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Children with Viral Respiratory Infections in the First Year of Life and Food Allergy at Age 5 Years
S168 Abstracts
657
Persistent Cough: The Link Between Asthma and Chlamydia pneumoniae Respiratory Infections M. G. Ghoshhajra, A. A. Petrov; University of Pittsburgh Medical Center, Pittsburgh, PA. RATIONALE: Chlamydia pneumoniae respiratory infections may play an important role in the exacerbation of asthma. We report a case of severe persistent asthma and intractable cough resistant to all prior therapy that improved after the patient was diagnosed with Chlamydia pneumoniae infection and treated with four weeks of telithromycin. METHODS and RESULTS: Mr. W is a 48-year-old atopic Caucasian male who presented for evaluation of severe persistent asthma with recurrent exacerbations characterized by violent intractable dry cough. In the past, his cough had not responded to high-dose systemic steroids, Omalizumab, or standard asthma therapy including inhaled steroids, long-acting beta agonists, and leukotriene inhibitors. During one of his many hospitalizations for asthma exacerbations, bronchoscopy revealed possible Herpes and Candida infections but appropriate treatment did not improve his cough. Immune deficiency evaluation, including quantitative immunoglobulins and Pneumococcal titers, was normal. A hypersensitivity pneumonitis panel and high-resolution CT of the chest were unremarkable. Repeated PFTs demonstrated a mild restrictive pattern (normal FEV1, FVC 79% of predicted) with no reversibility and normal diffusing capacity. Mycoplasma IgG antibody was negative. Chlamydia pneumoniae IgG titer was elevated at 1:128, a four-fold increase from the normal reference level. The patient was treated with a four-week course of telithromycin. Subsequently, his persistent cough fully resolved and his IgG titer normalized to 1:32. CONCLUSIONS: Chlamydia pneumoniae infection is often linked to asthma exacerbation. We demonstrate that diagnosis of Chlamydia pneumoniae infection and treatment with telithromycin can dramatically improve asthma exacerbations characterized by intractable cough.
658
MONDAY
Asthma at 6 Yrs is Not Associated with Overweight Status or Pro-Inflammatory Markers in a High-Risk-for-Asthma Birth Cohort S. L. Friedlander, K. A. Roberg, M. D. Evans, R. E. Gangnon, Z. Zhang, H. J. Lai, J. E. Gern, R. F. Lemanske, Jr.; University WI - Madison, Madison, WI. RATIONALE: Multiple adult studies have revealed an association between asthma and obesity, but the relationship in young children is less clear. Hypothesized mechanisms for this relationship include obesityrelated proinflammatory and immunomodulatory hormones. METHODS: Utilizing the Childhood Origins of Asthma (COAST) cohort, 285 children with a parent with respiratory allergies and/or asthma were studied. Asthma was defined by cross-sectional evaluation at age 6 by physician diagnosis, frequent albuterol or asthma-controller medication use, a step-up plan during illness, or prednisone use for an asthma exacerbation. Wheezing phenotypes up to 6yrs (never wheezed, transient, late onset, and persistent wheezing) were additionally categorized. At-risk-for-overweight (AROW) was defined as age-gender adjusted BMI >85%. Plasma IL-6 and leptin levels were prospectively analyzed from birth to age 5yrs by ELISA. RESULTS: The rates of AROW children were 22%(3yo), 23%(5yo), and 23%(6yo). Overweight status played no role in the association between asthma at age 6 and AROW from ages 3-6. There were also no significant associations between wheezing phenotypes and overweight status. When evaluated by wheezing phenotypes or asthma status, there were no significant associations with either IL-6 or leptin at ages 3 and 5. CONCLUSIONS: When using a strict definition of asthma at 6yrs, there was no association with overweight status in children up to age 6. Similarly, plasma IL-6 and leptin levels were not associated with asthma status or wheezing phenotypes. Although wheezing histories have been associated with obesity up to 5yo in the COAST group, this was not seen when asthma was more comprehensively defined in this high-risk cohort. Funding: NIH grants M01 RR03186, R01 HL61879, and P01 HL70831, and GlaxoSmithKline Allergy Fellowship Award (SLF)
J ALLERGY CLIN IMMUNOL JANUARY 2007
659
