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Efficacy of Airway Anti-Inflammatory Treatments Evaluated with Airway Inflammation Markers in Patients with Cough Variant Asthma: Budesonide versus Montelukast
S176 Abstracts
685
The Case of the Polysaccharide Blues
SUNDAY
R. Gupta, H. J. Wedner; Internal Medicine, Barnes Jewish Hospital, St. Louis, MO. CASE HISTORY: A 60 yo white female was evaluated for possible immunodeficiency because of recurrent severe sinus infections. A lymphocyte subset panel was normal, including CD3, CD4, CD8, and CD19. Tetanus antibody titers were normal. Pneumococcal antibody titers drawn 1 month after administration of the pneumococcal 23-valent vaccine were suboptimal. IgG responses were less than 2-fold to 5 out of the 6 polysaccharide antigens in the serotype panel. Interestingly, one month after administration of the pneumococcal 7-valent conjugate vaccine, antibody levels were all normal. There was at least a 4-fold increase in all 6 of the anti-pneumococcal antibodies tested. DISCUSSION: A subset of elderly patients respond inadequately to the capsular polysaccharides in the 23-valent pneumococcal vaccine. This interesting case illustrates an elderly patient with chronic sinusitis who responded poorly to the capsular polysaccharides in the 23-valent vaccine. She did respond appropriately to the pneumococcal 7-valent vaccine in which the polysaccharides are directly conjugated to the protein carrier CRM197 of diphtheria toxin. Given the patient’s normal T-lymphocyte populations, it is not surprising that she had an appropriate antibody response to the T-cell dependent vaccine. Why our patient had a suboptimal antibody response to the T-cell independent process of responding to capsular polysaccharides is not clear. It is likely that multiple factors, such as antibody-mediated opsonophagocytosis may come into play. It is clear, however, that patients who fail to respond to an unconjugated vaccine should be revaccinated with a conjugated vaccine and evaluated before being declared as having common variable immunodeficiency and treated with IVIG. Efficacy of Airway Anti-Inflammatory Treatments Evaluated with Airway Inflammation Markers in Patients with Cough Variant Asthma: Budesonide versus Montelukast T. T. Shimoda, R. R. Kishikawa, S. S. Shoji, S. S. Nishima; Clinical Research Center, Fukuoka National Hospital, Fukuoka, JAPAN. RATIONALE: Airway hyperresponsiveness from inflammation is the primary cause of refractory cough in cough variant asthma (CVA). In this study, anti-inflammatory drugs, inhaled steroids and an oral leukotriene receptor antagonist, were evaluated for CVA treatment with airway inflammatory markers. METHODS: Seventy-four untreated patients with CVA randomly received budesonide (800 g/day, n=18 and 400 g/day, n=17), montelukast (10 mg/day, n=21), or need-based inhaled 2-adrenergic agonist (n=18) for 6 months. RESULTS: Budesonide and montelukast improved inflammation (significant decreases in eNO and sputum eosinophil), hyperresponsiveness (a significant increase in PC20) and cough. The improvement was greater with budesonide 800g/day (eNO, 47.2 to17.3 ppb; log PC20, 6.6 to 8.9 g/ml; and cough score, 77.0 to 10.0) than with budesonide 400g/day (46.1 to 23.5 ppb, 6.9 to 8.4 g/ml, and 75.0 to 26.1, respectively) (p=0.03), or with montelukast (42.5 to 24.5 ppb, 6.7 to 8.5 g/ml, and 78.3 to 22.6, respectively) (p=0.03). The similarity was found with the latter two treatments. The three treatments significantly and similarly suppressed eosinophil percentage from 5.2 to 0.5, 5.6 to 1.0 and 5.5 to 0.7. No parameter changes were significant with -agonist (eNO, 48.3 to 45.2 ppb; sputum eosinophil, 4.8 to 3.9%; log PC20, 6.5 to 5.9 g/ml; and cough, 69.0 to 53.0). CONCLUSIONS: In patients with CVA, budesonide 800 g/day was more effective than budesonide 400 g/day or montelukast 10 mg/day in
686
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
reducing airway inflammation and cough. Budesonide 800 g/day followed by maintenance doses of either budesonide 400 g/day or montelukast 10 mg/day is proposed as an effective treatment for CVA. Urine LTE4 Levels and Lung Function Declines are Highly Correlated in Urban Children with Moderate to Severe Asthma Despite Use of Inhaled Corticosteroids and Long-acting Bronchodilators N. Rabinovitch; Pediatrics, National Jewish Medical and Research Center, Denver, CO. RATIONALE: Most studies of cystenyl leukotriene effects in asthma have focused on adults with milder disease. Few studies have examined the role of leukotrienes in children with moderate to severe asthma who are already taking inhaled corticosteroids (ICS) and long-acting bronchodilators (LABAs). METHODS: 50 children with moderate-to-severe asthma were followed with daily measurements of urinary leukotriene E4 (LTE4) as well as monitoring of forced expiratory volume in 1 second (FEV1) and medication use. RESULTS: Daily variability in urinary LTE4 was associated (p= 0.008) with clinically significant declines in the following day’s FEV1, averaging approximately 5% per 25th-75th interquartile range (IQR) change in LTE4. LTE4 levels were also associated (p=0.03) with increased bronchodilator use on the day after urine collection. This association of LTE4 and abnormal lung function was greater (p=0.009) in those children with lower mean FEV1/FVC ratios and was blunted in children taking leukotriene receptor antagonists (LTRAs) (p=0.05) but not in those taking ICS and LABA therapy without LTRAs (p=0.88). CONCLUSIONS: Urine LTE4 levels serve as an important predictor of acute declines in pulmonary function among urban children with persistent airway obstruction despite ICS/LABA therapy. Funding: EPA R825702 and Thrasher Research Fund 02816
687
Relationship between Exhaled Nitric Oxide and Methacholine Bronchial Provocative Test in Asthmatic Children C. Direkwattanachai1, W. Teawsomboonkit1, C. Sasisakulporn2; 1Division of Allergy/Immunology, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, THAILAND, 2Research Center, Ramathibodi Hospital, Mahidol University, Bangkok, THAILAND. RATIONALE: Exhaled nitric oxide may serve as a non-invasive marker of airway inflammation, but its relationship with airway responsiveness (BHR) is not clearly defined. METHODS: Thirty asthmatic children aged 7-15 years were included in the study. All subjects did not have either allergic rhinitis or any respiratory tract infection during previous month. Fractional exhaled nitric oxide (FENO) was measured and methacholine provocation test as PD20 were performed in the patients. The correlation of FENO level and PD20 was evaluated. RESULTS: The mean levels of FENO and PD20 of the subjects were 37.75 ± 33.6 ppb and 66.03 ± 81.1 breath units, respectively. There was a significantly correlation between FENO levels and PD20 in our asthmatic children (r2 = 0.504, P < 0.004). CONCLUSIONS: Measurement of exhaled nitric oxide level, which is a safe and simple procedure, is comparable to methacholine provocation test. Exhaled NO is a suitable measure for airway inflammation in bronchial asthmatic patient. Funding: Ramathibodi Hospital, Mahidol University
688
685
The Case of the Polysaccharide Blues
SUNDAY
R. Gupta, H. J. Wedner; Internal Medicine, Barnes Jewish Hospital, St. Louis, MO. CASE HISTORY: A 60 yo white female was evaluated for possible immunodeficiency because of recurrent severe sinus infections. A lymphocyte subset panel was normal, including CD3, CD4, CD8, and CD19. Tetanus antibody titers were normal. Pneumococcal antibody titers drawn 1 month after administration of the pneumococcal 23-valent vaccine were suboptimal. IgG responses were less than 2-fold to 5 out of the 6 polysaccharide antigens in the serotype panel. Interestingly, one month after administration of the pneumococcal 7-valent conjugate vaccine, antibody levels were all normal. There was at least a 4-fold increase in all 6 of the anti-pneumococcal antibodies tested. DISCUSSION: A subset of elderly patients respond inadequately to the capsular polysaccharides in the 23-valent pneumococcal vaccine. This interesting case illustrates an elderly patient with chronic sinusitis who responded poorly to the capsular polysaccharides in the 23-valent vaccine. She did respond appropriately to the pneumococcal 7-valent vaccine in which the polysaccharides are directly conjugated to the protein carrier CRM197 of diphtheria toxin. Given the patient’s normal T-lymphocyte populations, it is not surprising that she had an appropriate antibody response to the T-cell dependent vaccine. Why our patient had a suboptimal antibody response to the T-cell independent process of responding to capsular polysaccharides is not clear. It is likely that multiple factors, such as antibody-mediated opsonophagocytosis may come into play. It is clear, however, that patients who fail to respond to an unconjugated vaccine should be revaccinated with a conjugated vaccine and evaluated before being declared as having common variable immunodeficiency and treated with IVIG. Efficacy of Airway Anti-Inflammatory Treatments Evaluated with Airway Inflammation Markers in Patients with Cough Variant Asthma: Budesonide versus Montelukast T. T. Shimoda, R. R. Kishikawa, S. S. Shoji, S. S. Nishima; Clinical Research Center, Fukuoka National Hospital, Fukuoka, JAPAN. RATIONALE: Airway hyperresponsiveness from inflammation is the primary