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27 Histamine hyperreactivity in allergic and idiopathic rhinitis
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EFFECT OF HISTMtINE _-__~
AND RAGWEEDNASAL PROVOCATION ON EUSTACHIAN TUBE FUNCTION. S. Gold MD, J.Besnstein MD, and J.W.Georgitis MD,Buffalo, NY, andton-Salem. NC. It has been suggested that middle ear problems may be related to nasal allergies. Eustachian tube function (ETF) was evaluated during nasal provocation testing (NPT) in 10 ragweed-allergic and 8 non-allergic subjects. Using the Okuda technique of anterior NPT,increasing concentrations of histamine or ragweed are placed directly on both inferior nasal turbinates until sneezing, rhinorrhea, nasal congestion and mucosal edema appear. Eustachian tube function was assessed by the performance of the g-step inflation-deflation tympanometric test (IDTT). IDTT was done immediately before and after each NPT. Definite changes of > than 10 mm water pressure were indicative of normal ETF. Each subject developed classical symptoms of allergic rhinitis after each NPT. Eight of the 10 allergic subjects underwent repetitive ragweed NPT; 7/8 non-atopic patients had multiple histamine NPT. Changes in ETF occurred in 7/40 histamine challenges and 14146 ragweed challenges. Four of these 14 changes exhibited a gain in ETF. These changes in ETF following either histamine or ragweed NPT were not significant. This study of allergic and non-allergic patients indicates that NPT with histamine or ragweed does not cause significant eustachian tube dysfunction. Further investigations are needed to explore the interaction between chronic rhinitis and eustachian tube dysfunction.
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EUSTACHIAN TUBE OBSTRUCTION (ETO) AFTER PROVOCATIVE INTRANASAL CHALLENGE WITH HOUSE DUST MITE. D. Skoner, M.D., A. Chamovitz, M.D., W. Doyle, C. Bluestone, M.D. and P. Fireman, M.D. Ph.D., Pittsburgh, Pennsylvania Previous studies have demonstrated that intranasal challenge with pollens in allergic rhinitis patients provoked immune mediated ET0 To delineate which was antigen dose dependent. additional antigens which may provoke ETO, the perennial antigen, Dermatophagoides farinae (DF), Adults with perennial allergic rhiwas studied. nitis and positive skin tests to DF were challenged by intranasal inhalation of pre-measured antigendoseswith increments from 0.5 to 10 mg. ET0 and nasal obstruction (NO) were assessed preand post-challenge by g-step pressure swallow tympanometry and anterior rhinomanometry, respecOf 40 ears (23 patients) studied, 6 tively. ears had ET0 prior to intranasal challenge, 5 developed ET0 at 0.5 mg, 2 at 1.0 mg, 11 at 5.0 mg in 18 and 4 at 10.0 mg. ET0 did not develop ears after doses up to 10.0 mg. ET0 resolved The antigen within 2 hours in 39 of 40 ears. doses required to provoke ET0 and NO were inversely proportional to patients' serum IgE antibody to DF (RAST) (p cO.05) which ranged from Control intra1.2 to 30.9% B/T (median 17). nasal challenge with dry lactose did not proby voke ETO. In summary, ET0 and NO provoked intranasal challenge with the perennial allergen DF are immune mediated and antigen dose depenAllergic rhinitis and NO generally predent. anticeded the development of ETO. The observed gen-induced ET0 may contribute to development of otitis media with effusion.
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HISTAMINE HYPERREACTIVITY IN ALLERGIC AND IRIDPATHIC RHINITIS. Howard Druce, M.D., Ralph Wright, R.N., David Ramos, Gordon Raphael, M.D., and Michael Kaliner, M.D., Bethesda, Maryland. Allergic rhinitis subjects (AR) are hyperreactive to nasal methacholine (MC); are they hyperreactive to histamine (H) as well? Nasal challenge with H or saline (S) was followed by collection of nasal secretions (by suction catheter, 6 cm along nasal floor) in AR (n=17), idiopathic rhinitis (IR, n=lO), and normals (NL, n=13). Protocol consisted of 4 prewashes with 4 ml S followed by either S 0.3 ml every 10 min x 4 or H (100, 1000, 3000, 1.0000pq) every 10 min. Prewash proteins (Lowry) were similar in the 3 groups as well as S control challenges. Table shows mean protein (pg + SEMI after tl challenge: Histamine Dose (psJO.3 ml) Final 3cw 100 1000 10000 Prewash 201t59 319?225* 4821135" NL 104+36 X15*37 IR 159+70 565+173+ 965?414* 862s?73* 1068&424* AR 248+65 1576-1436+ 1206*252+ 1176Q49+ 1027%L96+ * Pi.05 compared to final prewash + Pc.05 compared to final Prewash and NL group Therefore, AR respond with protein secretion to H challenge far more vigorously than NL, both in magnitude and sensitivity. IR are hyperresponsive, but not as sensitive as AR. The effect of Atropine (10 or 25 pg) was studied on this protocol in 3 subjects. It did not affect H induced protein release. Thus, AR (and IR) demonstrate nasal hyperreactivity to MC and H by a pathway other than that involvina muscarinic cholinergic stimulation.
