The relationship of the bronchodilator response phenotype to poor asthma control in children with normal spirometry.

OBJECTIVE: To determine the relationship of poor asthma control to bronchodilator response (BDR) phenotypes in children with normal spirometry. STUDY DESIGN: Children with asthma were assessed for clinical indexes of poorly controlled asthma. Pre- and post-bronchodilator spirometry were performed, and the percent BDR was determined. Multivariate logistic regression assessed the relationship of the clinical indices to BDR at ≥ 8%, ≥ 10%, and ≥ 12% BDR thresholds. RESULTS: There were 510 controller naïve children and 169 on controller medication. In the controller naïve population the mean age (± 1 SD) was 9.5 (3.4); 57.1% were male, 85.7% Hispanic. Demographics were similar in both populations. In the adjusted profile, significant clinical relationships were found particularly to positive BDR phenotypes ≥ 10% and ≥ 12% versus negative responses including younger age, (OR 2.0, 2.5; P < .05), atopy (OR 1.9, 2.6; P < .01), nocturnal symptoms in females (OR 3.4, 3.8; P < .01); ß2 agonist use (OR 1.7, 2.8; P < .01); and exercise limitation (OR 2.2, 2.5; P < .01) only in the controller naïve population. CONCLUSIONS: The BDR phenotype ≥ 10% is significantly related to poor asthma control, providing a potentially useful objective tool in controller naïve children even when the pre-bronchodilator spirometry result is normal.

Value of the bronchodilator response in assessing controller naïve asthmatic children.

OBJECTIVE: To define the bronchodilator response (BDR) cutoff point that best identified asthma to determine the frequency of abnormal spirometry results across severity. STUDY DESIGN: Controller naïve children were evaluated with clinical criteria alone to establish a diagnosis of asthma and severity classification, then compared with the BDR, which was calculated as the percent change from the initial forced expiratory volume in 1 second. Receiver operator characteristic analysis determined the cutoff point for asthma diagnosis that gave the best combination of sensitivity and specificity. RESULTS: Children with asthma (n = 346) and 51 children without asthma, aged 4 to 17 years, who met entry criteria for spirometry were identified. The mean BDR in asthmatics was 8.6% (95% CI, 7.5-9.8), compared with 2.2% (95% CI, 0.2-4.3) for non-asthmatics (P < .001). A BDR > or = 9% best differentiated these populations with a sensitivity rate of 42.5% and a specificity rate of 86.3%. Abnormal spirometry results, defined as a BDR > or = 9%, a forced expiratory volume in 1 second < 80% predicted, or both, ranged from 44.4% for mild intermittent bronchial asthma to 57.0% for severe persistent bronchial asthma. CONCLUSION: Spirometric criteria that include BDR can potentially identify children who have clinically mild asthma and might benefit from controller therapy.

The Breathmobile: a novel comprehensive school-based mobile asthma care clinic for urban underprivileged children.

Urban minority children have higher rates of asthma morbidity due to multiple factors. Many school-based programs have been funded to improve asthma management, especially for these "high-risk" inner-city children with asthma. Here we report the outcomes of the Children's Hospital of Orange County Breathmobile program, which is a school-based asthma program that combines the use of a mobile clinic and a pediatric asthma specialist. Baseline evaluations included a detailed history and physical, skin prick test to common allergens, spirometry measurements, and asthma severity classification based on the current National Asthma Education and Prevention Program guidelines. From April 2002 to September 2005, a total of 1321 children were evaluated for asthma. Analysis of the 1112 (84%) children diagnosed with asthma showed a population mean age of 7.8 years, 81% Latino ethnicity, and 73% with persistent disease. At baseline, only 24% of children with persistent asthma were on daily anti-inflammatory medications, which increased to 78% by the first follow-up visit. In the year prior to entry into the program, 64% had school absenteeism related to asthma (38% >10 days), 45% had emergency room (ER) visits (28% >1), and 19% had hospitalizations (9% >1). There was a significant reduction (p < .001) in the annual rates of ER visits, hospitalizations, and school absenteeism when comparing pre- and postentry into the program. These data suggest that a mobile asthma van clinic at the school site with an asthma specialist could be an effective model in reducing morbidity in the underserved child with asthma. Further studies are necessary to determine whether this model is applicable to other inner-city settings.