Children with Viral Respiratory Infections in the First Year of Life and Food Allergy at Age 5 Years E. L. Anderson, K. S. Dillie, M. D. Evans, K. A. Roberg, L. E. P. Salazar, D. F. DaSilva, T. E. Pappas, C. J. Tisler, R. Gangnon, C. Ober, J. E. Gern, R. F. Lemanske, Jr.; University of Wisconsin School of Medicine and Public Health, Madison, WI. RATIONALE: To evaluate the potential relationships between early childhood wheezing related to specific viral illnesses with the subsequent development of food allergy and asthma. METHODS: Nasal lavage samples obtained from participants in the Childhood Origins of ASThma project (COAST) during infancy were analyzed (culture and PCR) for RSV and rhinovirus (RV) during acute respiratory illnesses. Food allergy was diagnosed at age 5 years by convincing history and testing blood specimens for milk and egg white-specific IgE by flouroenzyme immunoassay (UnicapÒ 100, Pharmacia Diagnostics). Children were evaluated for asthma at age 6 years. RESULTS: Children with one or more wheezing illnesses in the first year of life were more likely to develop confirmed food allergy at age 5 than children who did not wheeze (16% vs.7%, p 5 0.06). Specifically, wheezing with RV or RSV infections in the first year of life was associated with food allergy at age 5 (RSV: 22% vs. 8%, p 5 0.02; RV: 22% vs. 8%, p 5 0.02). Children with food allergy at age 5 were more likely to have asthma at age 6 than children without food allergy (60% vs. 25%, p 5 0.002). CONCLUSIONS: In addition to confirming previous reports that food allergy is a risk factor for asthma, these findings conversely demonstrate that wheezing with specific viral respiratory infections in children during infancy is a risk factor for subsequent food allergy. Funding: NIH grants M01 rr03186, R01 HL61879, P01 HL70831
660
Parental Smoking Modifies Effects Of Genetic Variation In Tumor Necrosis Factor-a On Childhood Asthma H. Wu1, I. Romieu2, J. Sienra-Monge3, B. Rio-Navarro3, D. M. Anderson1, E. W. Dunn1, L. L. Steiner4, I. Lara-Sanchez2, S. London1; 1National Institute of Environmental Health Sciences, Research Triangle Park, NC, 2 National Institute of Public Health, Cuernavaca, MEXICO, 3Hospital Infantil de Mexico Federico Gomez, Mexico City, MEXICO, 4Roche Molecular Systems, Alameda, CA. RATIONALE: Polymorphisms in the pro-inflammatory cytokine genes tumor necrosis factor-a (TNF) and lymphotoxin-a (LTA, also called TNF-b) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand tobacco smoke and ozone bothstimulate TNF production. We investigated whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by ETS in a Mexican population with high ozone exposure. METHODS: We genotyped 6 tagging single nucleotide polymorphisms (SNPs) in TNF and LTA in 596 nuclear families consisting of asthmatics aged 4 to 17 years and their parents in Mexico City. Atopy was determined by skin prick tests. RESULTS: The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) 5 1.54; 95% confidence interval (CI), 1.04-2.28], especially among children of nonsmoking parents (RR 5 2.06; 95% CI, 1.19-3.55, P for interaction 5 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR 5 2.21; 95% CI, 1.14-4.30, P for interaction 5 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. CONCLUSIONS: Genetic variation in TNF may contribute to childhood asthma and associations may be modified by parental smoking.
657
Persistent Cough: The Link Between Asthma and Chlamydia pneumoniae Respiratory Infections M. G. Ghoshhajra, A. A. Petrov; University of Pittsburgh Medical Center, Pittsburgh, PA. RATIONALE: Chlamydia pneumoniae respiratory infections may play an important role in the exacerbation of asthma. We report a case of severe persistent asthma and intractable cough resistant to all prior therapy that improved after the patient was diagnosed with Chlamydia pneumoniae infection and treated with four weeks of telithromycin. METHODS and RESULTS: Mr. W is a 48-year-old atopic Caucasian male who presented for evaluation of severe persistent asthma with recurrent exacerbations characterized by violent intractable dry cough. In the past, his cough had not responded to high-dose systemic steroids, Omalizumab, or standard asthma therapy including inhaled steroids, long-acting beta agonists, and leukotriene inhibitors. During one of his many hospitalizations for asthma exacerbations, bronchoscopy revealed possible Herpes and Candida infections but appropriate treatment did not improve his cough. Immune deficiency evaluation, including quantitative immunoglobulins and Pneumococcal titers, was normal. A hypersensitivity pneumonitis panel and high-resolution CT of the chest were unremarkable. Repeated PFTs demonstrated a mild restrictive pattern (normal FEV1, FVC 79% of predicted) with no reversibility and normal diffusing capacity. Mycoplasma IgG antibody was negative. Chlamydia pneumoniae IgG titer was elevated at 1:128, a four-fold increase from the normal reference level. The patient was treated with a four-week course of telithromycin. Subsequently, his persistent cough fully resolved and his IgG titer normalized to 1:32. CONCLUSIONS: Chlamydia pneumoniae infection is often linked to asthma exacerbation. We demonstrate that diagnosis of Chlamydia pneumoniae infection and treatment with telithromycin can dramatically improve asthma exacerbations characterized by intractable cough.
