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Characteristics of children with allergic rhinitis and chronic mouth breathing
J ALLERGY CLIN IMMUNOL VOLUME 109, NUMBER 1
minute intervals, during randomized paired sessions. Symptom scores, sneeze and cough counts, nasal secretion weights, nasal conductance (rhinomanometry), middle ear pressure (tympanometry), eustachian tube function (sonotubometry) and pulmonary function (spirometry) were assessed before and after the histamine challenge, after each dose of IL- 1[3 or placebo and then at 90 minutes, 2, 3, 4, 6 and 24 hours. At the doses utilized, intranasal challenge with IL-1]3 was well tolerated. At the 24 hour postchallenge endpoint, a significant effect of challenge substance was documented for nasal secretion weights in all subjects (n=30). There was a trend toward an increased effect in allergic as compared to non-allergic subjects; however, none of the inter-group differences achieved statistical significance. Following intranasal challenge with 1L-l[3 and placebo, mean (+ SEM) 24 hour secretion weights (gins) were 9.61 + 5.24 and 6.92 + 3.76 in symptomatic allergic subjects, 4.97 + 0.38 and 2.28 + 0.38 in asymptomatic allergic subjects, 2.60 + 0.84 and 1.89 + 0.71 in non-allergic subjects, and 5.73 + 3.38 and 3.70 + 2.28 in all subjects (p < 0.05), respectively. There were no differences between placebo and IL-I~ challenge for any of the other measured parameters. These results show that local IL- 113at relatively low doses can provoke increased nasal secretions, an effect that is exacerbated in subjects with allergic rhinitis.
802Th2 Priming Induced by Intranasal Exposure,o So]uble Protein Antigens Stephanie Eisenbarth, Christina Herrick, Kim Bottomly Yale University, New Haven, CT The mechanism of T helper type 2 cell (Th2) priming upon inhaled allergen exposure remains unclear. The majority of murine models of asthma currently induce a Th2 response using antigen injected intraperitoneally with Aluminum hydroxide (alum) to induce eosinophilic pulmonary inflammation and airway hyperresponsiveness. Our objective was to establish and to evaluate the factors required for effective Th2 priming in response to inhaled protein antigens, such as Ovalbumin (OVA). Our lab has developed an intranasal (i.n.) sensitization model, without the use of alum, which initiates effective Th2 priming and T cell recruitment to the lung. Optimal lung inflammation was seen following sensitization with three days of 100 ug ofi.n. OVA followed two weeks later by i.n. challenge with 25 ug OVA over a six day period. Both Balb/c and C57BL/6 mice have been sensitized effectively using this protocol. The allergic response in this model reproduces the key characteristics of asthma, namely, pulmonary inflammation dominated by eosinophilia, mucus hypersecretion in the airways and elevated levels of serum IgE and lgG1. Furthermore, the data showed that four days after initial i.n. exposure, the production of Th2 cytokines could be observed in the draining lymph nodes. After secondary airway challenge with OVA, the production of Th2 cytokines by lung inflammatory cells was observed (700 pg/mL of IL-5,590 pg/mL of IL-13) but no IFN-gamma was detected upon re-stimulation with OVA and antigen presenting cells. Both the induction of Th2 responses and the airway eosinophilia depend on the production of IL-4 in that neither were observed in IL-4 deficient mice. Since human exposure to Toll-like receptor (TLR) ligands has been correlated with asthma severity, we are currently using the inhalational model to investigate the role of TLR ligands in the initiation, maintenance and severity of the allergic inflammation observed in this murine model.
