Current allergy and asthma reports
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Curr Allergy Asthma Rep · Sep 2010
ReviewImmune dysregulation in the pathogenesis of pulmonary alveolar proteinosis.
Pulmonary alveolar proteinosis (PAP) is a rare disease of the lung characterized by the accumulation of surfactant-derived lipoproteins within pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and increased infections. The disease is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. The underlying molecular mechanisms causing deficiencies in GM-CSF signaling are as follows: 1) high levels of neutralizing GM-CSF autoantibodies observed in autoimmune PAP; 2) mutations in CSF2RA, the gene encoding the alpha chain of the GM-CSF receptor, observed in hereditary PAP; and 3) reduced numbers and function of alveolar macrophages as a result of other clinical diseases seen in secondary PAP. Recent studies investigating the biology of GM-CSF have revealed that not only does this cytokine have an indispensable role in lung physiology, but it is also a critical regulator of innate immunity and lung host defense.
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Severe asthma presents significant management challenges. Patients can be difficult to control despite use of current standard-of-care therapy, including inhaled corticosteroids and long-acting beta-agonists. Alternative diagnoses, noncompliance, and comorbidities all can influence asthma control, future risk, and response to currently available therapy. ⋯ Severe asthma has a distinct pathophysiology including airway remodeling that contributes to the decreased effectiveness of standard therapy. Multiple phenotypes exist within severe asthma that likely require distinct therapeutic approaches to achieve control and improve long-term health outcomes. New therapeutic approaches to these distinct phenotypes will improve our understanding and treatment of this difficult-to-manage disease.
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A growing number of studies show that regular use of acetaminophen (paracetamol) carries a dose-dependent risk of developing allergies in general and asthma in particular and of worsening other respiratory diseases and lung function. The most disturbing finding has come from the population-based Avon Longitudinal Study of Parents and Children, in which use of paracetamol-but not aspirin-in late pregnancy was positively associated with asthma when comparing children whose mothers took paracetamol "sometimes" and "most days/daily" with those whose mothers never took it. ⋯ In this review, we present data from the most important studies published since 2000. Although the pathophysiology remains unclear, the available data justify a warning to the general public that the uncritical use of over-the-counter acetaminophen can lead to the development of allergies and asthma, even in utero.
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Curr Allergy Asthma Rep · Mar 2009
ReviewAspirin sensitivity and desensitization for asthma and sinusitis.
NSAIDs-including aspirin (ASA)-that inhibit cyclooxygenase (COX)-1 induce nonallergic hypersensitivity reactions consisting of attacks of rhinitis and asthma. Such reactions occur exclusively in a subset of asthmatic patients who also have underlying nasal polyps and chronic hyperplastic eosinophilic sinusitis. We now refer to their underlying inflammatory disease of the entire respiratory tract as aspirin-exacerbated respiratory disease. This review focuses on descriptions of these patients; methods available to diagnose ASA-exacerbated respiratory disease; the unique ability of all NSAIDs that inhibit COX-1 to cross-react with ASA; lack of cross-reactivity with selective COX-2 inhibitors; an update on pathogenesis; and current thoughts about treatment, including ASA desensitization and daily ingestion of ASA itself.
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Asthma is an increasingly prevalent disease, particularly in industrialized countries. With modern treatment, many patients can expect good asthma control; however, a significant minority continue to have excessive symptoms. Bronchial thermoplasty is a novel approach to treating asthma in which the hypertrophied airway smooth muscle present in the asthmatic airway is specifically targeted and depleted using thermal energy. In this article, we review the early animal and human development of the technique, summarize the randomized trials carried out in patients to date, discuss proposed mechanisms of action, and suggest directions for future work.