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Circadian changes in the sputum of asthmatics and healthy controls
$13B Abstracts
265 Forced Oscillation Using Impulse Oscillometry (lOS)Detects False Negative Spirometry in Symptomatic Patients with Reactive Airways C. K. S a a d e h j,2, M. Goldman 3, P. Gaylor 1,4, J. M. Malacara 1,2, M. McGee 1, M. Gaylor 2, C. SaadehS; IAllergy ARTS, Amarillo, TX, 2Amarillo Center for Clinical Research, Amarillo, TX, 3Clinical Trials Unit, Drew University of Medicine, Los Angeles, CA, 4University of Arizona, Phoenix, AZ, 5Allergy ARTS, Amarillo, TX. RATIONALE: Forced oscillation is reported to be more sensitive than spirometry for detecting early small airway disease and evaluating response to therapeutic or bronchial challenge. METHODS: To determine whether normal spirometry and absence of a bronchodilator response ruled out reactive airways, 60 patients 4-62 yrs referred for evaluation, whose FEV1 was WNL upon presentation were evaluated. Patients underwent forced oscillation using Impulse Oscillometry (lOS, Jaeger) and spirometry prior to and 20-60 minutes after nebulized levalbuterol. Baseline FEV1 was 81-128% predicted prior to beta agonist (BA), and 91-128% of post BA. lOS measures included resistance at 5 and 20 Hz (R5, R20), and integrated low frequency reactance (AX). Baseline R5 was abnormal (n=42), R20 (26) and AX (58). Pre to Post BA increases in FEV 1 averaged 3.1% with >8% and >200 ml changes in 12 patients, lOS changes were judged significant if >2 SD of pre BA mean values and >15% of pre BA mean values for R5/R20 or >20% for AX. Significant post BA decreases in lOS R5, R20, AX occurred in 46, 25 and 55 subjects. Follow up IOS testing in 26 subjects 3-6 wks after treatment for showed improvement in R5, R20 and/or AX in 22 subjects. CONCLUSIONS: We conclude that FEVI WNL and/or absence of >8% improvement in FEVI post BA does not rule out reactive airway disease. We conclude also that R5, and AX are more sensitive indicators of reactive airway than FEVI at baseline and in response to BA. Funding: Amarillo Center for Clinical Research
266 asHLAa Strong Association in ASA-lntolerant Asthma (AIA): DPBI*0301 Marker in Korean Patients J. Choi; Allergy and Rheumatology, Ajou University School of Medicine, Suwon city, REPUBLIC OF KOREA. RATIONALE: A possible involvement of immune mechanisms associated with some HLA genotypings has been suggested in Caucasian patients with AIA. This study was aimed to evaluate HLA associations in AIA compared to ASA-tolerant asthma (ATA) and normal controls based on Asian population. M E T H O D S : 88 AIA showing positive results on lysine-ASA bronchoprovocation test, 70 ATA patients and 91 healthy normal controls were enrolled. HLA-DRB 1, DQB 1, and DPBI genotypings were performed by direct DNA sequencing analysis using ABI-3100 automated DNA sequence analyzer. RESULTS: The frequency of DPBI*0301 in AIA (14.2%) was significantly higher than those of ATA (3.6%) and controls (2.2%) (p=0.001; OR: 6.6; 95% CI 2.2-19.9, p<0.001, OR; 8.6; 95% CI: 2.9-26.0). Moreover, 9 (36%) of 25 A1A patients with DPB 1"0301 had HLA DQ*02, and 7 (77.8%) of 9 patients showing linkage disequilibrium had HLA DR*03011. The frequencies of DRB 1"03011 and DRB 1" 1301 in AIA were significantly higher than those of ATA (p<0.05, respectively), however, the frequency of DQBI*0604 in AIA was significantly lower than that of ATA (p<0.05). CONCLUSIONS: These findings suggest that HLA DPBI*0301 linked with DQ*02 and DR*03011 can be a strong genetic marker for the prevalence of AIA. Funding: Grant Monies. This study was funded by a grant of the Koran Health 21 R&D project, Ministry of Health & Welfare, Republic of Korea (OI-PJIO-PG6-OIGN14-O07).
