The Ecological Relationship Between the Trends of Asthma and Invasive Pneumococcal Disease in Rochester, Minnesota

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Relationship Between Asthma Control and Activity Limitation: Insights From the REACT Study T. Haselkorn1, C. A. Jones2, H. Chen3, M. Rhoa4, D. P. Miller5, S. P. Peters6, S. T. Weiss7; 1EpiMetrix, Inc., Sunnyvale, CA, 2University of Southern California, Los Angeles, CA, 3University of California San Francisco, San Francisco, CA, 4Genentech, Inc., South San Francisco, CA, 5ICON Clinical Research, San Francisco, CA, 6Wake Forest University Health Sciences Center for Human Genomics, Winston-Salem, NC, 7Channing Laboratory, Harvard Medical School, Boston, MA. RATIONALE: We evaluated the association between uncontrolled asthma and activity limitations and determined if the association varied demographically. METHODS: A census-representative sample of 1,812 patients 18 years with moderate-to-severe asthma completed the Asthma Control Test (ACT) and a 14-item survey pertaining to asthma-related activity limitations. Response frequencies for each item were cross-tabulated by control status, using an ACT score of 19 to define control. Results were further stratified according to patient demographics. RESULTS: Patients with controlled (n 5 809) and uncontrolled (n 5 1003) asthma reported activity limitations. Uncontrolled patients were significantly more limited (p < 0.01) in 13 of the 14 activities compared with controlled patients. For uncontrolled patients, the most limited activities (i.e., ‘‘rarely do this because of asthma’’) included going places where cigarette smoke is present (36%), participating in sports (28%), going places where dust/mold/ other allergens are present (27%), and outdoor winter activities (26%). Limitations varied with gender and age, depending on the activity. Uncontrolled asthma was more likely to limit spending time outdoors during allergy season for women (26.8% uncontrolled vs. 9.5% controlled) compared with men (17.2% uncontrolled vs. 12.0% controlled). The relationship between asthma control and going places where cigarette smoke is present was statistically significant for young adults (age 18-30, p 5 0.007) but not older adults (age 51, p 5 0.87). CONCLUSIONS: Uncontrolled asthma is associated with limitations in a range of activities and manifests differently across demographic strata. This heterogeneity suggests that clinicians should consider activity limitations when evaluating their asthma patients and decreasing limitations may be an important goal of treatment. Funding: Supported by Genentech, Inc., South San Francisco, CA.

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Morning and Afternoon Repeated Measurements of Offline Exhaled Nitric Oxide and Exhaled Breath Condensate pH A. Divjan1, K. Ghouri1, G. L. Chew1, R. L. Miller2, M. S. Perzanowski1; 1 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 2Division of Pulmonary, Allergy, and Critical Care Medicine, College of Physician’s and Surgeons, Columbia University, New York, NY. RATIONALE: Offline forced exhaled NO (FENO) and exhaled breath condensate (EBC) pH provide valuable field study tools for assessing airway inflammation; however, better characterization of within-subject variability and influences of ambient NO and ozone are needed. METHODS: Morning and afternoon FENO and EBC were collected from 5 nonsmoking adults in centrally air-conditioned rooms on 10 summer days (n 5 100 collections). FENO was measured (mean of 3 balloons) using Sievers offline collection device (GE Instruments, Bolder, CO). EBC was collected using RTubesÒ (Respiratory Research, Charlottesville, VA). EBC pH was measured after de-aeration. Ambient indoor (room air) NO was measured during collection. Highest hourly outdoor ozone concentrations on collection days were recorded from a central city site. RESULTS: There were no significant differences between the mean morning and afternoon FENO (8.0 vs. 7.8 ppb, p 5 0.76) or EBC pH (8.11 vs. 8.05, p 5 0.18) levels. There was no correlation between FENO and EBC pH (r 5 0.052, p 5 0.61); however, diurnal change in FENO (afternoon-morning, mean change -0.24 ppb) and diurnal change in EBC pH (mean change -0.052) correlated inversely (r 5 -0.34, p 5 0.016). While no association between ambient NO and FENO was observed (r 5 0.05, p 5 0.61), diurnal change FENO correlated with change in ambient

J ALLERGY CLIN IMMUNOL FEBRUARY 2008

NO (mean -5.1 ppb) (r 5 0.52, p 5 <0.001). In addition, outdoor ozone concentrations (mean 56 ppb, min-max 5 21-109 ppb) correlated inversely (r 5 -0.39, p < 0.001) with ambient indoor NO (mean 7.2 ppb, min-max 5 <1-35.6 ppb). CONCLUSIONS: FENO collected offline and EBC pH showed little variation between morning and afternoon measurements; however, small diurnal changes in FENO were associated with changes in ambient NO and EBC pH. Funding: NIEHS

