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Correlation Of Exhaled Breath Temperature With Age In Chronic Respiratory Diseases
AB148 Abstracts
518
SUNDAY
Exhaled Nitric Oxide Performance Compared To Methacholine Challenge In Asthma Andrew Nickels, MD, Dr. Kaiser G. Lim, MD, FAAAAI, Dr. Paul Scanlon, MD, Kenneth Parker; Mayo Clinic, Rochester, MN. RATIONALE: Exhaled nitric oxide (FeNO) and Methacholine challenge (MCH) are both utilized in the detection and management of asthma. We hypothesize that FeNO can decrease the need for MCH testing. _ 18 years presenting METHODS: Retrospective chart review of patients > to a tertiary referral center seen between 11/01/2009 - 8/31/2013 who received FeNO and MCH within 2 weeks and diagnosis of asthma was used for both procedures. RESULTS: 197 patients were identified. Demographics: 129 (65.5%) females and 68 (34.5%) males; 188 (95.4%) Caucasian, 6 (3.0%) Black, 3 (1.5%) Asian. Average age was 49.6 years (SD +/- 17.1 years). Mean BMI 30.6 (SD +/-7.0). 29 patients were positive for both MCH and FeNO, 31 patients had a positive MCH but negative FeNO, 22 patients had a negative MCH but positive FeNO, and 115 patients had both a negative (p<0.01). Directly comparing FeNO to MCH yielded: sensitivity 48.33% (95% CI: 35.23% to 61.60%), specificity 83.94% (95% CI: 76.70% to 89.65%), positive likelihood ratio 3.01 (95% CI: 1.89 to 4.79), negative likelihood ratio 0.62 (95% CI: 0.48 to 0.79), positive predictive value 56.86 (95% CI: 42.25% to 70.65%), and negative predictive value 78.77% (95% CI: 71.24% to 85.09%) CONCLUSIONS: FeNO and methacholine responsiveness measure different biological phenomenon. In patients suspected of asthma, a strategy of FeNO at the point-of-care may reduce but not eliminate the need for MCH testing.
519
Serum Interleukin 13 (IL-13) and Surfactant Protein D (SP-D) Expression Is Differentially Associated With Disease Status In Pediatric Asthma Patients Dr. Vasiliki Gemou-Engesaeth, MD, PhD1, Dr. N. Laliotou, MD1, Prof. Chris J. Corrigan, MD, PhD, FAAAAI2, Prof. George P. Chrousos, MD, PhD1, Dr. Angela Haczku, MD, PhD, FAAAAI3; 1National & Kapodistrian University of Athens, Greece, 2King’s College London School of Medicine, London, United Kingdom, 3University of Pennsylvania, Philadelphia, PA. RATIONALE: Allergic airway inflammation is associated with a negative regulatory feedback between IL-13 and the immunoprotective SP-D in mice but the relevance of this to human asthma is not known. We hypothesized that serum IL-13 and SP-D expression would reflect disease status in asthmatic children. METHODS: SP-D and IL-13 serum levels were measured in 17 atopic and 8 nonatopic children (7 to 16 years old) with inadequately controlled asthma, and in 15 non-asthmatic controls matched for age and atopic status, in duplicates of dilutions (1:5 and 1:10) by ELISA (BioVendor and RayBiotech, Inc., respectively). The inter-assay and inter-experimental variability was <10% for both assays. Measurements were repeated in asthmatic children 4 to 6 months after initiation or escalation of inhaled glucocorticoid therapy (n510) and after initiation of inhaled Sodium Cromoglycate (n57) given according to the American Thoracic Society Criteria and European Consensus Guidelines. RESULTS: Expression of IL-13 (ranged between 0-171 pg/ml) was significantly greater in the asthmatic samples than in controls (25.662.7 vs. 12.662.0 p50.0001). In contrast, SP-D levels (ranged between 19-373 ng/ml) were significantly higher in the controls than in asthmatics (148.265.9 vs. 200.2620.2; p50.0219). Inhaled glucocorticoids or sodium cromoglycate did not change IL-13 or SP-D serum levels significantly although the sodium cromoglycate-treated patients showed a trend for reduced IL-13 (41.0621.1 vs. 19.267.6 pg/ml). CONCLUSIONS: Serum levels of IL-13 and SP-D inversely associated with presence of moderate to severe asthmatic airway inflammation in children suggesting that these biomarkers may be useful noninvasive indicators of disease status in childhood asthma.
