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Human Rhinovirus Precipitates Acute Wheezing, Preferentially Over Upper Respiratory Illness, in School-aged Children With Underlying Asthma
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Usefulness Of Exhaled Nitric Oxide In Asthma Diagnosis M. Pedrosa, N. Cancelliere, P. Barranco, B. San Jose´, S. Quirce; University Hospital La Paz, Madrid, SPAIN. RATIONALE: Inflammation is known to underlie the pathogenesis of asthma. Nevertheless, diagnosis is made by clinical history, reversible airway obstruction and bronchial hyperresponsiveness according to international guidelines. Exhaled nitric oxide is a non-invasive inflammatory marker. The aim of the study was to assess the sensitivity and specificity of FeNO in asthma diagnosis. METHODS: Sixty-four consecutive patients reporting asthma symptoms were included in the study. All of them underwent methacholine challenge test following the five-breath dosimeter protocol, after measurement of exhaled nitric oxide with a portable device. RESULTS: Twenty-three of the 64 patients were diagnosed with asthma. A positive MCh challenge was correlated with higher FeNO levels and with basal FEV1. No correlation was found between PC20 and FeNO levels. ROC curves were built for FeNO levels (AUC: 0.79). A cut-off point for FeNO level was calculated with maximal specificity and sensitivity for asthma diagnosis (39.5 ppb). CONCLUSIONS: FeNO as marker of inflammation is highly correlated with functional parameters (MCh) in asthmatic patients. A cut-off point of 39.5 ppb was calculated for asthma diagnosis in our population. The use of FeNO measurement may be a helpful tool for asthma diagnosis in patients not able of performing MCh challenges.
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Asthma Control, Quality of Life and Successful Sputum Induction S. Majewski1, P. Cichocki1, M. Stepnicka-Bindemann2, P. Gorski1; 1Department of Pulmonology and Allergy, Medical University of Lodz, Lodz, POLAND, 2Norbert Barlicki Memorial Teaching Hospital No. 1, Lodz, POLAND. RATIONALE: Induced sputum is widely used in clinical practice and scientific studies. However, some asthmatics are unable to expectorate sputum of good quality and quantity necessary for further processing. Therefore we aimed at comparing Mini Asthma Quality of Life Questionnaire (MiniAQLQ) score and Asthma Control Questionnaire (ACQ) score between groups of asthmatics expectorating and unexpectorating the sputum. METHODS: 41 non-smoking subjects with symptomatic asthma confirmed by positive reversibility test with salbutamol or methacholine challenge filled in Mini Asthma Quality of Life Questionnaire and Asthma Control Questionnaire before sputum induction. RESULTS: 25 (60%) asthmatics produced sputum eligible for the processing. This group tended to have lower ACQ score (0,9160,66 vs 1,3260,79; p50,078), higher MiniAQLQ overall score (5,5761,0 vs 4,9461,1; p 5 0,065) and MiniAQLQ symptoms domain score (5,4261,69 vs 4,6761,31; p50,063). MiniAQLQ activities domain score was significantly higher in asthmatics expectorating sputum (6,0160,93 vs 5,1461,44; p50,024). CONCLUSIONS: These results suggest that successful sputum induction may be expected in patients with better asthma control and better quality of life.
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Human Rhinovirus Precipitates Acute Wheezing, Preferentially Over Upper Respiratory Illness, in School-aged Children With Underlying Asthma J. A. Zea-Hernandez1,2, N. Bhat3, M. E. Serra2, Y. Mohamed1, D. Kraft1, A. Chen3, G. K. Siberry4, B. E. Shepherd1, E. K. Miller1, F. P. Polack1,2; 1 Vanderbilt University, Nashville, TN, 2Fundacion Infant, Buenos Aires, ARGENTINA, 3Johns Hopkins University, Baltimore, MD, 4National Institutes of Health, Bethesda, MD. RATIONALE: The role of rhinovirus (HRV)-induced wheezing compared to HRV-induced upper respiratory illness (URI) in school-aged children with underlying asthma has not been determined. METHODS: We performed a case-control study of 5-18 year-old asthmatic children in Baltimore and Buenos Aires presenting with active wheezing and controls presenting with URI in the absence of wheezing. Respiratory specimens were tested by MultiCode-Plx Assay for HRV, respiratory syncytial virus, parainfluenza viruses, influenza viruses, human metapneumovirus, adenoviruses and coronaviruses. Specimens were also tested by real-time RT-PCR for HRV. To determine the HRV clade, the VP4/VP2 gene was sequenced from HRV-positive specimens. RESULTS: Of 478 samples from children enrolled and tested, 44.3% were positive for HRV and 17.5% were positive for other viruses. During the 2year study period, HRV infection was associated with exacerbations (54% case vs 36.7% control, p2 prior asthma hospitalizations were at greater risk of wheezing compared to those with < 2 of prior asthma hospitalizations (p<0.001; OR52.59,95%CI1.62-4.14). Moderate to severe baseline asthma severity was associated with less acute wheezing (p<0.001, OR50.17, CI50.1-0.3), and use of inhaled corticosteroids was associated with less acute wheezing (46.7% cases vs 61% controls, p50.002). CONCLUSIONS: Human rhinoviruses may precipitate wheezing, preferentially, over URI alone, in school-aged children with underlying asthma. HRV infection, mild baseline severity and > 2 previous asthma hospitalizations are risk factors for wheezing exacerbations among asthmatics. The use of inhaled corticosteroids is protective for acute wheezing in asthmatic children.