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Predictors of Short-Term Outcomes After Discharge in Hospitalized Pediatric Asthmatics F. I. Khan1, A. P. Baptist2; 1Wayne State University, Children’s Hospital of Michigan, Detroit, MI, 2Wayne State University, Department of Internal Medicine, Detroit, MI. RATIONALE: Our aim was to evaluate demographic, subjective and measured factors as predictors of poor outcome at two-weeks after discharge of an asthma-related hospitalization. METHODS: Children aged 6-17 years admitted for an asthma exacerbation were eligible for the study. Demographics, NAEPP asthma severity, Asthma Control Test (ACT) and the Integrated Therapeutics Group Child Asthma Short Form (ITG-CASF), an asthma-specific quality-of-life measure, were collected at discharge. Patient’s perception of dyspnea was assessed using a pictoral scale. Fraction of exhaled nitric oxide (FeNO), spirometry and PEFR measurements were also performed. Patients were followed-up by telephone 14-days after discharge to evaluate symptom persistence (limitation of activity) and relapse (readmission, ED or unscheduled doctor’s visit or additional oral steroids). Univariate analysis was performed to determine correlation. RESULTS: Sixty-nine subjects were enrolled, 47 of which completed the study. Twenty-two (46.8%) patients had symptom persistence after discharge and five (10.6%) had relapsed by the 14-day follow-up. Limitation of activity correlated with younger age (P 5.050) and presence of dyspnea at discharge as perceived by the patient (P 5.031). Relapse was predicted by a lower FEV1 (P 5.011) at time of discharge. Well-controlled asthma (score of 19 or higher on the ACT) at 14-days correlated well with the ITG-CASF at discharge (P 5.041). FeNO did not correlate with symptom persistence, relapse, NAEPP severity classification, the ACT, ITGCASF, spirometry or PEFR. CONCLUSIONS: Using tools such as dyspnea scales, the ITG-CASF, ACT and spirometry in hospitalized pediatric asthmatics may help to predict symptom persistence or relapse after discharge. Funding: American College of Allergy Asthma and Immunology

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The Ecological Relationship Between the Trends of Asthma and Invasive Pneumococcal Disease in Rochester, Minnesota A. Y. Kung, H. Kita, B. P. Yawn, M. E. McGree, A. L. Weaver, K. H. Yoo, P. H. Wollan, T. G. Boyce, R. M. Jacobson, Y. J. Juhn; Mayo Clinic, Rochester, MN. RATIONALE: A previous study reported asthmatic patients have increased risk of invasive pneumococcal disease (IPD). However, it is unknown whether the rising trend of asthma incidence results in an impact on the trend of IPD incidence at a population level (i.e., ecological relationship). We assessed the trend of IPD incidence in relation to the previously reported trend of asthma incidence between 1964 and 1983 in Rochester, Minnesota. METHODS: The study subjects were Rochester, Minnesota residents between 1964 and 1983. We used a population-based computer-linked medical diagnosis system to identify all individuals with diagnoses potentially including IPD. All records were reviewed using explicit predetermined criteria. IPD incidence was calculated in an interval of every five years due to a small number of incidence cases of IPD per year. All asthmatic individuals were similarly (i.e., predetermined criteria) identified by a previous study between 1964 and 1983. The age- and sexadjusted annual IPD incidence was calculated using the 2000 total U.S. population.

Abstracts S161

J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2

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Longitudinal Validation of the Asthma Control Test in Moderate Persistent Asthma N. Kwon1, J. Shim2, Y. Lee3, S. Uh4, K. Jung5, S. Park6, Y. Lee1; 1 GLAXOSMITHKLINE, SEOUL, REPUBLIC OF KOREA, 2Department of Internal Medicine, Korea University, SEOUL, REPUBLIC OF KOREA, 3Department of Internal Medicine, Chonbuk National University Medical School, JEONJU, REPUBLIC OF KOREA, 4Department of Internal Medicine, Soonchunhyang University, SEOUL, REPUBLIC OF KOREA, 5Department of Internal Medicine, Hallym University, ANYANG, REPUBLIC OF KOREA, 6Department of Internal Medicine, Pusan national University, PUSAN, REPUBLIC OF KOREA. RATIONALE: The Asthma Control Testä (ACTä) is a robust tool for the measurement of asthma control. The responsiveness of the ACT over longer period has not been confirmed. METHODS: The SUCCESS was a, prospective, randomized, open-label, parallel group study to evaluate the efficacy of the inhaled salmeterol/ fluticasone propionate combination (SFC) compared with usual care asthma medications over 12 months. The primary endpoint was a change in mean morning PEFR over 52 weeks. The mini Asthma-related Quality of Life (AQLQ) and the ACTwere measured as assessing asthma control. A post-hoc analysis was done for the longitudinal validity of Korean version of the ACT. RESULTS: The ACT was responsive to changes in asthma control as asessed by FEV1 (r 5 0.37, p < 0.0001), and AQLQ scores (r 5 0.6842, p < 0.0001) over 52 week period and the correlation was consistently observed at each clinic visit. The internal consistency reliability of the ACT was 0.79 (Cronbach’s a) at baseline (n 5 417) and 0.87 at week 52 (n 5 358). Testretest reliability at all clinic visits during treatment period was 0.85 (n 5 346). Criterion validity was demonstrated by significant correlations between the baseline ACT scores and baseline values of PEFR (r 5 0.31, p < 0.0001) and mini-AQLQ scores (r 5 0.71, p < 0.0001). CONCLUSIONS: The ACT is reliable and responsive to changes in asthma control over 52 week period in Korean patients with bronchial asthma. Funding: GLAXOSMITHKLINE

