Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Antigen Reduces Nasal Transepithelial Electric Potential Differences and Alters Ion Transport in Allergic Rhinitis in Vivo Eri Suzumura & Kazuhiko Takeuchi To cite this article: Eri Suzumura & Kazuhiko Takeuchi (1992) Antigen Reduces Nasal Transepithelial Electric Potential Differences and Alters Ion Transport in Allergic Rhinitis in Vivo, Acta Oto-Laryngologica, 112:3, 552-558 To link to this article: http://dx.doi.org/10.3109/00016489209137439
Published online: 08 Jul 2009.
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Date: 15 March 2016, At: 10:28
Acta Otolaryngol (Stockh) 1992; 112 552-558
Antigen Reduces Nasal Transepithelial Electric Potential Differences and Alters Ion Transport in Allergic Rhinitis in Viva ERI SUZUMURA and KAZUHIKO TAKEUCHI From the Department of Otorhinolaryngology, Mie University School of Medicine, nu.Japan
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Suzumura E, Takeuchi K. Antigen reduces nasal transepithelial electric potential differences and alters ion transport in allergic rhinitis in vivo. Acta Otolaryngol (Stockh) 1992; 112: 552-558. The change of ion transport in acute allergic reactions in vivo was studied by measuring the nasal transepithelial potential difference (PD) in patients with nasal allergy to Japanese cedar pollens. Comparison of nasal PD in the pollen s a w n revealed a lower PD in the allergic patients than in the normal control subjects. We challenged the patients with allergen in the non-pollen season and measured the time course change of nasal PD and rate of inhibition of PD by amiloride and indomethacin. Nasal PD reached the lowest value I5 min after nasal allergen challenge. Percent inhibition of PD by amiloride wasgreater without the allergen challenge than it was in those patients afteF allergen challenge (51.7% versus 29.4%, ptO.01). Indomethacin did not chaw PD without allergen challenge, whereas it depressed nasal PD by 25.1 % after allergen challenge. These results suggest that decreased sodium absorption and increased chloride secretion occw in local allergic reactions. Both changes may contribute to the increase in fluid transport towards the lumen, and this may lead to abnormalities of nasal secretion during acute allergic reactions. Key words: amiioride. indomethacin. nmal epithelium, acute allergic reaction, transepithelial potential difference.
INTRODUCTION Abnormality of nasal secretion is a feature of acute allergic reaction in the nose. Changes in airway epithelial ion transport may contribute to this abnormality by affecting epithelial water secretion (1) as well as glandular secretion (2). A variety of inflammatory mediators and neurotransmitters have been found to affect airway epithelial ion transport (3). However, the influence of these mediators has been studied primarily in vitro by using excised respiratory epithelia (4, 3, and only the effects of single substances have been examined. Moreover, the relevance of these data to local allergic reaction in vivo, where neural mechanisms may be important (6), remains undefined. The objective of this investigation was to examine the changes in epithelial ion transport in the nose in allergic rhinitis, in vivo. We examined the nasal potential difference (PD) in patients allergic to Japanese cedar pollens (Cryptomeria Japonica, Sugi in Japanese). About 10% of the total population in Japan are considered to be allergic to this pollen, showing allergic symptoms from February to April (7). First, we compared the nasal PD of allergic patients with that of normal control subjects in the pollen season of Japanese cedar. Since the allergic patients showed a lower nasal PD than that of control subjects in the pollen season, we challenged the patients with the allergen in the non-pollen season to observe the time course change of nasal PD. In order to determine what ion transport mechanism is changed, we examined the percent inhibition of PDs by amiloride and indomethacin, both with and without antigen challenge. METHODS
Subjects Nasal PD measurements were studied in 3 groups: Group A: 14 patients with Japanese cedar pollinosis who visited Mie University Hospital in the pollen season of Japanese cedar (4 men
Ion transport in acute alleraic reaction 553
Acta Otolaryngol (Stockh) 112
PUMP
PLASTIC SYRINGE
(7
I
Downloaded by [ECU Libraries] at 10:28 15 March 2016
AGAR BRIDGE
P.D. AMPLIF'ER
RECORDER
Fig. I . Diagram of expenmental apparatus used to measure in vivo nasal PD.
SUBCUTANEOUS NEEDLE
and 10 women, mean age 26 years, range 11 to 44 years), Group B: 14 normal volunteers without any allergy who were medical or paramedical personnel (10 men and 4 women, mean age 25 years, range 22 to 29 years), Group C: 15 medical students with Japanese cedar pollinosis (9 men and 6 women, mean age 23 years, range 21 to 25 years). Japanese cedar pollinosis was diagnosed by a positive intradermal skin test to Japanese cedar pollen antigen, seasonal nasal symptoms, and rhinoscopic findings; red or pale coloring of the inferior turbinates, hypertrophy of nasal mucosa, and watery or mucoid secretion in the nasal cavities. These examinations were performed in the pollen season. None of the subjects had a history of allergies to other antigens. Non allergic subjects had neither seasonal nasal complaints nor a history of nasal disease. The subjects did not take any medication chronical1Y.
