Peripheral and tissue eosinophilia are usually associated with a variety of inflammatory, malignant, and infectious conditions.

As the presence of eosinophils in the tissues may cause significant cellular damage to vital organs such as the heart, tissue eosinophilia should be diagnosed and treated promptly. One operative way to evaluate eosinophilic disorders is to classify them into extrinsic and intrinsic. While extrinsic eosinophilic disorders are usually due to the production of eosinopoietic factors derived from T cells or tumor cells, the intrinsic types generally are the result of genetic mutations in the eosinophilic lineage. As we understand more the biology of eosinophils, only a few eosinophilic disorders remain idiopathic.

The purpose of this article is to help the clinician classify in an operational manner most eosinophilic disorders, using the extrinsic and intrinsic model. This may facilitate not only a better understanding of the role of eosinophils in these disorders, but also help the systematic clinical work-up and potential treatment of affected patients.

 

Purpose of review: This review summarizes the importance of macrolide therapy in the treatment of asthma, discusses macrolide mechanisms of action, and outlines new clinical data supporting their use. The effects of macrolides on both the innate and adaptive immune responses are discussed. Recent findings: Subacute bacterial infection with both typical and atypical organisms contributes to poor asthma control. Identification of pathogens using polymerase chain reaction (PCR) and cultures from bronchoscopic samples directs antibiotic therapy and improves asthma control. PCR identification of Mycoplasma pneumoniae and Chlamydophila pneumoniae in asthmatics best identifies the macrolide responsive phenotype. Summary: Because of their effect on protein synthesis, macrolides have both antimicrobial and anti-inflammatory properties. Both mechanisms appear to be important in their clinical efficacy in treating a wide variety of pulmonary disorders, including asthma.

Purpose of review: Severe asthma remains a condition in search of deeper understanding and of newer effective therapies. Risk factors for developing severe asthma, phenotyping of disease, characterizing the inflammatory response and understanding of poor therapeutic responses to corticosteroids are important areas of research. The development of biomarkers for phenotypic diagnosis and prognostic reasons is important. Recent findings: Severe asthma has been defined as asthma that does not respond adequately to asthma medications, particularly corticosteroids, with continuing loss of control of asthma and future risk of exacerbations and side effects from corticosteroid therapy. This is a heterogeneous condition and cluster analyses have yielded phenotypes on the basis of age of onset of disease, sex, lung function, atopy and questionnaire data. Use of sputum eosinophil counts has further defined a group with persistent eosinophilic inflammation despite corticosteroid therapy, and a noneosinophilic group with uncontrolled asthma. Summary: Use of a single biomarker provides value in phenotyping and in predicting response to treatment but many more biomarkers such as those derived from -omic approaches remain to be used in the analysis. A systems biology approach to finding novel biomarkers is the way forward to stratify severe asthma so that appropriate and distinct therapies can be selected for each subtype.

Purpose of review: This review critically assesses recently published literature on predicting asthma exacerbations in children, while also providing general recommendations for future research in this field. Recent findings: Current evidence suggests that every effort should be made to provide optimal treatment to achieve adequate asthma control, as this will significantly reduce the risk of severe disease exacerbations. Children who have had at least one asthma exacerbation in the previous year are at highest risk for subsequent exacerbations, regardless of disease severity and/or control. Although several tools and biomarkers to predict asthma exacerbations have been recently developed, these approaches need further validation and/or have only had partial success in identifying children at risk. Summary: Although considerable progress has been made, much remains to be done. Future studies should clearly differentiate severe asthma exacerbations due to inadequate asthma control from those occurring in children whose asthma is well controlled, utilize standardized definitions of asthma exacerbations, and use a systematic approach to identify the best predictors after accounting for the multiple dimensions of the problem. Our ability to correctly predict the development of severe asthma exacerbations in an individual child should improve in parallel with increased knowledge and/or understanding of the complex interactions among genetic, environmental (e.g. viral infections) and lifestyle (e.g. adherence to treatment) factors underlying these events.