Nasal passage patency in patients with allergic rhinitis measured by acoustic rhinometry: nasal responses after allergen and histamine provocation

Nasal passage patency in patients with allergic rhinitis measured by acoustic rhinometry: nasal responses after allergen and histamine provocation

Auris Nasus Larynx 25 (1998) 261 – 267 Nasal passage patency in patients with allergic rhinitis measured by acoustic rhinometry: nasal responses afte...

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Auris Nasus Larynx 25 (1998) 261 – 267

Nasal passage patency in patients with allergic rhinitis measured by acoustic rhinometry: nasal responses after allergen and histamine provocation Yukinori Miyahara, Kotaro Ukai *, Mikikazu Yamagiwa, Chikahisa Ohkawa, Yasuo Sakakura Department of Otorhinolaryngology, Mie Uni6ersity School of Medicine, 174 – 2 Edobashi, Tsu, Mie 514, Japan Received 1 September 1997; accepted 14 November 1997

Abstract We investigated nasal passage patency after allergen and histamine provocation in patients with allergic rhinitis by acoustic rhinometry. In total, 75 outpatients with allergic rhinitis were studied. The threshold of nasal hypersensitivity to histamine was measured by the 10 ml instillation of serial 10-fold dilution in the ipsilateral nasal cavity. Nasal provocation testing to specific antigen was applied to the anterior part of inferior turbinate in bilateral sides in sitting position. Measurement of nasal patency by acoustic rhinometry was repeated three times in each nasal cavity. The minimal cross-sectional area and total volume of nasal cavity were measured in an individual subject. The minimal cross-sectional area and total volume in the histamine challenged-side significantly decreased on the 10 − 2, 10 − 1, 10 − 0 of end point, and up to 30 min after challenge with the threshold dose, but not in the unchallenged side. This means acoustic reflection technique is sensitive at least 100-fold in comparison with classical method like findings by anterior rhinoscopy and symptom scores. Nasal passage patency after bilateral allergen provocation showed predominant in the unilateral side, suggesting the cross over-reflex effects.It was concluded that acoustic rhinometry is one of the highly quantitative and sensitive method which can observe the change of nasal congestion. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Acoustic rhinometry; Antigen; Histamine; Allergic rhinitis; Minimal cross-sectional area; Nasal cavity volume

Abbre6iations: AR, acoustic rhinometry; VOL, nasal cavity volume; A-min, minimum cross-sectional area in nasal cavity; S.E., standard error; RAST, radioallergo-sorbent test. * Corresponding author. Tel.: + 81 59 2321111; fax: + 81 59 2329582.

1. Introduction One of the characteristic features of allergic airway diseases is the extreme sensitivity of the

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respiratory mucosa to physical [1], chemical [2] and pharmacologic [3] stimuli. These patients develop a greater swelling of mucosa in response to a wide variety of stimuli than do healthy subjects [4]. Usually the nasal congestion has been evaluated by grading of the inferior turbinate swelling using rhinoscopy, which is a semiquantitative method [5]. The measurement of nasal resistance using rhinomanometry is a quantitative and objective method compared with grading of the inspection. The absolute resistance, however, and changes of resistance are difficult to interpret both functionally and pathoanatomically. Furthermore, there is an unsatisfactory correlation between the subjective perception of nasal congestion and the objective results for the nasal passage used these instruments. Another problem with rhinomanometry is that it is technically complicated and some subjects are not able to carry out the necessary maneuvers. Acoustic rhinometry (AR), based on Jackson’s algorithm [6] to calculate area-distance function of airway in the lung, was introduced as a new objective method for assessing the geometry of the nasal cavity by Hilberg et al. [7]. This method has made it possible to easily estimate nasal airway volume changes caused by vascular reactions of the nasal mucosa. The purpose of this investigation was to assess the value of this method on the nasal congestion after specific antigen- and nonspecific histamineprovocation in patients with allergic rhinitis.

2. Materials and methods

2.1. Subjects A total of 75 outpatients with allergic rhinitis, who had been referred to Mie University Hospital between January, 1991 and October, 1992, and showed nasal eosinophilia, positive skin test and/ or positive RAST in serum, were studied. A total of 30 for nasal hypersensitivity to histamine, who had perennial or seasonal allergic rhinitis and composed of 12 males and 18 females in age between 7 and 61 years with a mean age of 31

years, and 45 including 23 cases treated by hyposensitization therapy to house dust-mite (mean duration of 29 months) for nasal provocation test to specific antigen, who had perennial rhinitis, and composed of 32 males and 13 females in age between 6 and 61 years with a mean age of 22 years, were able to participate. All participants gave their informed consent.

2.2. Nasal hypersensiti6ity testing to histamine The threshold of nasal hypersensitivity to histamine was measured by using histamine hydrochloride. Microliters of serial 10-fold dilution starting from 102 to 105 mg/ml were used. Each dilution was applied to the anterior part of inferior turbinate in either side by using a dropper. Application was stopped whenever an attack of sneezing occurred within 1 min after instillation.