Measurements of the electric PD across the nasal epithelium The technique for measuring nasal epithelial PD was based on a previously reported method (8-9). Briefly, the reference bridge, a 21-gauge needle filled with physiological saline in 4 % agar, was inserted into the subcutaneous space of the forearm. The exploring bridge was constructed of a thin polyethylene tube, marked at 0.5 cm intervals and perfused with Ringer's solution at a rate of 0.2 ml/min. Both bridges were linked by an Ag/AgCI electrode to the input of a high impedance voltmeter (Fig. 1). The conductivity of the bridges was assessed by a preliminary measurement of skin PD. If a stable PD could not be recorded, the reference bridge was replaced, perfusion bridge flushed, and the test repeated. The position of the exploring bridge on the nasal mucosa was viewed through a rhinoscope. Because the epithelium of the inferior surface of the inferior turbinate at sites I cm posterior to the anterior tip is a well differentiated columnar, ciliated epithelium, where the magnitude of the PD is relatively high (8), nasal PD was measured at this point. Comparison of nasal PD between controls and allergic patients afer antigen challenge (GroupsA and B) The study was performed in the pollen season of Japanese cedar (March, 1990). Disks containing pollen extract (20 pg/ml in protein nitrogen; Torii Pharmaceutical Co., Tokyo, Japan) were put on the medial surface of the inferior turbinates bilateralIy for five min. Since the nasal symptoms of the patients are variable even in the pollen season and partially
554 E. Srizumura and K. Takeuchi
Acia ~okryngol(Stockh) I 12
dependent on the weather, we challenged the antigen t o induce a maximal acute allergic reaction. Both control subjects and allergic patients were challenged. Fifteen rnin after the allergen challenge, by the time positive immediate nasal responses were fully recognized, the nasal P D was measured. Nasal secretion filling the nasal cavities were gently suctioned before the P D measurements.
Time course change of nasal PD in allergic reaction (Group C) The study was performed out of the pollen season of Japanese cedar (May, 1990). After a stable baseline PD ofthe site was recorded for 1 min, antigen was challenged. Because controls showed no significant change before and after 15 rnin antigen challenge (-21.5 mV and -23.2 mV, respectively, n=3), time course change was obtained from allergic subjects by recording 5-s measurements every 5 rnin up to 20 min.
Downloaded by [ECU Libraries] at 10:28 15 March 2016
Efl&s of application of pharmacologic agents to the luminal surface with or without allergen challenge (Group C) The study was performed out of the pollen season of Japanese cedar (June-July, 1990). AmilorideHCl( M) or indomethacin M) were applied to the nasal mucosal surface through a second catheter. From subjects in Group C, we randomly selected 9 subjects as allergic control and 13 subjects as allergic test group (7 subjects were overlapping). To examine the effects of allergen challenge by amiloride, we applied amiloride without allergen challenge (allergic control), or 15 rnin after allergen challenge (allergic test group). Indomethacin was first dissolved in a small volume of dimethylsulfoxide, and was applied similarly (allergic control: n=5, allergic test group: n= 10, 5 subjects were overlapping). Because the action of the drugs on the airway epithelium is rapid (9), the effects on PD was monitored for 5 min. The procedure was approved by the Mie University Committee on the Right of Human Subjects, and informed consent was obtained.