658
MONDAY
Asthma at 6 Yrs is Not Associated with Overweight Status or Pro-Inflammatory Markers in a High-Risk-for-Asthma Birth Cohort S. L. Friedlander, K. A. Roberg, M. D. Evans, R. E. Gangnon, Z. Zhang, H. J. Lai, J. E. Gern, R. F. Lemanske, Jr.; University WI - Madison, Madison, WI. RATIONALE: Multiple adult studies have revealed an association between asthma and obesity, but the relationship in young children is less clear. Hypothesized mechanisms for this relationship include obesityrelated proinflammatory and immunomodulatory hormones. METHODS: Utilizing the Childhood Origins of Asthma (COAST) cohort, 285 children with a parent with respiratory allergies and/or asthma were studied. Asthma was defined by cross-sectional evaluation at age 6 by physician diagnosis, frequent albuterol or asthma-controller medication use, a step-up plan during illness, or prednisone use for an asthma exacerbation. Wheezing phenotypes up to 6yrs (never wheezed, transient, late onset, and persistent wheezing) were additionally categorized. At-risk-for-overweight (AROW) was defined as age-gender adjusted BMI >85%. Plasma IL-6 and leptin levels were prospectively analyzed from birth to age 5yrs by ELISA. RESULTS: The rates of AROW children were 22%(3yo), 23%(5yo), and 23%(6yo). Overweight status played no role in the association between asthma at age 6 and AROW from ages 3-6. There were also no significant associations between wheezing phenotypes and overweight status. When evaluated by wheezing phenotypes or asthma status, there were no significant associations with either IL-6 or leptin at ages 3 and 5. CONCLUSIONS: When using a strict definition of asthma at 6yrs, there was no association with overweight status in children up to age 6. Similarly, plasma IL-6 and leptin levels were not associated with asthma status or wheezing phenotypes. Although wheezing histories have been associated with obesity up to 5yo in the COAST group, this was not seen when asthma was more comprehensively defined in this high-risk cohort. Funding: NIH grants M01 RR03186, R01 HL61879, and P01 HL70831, and GlaxoSmithKline Allergy Fellowship Award (SLF)
J ALLERGY CLIN IMMUNOL JANUARY 2007
659
Children with Viral Respiratory Infections in the First Year of Life and Food Allergy at Age 5 Years E. L. Anderson, K. S. Dillie, M. D. Evans, K. A. Roberg, L. E. P. Salazar, D. F. DaSilva, T. E. Pappas, C. J. Tisler, R. Gangnon, C. Ober, J. E. Gern, R. F. Lemanske, Jr.; University of Wisconsin School of Medicine and Public Health, Madison, WI. RATIONALE: To evaluate the potential relationships between early childhood wheezing related to specific viral illnesses with the subsequent development of food allergy and asthma. METHODS: Nasal lavage samples obtained from participants in the Childhood Origins of ASThma project (COAST) during infancy were analyzed (culture and PCR) for RSV and rhinovirus (RV) during acute respiratory illnesses. Food allergy was diagnosed at age 5 years by convincing history and testing blood specimens for milk and egg white-specific IgE by flouroenzyme immunoassay (UnicapÒ 100, Pharmacia Diagnostics). Children were evaluated for asthma at age 6 years. RESULTS: Children with one or more wheezing illnesses in the first year of life were more likely to develop confirmed food allergy at age 5 than children who did not wheeze (16% vs.7%, p 5 0.06). Specifically, wheezing with RV or RSV infections in the first year of life was associated with food allergy at age 5 (RSV: 22% vs. 8%, p 5 0.02; RV: 22% vs. 8%, p 5 0.02). Children with food allergy at age 5 were more likely to have asthma at age 6 than children without food allergy (60% vs. 25%, p 5 0.002). CONCLUSIONS: In addition to confirming previous reports that food allergy is a risk factor for asthma, these findings conversely demonstrate that wheezing with specific viral respiratory infections in children during infancy is a risk factor for subsequent food allergy. Funding: NIH grants M01 rr03186, R01 HL61879, P01 HL70831
660
Parental Smoking Modifies Effects Of Genetic Variation In Tumor Necrosis Factor-a On Childhood Asthma H. Wu1, I. Romieu2, J. Sienra-Monge3, B. Rio-Navarro3, D. M. Anderson1, E. W. Dunn1, L. L. Steiner4, I. Lara-Sanchez2, S. London1; 1National Institute of Environmental Health Sciences, Research Triangle Park, NC, 2 National Institute of Public Health, Cuernavaca, MEXICO, 3Hospital Infantil de Mexico Federico Gomez, Mexico City, MEXICO, 4Roche Molecular Systems, Alameda, CA. RATIONALE: Polymorphisms in the pro-inflammatory cytokine genes tumor necrosis factor-a (TNF) and lymphotoxin-a (LTA, also called TNF-b) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand tobacco smoke and ozone bothstimulate TNF production. We investigated whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by ETS in a Mexican population with high ozone exposure. METHODS: We genotyped 6 tagging single nucleotide polymorphisms (SNPs) in TNF and LTA in 596 nuclear families consisting of asthmatics aged 4 to 17 years and their parents in Mexico City. Atopy was determined by skin prick tests. RESULTS: The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) 5 1.54; 95% confidence interval (CI), 1.04-2.28], especially among children of nonsmoking parents (RR 5 2.06; 95% CI, 1.19-3.55, P for interaction 5 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR 5 2.21; 95% CI, 1.14-4.30, P for interaction 5 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. CONCLUSIONS: Genetic variation in TNF may contribute to childhood asthma and associations may be modified by parental smoking.