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Risk factors for new-onset cat sensitization among adults: A population-based international cohort study

Background: Cat exposure during childhood has been shown to increase the risk of developing cat sensitization, while the effect of cat exposure in adulthood has not yet been established.

Objective: To evaluate new-onset sensitization to cat in adulthood in relation to changes in cat keeping.

Methods: A total of 6292 European Community Respiratory Health Survey I (ECRHS I) participants aged 20 to 44 years from 28 European centers, who were not sensitized to cat, were reevaluated 9 years later in ECRHS II. Present and past cat ownership and total and specific IgE levels were assessed in both surveys. Allergen-specific sensitization was defined as a specific serum IgE level of 0.35 kU/L or more.

Results: A total of 4468 subjects did not have a cat in ECRHS I or ECRHS II, 473 had a cat only at baseline, 651 acquired a cat during the follow-up, and 700 had a cat at both evaluations. Two hundred thirty-one subjects (3.7%) became sensitized to cat. In a 2-level multivariable Poisson regression model, cat acquisition during follow-up was significantly associated with new-onset cat sensitization (relative risk = 1.85, 95% CI 1.23-2.78) when compared with those without a cat at both surveys. Preexisting sensitization to other allergens, a history of asthma, nasal allergies and eczema, and high total IgE level were also significant risk factors for developing cat sensitization, while cat ownership in childhood was a significant protective factor.

Conclusion: Our data support that acquiring a cat in adulthood nearly doubles the risk of developing cat sensitization. Hence, cat avoidance should be considered in adults, especially in those sensitized to other allergens and reporting a history of allergic diseases.

The role of the small airways in the clinical expression of asthma in adults

Background: The clinical relevance of increased ventilation heterogeneity, a marker of small-airways disease, in asthmatic patients is unclear. Ventilation heterogeneity is an independent determinant of airway hyperresponsiveness (AHR), improves with bronchodilators and inhaled corticosteroids (ICSs), and worsens during exacerbations, but its relationship to asthma control is unknown.

Objective: We sought to determine the association between ventilation heterogeneity and current asthma control before and after ICS treatment.

Methods: Adult subjects with asthma had lung function and asthma control (5-item Asthma Control Questionnaire [ACQ-5 score] ≥1.5 = poorly controlled, ACQ-5 score ≤0.75 = well controlled) measured at baseline. A subgroup with AHR had repeat measurements after 3 months of high-dose ICS treatment. The indices of ventilation heterogeneity in the regions of the lung where gas transport occurs predominantly through convection (ventilation heterogeneity in convection-dependent airways [Scond]) and through diffusion (ventilation heterogeneity in diffusion-dependent airways [Sacin]) were derived by using the multiple-breath nitrogen washout technique.

Results: At baseline (n = 105), subjects with poorly controlled asthma had worse FEV1, fraction of exhaled nitric oxide measured at 200 mL/s (Feno), Scond, and Sacin values. In the treatment group (n = 50) spirometric, Feno, residual volume (RV)/total lung capacity (TLC), AHR, and Scond values significantly improved. Asthma control also improved (mean ACQ-5 score, 1.3-0.7; P < .0001). The change in ACQ-5 score correlated with changes in Feno (rs = 0.31, P = .03), Sacin (rs = 0.32, P = .02), and Scond (rs = 0.41, P = .003) values. The independent predictors of a change in asthma control were changes in Scond and Sacin values (model r2 = 0.20, P = .005).

Conclusions: Current asthma control is associated with markers of small-airways disease. Improvements in ventilation heterogeneity with anti-inflammatory therapy are associated with improvements in symptoms. Sensitive measures of small-airway function might be useful in monitoring the response to therapy in asthmatic subjects.

New approaches to personalized medicine for asthma: Where are we?

Access to an electronic medical record is essential for personalized medicine. Currently, only 40% of US physicians have such access, but this is rapidly changing. It is expected that 100,000 Americans will have their whole genome sequenced in 2012.

The cost of such sequencing is rapidly dropping, and is estimated to be $1000 by 2013. These technological advances will make interpretation of whole genome sequence data a major clinical challenge for the foreseeable future.

At present, a relatively small number of genes have been identified to determine drug treatment response phenotypes for asthma. It is anticipated that this will dramatically increase over the next 10 years as personalized medicine becomes more of a reality for asthma patients.

Advances in mechanisms of asthma, allergy, and immunology in 2011

2011 was marked by rapid progress in the identification of basic mechanisms of allergic disease and the translation of these mechanisms into human cell systems. Studies published in the Journal of Allergy and Clinical Immunology this year provided new insights into the molecular determinants of allergenicity, as well as the environmental, cellular, and genetic factors involved in sensitization to allergens.

Several articles focused on mechanisms of allergen immunotherapy and the development of novel strategies to achieve tolerance to allergens. Additional studies identified substantial contributions from TH17-type cells and cytokines to human disease pathogenesis.

Finally, new therapeutic applications of anti-IgE were identified. The highlights of these studies and their potential clinical implications are summarized in this review.

Fungi and allergic lower respiratory tract diseases

Asthma is a common disorder that in 2009 afflicted 8.2% of adults and children, 24.6 million persons, in the United States. In patients with moderate and severe persistent asthma, there is significantly increased morbidity, use of health care support, and health care costs.

Epidemiologic studies in the United States and Europe have associated mold sensitivity, particularly to Alternaria alternata and Cladosporium herbarum, with the development, persistence, and severity of asthma. In addition, sensitivity to Aspergillus fumigatus has been associated with severe persistent asthma in adults. Allergic bronchopulmonary aspergillosis (ABPA) is caused by A fumigatus and is characterized by exacerbations of asthma, recurrent transient chest radiographic infiltrates, coughing up thick mucus plugs, peripheral and pulmonary eosinophilia, and increased total serum IgE and fungus-specific IgE levels, especially during exacerbation. The airways appear to be chronically or intermittently colonized by A fumigatus in patients with ABPA.

ABPA is the most common form of allergic bronchopulmonary mycosis (ABPM); other fungi, including Candida, Penicillium, and Curvularia species, are implicated. The characteristics of ABPM include severe asthma, eosinophilia, markedly increased total IgE and specific IgE levels, bronchiectasis, and mold colonization of the airways. The term severe asthma associated with fungal sensitization (SAFS) has been coined to illustrate the high rate of fungal sensitivity in patients with persistent severe asthma and improvement with antifungal treatment. The immunopathology of ABPA, ABPM, and SAFS is incompletely understood. Genetic risks identified in patients with ABPA include HLA association and certain TH2-prominent and cystic fibrosis variants, but these have not been studied in patients with ABPM and SAFS.

Oral corticosteroid and antifungal therapies appear to be partially successful in patients with ABPA. However, the role of antifungal and immunomodulating therapies in patients with ABPA, ABPM, and SAFS requires additional larger studies.

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