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
520
Correlation Of Exhaled Breath Temperature With Age In Chronic Respiratory Diseases Dr. Radoslaw Gawlik, MD1, Dr. Malgorzata Rajzer-Wrobel2, Dr. Dariusz Ziora2, Prof. Lawrence M. DuBuske, MD, FAAAAI3; 1Silesian Medical University, Katowice, Poland, 2Silesian Medical University, Poland, 3 George Washington University School of Medicine, Washington, DC. RATIONALE: Asthma exacerbations may be associated with increased exhaled breath temperature. Chronic obstructive lung disease may be influenced by vascular inflammation. There may be a relationship between exhaled breath temperature and patient age in asthma and COPD. METHODS: 124 patients with COPD and asthma (72 male and 52 women) were studied, ranging from 42 to 81 years old, mean age 58.4 years. 30 healthy control subjects were assessed. Patients with acute respiratory infection or disease exacerbation in the last month were excluded. All exhaled breath tests were performed in the same room, at similar times of day with ambient temperatures between 20 and 238C and humidity 55% and 70%. Exhaled breath temperature was measured using an X-Halo device (Delmedica,Singapore). Mean temperature value was calculated by 3 consecutive measurements 1 day apart. RESULTS: EBT values were almost 2.08C higher in the control group (EBT 5 33.918C), compared to patients with chronic obstructive respiratory disease (EBT5 31.698C) and asthma (EBT5 30.898C). Inverse correlation was seen between patient age and EBT (r50.54; p<0.05). CONCLUSIONS: An inverse correlation exists between patient age and EBT in asthma and COPD patients not in exacerbation. COPD and asthma patients had lower EBT at baseline then healthy controls. This may reflect underlying chnages in vascularity in both diseases compared with healthy controls without chronic respiratory diseases.
521
Peripherally Induced Foxp3+ Regulatory T Cells Mediates The Immunomodulatory Effect Of Intravenous Immunoglobulin In An Experimental Model Of Allergic Airway Disease Dr. Amir Hossein Massoud, PhD1,2, Mr. Gabriel N. Kaufman, MSc1,2, Dr. Ciriaco Piccirillo, PhD2, Dr. Bruce D. Mazer, MD, FAAAAI1,3; 1Meakins-Christie Laboratories, Research Institute - McGill University Health Centre, Montreal, QC, Canada, 2McGill University Health Centre, Montreal, QC, Canada, 3Montreal Children’s Hospital, Montreal, QC, Canada. RATIONALE: IVIg is a polyclonal IgG preparation with potent immunemodulating properties. We demonstrated that IVIg protects against airway hyperreactivity (AHR) and airway inflammation in mouse models of allergic airway disease, accompanied by peripheral induction of Foxp3+ regulatory T-cells (iTreg). The requirement of IVIg-induced iTreg and their antigen-specificity in attenuation of AHR and airway inflammation remains unknown. METHODS: We utilized DEREG mice, carrying a transgenic diphtheria toxin receptor under the control of the Foxp3 promoter, allowing for selective depletion of Foxp3+Treg by the application of diphtheria toxin (DT). Mice were sensitized and challenged with ovalbumin (OVA) and treated with IVIg. AHR was measured using a FlexiVent small animal ventilator. Total and antigen-specific IgE, as well as pro-inflammatory cytokines levels were determined in serum and alveolar lavage, using ELISA. RESULTS: In the absence of Treg, due to multiple DT doses before and after the treatment, IVIg was not able to attenuate AHR, diminish IgE levels and Th-2 type cytokine production, nor alleviate airway inflammation. However, mice in which the pre-established Treg cells (nTreg) were depleted before but not following IVIg treatment demonstrated an induction of Foxp3+Treg to IVIg therapy and did not develop AHR and airway inflammation to allergen-challenge. Adoptive transfer of enriched IVIginduced iTreg from OVA-IVIg treated mice failed to transfer protection to mice exposed to ragweed, but was protective in OVA-sensitized and challenged mice. CONCLUSIONS: Treg can be induced from effector CD4+T-cells in the absence of nTreg. IVIg-induced antigen specific Treg are capable of suppressing all aspects of antigen-driven airway inflammation in an antigenspecific manner.