cause of refractory cough in cough variant asthma (CVA). In this study, anti-inflammatory drugs, inhaled steroids and an oral leukotriene receptor antagonist, were evaluated for CVA treatment with airway inflammatory markers. METHODS: Seventy-four untreated patients with CVA randomly received budesonide (800 g/day, n=18 and 400 g/day, n=17), montelukast (10 mg/day, n=21), or need-based inhaled 2-adrenergic agonist (n=18) for 6 months. RESULTS: Budesonide and montelukast improved inflammation (significant decreases in eNO and sputum eosinophil), hyperresponsiveness (a significant increase in PC20) and cough. The improvement was greater with budesonide 800g/day (eNO, 47.2 to17.3 ppb; log PC20, 6.6 to 8.9 g/ml; and cough score, 77.0 to 10.0) than with budesonide 400g/day (46.1 to 23.5 ppb, 6.9 to 8.4 g/ml, and 75.0 to 26.1, respectively) (p=0.03), or with montelukast (42.5 to 24.5 ppb, 6.7 to 8.5 g/ml, and 78.3 to 22.6, respectively) (p=0.03). The similarity was found with the latter two treatments. The three treatments significantly and similarly suppressed eosinophil percentage from 5.2 to 0.5, 5.6 to 1.0 and 5.5 to 0.7. No parameter changes were significant with -agonist (eNO, 48.3 to 45.2 ppb; sputum eosinophil, 4.8 to 3.9%; log PC20, 6.5 to 5.9 g/ml; and cough, 69.0 to 53.0). CONCLUSIONS: In patients with CVA, budesonide 800 g/day was more effective than budesonide 400 g/day or montelukast 10 mg/day in
686
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
reducing airway inflammation and cough. Budesonide 800 g/day followed by maintenance doses of either budesonide 400 g/day or montelukast 10 mg/day is proposed as an effective treatment for CVA. Urine LTE4 Levels and Lung Function Declines are Highly Correlated in Urban Children with Moderate to Severe Asthma Despite Use of Inhaled Corticosteroids and Long-acting Bronchodilators N. Rabinovitch; Pediatrics, National Jewish Medical and Research Center, Denver, CO. RATIONALE: Most studies of cystenyl leukotriene effects in asthma have focused on adults with milder disease. Few studies have examined the role of leukotrienes in children with moderate to severe asthma who are already taking inhaled corticosteroids (ICS) and long-acting bronchodilators (LABAs). METHODS: 50 children with moderate-to-severe asthma were followed with daily measurements of urinary leukotriene E4 (LTE4) as well as monitoring of forced expiratory volume in 1 second (FEV1) and medication use. RESULTS: Daily variability in urinary LTE4 was associated (p= 0.008) with clinically significant declines in the following day’s FEV1, averaging approximately 5% per 25th-75th interquartile range (IQR) change in LTE4. LTE4 levels were also associated (p=0.03) with increased bronchodilator use on the day after urine collection. This association of LTE4 and abnormal lung function was greater (p=0.009) in those children with lower mean FEV1/FVC ratios and was blunted in children taking leukotriene receptor antagonists (LTRAs) (p=0.05) but not in those taking ICS and LABA therapy without LTRAs (p=0.88). CONCLUSIONS: Urine LTE4 levels serve as an important predictor of acute declines in pulmonary function among urban children with persistent airway obstruction despite ICS/LABA therapy. Funding: EPA R825702 and Thrasher Research Fund 02816
687
Relationship between Exhaled Nitric Oxide and Methacholine Bronchial Provocative Test in Asthmatic Children C. Direkwattanachai1, W. Teawsomboonkit1, C. Sasisakulporn2; 1Division of Allergy/Immunology, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, THAILAND, 2Research Center, Ramathibodi Hospital, Mahidol University, Bangkok, THAILAND. RATIONALE: Exhaled nitric oxide may serve as a non-invasive marker of airway inflammation, but its relationship with airway responsiveness (BHR) is not clearly defined. METHODS: Thirty asthmatic children aged 7-15 years were included in the study. All subjects did not have either allergic rhinitis or any respiratory tract infection during previous month. Fractional exhaled nitric oxide (FENO) was measured and methacholine provocation test as PD20 were performed in the patients. The correlation of FENO level and PD20 was evaluated. RESULTS: The mean levels of FENO and PD20 of the subjects were 37.75 ± 33.6 ppb and 66.03 ± 81.1 breath units, respectively. There was a significantly correlation between FENO levels and PD20 in our asthmatic children (r2 = 0.504, P < 0.004). CONCLUSIONS: Measurement of exhaled nitric oxide level, which is a safe and simple procedure, is comparable to methacholine provocation test. Exhaled NO is a suitable measure for airway inflammation in bronchial asthmatic patient. Funding: Ramathibodi Hospital, Mahidol University
688