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Mechanisms of IgE Inflammation

 

The prevalence of diseases such as allergic asthma and rhinitis continues to increase in the United States, affecting millions of people. It is well-established that allergy contributes to the pathogenesis of most asthma, especially in children and young adults. Despite current therapy (eg, inhaled corticosteroids, anti-leukotrienes, and bronchodilators), patients with moderate to severe asthma remain symptomatic and experience frequent exacerbations of disease requiring oral corticosteroids, emergency department treatments, and hospitalizations.

Allergic diseases are traditionally referred to as immediate or type 1 hypersensitivity reactions, with IgE as a critical factor. IgE is involved in allergic inflammation, especially in early-phase response, but it may also be involved in the late-phase allergic response. A direct correlation between serum IgE levels and asthma exists. As logarithm IgE values increase, asthma prevalence increases linearly, even in patients who are categorized as having nonallergic asthma. In addition, there is a significant, although low association in allergic rhinitis with IgE levels and positive skin test reactivity to pollens.

Recent advances in our understanding of the role of IgE in allergic inflammation have led to the development of a monoclonal antibody to IgE that reduces IgE levels, thereby reducing allergic inflammation. This review aims to provide an overview of the basic science of the IgE molecule and the clinical efficacy of anti-IgE therapy in allergic and asthmatic diseases.

Advance care planning in chronic obstructive pulmonary disease: barriers and opportunities

Experts in palliative care have increasingly recognized the global epidemic of chronic obstructive pulmonary disease (COPD), its astonishing rise in prevalence, and its profound impact on patients' quality of life and functional capacity. Unfortunately, patients with COPD receive less advance care planning (ACP) and palliative care as compared with patients with other diseases with similar prognoses. This review highlights recent advances in identifying barriers to ACP and opportunities for providing more effective and timely palliative care.

Recent findings: Patients with COPD identify dyspnea as their most disabling symptom. Disease-directed care provides only partial relief from dyspnea, which eventually becomes refractory and requires transition to palliative care. Throughout all stages of COPD, however, integrating palliative care with disease-directed treatments improves patients' well being and functional capacities. Observational studies have identified multiple barriers to effective ACP. Because of the unique disease trajectory of COPD, professional groups have proposed new models for palliative care specifically tailored to COPD.

Summary: Patients with COPD benefit from better integration of palliative and disease-specific care throughout the course of their disease from diagnosis to death. Pulmonary rehabilitation may provide a platform for coordinating integrated care. Health agencies will increasingly expect better coordination of services for patients with this progressive, disabling, and eventually terminal disease.

Is the aging process accelerated in chronic obstructive pulmonary disease?

Recent research suggests that chronic obstructive pulmonary disease (COPD) may be a disease of accelerated aging. The senescence hypothesis of COPD pathogenesis is supported by in-vitro, in-vivo and clinical studies.

The purpose of this review is to provide a comprehensive overview of the senescence hypothesis of COPD and summarize methods that are used to assess cellular aging.

Recent findings: Accelerated aging due to exposure to cigarette smoke is hypothesized to induce rapid progression of COPD. Recent studies have shown that COPD patients have enhanced expression of senescence-associated proteins in the lung and in the peripheral circulation compared to healthy controls. Murine models of accelerated aging demonstrate spontaneous emphysematous changes in the lungs, while lungs of COPD patients demonstrate enhanced markers of senescence in fibroblasts and alveolar cells. More recently, studies of telomeres, which shorten with cellular aging, have shown that COPD patients may experience accelerated telomere attrition compared with healthy controls. However, studies to date have been relatively small and have produced heterogeneous results.

Summary: The evidence for the role of accelerated aging in COPD progression is growing and senescence is one possible molecular pathway by which COPD occurs.

Effects of pulmonary rehabilitation on quality of life in chronic obstructive pulmonary disease patients

Pulmonary rehabilitation plays a key role in the management of chronic obstructive pulmonary disease (COPD). Although the American Thoracic Society recently provided a grade of 1A for evidence of health-related quality of life (HRQoL) benefits related to pulmonary rehabilitation, knowledge about the psychological and behavioral processes explaining the impact of pulmonary rehabilitation on HRQoL in COPD patients remains limited. This review describes the state of knowledge over the past year concerning HRQoL benefits after pulmonary rehabilitation and suggests avenues for future research.

Recent findings: HRQoL outcomes related to pulmonary rehabilitation explores five themes: optimizing pulmonary rehabilitation components to improve HRQoL; characterization of a responder phenotype; suitability of pulmonary rehabilitation following acute exacerbations; exploration of psychological and behavioral mechanisms explaining pulmonary rehabilitation benefits; and long-term maintenance of HRQoL benefits after pulmonary rehabilitation.

Summary: Evidence supports the use of pulmonary rehabilitation to improve HRQoL in patients with moderate-to-severe COPD. However, it is unclear how pulmonary rehabilitation improves HRQoL and which characteristics confer the greatest HRQoL benefits. Moreover, most studies failed to provide a compelling theoretical rationale for the intervention employed. Future research should focus on improving the understanding of the psychological mechanisms implicated in the adoption and maintenance of healthy behavior.

Immediate and short-term consequences of secondhand smoke exposure on the respiratory system

This review critically evaluates the existing biological evidence regarding the immediate and short-term respiratory consequences of secondhand smoke (SHS).

Recent findings: A 1-h exposure to SHS at bar/restaurant levels generates a marked inflammatory reaction and significant decrements on lung function. These deleterious effects of SHS are exacerbated when physical activity follows the SHS exposure, particularly in less fit individuals. The main respiratory effect mechanisms of SHS include a direct induction of growth factors resulting in airway remodelling and alterations in nitric oxide regulation. Pharmacological agents that increase either apical membrane chloride conductance or basolateral membrane potassium conductance may be of therapeutic benefit in patients with diseases related to SHS exposure. Moreover, treatment with statins has shown beneficial effects towards preventing the SHS-induced pulmonary hypertension, vascular remodelling, and endothelial dysfunction.

Summary: Based on recently discovered evidence, even brief and short-term exposures to SHS generate significant adverse effects on the human respiratory system. Future research directions in this area include the concentrations of tobacco smoke constituents in the alveolar milieu following SHS exposure, individual susceptibility to SHS, as well as pharmacological treatments for reversing the SHS-induced airway remodelling.

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