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Biochemical Analysis of CVID-Associated TACI Mutations A. J. Fried, H. H. Jabara, R. S. Geha; Children’s Hospital Boston, Boston, MA. RATIONALE: Monoallelic and biallelic mutations of the gene TNFRSF13B, encoding the transmembrane activator, calcium-modulator and cyclophilin ligand interactor (TACI) are found in ~10% of patients with CVID. The most common mutations, C104R and A181E, have been found in 1% of healthy subjects. Other mutations have been found to date only in CVID patients. We examined whether these mutations represent normal variants or variants that disrupt TACI function. METHODS: Point mutations that correspond to those found in CVID patients were introduced into plasmid DNA encoding TACI. T293 cells were transfected with either wild type (WT) TACI, mutated TACI, or both. TACI surface expression and binding of BAFF ligand were analyzed by FACS. BAFF driven NF-kB activation was measured by a luciferase reporter gene assay. RESULTS: The effects of TACI missense mutations fell into three categories 1) No effect on either TACI surface expression, ligand-binding or NF-kB signaling. 2) Reduced TACI surface expression, poor ligand binding and NF-kB signaling 3) No effect on surface expression but abrogation of ligand binding and NF-kB signaling. None of the mutants studied to date interfered with NF-kB signaling of WT TACI in a dominant negative manner. CONCLUSIONS: A number of missense mutations associated with CVID were found to disrupt TACI function. In vitro studies might be useful in distinguishing clinically significant mutations from normal variants.
SATURDAY
Abstracts AB7
J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2
Usefulness Of Exhaled Nitric Oxide In Asthma Diagnosis M. Pedrosa, N. Cancelliere, P. Barranco, B. San Jose´, S. Quirce; University Hospital La Paz, Madrid, SPAIN. RATIONALE: Inflammation is known to underlie the pathogenesis of asthma. Nevertheless, diagnosis is made by clinical history, reversible airway obstruction and bronchial hyperresponsiveness according to international guidelines. Exhaled nitric oxide is a non-invasive inflammatory marker. The aim of the study was to assess the sensitivity and specificity of FeNO in asthma diagnosis. METHODS: Sixty-four consecutive patients reporting asthma symptoms were included in the study. All of them underwent methacholine challenge test following the five-breath dosimeter protocol, after measurement of exhaled nitric oxide with a portable device. RESULTS: Twenty-three of the 64 patients were diagnosed with asthma. A positive MCh challenge was correlated with higher FeNO levels and with basal FEV1. No correlation was found between PC20 and FeNO levels. ROC curves were built for FeNO levels (AUC: 0.79). A cut-off point for FeNO level was calculated with maximal specificity and sensitivity for asthma diagnosis (39.5 ppb). CONCLUSIONS: FeNO as marker of inflammation is highly correlated with functional parameters (MCh) in asthmatic patients. A cut-off point of 39.5 ppb was calculated for asthma diagnosis in our population. The use of FeNO measurement may be a helpful tool for asthma diagnosis in patients not able of performing MCh challenges.
