Investigation of patient-specific characteristics associated with treatment outcomes for chronic urticaria.

BACKGROUND: Identifying clinical characteristics of patients with chronic urticaria (CU) responsive to medication may help guide clinicians select treatment. OBJECTIVE: The objective of this study was to investigate patient characteristics and medication use associated with urticaria control. METHODS: A retrospective longitudinal chart review of adult patients with CU was conducted at a multisite allergy practice. Inclusion criteria required at least 4 CU office visits to allow for pre- and posttreatment assessment. Control corresponding to medication(s) used was assessed each visit. Univariate analysis followed by multiple logistic regression was performed. RESULTS: A total of 221 patients with CU were included; 140 (63%) achieved complete control. The average time to control was 1.4 ± 2.7 years, which required 1-3 classes of medications. Dermatographia odds ratio (OR) = 1.85 (95% CI 1.3-2.7) or other physical urticarias, OR = 1.51 (1-2.4) and neutrophilic infiltrates on skin biopsy were markers of poor control. Thyroid autoantibodies were associated with better control using an H1-antihistamine. Whereas 22% were controlled on a second-generation H1-receptor antagonist plus a leukotriene receptor antagonist (LTRA), an additional 33% were controlled when cyclosporine was added. Use of a first or second H1-antagonist or LTRA was associated with a 3.5-16.9 times higher odds of complete CU control in those with dermatographia. The odds of achieving control for other forms of physical urticaria was greatest when colchicine was added (aOR = 32.6 [12.7-83.2]). CONCLUSIONS: Patient-specific CU characteristics associated with medication-disease control may be useful for selecting treatment regimens. A subset of CU patients remains poorly controlled that indicates an unmet need for novel therapeutic agents.

Optimum predictors of childhood asthma: persistent wheeze or the Asthma Predictive Index?

BACKGROUND: The Asthma Predictive Index (API) and persistent wheezing phenotypes are associated with childhood asthma, but previous studies have not assessed their ability to predict objectively confirmed asthma. OBJECTIVE: To determine whether the University of Cincinnati API Index (ucAPI) and/or persistent wheezing at age 3 can accurately predict objectively confirmed asthma at age 7. METHODS: Data from the Cincinnati Childhood Allergy and Air Pollution Study, a high-risk prospective birth cohort, was used. Asthma was defined as parent-reported or physician-diagnosed asthma objectively confirmed by a change in FEV1 of ≥12% after bronchodilator or a positive methacholine challenge (PC20 ≤ 4 mg/mL); or as prior treatment with daily asthma controller medication(s). Multivariate logistic regression was used to investigate the relationship between confirmed asthma at age 7 and a positive ucAPI (adapted and modified from prior published API definitions) and persistent wheezing at age 3. RESULTS: At age 7, 103 of 589 children (17.5%) satisfied the criteria for asthma. Confirmed asthma at age 7 was significantly associated with a positive ucAPI (adjusted odds ratio [aOR] 13.3 [95% CI, 7.0-25.2]; P < .01) and the persistent wheezing phenotype (aOR 9.8 [95% CI, 4.9-19.5]; P < .01) at age 3. Allergic persistent wheezing was associated with a significantly higher risk of asthma (aOR 10.4 [95% CI, 4.1-26.0]; P < .01) than nonallergic persistent wheezing (aOR 5.4 [95% CI, 2.04-14.06]; P < .01). CONCLUSION: Both a positive ucAPI and persistent wheeze at age 3 were associated with objectively confirmed asthma at age 7; however, the highest risk was associated with ucAPI. These results demonstrate the ucAPI as a clinically useful tool for predicting future asthma in school-age children.

Asthma screening of inner city and urban elementary school-aged children.