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EFFECT OF RAGWEEDNASAL PROVOCATION ON MLKXSAL REACTIVITY IN ALLERGIC SUBJECTS. Jew. Gtorgii--s MD. Winston-Salem. N.C. Nasal provocation testing (NPT) with histamine in non-atopic subjects show increase reactivity in one nasal passage compared to the other. The study examines this response in ragweed-allergic patients undergoing NPT with aqueous mixed ragweed (Rw). Twenty-six ragweed-sensitive pts underwent ragweed NPT outside the pollen season. Serial lo-fold dilutions of Rw were placed directly on both inferior nasal turbinates in doses ranging from .005 mcg to 500 mcg. Results were monitored by changes in nasal airway resistance (Rn) and appearance of symptoms. Twenty-five of the 26 pts had a positive ragweed NPT with symptoms of sneezing, rhinorrhea, congestion, itching and mucosal pallor/edema. Only one NPT out of 72 caused a late reaction. There was no wheezing or anaphylactic symptoms. The provocative dilution for Rw was fairly consistent in 15/20 pts having repeated NPT. A direct relation was noted between changes in Rn and Rw dose. An increase in Rn by 100% occurred principally in one nasal passage in 23/26 pts.In 11/20 pts, the responsive side changed to the opposite nasal passage during subsequent NPT. These results indicate that NPT with ragweed is a safe and useful method in assessing the degree of nasal sensitivity to antigen. Like the normal response to histamine, the allergic nasal mucosa exhibits a unilateral responsiveness to ragweed. These findings corroborate the common complaint by patients of unilateral and alternating nasal itching and congestio:? during ragweed season.
26
EFFECT OF HISTMtINE _-__~
AND RAGWEEDNASAL PROVOCATION ON EUSTACHIAN TUBE FUNCTION. S. Gold MD, J.Besnstein MD, and J.W.Georgitis MD,Buffalo, NY, andton-Salem. NC. It has been suggested that middle ear problems may be related to nasal allergies. Eustachian tube function (ETF) was evaluated during nasal provocation testing (NPT) in 10 ragweed-allergic and 8 non-allergic subjects. Using the Okuda technique of anterior NPT,increasing concentrations of histamine or ragweed are placed directly on both inferior nasal turbinates until sneezing, rhinorrhea, nasal congestion and mucosal edema appear. Eustachian tube function was assessed by the performance of the g-step inflation-deflation tympanometric test (IDTT). IDTT was done immediately before and after each NPT. Definite changes of > than 10 mm water pressure were indicative of normal ETF. Each subject developed classical symptoms of allergic rhinitis after each NPT. Eight of the 10 allergic subjects underwent repetitive ragweed NPT; 7/8 non-atopic patients had multiple histamine NPT. Changes in ETF occurred in 7/40 histamine challenges and 14146 ragweed challenges. Four of these 14 changes exhibited a gain in ETF. These changes in ETF following either histamine or ragweed NPT were not significant. This study of allergic and non-allergic patients indicates that NPT with histamine or ragweed does not cause significant eustachian tube dysfunction. Further investigations are needed to explore the interaction between chronic rhinitis and eustachian tube dysfunction.