803 CarbonicAnhydraseExpressionin Allergic Rhinitis Eva Anne Berkes Scripps Research Institute, La Jolla, CA Nasal mucosal pH has been observed to shift from acidic (pH range of 5.5-6.5 in normal nasal mucosa) towards alkaline (pH range of 7.2-8.3) in allergic rhinitis. This alkaline pH may enhance the allergic inflammatory response: a basic tissue environment appears to favor eosinophil infiltration and lifespan. How this increase in pH seen in allergic rhinitis occurs is unknown. We propose that the bicarbonate-generating enzyme carbonic anhydrase may be responsible for this alkalinization. Studies of carbonic anhydrase expression in the respiratory tract are very limited; however, the hypoxia-inducible cell surface carbonic anhydrase XII isoenzyme has been
Abstracts
$263
found in biopsies of normal human nasal tissue. This study aimed to determine whether carbonic anhydrase XII was expressed nasal scrapings from human subjects with symptomatic allergic rhinitis. RNA was isolated from nasal scrapings from 2 subjects with allergic rhinitis, as well as 2 subjects without atopic disease (as defined by clinical history, eosinophils on nasal scrape, and skin reactivity to standard allergen prick screen). Complimentary DNA was generated from RNA using reverse transcriptase technology. Standard non-quantitative PCR analysis was performed using primers for carbonic anhydrase XII and the housekeeping gene GAPDH in each case. Amplification products of carbonic anhydrase XII were observed in allergic rhinitis nasal scrapings but were absent in normal nasal tissue. GAPDH was observed to be expressed in all cases. Therefore, allergic inflammation appears to involve carbonic anhydrase XII expression, whereas this isoenzyme is not expressed in normal nasal tissue. The alkaline mucosal pH observed in allergic rhinitis may therefore be due to the bicarbonate-secreting action of carbonic anhydrase. We are currently involved in further research to more fully evaluate the role of carbonic anhydrase in generating pH change in nasal allergic disease.
~'~A Characteristics of Children With Allergic Rhinitis and Chronic
8 V " l r Mouth Breathing
Candida Rizzo, Sara Hauache, Nelson Naspitz, Shirley Pignatari, Patricia Junqueira, Marcia Hallinan, Luc Weckx, Charles Naspitz University Federal de Sao Paulo, S~o Paulo, Brazil Nasal obstruction in children can be caused by a variety of factors such as allergic rhinitis, adenoid and/or tonsils hypertrophy, nasal deformities etc. Chronic mouth breathing is related to altered facial growth, language and sleep disorders. OBJECTIVE: The purpose of this study was to evaluate several conditions associated with mouth or nasal breathing in children with allergic rhinitis. SUBJECTS AND METHODS: 238 children, 158 boys and 80 girls, between 6 and 13 years of age, with a clinical diagnosis of allergic rhinitis, participated in the study. There were 145 children in the group of mouth breathers and 93 in the group of nasal breathers. Subjects and their families were submitted to a detailed questionnaire for: other allergic conditions besides rhinitis (1), periodontal diseases/tonsil-pharyngitis/halitosis (2), sinusitis (>2 times/year) (3), breast feeding greater than or equal to 5 months (4), pacifier use (5), thumb sucker (6), speech disorders (7), voice disorders (8), sleep disorders (9), poor school performance (10), parental allergy (11), parental oral breathing (12),home exposure to domestic pets (13), home exposure to cockroaches (14) and parental smoking (15). All children were skin-tested by prick test to Dermatophagoides pteronyssinus (IPI-ASAC Brazil; 112 150 UBE/ml). A positive test had a mean wheal diameter greater than or equal to 3 mm. The prevalence of the several variables studied was compared between oral and nasal breather groups by the chi-square test. The significant results were assessed by multiple logistic regression analysis. RESULTS: Positive skin prick tests were obtained in 134/143 of mouth breathers and in 85/93 of nasal breathers. There was a higher frequency of speech disorders (OR=2.96, 95% IC=1.33 - 6.57, p=0.008), poor school performance (OR=2.15, 95%IC=0.96 - 4.82, p=0.063), sleep disorders (OR=3.23, 95 %IC= 1.70 - 6.14, p<0.001), home exposure to domestic pets (OR=2.43, 95% IC=1.20 - 4.92, p=0.013) and home exposure to roaches (OR=1.92, 95%IC=0.99 - 3.74, p=0.054) in the oral breather group. A protective effect against mouth breathing was found for breast-feeding greater than or equal to 5 months (OR=0.30, 95%IC=0.15 to 0.58, p<0.001), other allergic conditions (OR=0.43, 95%IC-0.21 to 0.86, p=0.018) and pacifier use (OR=0.33, 95%IC=0.17 to 0.63, p=0.001). CONCLUSIONS: This study has shown several associated factors for mouth breathing in children with rhinitis. The majority of these patients are atopic, independent of the respiratory pattern. Our data reinforces the importance of breast-feeding and in diminishing house exposure to pets and cockroaches. Further prospective investigations are needed to confirm our findings and identify other risk factors associated to oral breathing, allowing early interventions.