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Elevated Fractional Exhaled Nitric Oxide (FeNO) is Positively Associated with the Risk of Subsequent Cold Symptoms L. E. P. Salazar, M. D. Evans, E. L. Anderson, D. D. F. DaSilva, R. A. Grabher, K. M. Hanson, W. K. Kim, T. E. Pappas, K. A. Roberg, C. J. Tisler, R. E. Gangnon, R. F. Lemanske, Jr, , J. E. Gern; University of Wisconsin-Madison, Madison, WI. RATIONALE: Common colds are frequently responsible for cold symptoms and acute asthma, but responses to viral infections are quite variable. The goal of this study is to determine whether baseline measurements of lung function or fractional exhaled nitric oxide (FeNO) modify the risk of respiratory symptoms or acute asthma during a peak common cold season. METHODS: Measurements of FeNO were completed on 30 asthmatic children ages 6-8 years using the online technique with the NIOXÒ system (Aerocrine, AB, Stockholm, Sweden). FeNO was calculated from three maneuvers that were within 2.5 ppb or 10%. Spirometry maneuvers were obtained by modified ATS standards using the JaegerÒ Masterscope system. Following this visit, diary cards were used to track symptoms on a

4-point rating system for rhinitis, wheeze, and cough during a peak common cold season (September 2006). RESULTS: Children who reported at least 2 consecutive days of cold symptoms had significantly higher baseline FeNO values compared to children with fewer symptoms (geometric mean 17.5 ppb versus 10.0 ppb, p 5 0.03). In contrast, recurrent asthma symptoms were not associated with increased FeNO (14.1 ppb vs. 10.8 ppb, p 5 0.18). Finally, recurrent cold and asthma symptoms were not associated with differences in pre- or postbronchodilator spirometry. CONCLUSIONS: The association between elevated FeNO levels and developing respiratory illness during common cold season suggests the possibility that baseline airway inflammation is a risk factor for more severe viral respiratory infections and clinical symptoms. Funding: R01 HL0800721

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The Fraction of Nitric Oxide and Influencing Factors among Healthy Young Adults in Korea S. Kim, T. Kim, J. Sohn, H. Yoon, D. Shin, S. Park; Hanyang University College of Medicine, Seoul, REPUBLIC OF KOREA. RATIONALE: The fraction of nitric oxide in exhaled air (FeNO) is a good index of airway inflammation such as asthma. While it was suggested that measurement of FeNO can be used for selection of patients with airway diseases, reference values of FeNO in normal population are not well defined yet. This study is to establish reference value of FeNO for adult population without respiratory diseases and to determine which factors are related with the levels of FeNO. METHODS: Fifty six medical students, aged between 23 and 32, were enrolled for this study and evaluated for smoking status and asthma by a questionnaire. FeNO was measured using a NO analyzer (NOA280; Bouler, Co, USA) according to the recommendations by ATS and ERS. Spirometry, skin prick test to common aeroallergens and methacholine bronchial provocation test was performed. Logarithm-transformed FeNO was used for analysis. RESULTS: The geographic mean FeNO for the subjects was 28.6 parts per billion (ppb) with 95% reference intervals (RI), 11.2 to 73.0. Levels of FeNO of smokers (21.76 ppb; 95% RI, 8.9 to 53.5) was significantly lower than those of nonsmokers (30.6 ppb; 95% RI, 12.3 to 76.1). There was no significant correlation between sex and FeNO or between atopy and FeNO. CONCLUSIONS: The presented reference range of FeNO may be used in selection of patients with airway disease in young adults. Funding: the Korea Health 21 R&D Project, Ministry of Health & Welfare, Korea (Grant No 0412-CR03-0704-0001)

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RESULTS: Between 1964 to 1983, overall asthma incidence rates increased from 183 per 100,000 in 1964 to 284 per 100,000 in 1983. During the same study period, IPD incidence increased from 10.0 per 100,000 (95% CI: 6.1-13.9) between 1964 and 1968 to 15.9 per 100,000 (95% CI: 11.8-20.0) between 1979 and 1983. CONCLUSIONS: The increased incidence of IPD during our study period may correspond with the previously observed rise in asthma incidence in Rochester, Minnesota reflecting the relationship between asthma and IPD at an individual level. Further analyses are underway to clarify this ecological relationship. Funding: Mayo Clinic