J ALLERGY CLIN IMMUNOL FEBRUARY 2003
67 Bronchial Challenge Tests in Asthmatics Sensitized to Cats: Influence of the Particle Size on Systemic InflammatoryMarkers F. Lieutier-Colas I, A. Purohit I, P. Meyer 2, A. Verot ], C. Sohy 1, G. Pauli ], E de Blayl; 1pulmonology, Hrpitaux Universitaires de Strasbourg, Strasbourg, FRANCE, 2Biostatistique et Informatique Medicale, Facult6 de Mrdecine, Strasbourg, FRANCE. We have demonstrated that immediate bronchial response to major cat allergen is localized in large airways. Moreover, small particles induce late symptoms and decrease peripheral airway caliber (J Allergy Clin Immunol 2002; 109:$32). AIM: We assessed systemic inflammatory response to cat allergen according to the droplet particle size. METHODS: 19 cat-sensitized intermittent asthmatics provided informed consent and underwent 3 cat allergen bronchial challenge tests (BCT), each with a different nebulizer. Urine and blood were collected before the BCT and thereafter at 15 minutes, 3, 6 and 24 h. Serum SCF, IL-5, RANTES, ECP and urinary Leukotriene E4 (LTE4) were measured, and eosinophils counted. Enzyme-immunoassays of urine samples measured LTE4. RESULTS: Urine LTE4 levels had increased 3 h after each cat BCT (p=0.04), as had serum SCF (p=0.001), RANTES (p=0.03), and ECP (p=0.006) and eosinophil counts (p=0.02) at 24 hours. Three hours after BCT with 1.4 ~m particles, 1L5 levels were higher than with 4.8 I.tm and 10.3 ~m particles; 24 hours after BCT with 1.4 ~m particles, RANTES was significantly higher than with the other size particles (p=0.03); as well, eosinophil counts and ECP were higher and significantly correlated (r=0.43; p=0.01 ). C O N C L U S I O N : The association of late bronchial symptoms and increased eosinophilic inflammation after inhalation of small particles carrying cat allergen suggests that late bronchial response is mainly localized in small airways. Funding: The Conseil Rdgional Alsace and the H&pitaux Universitaires de Strasbourg supported this work and Pharmacia provided the reagents.
268
Circadian Changes in the Sputum of Asthmatics and Healthy Controls
T. A. Popov, M. S. Shenkada, A. V. Tzoncheva, M. P. Pravtchanska, T. B. Mustakov, M. P. Baleva; Medical University Sofia, Sofia, BULGARIA. RATIONALE: Asthma is a disease having classical circadian fluctuations. The aim of this study was to examine the cellular content and ECP levels in sputum which was collected in the morning and at night. METHODS: Thirteen asthmatics (8 men, aged 25-54 years) with uncontrolled asthma, and 10 healthy subjects (6 men, aged 25-50 years) volunteered for this study. Subjects were induced to produce sputum between 8.00 and 9.00 a.m. and 8:00 and 9:00 p.m., with simultaneously obtained blood to measure cortisol levels. RESULTS: The asthmatics had more cells in their sputum than the controls; no significant morning versus evening difference was noted in asthmatic specimens, while the controls had a well defined morning peak in cellular content of sputum. The control subjects had significantly fewer eosinophils and lower ECP levels with a morning peak in eosinophils and ECP, in contrast to asthmatics, who did not show significant morning versus evening differences in these parameters. Macrophages were increased in the evening samples of both the asthmatics and the controls. No significant correlations between the circadian cortisol shift and any of the sputum indices were found. CONCLUSIONS: Sputum content undergoes circadian changes, which differ in healthy subjects versus uncontrolled asthmatic patients, in whom normal circadian variances of sputum cellular content, ECP expression, and eosinophil content appears to be abolished. Funding: Grant L221/1999 ~f the Bulgarian Ministry of Education and Science