minute intervals, during randomized paired sessions. Symptom scores, sneeze and cough counts, nasal secretion weights, nasal conductance (rhinomanometry), middle ear pressure (tympanometry), eustachian tube function (sonotubometry) and pulmonary function (spirometry) were assessed before and after the histamine challenge, after each dose of IL- 1[3 or placebo and then at 90 minutes, 2, 3, 4, 6 and 24 hours. At the doses utilized, intranasal challenge with IL-1]3 was well tolerated. At the 24 hour postchallenge endpoint, a significant effect of challenge substance was documented for nasal secretion weights in all subjects (n=30). There was a trend toward an increased effect in allergic as compared to non-allergic subjects; however, none of the inter-group differences achieved statistical significance. Following intranasal challenge with 1L-l[3 and placebo, mean (+ SEM) 24 hour secretion weights (gins) were 9.61 + 5.24 and 6.92 + 3.76 in symptomatic allergic subjects, 4.97 + 0.38 and 2.28 + 0.38 in asymptomatic allergic subjects, 2.60 + 0.84 and 1.89 + 0.71 in non-allergic subjects, and 5.73 + 3.38 and 3.70 + 2.28 in all subjects (p < 0.05), respectively. There were no differences between placebo and IL-I~ challenge for any of the other measured parameters. These results show that local IL- 113at relatively low doses can provoke increased nasal secretions, an effect that is exacerbated in subjects with allergic rhinitis.
802Th2 Priming Induced by Intranasal Exposure,o So]uble Protein Antigens Stephanie Eisenbarth, Christina Herrick, Kim Bottomly Yale University, New Haven, CT The mechanism of T helper type 2 cell (Th2) priming upon inhaled allergen exposure remains unclear. The majority of murine models of asthma currently induce a Th2 response using antigen injected intraperitoneally with Aluminum hydroxide (alum) to induce eosinophilic pulmonary inflammation and airway hyperresponsiveness. Our objective was to establish and to evaluate the factors required for effective Th2 priming in response to inhaled protein antigens, such as Ovalbumin (OVA). Our lab has developed an intranasal (i.n.) sensitization model, without the use of alum, which initiates effective Th2 priming and T cell recruitment to the lung. Optimal lung inflammation was seen following sensitization with three days of 100 ug ofi.n. OVA followed two weeks later by i.n. challenge with 25 ug OVA over a six day period. Both Balb/c and C57BL/6 mice have been sensitized effectively using this protocol. The allergic response in this model reproduces the key characteristics of asthma, namely, pulmonary inflammation dominated by eosinophilia, mucus hypersecretion in the airways and elevated levels of serum IgE and lgG1. Furthermore, the data showed that four days after initial i.n. exposure, the production of Th2 cytokines could be observed in the draining lymph nodes. After secondary airway challenge with OVA, the production of Th2 cytokines by lung inflammatory cells was observed (700 pg/mL of IL-5,590 pg/mL of IL-13) but no IFN-gamma was detected upon re-stimulation with OVA and antigen presenting cells. Both the induction of Th2 responses and the airway eosinophilia depend on the production of IL-4 in that neither were observed in IL-4 deficient mice. Since human exposure to Toll-like receptor (TLR) ligands has been correlated with asthma severity, we are currently using the inhalational model to investigate the role of TLR ligands in the initiation, maintenance and severity of the allergic inflammation observed in this murine model.
