Patient self-management of acute asthma: adherence to national guidelines a decade later.

BACKGROUND AND OBJECTIVES: Children in the emergency department (ED) with acute asthma were enrolled to assess the impact of asthma on their activities of daily living and evaluate their access to care and preventive strategies, determine the proportion who adhered to the National Heart, Lung, and Blood Institute (NHLBI) guidelines for proper steps to take at home during an acute asthma exacerbation, and compare adherence rates for those with persistent and mild intermittent asthma. DESIGN AND METHODS: Children 2 to 18 years old who presented to the Children's Hospital of Philadelphia's ED with acute asthma exacerbations were enrolled prospectively. Parents and patients completed the 108-item Asthma Exacerbation Response Questionnaire with a focus on determining the home management steps they took both at the onset of the asthma exacerbation and just before coming to the ED. RESULTS: Among the 433 children studied, 76% had at least 1 doctor visit, 75% had at least 1 ED visit, and 43% had at least 1 hospitalization for asthma in the preceding 12 months. Overall, 64% had persistent asthma by NHLBI criteria, yet just 4% were cared for by an allergist or pulmonologist, 38% took daily anti-inflammatory therapy, and 18% received a daily inhaled corticosteroid. Also, 48% did not use a holding chamber with their metered-dose inhalers, and 66% did not use their peak flow meters. Regarding exacerbation response, 71% did not have a written action plan, and 89% did not maintain a symptom diary. Both at the onset of wheezing and just before coming to the ED, administration of a beta2-agonist was the only step that the majority of children performed. One-third or fewer followed the other steps recommended by the NHLBI, including using a peak flow meter, beginning oral corticosteroids, calling or going to see the doctor, or going to the ED. Children with persistent asthma were not more adherent to the guidelines than those with mild intermittent disease. CONCLUSIONS: Asthma has a significant adverse effect on the lives of these children. The NHLBI guidelines, first published a decade ago, were designed to reduce asthma's increasing morbidity and mortality, but this study uncovered a high rate of nonadherence with many aspects of the guidelines, including preventive strategies and home management of an exacerbation.

Cathepsin B cleavage and release of invariant chain from MHC class II molecules follow a staged pattern.

A staged pattern of cathepsin B cleavage of MHC class II alpha, beta-bound invariant (Ii) chain and release of fragments was defined. Charge-loss mutations in the Ii chain were created in three clusters of cathepsin B putative cleavage sites R78K80K83K86, K137K143, and R151K154. Products of HLA-DR1 alpha, beta and wild type (WT) or mutant Ii genes, co-transfected into COS1 cells, were cleaved by cathepsin B and immunoprecipitated by antibodies either to MHC class II chains or to different Ii epitopes. In WT Ii, cathepsin B digestion generated two forms of p21 Ii fragments: a p21 recognized by anti-C-terminus antibodies and a p21 recognized by an antibody to a determinant near the N-terminus. C-terminal p21 was released from MHC class II alpha, beta chains upon its formation while N-terminal p21 remained associated with MHC class II alpha, beta chains. Mutations at K137K143 inhibited the generation of N-terminal p21 by cathepsin B. Mutation at R78K80K83K86 led to an accumulation of MHC class II-bound N-terminal p21 without the appearance of MHC class II-bound p14, p10, and p6 fragments after cathepsin B digestion. These results indicate that cathepsin B cleaves wild type Ii first about K137K143 to produce a MHC class II-associated N-terminal p21, which is then cleaved about R78K80K83K86 to generate p14, p10 and finally p6 which still associates with MHC class II alpha, beta chains. This pattern of staged cleavage and release of Ii might be related to a concerted mechanism regulating the binding of antigenic peptides to MHC class II molecules.