The Journal of allergy and clinical immunology
-
J. Allergy Clin. Immunol. · Sep 2011
ReviewPathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches?
Current asthma therapy is based on the use of adrenergic bronchodilator and anti-inflammatory drugs the specificity, efficacy, duration of action, and safety of which have been derived through classical pharmacology and medicinal chemistry. That asthma is a T(H)2-type inflammatory disorder frequently associated with atopy and allergic comorbidities has led to a concentrated effort to find treatments that act selectively on this pathway. A systematic literature review was undertaken, as well as a review of the Web site Clinicaltrials.gov for ongoing trials. ⋯ A case is made for a different approach to drug discovery based on acquiring a greater understanding of asthma stratification, the relevant pathways involved, and the development of appropriate diagnostic tests enabling the targeting of selective treatments to those asthmatic phenotypes most likely to respond. The recognition that asthma is more than allergy mandates improved predictive animal models and an appreciation that many of the environmental insults that initiate, consolidate, and exacerbate asthma operate through an epithelium functioning in a disorderly fashion. An integrated model that places the epithelium at the forefront of asthma pathogenesis suggests that greater emphasis should be placed on therapeutics that increase the airways' resistance against the inhaled environment rather than focusing only on suppression of inflammation.
-
J. Allergy Clin. Immunol. · Sep 2011
ReviewEvidence of a genetic contribution to lung function decline in asthma.
There has been great progress in identifying new asthma susceptibility genes. In asthmatic subjects there is variable airway remodeling that includes features such as smooth muscle hypertrophy/hyperplasia, basement membrane thickening, and increased extracellular matrix deposition. Does airway remodeling have a genetic contribution in asthma? Data from different murine strains suggest there is a genetic contribution to the development and progression of airway remodeling. ⋯ To date, single nucleotide polymorphisms spanning ADAM33, ESR1, PLAUR, and VEGF have been associated with an excess decline in lung function in asthmatic subjects carrying the rare alleles (FEV(1), -13.0 to 55.2 mL/y excess). Interestingly these genes have overlapping functions in proteolytic pathways in the airways. There is accumulating evidence that genetic factors are important in the development of airway remodeling in asthmatic subjects, and further longitudinal studies with additional remodeling phenotypes and genome-wide association studies will identify novel susceptibility genes, leading to new approaches to target remodeling in asthmatic subjects.
-
J. Allergy Clin. Immunol. · Jan 2011
ReviewAdvances in pediatric asthma in 2010: addressing the major issues.
Last year's "Advances in pediatric asthma" concluded with the following statement: "If we can close these [remaining] gaps through better communication, improvements in the health care system and new insights into treatment, we will move closer to better methods to intervene early in the course of the disease and induce clinical remission as quickly as possible in most children." This year's summary will focus on recent advances in pediatric asthma that take steps moving forward as reported in Journal of Allergy and Clinical Immunology publications in 2010. Some of these recent reports show us how to improve asthma management through steps to better understand the natural history of asthma, individualize asthma care, reduce asthma exacerbations, and manage inner-city asthma and some potential new ways to use available medications to improve asthma control. It is clear that we have made many significant gains in managing asthma in children, but we have a ways to go to prevent asthma exacerbations, alter the natural history of the disease, and reduce health disparities in asthma care. Perhaps new directions in personalized medicine and improved health care access and communication will help maintain steady progress in alleviating the burden of this disease in children, especially young children.
-
J. Allergy Clin. Immunol. · Jul 2010
ReviewPractical approach to the patient with hypereosinophilia.
Markedly increased blood eosinophilia (ie, > or =1.5 x 10(9)/L), whether discovered fortuitously or found with signs and symptoms of associated organ involvement, commands diagnostic evaluation and often therapeutic interventions. This degree of hypereosinophilia is often but not uniformly associated with eosinophilic infiltration of tissues that can potentially lead to irreversible, life-threatening organ damage. ⋯ If evaluations exclude eosinophilia attributable to secondary causes or other eosinophil-related syndromes or organ-specific diseases, attention must be directed to considerations of varied other forms of the hypereosinophilic syndromes, which include myeloproliferative variants, lymphocytic variants, and many of still unknown causes. Cognizant of the capacities of eosinophils to mediate tissue damage, the varied causes for hypereosinophilia are considered, and a contemporary stepwise practical approach to the diagnosis and treatment of patients with hypereosinophilia is presented.
-
Epidemiologic associations between viral lower respiratory infections (LRIs) and asthma in later childhood are well known. However, the question of whether such infections cause asthma or unmask asthma in a susceptible host has still not been settled. Most early evidence centered on the role of the respiratory syncytial virus; however, recent studies highlight a potential role for human rhinovirus as a risk factor for asthma. ⋯ The risk of asthma after viral LRI is increased in the presence of allergic sensitization in early life and if the infection is more severe. Atopy-associated mechanisms also appear to be involved in viral-induced acute exacerbations of asthma, especially in prolonging symptomatology after the virus has been cleared from the lungs. Breaking the nexus between viral respiratory infections and asthma may be possible with interventions designed to inhibit atopy-related effectors mechanisms from participating in the host response to respiratory viral infections.