26
Asthma Control, Quality of Life and Successful Sputum Induction S. Majewski1, P. Cichocki1, M. Stepnicka-Bindemann2, P. Gorski1; 1Department of Pulmonology and Allergy, Medical University of Lodz, Lodz, POLAND, 2Norbert Barlicki Memorial Teaching Hospital No. 1, Lodz, POLAND. RATIONALE: Induced sputum is widely used in clinical practice and scientific studies. However, some asthmatics are unable to expectorate sputum of good quality and quantity necessary for further processing. Therefore we aimed at comparing Mini Asthma Quality of Life Questionnaire (MiniAQLQ) score and Asthma Control Questionnaire (ACQ) score between groups of asthmatics expectorating and unexpectorating the sputum. METHODS: 41 non-smoking subjects with symptomatic asthma confirmed by positive reversibility test with salbutamol or methacholine challenge filled in Mini Asthma Quality of Life Questionnaire and Asthma Control Questionnaire before sputum induction. RESULTS: 25 (60%) asthmatics produced sputum eligible for the processing. This group tended to have lower ACQ score (0,9160,66 vs 1,3260,79; p50,078), higher MiniAQLQ overall score (5,5761,0 vs 4,9461,1; p 5 0,065) and MiniAQLQ symptoms domain score (5,4261,69 vs 4,6761,31; p50,063). MiniAQLQ activities domain score was significantly higher in asthmatics expectorating sputum (6,0160,93 vs 5,1461,44; p50,024). CONCLUSIONS: These results suggest that successful sputum induction may be expected in patients with better asthma control and better quality of life.
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Human Rhinovirus Precipitates Acute Wheezing, Preferentially Over Upper Respiratory Illness, in School-aged Children With Underlying Asthma J. A. Zea-Hernandez1,2, N. Bhat3, M. E. Serra2, Y. Mohamed1, D. Kraft1, A. Chen3, G. K. Siberry4, B. E. Shepherd1, E. K. Miller1, F. P. Polack1,2; 1 Vanderbilt University, Nashville, TN, 2Fundacion Infant, Buenos Aires, ARGENTINA, 3Johns Hopkins University, Baltimore, MD, 4National Institutes of Health, Bethesda, MD. RATIONALE: The role of rhinovirus (HRV)-induced wheezing compared to HRV-induced upper respiratory illness (URI) in school-aged children with underlying asthma has not been determined. METHODS: We performed a case-control study of 5-18 year-old asthmatic children in Baltimore and Buenos Aires presenting with active wheezing and controls presenting with URI in the absence of wheezing. Respiratory specimens were tested by MultiCode-Plx Assay for HRV, respiratory syncytial virus, parainfluenza viruses, influenza viruses, human metapneumovirus, adenoviruses and coronaviruses. Specimens were also tested by real-time RT-PCR for HRV. To determine the HRV clade, the VP4/VP2 gene was sequenced from HRV-positive specimens. RESULTS: Of 478 samples from children enrolled and tested, 44.3% were positive for HRV and 17.5% were positive for other viruses. During the 2year study period, HRV infection was associated with exacerbations (54% case vs 36.7% control, p2 prior asthma hospitalizations were at greater risk of wheezing compared to those with < 2 of prior asthma hospitalizations (p<0.001; OR52.59,95%CI1.62-4.14). Moderate to severe baseline asthma severity was associated with less acute wheezing (p<0.001, OR50.17, CI50.1-0.3), and use of inhaled corticosteroids was associated with less acute wheezing (46.7% cases vs 61% controls, p50.002). CONCLUSIONS: Human rhinoviruses may precipitate wheezing, preferentially, over URI alone, in school-aged children with underlying asthma. HRV infection, mild baseline severity and > 2 previous asthma hospitalizations are risk factors for wheezing exacerbations among asthmatics. The use of inhaled corticosteroids is protective for acute wheezing in asthmatic children.
28
Biochemical Analysis of CVID-Associated TACI Mutations A. J. Fried, H. H. Jabara, R. S. Geha; Children’s Hospital Boston, Boston, MA. RATIONALE: Monoallelic and biallelic mutations of the gene TNFRSF13B, encoding the transmembrane activator, calcium-modulator and cyclophilin ligand interactor (TACI) are found in ~10% of patients with CVID. The most common mutations, C104R and A181E, have been found in 1% of healthy subjects. Other mutations have been found to date only in CVID patients. We examined whether these mutations represent normal variants or variants that disrupt TACI function. METHODS: Point mutations that correspond to those found in CVID patients were introduced into plasmid DNA encoding TACI. T293 cells were transfected with either wild type (WT) TACI, mutated TACI, or both. TACI surface expression and binding of BAFF ligand were analyzed by FACS. BAFF driven NF-kB activation was measured by a luciferase reporter gene assay. RESULTS: The effects of TACI missense mutations fell into three categories 1) No effect on either TACI surface expression, ligand-binding or NF-kB signaling. 2) Reduced TACI surface expression, poor ligand binding and NF-kB signaling 3) No effect on surface expression but abrogation of ligand binding and NF-kB signaling. None of the mutants studied to date interfered with NF-kB signaling of WT TACI in a dominant negative manner. CONCLUSIONS: A number of missense mutations associated with CVID were found to disrupt TACI function. In vitro studies might be useful in distinguishing clinically significant mutations from normal variants.
SATURDAY
Abstracts AB7
J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2