Data analysis Because the PD of the left nasal cavity had a significant positive correlation to that of the right in both groups,the PD is expressed as the mean of measurements from both sides. All values, unless otherwise indicated, represent mean 2 SE. The paired r-test was used to compare the values of PDs in time course change, and before and after drug applications. The unpaired ttest was used to compare the mean values of PD in allergic subjects with controls, and % inhibition by drugs in allergic control with allergic test group. A pvalue of (0.05 was considered to be statistically significant. RESULTS Allergic patients showed sneezing, nasal obstruction, and watery secretion by nasal challenge of allergen, while controls showed no significant nasal symptoms. The PD was - 12.3 ? 1.O mV in the 14 allergic patients and -21.02 1.9 mV in the 14 control subjects. There was a significant statistical difference between the two groups (Fig. 2, p t 0 . 0 1 ) .The PD of the right nasal cavities correlated positively to that of the left side in both groups with correlation coefficients0.643 (p
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Antigen Reduces Nasal Transepithelial Electric Potential Differences and Alters Ion Transport in Allergic Rhinitis in Vivo Eri Suzumura & Kazuhiko Takeuchi To cite this article: Eri Suzumura & Kazuhiko Takeuchi (1992) Antigen Reduces Nasal Transepithelial Electric Potential Differences and Alters Ion Transport in Allergic Rhinitis in Vivo, Acta Oto-Laryngologica, 112:3, 552-558 To link to this article: http://dx.doi.org/10.3109/00016489209137439
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 6
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [ECU Libraries]
Date: 15 March 2016, At: 10:28
Acta Otolaryngol (Stockh) 1992; 112 552-558
Antigen Reduces Nasal Transepithelial Electric Potential Differences and Alters Ion Transport in Allergic Rhinitis in Viva ERI SUZUMURA and KAZUHIKO TAKEUCHI From the Department of Otorhinolaryngology, Mie University School of Medicine, nu.Japan
Downloaded by [ECU Libraries] at 10:28 15 March 2016
Suzumura E, Takeuchi K. Antigen reduces nasal transepithelial electric potential differences and alters ion transport in allergic rhinitis in vivo. Acta Otolaryngol (Stockh) 1992; 112: 552-558. The change of ion transport in acute allergic reactions in vivo was studied by measuring the nasal transepithelial potential difference (PD) in patients with nasal allergy to Japanese cedar pollens. Comparison of nasal PD in the pollen s a w n revealed a lower PD in the allergic patients than in the normal control subjects. We challenged the patients with allergen in the non-pollen season and measured the time course change of nasal PD and rate of inhibition of PD by amiloride and indomethacin. Nasal PD reached the lowest value I5 min after nasal allergen challenge. Percent inhibition of PD by amiloride wasgreater without the allergen challenge than it was in those patients afteF allergen challenge (51.7% versus 29.4%, ptO.01). Indomethacin did not chaw PD without allergen challenge, whereas it depressed nasal PD by 25.1 % after allergen challenge. These results suggest that decreased sodium absorption and increased chloride secretion occw in local allergic reactions. Both changes may contribute to the increase in fluid transport towards the lumen, and this may lead to abnormalities of nasal secretion during acute allergic reactions. Key words: amiioride. indomethacin. nmal epithelium, acute allergic reaction, transepithelial potential difference.
INTRODUCTION Abnormality of nasal secretion is a feature of acute allergic reaction in the nose. Changes in airway epithelial ion transport may contribute to this abnormality by affecting epithelial water secretion (1) as well as glandular secretion (2). A variety of inflammatory mediators and neurotransmitters have been found to affect airway epithelial ion transport (3). However, the influence of these mediators has been studied primarily in vitro by using excised respiratory epithelia (4, 3, and only the effects of single substances have been examined. Moreover, the relevance of these data to local allergic reaction in vivo, where neural mechanisms may be important (6), remains undefined. The objective of this investigation was to examine the changes in epithelial ion transport in the nose in allergic rhinitis, in vivo. We examined the nasal potential difference (PD) in patients allergic to Japanese cedar pollens (Cryptomeria Japonica, Sugi in Japanese). About 10% of the total population in Japan are considered to be allergic to this pollen, showing allergic symptoms from February to April (7). First, we compared the nasal PD of allergic patients with that of normal control subjects in the pollen season of Japanese cedar. Since the allergic patients showed a lower nasal PD than that of control subjects in the pollen season, we challenged the patients with the allergen in the non-pollen season to observe the time course change of nasal PD. In order to determine what ion transport mechanism is changed, we examined the percent inhibition of PDs by amiloride and indomethacin, both with and without antigen challenge. METHODS
Subjects Nasal PD measurements were studied in 3 groups: Group A: 14 patients with Japanese cedar pollinosis who visited Mie University Hospital in the pollen season of Japanese cedar (4 men
Ion transport in acute alleraic reaction 553
Acta Otolaryngol (Stockh) 112
PUMP
PLASTIC SYRINGE
(7
I
Downloaded by [ECU Libraries] at 10:28 15 March 2016
AGAR BRIDGE
P.D. AMPLIF'ER
RECORDER
Fig. I . Diagram of expenmental apparatus used to measure in vivo nasal PD.
