Airways are More Reactive to Histamine than to Methacholine in Patients with Mild Airway Hyperresponsiveness, Regardless of Atopy

BACKGROUND: The airway muscles from allergen-sensitized animals in vitro show a heightened response to histamine, but not to carbachol. This study investigated whether the airway responsiveness to histamine in vivo is comparable to that of methacholine in human subjects with varying degrees of atopy. METHODS: One-hundred-and-sixty-eight consecutive adult asthma patients or volunteers underwent bronchoprovocation tests to both histamine and methacholine after determining their blood eosinophil counts, serum total IgE levels and skin test reactivity to 10 common aeroallergens. RESULTS: The responsiveness to histamine was significantly related to that to methacholine (r=0.609, p<0.001), but many individuals with a negative methacholine test response showed a positive response to histamine. The histamine-bronchial reactivity index (BRindex) was significantly higher than the methacholine-BRindex in subjects with a positive response to none (n=69, p<0.01) or only one (n=42, p<0.001) of histamine and methacholine, while there was no significant difference in the subjects with positive responses to both of them (n=57). The histamine-BRindex was significantly higher than the methacholine-BRindex in the subjects with mild histamine hyperresponsiveness (n=58, 1.28+/-0.01 vs. 1.20+/-0.02, respectively, p<0.001). Both histamine and methacholine responsiveness was significantly related to the atopy markers. However, the histamine-BRindex/methacholine-BRindex ratio of the atopics was not significantly different from that of the non-atopics. CONCLUSIONS: The airway responsiveness to histamine is comparable to that of methacholine in the subjects with positive responses to both histamine and methacholine, but the airway responsiveness to histamine is greater than that to methacholine in those subjects with mild airway hyperresponsiveness, regardless of atopy.

Airway Hyperresponsiveness to Hypertonic Saline as a Predictive Index of Exercise-Induced Bronchoconstriction

BACKGROUND: Changes in airway mucosal osmolarity are an underlying mechanism of bronchoconstrictive responses to exercise and hypertonic saline (HS). The purpose of this study was to examine whether an osmotic challenge test using HS can predict exercise-induced bronchospasm (EIB) in asthma patients. METHODS: Thirty-six young male asthmatic patients underwent bronchial challenge tests based on 4.5% HS, exercise (> 24h later), and methacholine (MCh) at the Chonnam National University Hospital. The relationships between responses to HS and exercise, and between MCh and exercise were evaluated. RESULTS: The maximal fall in forced expiratory volume in one second following exercise was significantly higher in the HS-responders (n=19) than in the HS-nonresponders (n=17, 35.9+/-4.1% vs. 17.9+/-2.7%, p< 0.001), and there was a significant correlation between the severity of EIB and HS-airway hyperresponsiveness (AHR). When compared with the MCh-AHR test in terms of predicting EIB, the HS-AHR test showed higher specificity (71.4% vs. 42.9%), but a lower sensitivity (58.6% vs. 89.7%) and negative predictive value (29.4% vs. 50.0%). At the moderate AHR cutoff value, the MCh-AHR test had a specificity that was comparable with and predictive values that were higher than those of the HS-AHR test. CONCLUSIONS: The HS-AHR test was more specific than the MCh-AHR test, but was less sensitive and had a poorer negative predictive value, which in combination preclude the use of the HS-AHR test as a screening tool for EIB. The MCh-AHR test had a cutoff value for moderate AHR that may be more useful for predicting EIB in asthmatic patients.

Late Local Urticaria as a Long-term Sequela of Allergen-Specific Immunotherapy

Local reaction to allergen-specific immunotherapy (SIT) usually appears within 30 minutes, but cases with exercise-induced urticaria at the SIT site 2-3 weeks after the last allergen injection have been reported. A 28-year-old man was treated with house dust mite-SIT for 5 years, due to asthma when he was an 11-year-old boy. On a treadmill exercise test for 50 minutes, erythema, swelling, and pruritus occurred at the SIT site, which lasted for one hour. There was no evidence of complement activation, and the skin biopsy specimens showed no apparent difference between the lesion and normal sites in the distribution of inflammatory cells and in mast cell degranulation. However, the morphine, but not the histamine, skin test responses were increased after the exercise. There must be a remaining long-term sequela of the SIT, including an increased releasability of mast cells, even after more than 10 years.

Increased Releasability of Skin Mast Cells after Exercise in Patients with Exercise-induced Asthma

The role of lung mast cells in exercise-induced asthma (EIA) is controversial. To investigate whether the skin mast cell releasability is increased after exercise in EIA, 49 young atopic men with or without asthma took part in a free-running test for 6 min and were given skin prick tests using morphine, a mast cell secretagogue, before and after the exercise. The mean diameters of the wheal induced by morphine in patients with EIA were not significantly different from those in patients without EIA before exercise, although the baseline lung function was significantly lower and the airway hyperresponsiveness, the peripheral blood eosinophil count, and the size of the wheal in response to Dermatophagoides pteronyssinus were significantly higher in patients with EIA. However, the differences of the morphine-induced wheal diameter between patients with EIA and those without EIA became significant at 120 min after exercise (p<0.05), while the responses to histamine were not significantly different. These results suggest that exercise increases the releasability of skin mast cells in EIA patients whose asthma/allergy are relatively severe.