803 CarbonicAnhydraseExpressionin Allergic Rhinitis Eva Anne Berkes Scripps Research Institute, La Jolla, CA Nasal mucosal pH has been observed to shift from acidic (pH range of 5.5-6.5 in normal nasal mucosa) towards alkaline (pH range of 7.2-8.3) in allergic rhinitis. This alkaline pH may enhance the allergic inflammatory response: a basic tissue environment appears to favor eosinophil infiltration and lifespan. How this increase in pH seen in allergic rhinitis occurs is unknown. We propose that the bicarbonate-generating enzyme carbonic anhydrase may be responsible for this alkalinization. Studies of carbonic anhydrase expression in the respiratory tract are very limited; however, the hypoxia-inducible cell surface carbonic anhydrase XII isoenzyme has been
Abstracts
$263
found in biopsies of normal human nasal tissue. This study aimed to determine whether carbonic anhydrase XII was expressed nasal scrapings from human subjects with symptomatic allergic rhinitis. RNA was isolated from nasal scrapings from 2 subjects with allergic rhinitis, as well as 2 subjects without atopic disease (as defined by clinical history, eosinophils on nasal scrape, and skin reactivity to standard allergen prick screen). Complimentary DNA was generated from RNA using reverse transcriptase technology. Standard non-quantitative PCR analysis was performed using primers for carbonic anhydrase XII and the housekeeping gene GAPDH in each case. Amplification products of carbonic anhydrase XII were observed in allergic rhinitis nasal scrapings but were absent in normal nasal tissue. GAPDH was observed to be expressed in all cases. Therefore, allergic inflammation appears to involve carbonic anhydrase XII expression, whereas this isoenzyme is not expressed in normal nasal tissue. The alkaline mucosal pH observed in allergic rhinitis may therefore be due to the bicarbonate-secreting action of carbonic anhydrase. We are currently involved in further research to more fully evaluate the role of carbonic anhydrase in generating pH change in nasal allergic disease.
~'~A Characteristics of Children With Allergic Rhinitis and Chronic
8 V " l r Mouth Breathing
Candida Rizzo, Sara Hauache, Nelson Naspitz, Shirley Pignatari, Patricia Junqueira, Marcia Hallinan, Luc Weckx, Charles Naspitz University Federal de Sao Paulo, S~o Paulo, Brazil Nasal obstruction in children can be caused by a variety of factors such as allergic rhinitis, adenoid and/or tonsils hypertrophy, nasal deformities etc. Chronic mouth breathing is related to altered facial growth, language and sleep disorders. OBJECTIVE: The purpose of this study was to evaluate several conditions associated with mouth or nasal breathing in children with allergic rhinitis. SUBJECTS AND METHODS: 238 children, 158 boys and 80 girls, between 6 and 13 years of age, with a clinical diagnosis of allergic rhinitis, participated in the study. There were 145 children in the group of mouth breathers and 93 in the group of nasal breathers. Subjects and their families were submitted to a detailed questionnaire for: other allergic conditions besides rhinitis (1), periodontal diseases/tonsil-pharyngitis/halitosis (2), sinusitis (>2 times/year) (3), breast feeding greater than or equal to 5 months (4), pacifier use (5), thumb sucker (6), speech disorders (7), voice disorders (8), sleep disorders (9), poor school performance (10), parental allergy (11), parental oral breathing (12),home exposure to domestic pets (13), home exposure to cockroaches (14) and parental smoking (15). All children were skin-tested by prick test to Dermatophagoides pteronyssinus (IPI-ASAC Brazil; 112 150 UBE/ml). A positive test had a mean wheal diameter greater than or equal to 3 mm. The prevalence of the several variables studied was compared between oral and nasal breather groups by the chi-square test. The significant results were assessed by multiple logistic regression analysis. RESULTS: Positive skin prick tests were obtained in 134/143 of mouth breathers and in 85/93 of nasal breathers. There was a higher frequency of speech disorders (OR=2.96, 95% IC=1.33 - 6.57, p=0.008), poor school performance (OR=2.15, 95%IC=0.96 - 4.82, p=0.063), sleep disorders (OR=3.23, 95 %IC= 1.70 - 6.14, p<0.001), home exposure to domestic pets (OR=2.43, 95% IC=1.20 - 4.92, p=0.013) and home exposure to roaches (OR=1.92, 95%IC=0.99 - 3.74, p=0.054) in the oral breather group. A protective effect against mouth breathing was found for breast-feeding greater than or equal to 5 months (OR=0.30, 95%IC=0.15 to 0.58, p<0.001), other allergic conditions (OR=0.43, 95%IC-0.21 to 0.86, p=0.018) and pacifier use (OR=0.33, 95%IC=0.17 to 0.63, p=0.001). CONCLUSIONS: This study has shown several associated factors for mouth breathing in children with rhinitis. The majority of these patients are atopic, independent of the respiratory pattern. Our data reinforces the importance of breast-feeding and in diminishing house exposure to pets and cockroaches. Further prospective investigations are needed to confirm our findings and identify other risk factors associated to oral breathing, allowing early interventions.