2.3. Nasal pro6ocation testing to specific antigen After a negative control challenge with Torii’s paper disc without antigen®, the Torii’s paper disc with specific antigen® was applied to the anterior part of each inferior turbinate in the sitting position. The typical nasal symptoms like sneeze, watery secretion and nasal blockade developed within 5 min after application in all of the provocated subjects. After 5 min of application, each Torii’s disc® was moved from the nasal cavity.

2.4. Acoustic rhinometry The experimental equipment for acoustic reflection measurements has been described previously [7] and will be briefly described here. The apparatus includes a computer (IBM AT-3) with an A/D-converter (Dash-16; Metrabyte, Taunton, MA) for data acquisition and processing, a trigger module (Model TM-11A; EG&G, Salem, MA), which produces the acoustic pulse, a wave tube (inner diameter, 1.5cm; length, 90cm) and a pieozo-electric microphone (Model 377; BBN, Cambridge, MA), and a 20 dB amplifier and a 10 kHz low-pass filter. A spark, generated by the trigger module, is discharged between two electrodes placed in the

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Fig. 1. A typical, normal area-distance curve by acoustic rhinometry. The integral of area distance curve between the tip of nose piece and posterior edge of nasal septum shows the total volume of nasal cavity in one side (shaded part).

end of the wave tube. This creates an acoustic pulse that propagates down the wave tube. It passes the microphone and enters the nasal cavity via the nosepiece, where it is reflected by changes in the local acoustic impedance resulting from changes in the cross-sectional area of the nasal cavity. The analog signal from the microphone is amplified, low pass-filtered, and digitalized at a sampling rate of 40 kHz. The data are converted to an area-distance function by software described previously. The cross-sectional areas are determined for a distance up to 20 cm with a spatial resolution of approximately 0.4 cm. The measurement itself lasts 8 ms, and it takes altogether 20 s for the complete data acquisition and storing process.

2.5. Experimental procedures Nosepieces with different diameters (i.d.; 9, 11, 13 mm) were used for nostrils of different sizes. Each measurement was repeated three times in each nasal cavity in order to assess the reproducibility of the measurements. Fig. 1 shows a typical, normal area-distance curve. From each measurement, the following dimensions were calculated: the minimal cross-sectional area (A-min) and total volume of the nasal cavity (VOL), by the integration of the area-distance curve between the nostril and the distance to posterior edge of nasal septum (Fig. 2) which were measured in an individual subject. For the histamine study, 10 ml of his-

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Fig. 2. Sagital view of nasal cavity. Nasal passage patency by acoustic rhinometry was measured on the tip of nosepiece to the choana (dotted area).

tamine was instilled into medial surface of the unilateral inferior turbinate. The measurements were performed on before and 5 min after the application of each serial dilution of histamine challenge and 10, 20, 30 min after the measurement of threshold of hypersensitivity to histamine. For the antigen provocation study, the paper disc was put on the medial surface of bilateral inferior turbinate. The measurements were done on the 5 min after control disc and 5, 15, 25 min after nasal challenge of specific antigen disc.

3. Results

3.1. Nasal hypersensiti6ity to histamine (Fig. 3a,b); Percent changes of A-min and VOL in the histamine challenged-side of 30 patients significantly decreased on the 10 − 2, 10 − 1 and 10 − 0 of end point, and these responses showed until 30 min after the challenge, compared with the pre-challenged values. On the other hand, those in the histamine unchallenged-side significantly decreased on the 10 − 3 and 10 − 2 of the end point.

2.6. Data analysis 3.2. Nasal pro6ocation to antigen Percent changes of A-min and VOL after to before nasal challenge of histamine or antigen (after-before/before ×100) was statistically analysed by Wilcoxon’s paired t-test. Value shows mean9 S.E.

The change of A-min and VOL before and after the challenge of control paper disc without allergen in the case of 58 nasal cavities did not show the significant difference between before and after

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the challenge. The change of A-min and VOL after the challenge of antigen in 45 subjects (90 sides) shows in Fig. 4a,b. All of 45 patients were able to divided on the non-responded and remarkable responded side, even though the antigen were challenged simultaneously on the each nasal turbinate. On the responded side, there was significant decrease more than 15% until 5 – 25 min after the challenge, compared with the pre-challenge values. On the other hand, there was no change except of A-min 25 min after the challenge in the non-responded side. The effect of immunotherapy on the VOL after the antigen challenge showed in Fig. 5. There was a significant decrease after the antigen challenge until 5 – 25 min in the untreated (22 subjects, 44 sides) and treated (23 subjects, 46

Fig. 4. Nasal passage patency after bilateral antigen provocation simultaneously; (a) VOL and (b) A-min measured by acoustic rhinometry. (“) Higher responded side; () lower unresponded side; *P B0.01, n =90.

sides) groups. There was no difference between both groups.

