Successful pharmacotherapy for asthma exacerbation in an asthmatic patient with long QT syndrome / 대한내과학회지

beta -Blockers can cause bronchospasm in asthma. beta 2-agonists prolong the QT interval and alter the clinical course of long QT syndrome (LQTS). We report a case of asthma exacerbation treated cautiously with beta 2-agonists in a patient with LQTS, while LQTS was controlled with low-dose beta 1-antagonists. A 31-year-old woman with LQTS visited the emergency room for asthma exacerbation. FEV1 was 0.5 L (18%) and QTc interval was 520 ms. Low doses of salbutamol or salmeterol were used and gradually increased, while monitoring the QT interval. Simultaneously, a low dose of atenolol was maintained. FEV1 was increased to 2.2 L (83%) without further QT prolongation or cardiac events. The case suggests that lower doses of beta 1-antagonists can be tried for cardiac diseases, even in the presence of asthma exacerbations. beta 2-Agonists may be initiated at lower doses and, if tolerated, the dose can be increased in asthmatic patients with a risk for QT prolongation.

The Inverse Association Between the Presence of Antibody to Hepatitis B Surface Antigen and Atopy in Young Adults

BACKGROUND: Some bacterial and viral infections may reduce the risk of atopy, and this is based on the concept of their ability to divert the immune system towards the Th1 responses. Most of the hepatitis B virus (HBV) infections occur in the developing countries and this is where atopic disorders are least prevalent. Th1 responses are important for the viral clearance of HBV and also for antibody production. The aim of the study is to investigate whether the presence of antibodies to the hepatitis B surface antigen (anti-HBs) is inversely associated with atopy in adults. METHODS: A random sample of 358 subjects, who were without hepatitis B surface antigen, was recruited; they were aged from 18 to 79 years (105 young adults aged 40 years). Determinations of the anti-HBs and skin prick tests using aeroallergens were performed. Those subjects with one or more positive skin reactions (a mean wheal diameter > or=3 mm) were considered atopic. RESULTS: The prevalence rate of atopy (p=0.035) or the sensitization to Dermatophagoides farinae (p=0.01) was significantly lower in the subjects with anti-HBs than in those subjects without anti-HBs for the young adults, but not for the older adults. The logistic regression analysis that was done on the young adults showed that the presence of anti-HBs was associated with a significantly lower risk of atopy (the odds ratio adjusted for confounding variables=0.40 [95% CI 0.16-0.98], p=0.046) or with the sensitization to D. farinae (0.20 [0.06-0.65], p=0.008). CONCLUSION: The presence of anti-HBs produced by a natural HBV infection or vaccination might be inversely associated with atopy in young adults.

Relationship between Dendritic Cells and Activated Eosinophils in Induced Sputum of Asthmatics

It has been suggested that dendritic cells (DCs) are critical antigen presenting cells for eosinophilic airway inflammation in a mouse model of asthma, and cysteinyl leukotrienes may play a role in DC trafficking in asthmatics. We investigated whether the number of DCs is increased in the induced sputum of both atopic and nonatopic asthmatics and is related to activated eosinophil count in the sputum. Sputum was induced by inhalation of hypertonic saline in 9 atopic and 12 nonatopic asthmatics and 10 nonatopic normal controls, and differential cell counts were performed. DCs and activated eosinophils were identified by immunocytochemistry with monoclonal antibodies (anti-CD1a and EG2, respectively). There were significantly higher percentages of eosinophils, EG2+ cells, and CD1a+ DC in the sputum of atopic and nonatopic asthmatics compared with normal controls, respectively. In asthmatics, the percentage of CD1a+ DC was significantly correlated with that of EG2+ cells (Rs=0.62, p=0.004). We demonstrated that the increased number of DCs was evident in the induced sputum of both atopic and nonatopic asthmatics, and the DC number was related to the activated eosinophil count, which suggests that DCs may contribute to the ongoing eosinophilic inflammation in asthmatic airways, and vice versa.

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.

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.

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.

