Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Dec 2012
ReviewThe role of air pollution in adult-onset asthma: a review of the current evidence.
The causes of adult-onset asthma are poorly established, and the asthmogenic role of air pollution has been investigated primarily in children. This review assesses the current evidence of the association between air pollution and asthma incidence among subjects free of asthma at least until late childhood. Seven publications from five study populations fulfilled the inclusion criteria (one case-control and six cohort studies). ⋯ Larger studies with more consistent definitions of phenotypes and exposure assessment for local traffic-related pollutants (e.g., ultrafine particles) are needed. Pooling existing cohorts such as in the ongoing European ESCAPE and TRANSPHORM consortia are promising steps. There is, however, a need for large-scale megacohorts to investigate these effects in standardized ways and to identify the most susceptible populations.
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Semin Respir Crit Care Med · Dec 2012
ReviewAirway hyperresponsiveness: new insights into the pathogenesis.
Airway hyperresponsiveness (AHR) is the most characteristic clinical feature of asthma. The pathogenesis of AHR in asthma is characterized by a variety of epithelial, microbial, and inflammatory triggers on one hand and abnormalities of effector structures in the airways such as smooth muscle cells, blood vessels, and nerves on the other hand. ⋯ This may be one reason for the observation that potent new antiinflammatory drugs for the treatment of asthma have only little impact on AHR. New therapeutic strategies are, therefore, needed to modulate structural and functional changes in the airways, especially in patients with treatment-resistant severe asthma.
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Severe asthma affects 5 to 10% of the asthma population but consumes a disproportionate amount of the global asthma budget (~50%) due to unscheduled health care utilization in primary care, hospitalizations due to severe exacerbations, and the costs of pharmacotherapy. A key challenge in managing severe asthma is to identify appropriate groups of patients that will respond best to existing and evolving therapies. Recent advances in our understanding of how to classify severe asthma using multivariate taxonomical approaches have provided a unique model of a stratified medicines approach. ⋯ A similar paradigm can be applied to other domains in severe asthma such as airway hyperresponsiveness, which may now be treated with the first mechanical therapy in airways disease (bronchial thermoplasty). At the same time it is important for the clinician to recognize and treat comorbid factors that make asthma difficult to manage such as poor adherence to medication, rhinosinusitis, and psychological comorbidity. Therefore it is of vital importance to develop a multidisciplinary approach to the management of severe asthma that is best applied within specialist centers with experience and wider access to national and international severe asthma networks.
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Semin Respir Crit Care Med · Dec 2012
Aspirin-exacerbated respiratory disease: update on pathogenesis and desensitization.
Aspirin-exacerbated respiratory disease (AERD) is a unique syndrome of airway inflammation that frequently occurs in patients with nasal polyposis, chronic sinusitis, and asthma. These patients tend to have progressive and recalcitrant sinus disease requiring frequent surgical intervention and in many cases systemic corticosteroids. Much about the pathogenesis of AERD remains unclear, but environmental factors likely play a prominent role in its development. ⋯ Given the prevalence and usefulness of aspirin and NSAID therapy in primary care clinics, an accurate diagnosis should be made in all patients. Desensitization is an effective treatment option for many patients. Recent advances have made this procedure considerably safer and outpatient aspirin desensitization is now the standard of care.
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Asthma is a heterogeneous disease, with wide variability in pathology, natural history, and response to therapy. Historically, treatment of asthma relied almost exclusively on clinical judgment and pulmonary function tests (spirometry or peak flows), despite the limitations of both. Physiological tests are one step removed from what the clinician needs to know, namely, the underlying activity and whether it is amenable to additional or alternative treatment. ⋯ Financial constraints applied by health providers and funding agencies have limited the use of induced sputum analysis and exhaled nitric oxide to date. However, evaluation of candidate biomarkers has provided important insights in clinical practice and in research settings. At the very least, existing techniques should have a regular place in severe asthma clinics, if not more widely, where heterogeneity is the norm and not all asthma is what it seems.