4. Discussion

Fig. 3. Nasal passage patency on unilateral instillation of histamine. (a) VOL and (b) A–min measured by acoustic rhinometry. (“) Histamine-challenged side; () un-challenged side; T, threshold; *P B 0.01, **PB 0.05, n=30.

Nasal blockade is caused by edema of the soft tissue of the nose, and by exudate and secretion which fills the nasal cavity. The ability to quantify this is of importance for evaluation of nasal hypersensitivity to histamine or nasal provocation to specific antigen. Rhinomanometry has been popularized as a method for assessing nasal blokade. However, this method has some disadvantages. A high degree of subject co-operation is required and the method can be time-consuming and often unsuitable for subjects with severely congested

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nasal airways. Thus, there is a requirement for a simple, non-invasive and reliable technique requiring minimal subject compliance. Recently, AR was introduced as a new objective method to assess the geometry of nasal cavity by Hilberg et al. [7]. Although it is impossible to express the sudden changes of nasal cavity, this method is a simple, reproducible, and relatively little subject co-operation and requires no airflow through the nose, so it can be used to obtain measurements from subjects with severely congested nasal airways. In this study, our data show that it is possible to observe the change of nasal passage up to 0.01 dose of threshold value on nasal mucosal hypersensitivity to histamine by using AR. Since the difference of threshold values of nasal hypersensitivity to histamine between in patients with and without allergic rhinitis is approximately 10-fold at the most [8], it is supposed that acoustic reflection technique is more sensitive at least 1000-fold than conventional method to measure the threshold of histamine-hypersensitivity, which have been decided by the grade of sneeze, watery rhinorrhea, or nasal blockade. After histamine challenge, percent changes of A-min and VOL in ipsilataral side reduced significantly at 0.01-, 0.1-, 1.0-folds of threshold and up to 30 min after challenge at threshold value of hypersensitivity, but not in the contralateral side except at 0.001 and 0.01 threshold dose. The decreased nasal passage patency after histamine challenge in ipsilataral side is likely to the in-

Fig. 5. The effect of immunotherapy on the percent changes of VOL after antigen challenge. () Untreated group (n = 44); (“) shows the treated group (n=46). *PB 0.01, **PB 0.05.

creased vascular permeability by direct action on H1 receptors on nasal vessels [9]. The role of reflexes in these changes remains undetermined, but it is clear that the venous sinusoids, which are the main determinant of nasal blockade, are controlled by sympathetic nerves [10]. In this study we found inconsistent decrease in nasal passage on the contralateral side that reached significance only with 0.001 and 0.01 threshold histamine challenge. The reason for this decrease in AR on contralateral side after histamine challenge is not apparent. We observed marked asymmetry of nasal passage patency after bilateral nasal allergen provocation in most subject’s noses. This study shows that nasal obstruction after bilateral nasal provocation of allergen is predominantly unilataral. This result suggests that there are two possibilities, that is, one is due to local effects in nasal vessels or nasal mucosa infiltrated with mast cells and/or eosinophils. Another possibility is a central nerve response to the contralateral side through the afferent nerve pathway. We investigated the correlation between the number of mast cells and eosinophils in scraping of inferior turbinate on the each side and the hyperreactivity to histamine and allergen, but there was no statistical difference between these factors (data not shown). Therefore, local effects due to inflammatory cells might be negligible on the assymmetry of nasal patency. Connell [11] reported that unilateral allergen challenge produced nasal congestion on the challenged side with decongestion on the contralateral side. Another investigators [12,13] examined that unilateral challenge with histamine or allergen produced the increase in nasal resistance on the challenged side, but no effect on contralateral side. Konno et al [14] found the increases in bilateral nasal blood flow with evidence of mucosal swelling after unilateral allergen challenge, but greater on the challenged side. Although not entirely consistent in their findings and conclusions, these studies suggest that a part of nasal congestion after nasal provocation is reflex-mediated and part is due to local effects in the nasal vessels, possible to mediators. After unilateral allergen provocation, mediator-induced

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changes should be most apparent near the site of release. Reflex effects apparently cross over and affect the non-provoked side. We evaluated the correlation between the percent changes of VOL and A-min 5 min after allergen challenge and the grade of swelling of inferior turbinate by the inspection, but these factors didn’t show a significant correlation (data not shown), suggesting unreliability of the inspection to the evaluation of nasal congestion. Tomkinson and Eccles [15] showed that no correlation was demonstrated between either AR or rhinomanometry and subjective sensation. Objective inspection of nasal mucosal swelling as well as subjective sensation of nasal blockade has indicated considerable discrepancy in comparison with the result of measurement by AR or rhinomanomatry. The effect of immunotherapy to house dust during 29 months in average on A-min and VOL after antigen challenge has not been shown in this study. This is consistent with clinical findings of poorly improved nasal congestion after immunotherapy [16]. In conclusion, this study indicates that the acoustic reflection technique is one of the most highly quantitative and sensitive methods for observing the change of nasal blockade.

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