OBJECTIVE: Currently, in the United States there is a lack of a standardized method to effectively screen school children with undiagnosed or poorly controlled asthma. The purpose of this proof-of-concept study was to assess the use of the American College of Allergy, Asthma, and Immunology's (ACAAI) Asthma Screening Questionnaire to identify elementary school-age children at risk for asthma (undiagnosed) or poorly controlled asthma. METHODS: Children in grades 3-5 from one urban and two suburban schools completed ACAAI's 14 question asthma screening questionnaire and had their peak expiratory flow (PEF) measured. Children were considered to have a positive asthma screen and be at risk for having undiagnosed or poorly controlled asthma if they answered 'yes' to more than three questions. Children were referred to a physician if they had a positive asthma screen, a previous history of asthma, or a low PEF. RESULTS: Of the 86 participants, 52 were identified as being at risk for asthma. The number was higher among children attending an urban versus suburban school (p = 0.04). The sensitivity and specificity of the screening questionnaire for identifying asthma risk were 90% and 66%, respectively, when the number of 'yes' responses for a positive screen was increased from three to five of 14 questions. CONCLUSIONS: The ACAAI's Asthma Screening Questionnaire identified 52 children at risk for undiagnosed or poorly controlled asthma. Our findings support the need to validate this questionnaire to be used in conjunction with PEFR for identifying elementary school children at risk for asthma.

Self-association of collagen triple helic peptides into higher order structures.

Interest in self-association of peptides and proteins is motivated by an interest in the mechanism of physiologically higher order assembly of proteins such as collagen as well as the mechanism of pathological aggregation such as beta-amyloid formation. The triple helical form of (Pro-Hyp-Gly)(10), a peptide that has proved a useful model for molecular features of collagen, was found to self-associate, and its association properties are reported here. Turbidity experiments indicate that the triple helical peptide self-assembles at neutral pH via a nucleation-growth mechanism, with a critical concentration near 1 mM. The associated form is more stable than individual molecules by about 25 degrees C, and the association is reversible. The rate of self-association increases with temperature, supporting an entropically favored process. After self-association, (Pro-Hyp-Gly)(10) forms branched filamentous structures, in contrast with the highly ordered axially periodic structure of collagen fibrils. Yet a number of characteristics of triple helix assembly for the peptide resemble those of collagen fibril formation. These include promotion of fibril formation by neutral pH and increasing temperature; inhibition by sugars; and a requirement for hydroxyproline. It is suggested that these similar features for peptide and collagen self-association are based on common lateral underlying interactions between triple helical molecules mediated by hydrogen-bonded hydration networks involving hydroxyproline.

Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders.

A missense mutation leading to the replacement of one Gly in the (Gly-Xaa-Yaa)n repeat of the collagen triple helix can cause a range of heritable connective tissue disorders that depend on the gene in which the mutation occurs. Osteogenesis imperfecta results from mutations in type I collagen, Ehlers-Danlos syndrome type IV from mutations in type III collagen, Alport syndrome from mutations in type IV collagen, and dystrophic epidermolysis bullosa from mutations in type VII collagen. The predicted rates of substitutions by different amino acids for glycine in the alpha1(I), alpha2(I), alpha1(III), alpha5(IV), and alpha1(VII) chains (encoded by COL1A1, COL1A2, COL3A1, COL4A5, and COL7A1, respectively) were compared with missense mutations in those chains that have been observed to cause disease. The spectrum of amino acids replacing Gly was not significantly different from that expected for the alpha1(VII) chains, suggesting that any Gly replacement will cause disease. The distribution of residues replacing Gly was significantly different from that expected for all other collagen chains studied, with a particularly strong bias seen for alpha1(I) and alpha1(III) collagen chains. The bias did not correlate with the degree of chemical dissimilarity between Gly and the replacement residues, but in some cases a relationship was observed with the predicted extent of destabilization of the triple helix. For alpha1(III) collagen chains, the more destabilizing mutations were identified more often than expected. For alpha1(I), the most destabilizing residues, Val, Glu, and Asp, and the least destabilizing residue, Ala, were underrepresented. This bias supports the hypothesis that the level of triple-helix destabilization determines clinical outcome.