Effects of Cytokine Milieu Secreted by BCG-treated Dendritic Cells on Allergen-Specific Th Immune Response

Bacillus Calmette-Guerin (BCG) is reported to suppress Th2 response and asthmatic reaction. Dendritic cells (DCs), the major antigen-presenting cells, infections with BCG are known to result in inducing various cytokines. Thus, DCs are likely to play a role in the effects of BCG on asthma. This study aims at investigating that cytokine milieu secreted by BCG-treated DCs directly enhances allergen-specific Th1 response and/or suppresses Th2 response in allergic asthma. DCs and CD3+ T cells were generated from Dermatophagoides farinae-sensitive asthmatics. DCs were cultured with and without BCG and subjected to flow cytometric analysis. IL-12 and IL-10 were determined from the culture supernatants. Some DCs were cocultured with T cells in the presence of D. farinae extracts after adding the culture supernatants from BCG-treated DCs, and IL-5 and IFN-gamma were determined. BCG-treated DCs enhanced significantly the expressions of CD80, CD86, and CD40, and the productions of IL-12 and IL-10. Addition of culture supernatants from BCG-treated DCs up-regulated production of IFN-gamma by T cells stimulated by DCs and D. farinae extracts (p0.05). The cytokine milieu secreted by BCG-treated DCs directly enhanced allergen-specific Th1 response, although did not suppress Th2 response.

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.

Suppressive effect of dehydroepiandrosterone on the development of asthmatic reaction in BALB/c mice / 천식및알레르기

BACKGROUND: Dehydroepiandrosterone (DHEA), an adrenal androgen, may regulate Th1/Th2 cytokines. OBJECTIVE: To determine whether DHEA have a preventive effect against the development of asthma, a Th2-associated disease. MATERIALS AND METHODS: Female BALB/c mice were fed with a standard diet incorporated with 0.1% (w/w) of DHEA for 1 week before sensitization with ovalbumin (OVA, 20 microgram i.p. twice with 2-week intervals). Enhanced pause (Penh) was monitored after 1% OVA inhalations for 3 successive days, and then the methacholine bronchoprovocation tests were performed using a whole-body plethysmography system. Analyses of inflammatory cells, cytokines, and OVA-specific IgE were carried out. RESULTS: Both the excessive airway narrowing (maximum Penh) and the airway hypersensitivity (PC200, mg/mL) to methacholine were significantly suppressed with the DHEA pretreatment (P<.05 and P<.01, respectively). However, the numbers of the inflammatory cells and the levels of interleukin (IL)-4, IL-5, and interferon (IFN)-gamma in the bronchoalveolar lavage fluid, the production of IL-4, IL-5, and IFN-gamma by Con A-stimulated splenocytes, and the serum IgE level in DHEA group were not significantly different from those in asthma group. CONCLUSION: DHEA pretreatment could suppress the development of asthmatic airway hyperresponsiveness without suppression of Th2 cytokines and airway inflammation.

Two cases of vocal cord dysfunction / 대한내과학회지

Vocal cord dysfunction (VCD), a condition that frequently mimics or confounds asthma, is characterized by a paradoxical adduction of the vocal cords on inspiration. The apposition of the vocal cords produces airflow obstruction sufficient to cause wheezing, chest tightness, shortness of breath, and cough. Misdiagnosis as asthma has led to inappropriate treatment, most notably with high-dose corticosteroids. Herein we report two cases of VCD who presented with chronic cough and episodic breathlessness, respectively. Flow-volume loops on spirometry were abnormal, with evidence of variable extrathoracic airway obstruction, manifested as flat or truncated inspiratory loops. Laryngoscopy or bronchoscopy demonstrated paradoxical adduction with posterior "chinking" of the vocal cords on inspiration. One case also had asthma and depressive illness. After the diagnosis of VCD, the clinical manifestations resolved with speech therapy and/or psychotherapy. VCD should be suspected in patients with asthma-like symptoms. An early diagnosis avoids unnecessary aggressive management.

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.

Upper airway hyperresponsiveness To methacholine in patients with suspected asthma / 천식및알레르기

BACKGROUND: Upper airway diseases, such as vocal cord dysfunction (VCD), masquerade as asthma. Bronchial hyperresponsiveness (BHR) to methacholine (MCh) has been demonstrated in only part of suspected asthma patients. Investigators have shown upper airway hyperresponsi- veness (UHR) in patients with VCD. OBJECTIVE: To determine the clinical importance of UHR and to evaluate the usefulness of UHR test in patients with suspected asthma. METHODS: Thirty-six consecutive patients with suspected asthma underwent a MCh inhalation challenge. BHR was determined with PC20 25% from the baseline, and upper airway obstruction (UAO) with MEF50/MIF50 > 1. RESULTS: Only 17 patients (47.2%) showed BHR. Also, the same proportion of subjects showed UHR, and the each combination of BHR/UHR was nearly equal in distribution (9 BHR+/UHR-, 8 BHR+/UHR+, 9 BHR-/UHR+, and 10 BHR-/UHR-). Patients with BHR-/UHR+ had significantly lower serum total IgE level than those with BHR-/UHR-. Eight patients with UHR and UAO showed significantly shorter duration of disease (p < 0.05), smaller numbers of atopy family history (p < 0.05), and lower serum total IgE level than the others (p < 0.05). CONCLUSION: Many patients with suspected asthma showed UHR, and about half of patients with negative MCh-BHR showed UHR that might be related to non-asthmatic diseases including VCD. Therefore, a routine UHR test may be warranted in detecting upper airway diseases in suspected asthma.