SUBCUTANEOUS NEEDLE
and 10 women, mean age 26 years, range 11 to 44 years), Group B: 14 normal volunteers without any allergy who were medical or paramedical personnel (10 men and 4 women, mean age 25 years, range 22 to 29 years), Group C: 15 medical students with Japanese cedar pollinosis (9 men and 6 women, mean age 23 years, range 21 to 25 years). Japanese cedar pollinosis was diagnosed by a positive intradermal skin test to Japanese cedar pollen antigen, seasonal nasal symptoms, and rhinoscopic findings; red or pale coloring of the inferior turbinates, hypertrophy of nasal mucosa, and watery or mucoid secretion in the nasal cavities. These examinations were performed in the pollen season. None of the subjects had a history of allergies to other antigens. Non allergic subjects had neither seasonal nasal complaints nor a history of nasal disease. The subjects did not take any medication chronical1Y.
Measurements of the electric PD across the nasal epithelium The technique for measuring nasal epithelial PD was based on a previously reported method (8-9). Briefly, the reference bridge, a 21-gauge needle filled with physiological saline in 4 % agar, was inserted into the subcutaneous space of the forearm. The exploring bridge was constructed of a thin polyethylene tube, marked at 0.5 cm intervals and perfused with Ringer's solution at a rate of 0.2 ml/min. Both bridges were linked by an Ag/AgCI electrode to the input of a high impedance voltmeter (Fig. 1). The conductivity of the bridges was assessed by a preliminary measurement of skin PD. If a stable PD could not be recorded, the reference bridge was replaced, perfusion bridge flushed, and the test repeated. The position of the exploring bridge on the nasal mucosa was viewed through a rhinoscope. Because the epithelium of the inferior surface of the inferior turbinate at sites I cm posterior to the anterior tip is a well differentiated columnar, ciliated epithelium, where the magnitude of the PD is relatively high (8), nasal PD was measured at this point. Comparison of nasal PD between controls and allergic patients afer antigen challenge (GroupsA and B) The study was performed in the pollen season of Japanese cedar (March, 1990). Disks containing pollen extract (20 pg/ml in protein nitrogen; Torii Pharmaceutical Co., Tokyo, Japan) were put on the medial surface of the inferior turbinates bilateralIy for five min. Since the nasal symptoms of the patients are variable even in the pollen season and partially
554 E. Srizumura and K. Takeuchi
Acia ~okryngol(Stockh) I 12
dependent on the weather, we challenged the antigen t o induce a maximal acute allergic reaction. Both control subjects and allergic patients were challenged. Fifteen rnin after the allergen challenge, by the time positive immediate nasal responses were fully recognized, the nasal P D was measured. Nasal secretion filling the nasal cavities were gently suctioned before the P D measurements.
Time course change of nasal PD in allergic reaction (Group C) The study was performed out of the pollen season of Japanese cedar (May, 1990). After a stable baseline PD ofthe site was recorded for 1 min, antigen was challenged. Because controls showed no significant change before and after 15 rnin antigen challenge (-21.5 mV and -23.2 mV, respectively, n=3), time course change was obtained from allergic subjects by recording 5-s measurements every 5 rnin up to 20 min.
Downloaded by [ECU Libraries] at 10:28 15 March 2016
Efl&s of application of pharmacologic agents to the luminal surface with or without allergen challenge (Group C) The study was performed out of the pollen season of Japanese cedar (June-July, 1990). AmilorideHCl( M) or indomethacin M) were applied to the nasal mucosal surface through a second catheter. From subjects in Group C, we randomly selected 9 subjects as allergic control and 13 subjects as allergic test group (7 subjects were overlapping). To examine the effects of allergen challenge by amiloride, we applied amiloride without allergen challenge (allergic control), or 15 rnin after allergen challenge (allergic test group). Indomethacin was first dissolved in a small volume of dimethylsulfoxide, and was applied similarly (allergic control: n=5, allergic test group: n= 10, 5 subjects were overlapping). Because the action of the drugs on the airway epithelium is rapid (9), the effects on PD was monitored for 5 min. The procedure was approved by the Mie University Committee on the Right of Human Subjects, and informed consent was obtained.
Data analysis Because the PD of the left nasal cavity had a significant positive correlation to that of the right in both groups,the PD is expressed as the mean of measurements from both sides. All values, unless otherwise indicated, represent mean 2 SE. The paired r-test was used to compare the values of PDs in time course change, and before and after drug applications. The unpaired ttest was used to compare the mean values of PD in allergic subjects with controls, and % inhibition by drugs in allergic control with allergic test group. A pvalue of (0.05 was considered to be statistically significant. RESULTS Allergic patients showed sneezing, nasal obstruction, and watery secretion by nasal challenge of allergen, while controls showed no significant nasal symptoms. The PD was - 12.3 ? 1.O mV in the 14 allergic patients and -21.02 1.9 mV in the 14 control subjects. There was a significant statistical difference between the two groups (Fig. 2, p t 0 . 0 1 ) .The PD of the right nasal cavities correlated positively to that of the left side in both groups with correlation coefficients0.643 (p