Current asthma guidelines may not identify young children who have experienced significant morbidity.

BACKGROUND: The current guideline for classifying asthma severity, the National Asthma Education Prevention Program (NAEPP) 2002, is not evidence-based. We had the opportunity to validate this guideline in an untreated inner-city population, both in those < or =5 and those >5 years of age. The basis for this retrospective validation model was to determine how well the NAEPP severity classification based on symptom-frequency criteria alone identified patients in those age groups demonstrating significant morbidity the previous year and thus the potential need for controller therapy. METHODS: Using a mobile asthma van (Breathmobile) at the school site, children not receiving controller medication were evaluated by an asthma specialist for severity according to NAEPP guideline clinical criteria. Validation was determined by the relationship of guideline severity to > or =2 emergency department (ED) visits, any hospitalization, health care utilization (any ED visit, hospitalization), number of exacerbations, and school absenteeism resulting from asthma the prior year. RESULTS: Eight hundred twenty-six asthmatic children were evaluated; 89 (10.8%) were < or =2 years, 222 (26.9%) were 3 to 5 years, and 515 (62.3%) were >5 years of age; 60.5% were male, and 80.9% were Hispanic. Classification of asthma severity included 34.4% with mild intermittent, 10.2% with mild persistent, 31.5% with moderate persistent, and 24.0% with severe persistent asthma categories. There were significantly more Hispanic children and children < or =5 years classified as having mild intermittant asthma. Morbidity was clearly related to severity in the overall population. However, although the health care utilization was significantly related to severity, it was borderline in those 3 to 5 years and nonsignificant in children < or =2 years. CONCLUSIONS: The NAEPP guidelines 2002, based on symptom-frequency criteria as assessed in this study, seem to offer a valid basis for classifying asthma severity in those >5 years of age but may underclassify younger children. Our data suggest that morbidity experienced in the prior year may provide a useful additional criterion for classifying asthma severity, particularly in those children < or =5 years of age.

Severe T- and B-cell immune deficiency associated with malignant thymoma.

BACKGROUND: Immunodeficiency with thymoma syndrome is a rare disorder that generally occurs after the fourth decade of life. Typically, thymic tumors are benign, and gradually developing immunodeficiency consists of hypogammaglobulinemia with low B-cell counts and an inverted CD4+/CD8+ T-cell ratio due to excessive CD8+ T cells. OBJECTIVE: To report the case of a 32-year-old, white man with an invasive malignant thymoma and profound combined T- and B-cell immunodeficiency associated with a normal CD4+/CD8+ T-cell ratio, absence of circulating B cells, and infection with an unusual organism. METHODS: The patient presented with a superior vena cava syndrome caused by a malignant thymoma. During chemotherapy and radiotherapy, he experienced recurrent episodes of pulmonary infections due to Haemophilus influenza and Serratia marcescens and persistent oral thrush. He was diagnosed as having thymoma and underwent immunological evaluation. RESULTS: Sixteen months after the diagnosis of thymoma, the immunological evaluation revealed profound lymphopenia, eosinopenia, very low counts of both CD4+ T cells and CD8+ T cells, and a normal CD4+/CD8+ ratio with negative delayed-type hypersensitivity skin test results. Hypogammaglobulinemia and absent specific antibody responses were associated with a lack of peripheral blood CD19+ B cells. Despite treatment with intravenous immunoglobulin, the patient died of respiratory insufficiency and sepsis secondary to a chronic pulmonary infection. CONCLUSIONS: Malignant thymoma may be associated with severe combined immunodeficiency. A normal CD4+/CD8+ ratio and the absence of peripheral B cells suggest a bone marrow defect that affects both T and B cells in the pathogenesis of this syndrome. Comprehensive immunological evaluation should be performed when thymoma is diagnosed to initiate an early and effective treatment to prevent life-threatening complications.