Airway hyperresponsiveness to hypertonic saline as a predictive index of exercise-induced bronchoconstriction / 대한내과학회지

BACKGROUND: Altered airway mucosal osmolarity is an underlying mechanism of bronchoconstrictive response to both exercise and hypertonic saline (HS). The purpose of this study was to examine whether the osmotic challenge test using HS could predict the exercise-induced bronchospasm (EIB) in asthma. METHODS: Thirty-six consecutive young male patients with asthma visited Chonnam National Univertisy Hospital underwent bronchial challenge tests using 4.5% HS, exercise (>24 hours later), and methacholine (MCh). The relationship in the responses between HS and exercise was observed in comparison with that between MCh and exercise. RESULTS: The maximal fall in forced expiratory volume in one second following exercise was significantly higher in the HS-responders (n=19) than that in the HS-nonresponders (n=17)(35.9 +/- 4.1% vs. 17.9 +/- 2.7%, p<0.001). There was a significant correlation between the severity of EIB and HS-airway hyperresponsiveness (AHR). Compared with the MCh-AHR test in diagnosing for EIB, the HS-AHR test showed a higher specificity (71.4% vs. 42.9%), but a lower sensitivity (58.6% vs. 89.7%) and a lower negative predictive value (29.4% vs. 50.0%). At the cutoff value for moderate AHR, the MCh-AHR test had specificity comparable with and predictive values higher than those of the HS-AHR test. CONCLUSION: The HS-AHR test was more specific than the MCh-AHR test, but less sensitive and had poor negative predictive value precluding from use of it as a screening test for EIB. The MCh-AHR test at the cutoff value for moderate AHR may be more useful in predicting EIB in asthma.

Clinical analysis of asthma patients with wheezing despite normal ventilatory function / 천식및알레르기

BACKGROUND: Wheezing is one of the characteristics of asthma, Intensity of wheezing is correlated with the severity of airway obstruction. However, some asthmatic patients may show wheezing despite normal ventilatory function. OBJECTIVE: To determine the cause of wheezing in asthmatic patients with normal ventilatory function. METHODS: Thirty-eight consecutive asthmatic patients with wheezing despite FEV1> or =80% of predicted value were retrospectively examined for clinical data. RESULTS: Twenty-seven patients (71.1%) were women. Sixteen patients (42.1%) showed airway obstruction based on the Intermountain Thoracic Society criteria. Patients with airway obstruction had significantly lower FEF50% than did those without it (P1 suggesting upper airway obstruction was observed in 7 of 16 (43.8%) patients. Associated diseases were rhinitis in 21 (55.3%) patients, sinusitis in 18 (47.4%), and postnasal drip syndrome in 3 (7.9%). CONCLUSIONS: Wheezing despite normal ventilatory function in asthma occurs more often in women. It may be related to reversible airway obstruction in nearly half patients and to upper airway obstruction such as rhinitis. in considerable numbers of the remaining patients.

Airway collapsibility indicating indication excessive airway narrowing in asthma / 천식및알레르기

BACKGROUND: It has been sugested that excessive airway narrowing in asthma may be detected by a decrease in forced vital capacity (FVC). A volume differrence between slow vital capacity (SVC) and FVC may be used as a surrogate index of airway collapse. OBJECTIVE: To investigate the relationship between an airway collapsibility index (CI) and airflow limitation or airway hyperresponsiveness in asthma. METHODS: Forty-six patients with suspected asthma and 21 normal control subjects were enrolled. CI was defined as a difference between SVC and FVC, and measured before and after a methacholine (MCh) bronchoprovocation test. Positive response to MCh was defined as a fall of FEV1 by more than 12%. RESULTS: CI significantly increased from 1.10+/-3.86% to 5.52+/-7.91% after MCh in the positive MCh group (n=19, p<0.01). Not only FVC but also SVC was significantly decreased after MCh. One-fifth of the decrease in FVC was caused by the increase in CI. Both FVC and SVC were significantly related to baseline FEV1 values and in percent change after MCh. Although CI was also significantly related to FEV1 in percent change after MCh. CI was significantly higher in the positive MCh group than in the control and was not significantly related to baseline FEV1 values. Furthermore, the relationship of CI values between before and after MCh was significant (r=0.622, p<0.01). CI was not significantly different according to the severity of MCh-PC20. CONCLUSION: Because the relationship between CI and the severity of airflow limitation or MCh-PC20 was less significant. CI may be better than FVC to represent the characteristic of excessive airway narrowing in asthma.