time when the estimate is made. Comparison of the symptoms estimated with two methods, a visual analogue scale (VAS) and telephone scoring system combined with a NRS show a strong correlation and symptom scores are similar. However, the patients find the latter system easier to use.
Phenylpropanolamine (PPA), a nasal decongestant given orally in sustained-release preparations, is commonly prescribed to relieve nasal blockage in viral infections of the upper airways and in allergic rhinitis. PPA in double the recommended dose has an excellent decongestive effect on the nasal mucosa of healthy subjects, and it has the same decongestive effect as oxymetazoline nasal spray, but the systolic and diastolic blood pressures also increase temporarily. When PPA is given in the recommended dose, as assessed by the telephone scoring system , it relieves nasal stuffiness in women with pregnancy rhinitis and has no effect on blood pressure.
The increase in oestrogen levels in blood during in vitro fertilization (IVF) in a group of healthy women causes hyperreactivity of the nasal mucosa after histamine challenge. However, no increase in nasal mucosal swelling is noted with low and high oestrogen levels before histamine challenge although perfusion and velocity tend to increase at high oestrogen levels as measured with laser Doppler flowmetry. The increase in perfusion and velocity after histamine challenge is lower at high than low oestrogen levels.
In the human nasal mucosa of healthy subjects, immunocytochemistry showed distinct oestrogen receptor (ER) beta positive cells in all sections. These cells, located subepithelially and close to the basal membrane, had no relation to the vascular or glandular structures or to the epithelium. They were comparatively large with a centrally-located nucleus. Immunoreactive signals for ER beta proteins were seen in their nuclei. Weak signals of ER beta immunostaining in the cytoplasm were also detected, which may indicate the presence of ER beta proteins in the cytoplasm. However, subglandular, endothelial and epithelial cells showed no immunoreactivity for ER beta in the nasal mucosa. Double immunostaining showed co-expression of ER beta with the specific mast cell marker, anti-human mast cell tryptase, in the vast majority of ER beta positive cells.
In conclusion, PPA in double the recommended dose has an excellent decongestive effect on the nasal mucosa of healthy subjects, and it has the same decongestive effect as oxymetazoline nasal spray. PPA given in the recommended dose relieves nasal stuffiness in women with pregnancy rhinitis and has no effect on blood pressure. These data indicate that PPA may be useful in the treatment of pregnancy rhinitis. In the human nasal mucosa of healthy subjects, we found ER beta positive cells. The increase in oestrogen levels in blood during IVF in a group of healthy women causes hyperreactivity of the nasal mucosa after histamine challenge. These findings indicate that oestrogen may play a role in the development of pregnancy rhinitis.
List of papers:
I. Graf P, Toll K, Palm J, Hallen H (1999). "Effects of sustained-release oral phenylpropanolamine on the nasal mucosa of healthy subjects." Acta Otolaryngol 119(7): 837-42
Pubmed
II. Hallén H, Djupesland P, Kramer J, Toll K, Graf P (2001). "Evaluation of a new method for assessing symptoms." ORL J Otorhinolaryngol Relat Spec 63(2): 92-5
Pubmed
III. Toll K, Graf P (2006). "Phenylpropanolamines decongestive effect on the nasalmucosa of pregnant women with nasal stuffiness." Rhinology 44(4): 274-7
Pubmed
IV. Toll K, Graf P, Backheden M, Stjärne P (2007). "Evidence that nasal mucosal hyperreactivity in healthy women is induced by high levels of estrogen." (Submitted)
V. Toll K, Canlon B, Dahlén B, Graf P, Henriksson E, Stjärne P (2007). "Oestrogen receptor beta in mast cells in the human nasal mucosa." (Submitted)
I. Graf P, Toll K, Palm J, Hallen H (1999). "Effects of sustained-release oral phenylpropanolamine on the nasal mucosa of healthy subjects." Acta Otolaryngol 119(7): 837-42
Pubmed
II. Hallén H, Djupesland P, Kramer J, Toll K, Graf P (2001). "Evaluation of a new method for assessing symptoms." ORL J Otorhinolaryngol Relat Spec 63(2): 92-5
Pubmed
III. Toll K, Graf P (2006). "Phenylpropanolamines decongestive effect on the nasalmucosa of pregnant women with nasal stuffiness." Rhinology 44(4): 274-7
Pubmed
IV. Toll K, Graf P, Backheden M, Stjärne P (2007). "Evidence that nasal mucosal hyperreactivity in healthy women is induced by high levels of estrogen." (Submitted)
V. Toll K, Canlon B, Dahlén B, Graf P, Henriksson E, Stjärne P (2007). "Oestrogen receptor beta in mast cells in the human nasal mucosa." (Submitted)
Issue date: 2007-10-19
Rights:
Publication year: 2007
ISBN: 978-91-7357-358-0
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