265 Forced Oscillation Using Impulse Oscillometry (lOS)Detects False Negative Spirometry in Symptomatic Patients with Reactive Airways C. K. S a a d e h j,2, M. Goldman 3, P. Gaylor 1,4, J. M. Malacara 1,2, M. McGee 1, M. Gaylor 2, C. SaadehS; IAllergy ARTS, Amarillo, TX, 2Amarillo Center for Clinical Research, Amarillo, TX, 3Clinical Trials Unit, Drew University of Medicine, Los Angeles, CA, 4University of Arizona, Phoenix, AZ, 5Allergy ARTS, Amarillo, TX. RATIONALE: Forced oscillation is reported to be more sensitive than spirometry for detecting early small airway disease and evaluating response to therapeutic or bronchial challenge. METHODS: To determine whether normal spirometry and absence of a bronchodilator response ruled out reactive airways, 60 patients 4-62 yrs referred for evaluation, whose FEV1 was WNL upon presentation were evaluated. Patients underwent forced oscillation using Impulse Oscillometry (lOS, Jaeger) and spirometry prior to and 20-60 minutes after nebulized levalbuterol. Baseline FEV1 was 81-128% predicted prior to beta agonist (BA), and 91-128% of post BA. lOS measures included resistance at 5 and 20 Hz (R5, R20), and integrated low frequency reactance (AX). Baseline R5 was abnormal (n=42), R20 (26) and AX (58). Pre to Post BA increases in FEV 1 averaged 3.1% with >8% and >200 ml changes in 12 patients, lOS changes were judged significant if >2 SD of pre BA mean values and >15% of pre BA mean values for R5/R20 or >20% for AX. Significant post BA decreases in lOS R5, R20, AX occurred in 46, 25 and 55 subjects. Follow up IOS testing in 26 subjects 3-6 wks after treatment for showed improvement in R5, R20 and/or AX in 22 subjects. CONCLUSIONS: We conclude that FEVI WNL and/or absence of >8% improvement in FEVI post BA does not rule out reactive airway disease. We conclude also that R5, and AX are more sensitive indicators of reactive airway than FEVI at baseline and in response to BA. Funding: Amarillo Center for Clinical Research
266 asHLAa Strong Association in ASA-lntolerant Asthma (AIA): DPBI*0301 Marker in Korean Patients J. Choi; Allergy and Rheumatology, Ajou University School of Medicine, Suwon city, REPUBLIC OF KOREA. RATIONALE: A possible involvement of immune mechanisms associated with some HLA genotypings has been suggested in Caucasian patients with AIA. This study was aimed to evaluate HLA associations in AIA compared to ASA-tolerant asthma (ATA) and normal controls based on Asian population. M E T H O D S : 88 AIA showing positive results on lysine-ASA bronchoprovocation test, 70 ATA patients and 91 healthy normal controls were enrolled. HLA-DRB 1, DQB 1, and DPBI genotypings were performed by direct DNA sequencing analysis using ABI-3100 automated DNA sequence analyzer. RESULTS: The frequency of DPBI*0301 in AIA (14.2%) was significantly higher than those of ATA (3.6%) and controls (2.2%) (p=0.001; OR: 6.6; 95% CI 2.2-19.9, p<0.001, OR; 8.6; 95% CI: 2.9-26.0). Moreover, 9 (36%) of 25 A1A patients with DPB 1"0301 had HLA DQ*02, and 7 (77.8%) of 9 patients showing linkage disequilibrium had HLA DR*03011. The frequencies of DRB 1"03011 and DRB 1" 1301 in AIA were significantly higher than those of ATA (p<0.05, respectively), however, the frequency of DQBI*0604 in AIA was significantly lower than that of ATA (p<0.05). CONCLUSIONS: These findings suggest that HLA DPBI*0301 linked with DQ*02 and DR*03011 can be a strong genetic marker for the prevalence of AIA. Funding: Grant Monies. This study was funded by a grant of the Koran Health 21 R&D project, Ministry of Health & Welfare, Republic of Korea (OI-PJIO-PG6-OIGN14-O07).