27
EUSTACHIAN TUBE OBSTRUCTION (ETO) AFTER PROVOCATIVE INTRANASAL CHALLENGE WITH HOUSE DUST MITE. D. Skoner, M.D., A. Chamovitz, M.D., W. Doyle, C. Bluestone, M.D. and P. Fireman, M.D. Ph.D., Pittsburgh, Pennsylvania Previous studies have demonstrated that intranasal challenge with pollens in allergic rhinitis patients provoked immune mediated ET0 To delineate which was antigen dose dependent. additional antigens which may provoke ETO, the perennial antigen, Dermatophagoides farinae (DF), Adults with perennial allergic rhiwas studied. nitis and positive skin tests to DF were challenged by intranasal inhalation of pre-measured antigendoseswith increments from 0.5 to 10 mg. ET0 and nasal obstruction (NO) were assessed preand post-challenge by g-step pressure swallow tympanometry and anterior rhinomanometry, respecOf 40 ears (23 patients) studied, 6 tively. ears had ET0 prior to intranasal challenge, 5 developed ET0 at 0.5 mg, 2 at 1.0 mg, 11 at 5.0 mg in 18 and 4 at 10.0 mg. ET0 did not develop ears after doses up to 10.0 mg. ET0 resolved The antigen within 2 hours in 39 of 40 ears. doses required to provoke ET0 and NO were inversely proportional to patients' serum IgE antibody to DF (RAST) (p cO.05) which ranged from Control intra1.2 to 30.9% B/T (median 17). nasal challenge with dry lactose did not proby voke ETO. In summary, ET0 and NO provoked intranasal challenge with the perennial allergen DF are immune mediated and antigen dose depenAllergic rhinitis and NO generally predent. anticeded the development of ETO. The observed gen-induced ET0 may contribute to development of otitis media with effusion.
28
HISTAMINE HYPERREACTIVITY IN ALLERGIC AND IRIDPATHIC RHINITIS. Howard Druce, M.D., Ralph Wright, R.N., David Ramos, Gordon Raphael, M.D., and Michael Kaliner, M.D., Bethesda, Maryland. Allergic rhinitis subjects (AR) are hyperreactive to nasal methacholine (MC); are they hyperreactive to histamine (H) as well? Nasal challenge with H or saline (S) was followed by collection of nasal secretions (by suction catheter, 6 cm along nasal floor) in AR (n=17), idiopathic rhinitis (IR, n=lO), and normals (NL, n=13). Protocol consisted of 4 prewashes with 4 ml S followed by either S 0.3 ml every 10 min x 4 or H (100, 1000, 3000, 1.0000pq) every 10 min. Prewash proteins (Lowry) were similar in the 3 groups as well as S control challenges. Table shows mean protein (pg + SEMI after tl challenge: Histamine Dose (psJO.3 ml) Final 3cw 100 1000 10000 Prewash 201t59 319?225* 4821135" NL 104+36 X15*37 IR 159+70 565+173+ 965?414* 862s?73* 1068&424* AR 248+65 1576-1436+ 1206*252+ 1176Q49+ 1027%L96+ * Pi.05 compared to final prewash + Pc.05 compared to final Prewash and NL group Therefore, AR respond with protein secretion to H challenge far more vigorously than NL, both in magnitude and sensitivity. IR are hyperresponsive, but not as sensitive as AR. The effect of Atropine (10 or 25 pg) was studied on this protocol in 3 subjects. It did not affect H induced protein release. Thus, AR (and IR) demonstrate nasal hyperreactivity to MC and H by a pathway other than that involvina muscarinic cholinergic stimulation.
111
EFFECT OF RAGWEEDNASAL PROVOCATION ON MLKXSAL REACTIVITY IN ALLERGIC SUBJECTS. Jew. Gtorgii--s MD. Winston-Salem. N.C. Nasal provocation testing (NPT) with histamine in non-atopic subjects show increase reactivity in one nasal passage compared to the other. The study examines this response in ragweed-allergic patients undergoing NPT with aqueous mixed ragweed (Rw). Twenty-six ragweed-sensitive pts underwent ragweed NPT outside the pollen season. Serial lo-fold dilutions of Rw were placed directly on both inferior nasal turbinates in doses ranging from .005 mcg to 500 mcg. Results were monitored by changes in nasal airway resistance (Rn) and appearance of symptoms. Twenty-five of the 26 pts had a positive ragweed NPT with symptoms of sneezing, rhinorrhea, congestion, itching and mucosal pallor/edema. Only one NPT out of 72 caused a late reaction. There was no wheezing or anaphylactic symptoms. The provocative dilution for Rw was fairly consistent in 15/20 pts having repeated NPT. A direct relation was noted between changes in Rn and Rw dose. An increase in Rn by 100% occurred principally in one nasal passage in 23/26 pts.In 11/20 pts, the responsive side changed to the opposite nasal passage during subsequent NPT. These results indicate that NPT with ragweed is a safe and useful method in assessing the degree of nasal sensitivity to antigen. Like the normal response to histamine, the allergic nasal mucosa exhibits a unilateral responsiveness to ragweed. These findings corroborate the common complaint by patients of unilateral and alternating nasal itching and congestio:? during ragweed season.