518
SUNDAY
Exhaled Nitric Oxide Performance Compared To Methacholine Challenge In Asthma Andrew Nickels, MD, Dr. Kaiser G. Lim, MD, FAAAAI, Dr. Paul Scanlon, MD, Kenneth Parker; Mayo Clinic, Rochester, MN. RATIONALE: Exhaled nitric oxide (FeNO) and Methacholine challenge (MCH) are both utilized in the detection and management of asthma. We hypothesize that FeNO can decrease the need for MCH testing. _ 18 years presenting METHODS: Retrospective chart review of patients > to a tertiary referral center seen between 11/01/2009 - 8/31/2013 who received FeNO and MCH within 2 weeks and diagnosis of asthma was used for both procedures. RESULTS: 197 patients were identified. Demographics: 129 (65.5%) females and 68 (34.5%) males; 188 (95.4%) Caucasian, 6 (3.0%) Black, 3 (1.5%) Asian. Average age was 49.6 years (SD +/- 17.1 years). Mean BMI 30.6 (SD +/-7.0). 29 patients were positive for both MCH and FeNO, 31 patients had a positive MCH but negative FeNO, 22 patients had a negative MCH but positive FeNO, and 115 patients had both a negative (p<0.01). Directly comparing FeNO to MCH yielded: sensitivity 48.33% (95% CI: 35.23% to 61.60%), specificity 83.94% (95% CI: 76.70% to 89.65%), positive likelihood ratio 3.01 (95% CI: 1.89 to 4.79), negative likelihood ratio 0.62 (95% CI: 0.48 to 0.79), positive predictive value 56.86 (95% CI: 42.25% to 70.65%), and negative predictive value 78.77% (95% CI: 71.24% to 85.09%) CONCLUSIONS: FeNO and methacholine responsiveness measure different biological phenomenon. In patients suspected of asthma, a strategy of FeNO at the point-of-care may reduce but not eliminate the need for MCH testing.
519
Serum Interleukin 13 (IL-13) and Surfactant Protein D (SP-D) Expression Is Differentially Associated With Disease Status In Pediatric Asthma Patients Dr. Vasiliki Gemou-Engesaeth, MD, PhD1, Dr. N. Laliotou, MD1, Prof. Chris J. Corrigan, MD, PhD, FAAAAI2, Prof. George P. Chrousos, MD, PhD1, Dr. Angela Haczku, MD, PhD, FAAAAI3; 1National & Kapodistrian University of Athens, Greece, 2King’s College London School of Medicine, London, United Kingdom, 3University of Pennsylvania, Philadelphia, PA. RATIONALE: Allergic airway inflammation is associated with a negative regulatory feedback between IL-13 and the immunoprotective SP-D in mice but the relevance of this to human asthma is not known. We hypothesized that serum IL-13 and SP-D expression would reflect disease status in asthmatic children. METHODS: SP-D and IL-13 serum levels were measured in 17 atopic and 8 nonatopic children (7 to 16 years old) with inadequately controlled asthma, and in 15 non-asthmatic controls matched for age and atopic status, in duplicates of dilutions (1:5 and 1:10) by ELISA (BioVendor and RayBiotech, Inc., respectively). The inter-assay and inter-experimental variability was <10% for both assays. Measurements were repeated in asthmatic children 4 to 6 months after initiation or escalation of inhaled glucocorticoid therapy (n510) and after initiation of inhaled Sodium Cromoglycate (n57) given according to the American Thoracic Society Criteria and European Consensus Guidelines. RESULTS: Expression of IL-13 (ranged between 0-171 pg/ml) was significantly greater in the asthmatic samples than in controls (25.662.7 vs. 12.662.0 p50.0001). In contrast, SP-D levels (ranged between 19-373 ng/ml) were significantly higher in the controls than in asthmatics (148.265.9 vs. 200.2620.2; p50.0219). Inhaled glucocorticoids or sodium cromoglycate did not change IL-13 or SP-D serum levels significantly although the sodium cromoglycate-treated patients showed a trend for reduced IL-13 (41.0621.1 vs. 19.267.6 pg/ml). CONCLUSIONS: Serum levels of IL-13 and SP-D inversely associated with presence of moderate to severe asthmatic airway inflammation in children suggesting that these biomarkers may be useful noninvasive indicators of disease status in childhood asthma.
