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Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens.

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Research on the pathogenesis of asthma has traditionally concentrated on environmental stimuli, genetic susceptibilities, adaptive immune responses, and end-organ alterations (particularly in airway mucous cells and smooth muscle) as critical steps leading to disease.

The focus of this cascade has been the response to allergic stimuli. An alternative scheme suggests that respiratory viruses and the consequent response of the innate immune system also drives the development of asthma as well as related inflammatory diseases. This conceptual shift raises the possibility that sentinel cells such as airway epithelial cells, DCs, NKT cells, innate lymphoid cells, and macrophages also represent critical components of asthma pathogenesis as well as new targets for therapeutic discovery.

A particular challenge will be to understand and balance the innate as well as the adaptive immune responses to defend the host against acute infection as well as chronic inflammatory disease.

Manipulating antioxidant intake in asthma: a randomized controlled trial.

Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes.

OBJECTIVE: The objective was to investigate the effects of a high-antioxidant compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma.

DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred.

RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo.

CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.

Therapeutical Measures to Control Airway Tolerance in Asthma and Lung Cancer.

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Airway tolerance is a specialized immunological surveillance which is activated by the cells of the lung to deal with and distinguish between innocuous and pathogenic inhalants. However, this distinction does not always occur.

Airway tolerance is necessary to avoid the development of allergic disorders, such as asthma, which is dominated by a pathological expansion of Th2 and Th17 cells in the airways. By contrast, tumor cells induce tolerogenic factors in their microenvironment to evade T-cell mediated anti-tumor-immune responses.

This review updates current understandings on the effect of the cytokines TGF-β, IL-10, and IL-17A on the lung immune responses to antigen, and analyzes their involvement in allergic asthma and lung cancer. The aim of the review is to evaluate where therapeutic intervention may be feasible and where it might fail. The multifunctional role of these cytokines further complicates the decision on the timing and concentration for their use as therapeutical targets. In fact, TGF-β has suppressive activity in early tumorigenesis, but may become tumor-promoting in the later stages of the disease. This dual behavior is sometimes due to changes in the cellular target of TGF-β, and to the expansion of the induced (i)-Tregs. Similarly, IL-17A has been found to elicit pro- as well as anti-tumor properties. Thus, this pro-inflammatory cytokine induces the production of IL-6 which interferes with Treg development. Yet IL-17A could promote tumor growth in conjunction with IL-6-dependent activation of Stat3.

Thus, understanding the mechanisms of airway tolerance could help to improve the therapy to both, allergic asthma and lung cancer. Hereby, asthma therapy aims to induce and maintain tolerance to inhaled allergens and therapy against lung cancer tries to inhibit the tolerogenic response surrounding the tumor.

Current best practice in pulmonary rehabilitation for chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a chronic condition that negatively affects several patient-centered outcomes. Among these, exercise capacity, dyspnea, and quality of life are the most relevant. In this article, factors contributing to exercise limitation, increase in exercise-induced dyspnea, quality of life deterioration, and other pathophysiological aspects in patients with COPD are analyzed in detail. Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. PR has been clearly shown to induce favorable and long-lasting effects on all patient-centered outcomes. In addition, PR appears to have positive (even if not...

Respiratory symptoms in asthma: The view through a wide-angle lens

In this issue of the Journal, 2 articles address the broad question of the clinical relevance of nonwheezing respiratory symptoms in 2 different populations: children with established asthma and children at risk for asthma. Bisgaard et al performed a secondary analysis of data collected in the context of a clinical trial of preschool-aged children with asthma and examined wheeze, cough, and difficulty breathing as predictors of exacerbations. The authors found that any combination of symptoms that included cough was a more sensitive predictor of an exacerbation the following day than combinations of symptoms including either wheeze or difficulty breathing and that half of the exacerbations were not preceded by parent-reported wheeze. The authors conclude that the more narrowly focused app...

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