J ALLERGY CLIN IMMUNOL FEBRUARY 2003
67 Bronchial Challenge Tests in Asthmatics Sensitized to Cats: Influence of the Particle Size on Systemic InflammatoryMarkers F. Lieutier-Colas I, A. Purohit I, P. Meyer 2, A. Verot ], C. Sohy 1, G. Pauli ], E de Blayl; 1pulmonology, Hrpitaux Universitaires de Strasbourg, Strasbourg, FRANCE, 2Biostatistique et Informatique Medicale, Facult6 de Mrdecine, Strasbourg, FRANCE. We have demonstrated that immediate bronchial response to major cat allergen is localized in large airways. Moreover, small particles induce late symptoms and decrease peripheral airway caliber (J Allergy Clin Immunol 2002; 109:$32). AIM: We assessed systemic inflammatory response to cat allergen according to the droplet particle size. METHODS: 19 cat-sensitized intermittent asthmatics provided informed consent and underwent 3 cat allergen bronchial challenge tests (BCT), each with a different nebulizer. Urine and blood were collected before the BCT and thereafter at 15 minutes, 3, 6 and 24 h. Serum SCF, IL-5, RANTES, ECP and urinary Leukotriene E4 (LTE4) were measured, and eosinophils counted. Enzyme-immunoassays of urine samples measured LTE4. RESULTS: Urine LTE4 levels had increased 3 h after each cat BCT (p=0.04), as had serum SCF (p=0.001), RANTES (p=0.03), and ECP (p=0.006) and eosinophil counts (p=0.02) at 24 hours. Three hours after BCT with 1.4 ~m particles, 1L5 levels were higher than with 4.8 I.tm and 10.3 ~m particles; 24 hours after BCT with 1.4 ~m particles, RANTES was significantly higher than with the other size particles (p=0.03); as well, eosinophil counts and ECP were higher and significantly correlated (r=0.43; p=0.01 ). C O N C L U S I O N : The association of late bronchial symptoms and increased eosinophilic inflammation after inhalation of small particles carrying cat allergen suggests that late bronchial response is mainly localized in small airways. Funding: The Conseil Rdgional Alsace and the H&pitaux Universitaires de Strasbourg supported this work and Pharmacia provided the reagents.
268
Circadian Changes in the Sputum of Asthmatics and Healthy Controls
T. A. Popov, M. S. Shenkada, A. V. Tzoncheva, M. P. Pravtchanska, T. B. Mustakov, M. P. Baleva; Medical University Sofia, Sofia, BULGARIA. RATIONALE: Asthma is a disease having classical circadian fluctuations. The aim of this study was to examine the cellular content and ECP levels in sputum which was collected in the morning and at night. METHODS: Thirteen asthmatics (8 men, aged 25-54 years) with uncontrolled asthma, and 10 healthy subjects (6 men, aged 25-50 years) volunteered for this study. Subjects were induced to produce sputum between 8.00 and 9.00 a.m. and 8:00 and 9:00 p.m., with simultaneously obtained blood to measure cortisol levels. RESULTS: The asthmatics had more cells in their sputum than the controls; no significant morning versus evening difference was noted in asthmatic specimens, while the controls had a well defined morning peak in cellular content of sputum. The control subjects had significantly fewer eosinophils and lower ECP levels with a morning peak in eosinophils and ECP, in contrast to asthmatics, who did not show significant morning versus evening differences in these parameters. Macrophages were increased in the evening samples of both the asthmatics and the controls. No significant correlations between the circadian cortisol shift and any of the sputum indices were found. CONCLUSIONS: Sputum content undergoes circadian changes, which differ in healthy subjects versus uncontrolled asthmatic patients, in whom normal circadian variances of sputum cellular content, ECP expression, and eosinophil content appears to be abolished. Funding: Grant L221/1999 ~f the Bulgarian Ministry of Education and Science