Peak Expiratory Flow Rate Underestimates Severity of Airflow Obstruction in Acute Asthma

BACKGROUND: Several investigators have demonstrated a considerable disagreement between FEV1 and PEFR to assess the severity of airflow obstruction. The purpose of this study was to examine whether the discrepancy between the two measurements affects the assessment in the severity of acute asthma. METHODS: Thirty-five consecutive asthma patients measured both FEV1 and PEFR at 0, 1hr, 1, 3, 5, 7 days of an emergency room admission using a spirometer and a Ferraris PEFR meter. The degree of discrepancy between FEV1 and PEFR expressed as % predicted values was determined. RESULTS: When predictive equations that recommended by the instrument manufacturers were used, PEFR measured with the PEFR meter (f-PEFR) was significantly higher than FEV1 at all time points, with 16.1% mean difference and unacceptable wide limits of agreement (-20.0~52.3%). The classification in severity was significantly different between FEV1 and f-PEFR (p < 0.001). The discrepancy was inter-instrumental in large part because f-PEFR was 10.1% higher than spirometric PEFR. Different predictive equations altered the degree of the differences but could not completely correct it. CONCLUSION: These results indicate that f-PEFR values underestimate the severity of airflow obstruction in acute asthma despite using recommended predictive equations. Therefore, these confounding factors should be considered when the severity of airflow obstruction is assessed with PEFR.

BCG infection during pre-sensitization or even post-sensitization inhibits airway sensitivity in an animal model of allergic asthma

The objective of this study is to investigate whether BCG infection before, during or after sensitization suppresses allergen-induced airway hyperresponsiveness and eosinophilic inflammation in allergic asthma rats, and to determine the required dose of BCG to induce such an inhibition. Eighty-seven Sprague-Dawley (SD) rats were sensitized and provoked with ovalbumin (OA). A pretreatment of 6 x 10(4) or 6 x 10(5) colony forming units (CFUs) of BCG or saline was done at four different times: 3 days before sensitization, at sensitization, 3 days before provocation, or at provocation. The assessment of tracheal smooth muscle (TSM) responsiveness to electrical field stimulation or acetylcholine (ACh) and bronchoalveolar lavage (BAL) were performed 1 day after OA provocation. Doses of 6 x 10(4) CFUs inhibited TSM sensitivity of rats infected 3 days before sensitization or at sensitization, but not 3 days before provocation or at provocation. However, doses of 6 x 10(5) CFUs significantly inhibited not only the airway eosinophilia of rats infected 3 days before sensitization or at sensitization, but also the TSM sensitivity of rats infected 3 days before provocation or at provocation. In conclusion, BCG infection suppresses the development of sensitivity of airway smooth muscle and airway eosinophilic inflammation in allergic asthma rats. Furthermore, a relatively high dose of BCG infection inhibits airway sensitivity, even after allergen sensitization.

BCG infection during pre-sensitization or even post-sensitization inhibits airway sensitivity in an animal model of allergic asthma

The objective of this study is to investigate whether BCG infection before, during or after sensitization suppresses allergen-induced airway hyperresponsiveness and eosinophilic inflammation in allergic asthma rats, and to determine the required dose of BCG to induce such an inhibition. Eighty-seven Sprague-Dawley (SD) rats were sensitized and provoked with ovalbumin (OA). A pretreatment of 6 x 10(4) or 6 x 10(5) colony forming units (CFUs) of BCG or saline was done at four different times: 3 days before sensitization, at sensitization, 3 days before provocation, or at provocation. The assessment of tracheal smooth muscle (TSM) responsiveness to electrical field stimulation or acetylcholine (ACh) and bronchoalveolar lavage (BAL) were performed 1 day after OA provocation. Doses of 6 x 10(4) CFUs inhibited TSM sensitivity of rats infected 3 days before sensitization or at sensitization, but not 3 days before provocation or at provocation. However, doses of 6 x 10(5) CFUs significantly inhibited not only the airway eosinophilia of rats infected 3 days before sensitization or at sensitization, but also the TSM sensitivity of rats infected 3 days before provocation or at provocation. In conclusion, BCG infection suppresses the development of sensitivity of airway smooth muscle and airway eosinophilic inflammation in allergic asthma rats. Furthermore, a relatively high dose of BCG infection inhibits airway sensitivity, even after allergen sensitization.