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
520
Correlation Of Exhaled Breath Temperature With Age In Chronic Respiratory Diseases Dr. Radoslaw Gawlik, MD1, Dr. Malgorzata Rajzer-Wrobel2, Dr. Dariusz Ziora2, Prof. Lawrence M. DuBuske, MD, FAAAAI3; 1Silesian Medical University, Katowice, Poland, 2Silesian Medical University, Poland, 3 George Washington University School of Medicine, Washington, DC. RATIONALE: Asthma exacerbations may be associated with increased exhaled breath temperature. Chronic obstructive lung disease may be influenced by vascular inflammation. There may be a relationship between exhaled breath temperature and patient age in asthma and COPD. METHODS: 124 patients with COPD and asthma (72 male and 52 women) were studied, ranging from 42 to 81 years old, mean age 58.4 years. 30 healthy control subjects were assessed. Patients with acute respiratory infection or disease exacerbation in the last month were excluded. All exhaled breath tests were performed in the same room, at similar times of day with ambient temperatures between 20 and 238C and humidity 55% and 70%. Exhaled breath temperature was measured using an X-Halo device (Delmedica,Singapore). Mean temperature value was calculated by 3 consecutive measurements 1 day apart. RESULTS: EBT values were almost 2.08C higher in the control group (EBT 5 33.918C), compared to patients with chronic obstructive respiratory disease (EBT5 31.698C) and asthma (EBT5 30.898C). Inverse correlation was seen between patient age and EBT (r50.54; p<0.05). CONCLUSIONS: An inverse correlation exists between patient age and EBT in asthma and COPD patients not in exacerbation. COPD and asthma patients had lower EBT at baseline then healthy controls. This may reflect underlying chnages in vascularity in both diseases compared with healthy controls without chronic respiratory diseases.
521
Peripherally Induced Foxp3+ Regulatory T Cells Mediates The Immunomodulatory Effect Of Intravenous Immunoglobulin In An Experimental Model Of Allergic Airway Disease Dr. Amir Hossein Massoud, PhD1,2, Mr. Gabriel N. Kaufman, MSc1,2, Dr. Ciriaco Piccirillo, PhD2, Dr. Bruce D. Mazer, MD, FAAAAI1,3; 1Meakins-Christie Laboratories, Research Institute - McGill University Health Centre, Montreal, QC, Canada, 2McGill University Health Centre, Montreal, QC, Canada, 3Montreal Children’s Hospital, Montreal, QC, Canada. RATIONALE: IVIg is a polyclonal IgG preparation with potent immunemodulating properties. We demonstrated that IVIg protects against airway hyperreactivity (AHR) and airway inflammation in mouse models of allergic airway disease, accompanied by peripheral induction of Foxp3+ regulatory T-cells (iTreg). The requirement of IVIg-induced iTreg and their antigen-specificity in attenuation of AHR and airway inflammation remains unknown. METHODS: We utilized DEREG mice, carrying a transgenic diphtheria toxin receptor under the control of the Foxp3 promoter, allowing for selective depletion of Foxp3+Treg by the application of diphtheria toxin (DT). Mice were sensitized and challenged with ovalbumin (OVA) and treated with IVIg. AHR was measured using a FlexiVent small animal ventilator. Total and antigen-specific IgE, as well as pro-inflammatory cytokines levels were determined in serum and alveolar lavage, using ELISA. RESULTS: In the absence of Treg, due to multiple DT doses before and after the treatment, IVIg was not able to attenuate AHR, diminish IgE levels and Th-2 type cytokine production, nor alleviate airway inflammation. However, mice in which the pre-established Treg cells (nTreg) were depleted before but not following IVIg treatment demonstrated an induction of Foxp3+Treg to IVIg therapy and did not develop AHR and airway inflammation to allergen-challenge. Adoptive transfer of enriched IVIginduced iTreg from OVA-IVIg treated mice failed to transfer protection to mice exposed to ragweed, but was protective in OVA-sensitized and challenged mice. CONCLUSIONS: Treg can be induced from effector CD4+T-cells in the absence of nTreg. IVIg-induced antigen specific Treg are capable of suppressing all aspects of antigen-driven airway inflammation in an antigenspecific manner.