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The role of mast cells in allergic inflammation

Publication year: 2011
Source: Respiratory Medicine, Available online 21 November 2011

Kawa Amin

The histochemical characteristics of human basophils and tissue mast cells were described over a century ago by Paul Ehrlich. When mast cells are activated by an allergen that binds to serum IgE attached to their FcɛRI receptors, they release cytokines, eicosanoids and their secretory granules. Mast cells are now thought to exert critical proinflammatory functions, as well as potential immunoregulatory roles, in various immune disorders through the release of mediators such as histamine, leukotrienes, cytokines chemokines, and neutral proteases (chymase and tryptase). The aim of this review is to describe the role of mast cells in allergic inflammation.Mast cells interact directly with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been shown to have inhibitory effects on mast cell degranulation and mediator release. This review shows that mast cells play an active role in such diverse diseases as asthma, rhinitis, middle ear infection, and pulmonary fibrosis.In conclusion, mast cells may not only contribute to the chronic airway inflammatory response, remodeling and symptomatology, but they may also have a central role in the initiation of the allergic immune response, that is providing signals inducing IgE synthesis by B-lymphocytes and inducing Th2 lymphocyte differentiation.

Current and emerging medical treatments for non–small cell lung cancer: A primer for pulmonologists

Publication year: 2011
Source: Respiratory Medicine, Available online 25 November 2011

Peter Mazzone, Tarek Mekhail

Pulmonary physicians commonly develop relationships with lung cancer patients through the evaluation and staging of the disease prior to the discussion of treatment options with oncologists. Given the relationship that develops, a pulmonologist is often asked about aspects of the treatment plan that may be slightly outside of their comfort zone. The aim of this overview of medical treatment of non–small cell lung cancer is to provide the pulmonologist with an overview of the evidence guiding current practice so that they can be more comfortable answering their patients’ questions while awaiting the expert opinion of the oncologist. We discuss standard chemotherapeutic agents, their common side effects, and their use in the adjuvant and neoadjuvant setting, as definitive therapy for locally advanced disease, as palliative therapy for advanced disease, and as maintenance therapy. We also discuss the mechanisms of action and side effects of targeted therapies (including inhibitors of vascular endothelial growth factor [VEGF], epidermal growth factor receptor [EGFR] signaling and the anaplastic lymphoma kinase [ALK] protein), their currently accepted uses, and upcoming phase III trials, the results of which may influence standard practice.

Do asthmatic smokers benefit as much as non-smokers on budesonide/formoterol maintenance and reliever therapy? Results of an open label study

Publication year: 2011
Source: Respiratory Medicine, Available online 26 November 2011

Onno C.P. van Schayck, John Haughney, Michel Aubier, Olof Selroos, Tommy Ekström, ...

BackgroundStudies with inhaled corticosteroids (ICS) in smoking asthmatics have mostly shown poorer treatment responses than in non-smoking asthmatics.MethodsEuroSMART, an open, randomised, 6-month study, compared budesonide/formoterol (SymbicortTurbuhaler)hNeither the Symbicort SMART posology nor the dry powder formulation, Turbuhaler, is currently approved in the US.maintenance and reliever therapy (Symbicort SMART) at two maintenance doses of budesonide/formoterol (160/4.5 μg), 1 × 2 and 2 × 2, in patients with asthma who were symptomatic despite treatment with ICS ± long-acting β2-agonists. The 8424 randomised patients included 886 smokers (11%; aged <40 years or with a smoking history <10 pack-years if older), who were compared with a propensity-matched group of non-smokers. At baseline, smokers had lower post-bronchodilator peak expiratory flow, lower peak flow reversibility and used more reliever medication per day. Severe asthma exacerbations were counted and changes in five-item Asthma Control Questionnaire (ACQ-5) scores from baseline calculated.ResultsThere were 48 and 47 exacerbations in smokers and non-smokers, respectively. Mean time to first severe exacerbation was not statistically different between the two groups. The mean change in ACQ-5 score was significantly greater in non-smokers. Considering the two treatment options there was a statistically significant prolonged time to first severe exacerbation with 2 × 2 versus 1 × 2 in the smokers, but not in the non-smokers. In smokers, the reductions in ACQ-5 scores, asthma symptoms, use of as-needed medication and awakenings were also all significant in favour of 2 × 2 with similar or greater changes than in smokers treated with 1 × 2.ConclusionAsthmatic patients with a limited smoking history benefit from treatment with budesonide/formoterol maintenance and reliever therapy with dosing 2 × 2 being superior to 1 × 2.

Intake of alcohol and risk of adult-onset asthma

To examine the association between intake of alcohol and risk of adult-onset asthma.

Methods : Using data from two multidisciplinary questionnaire surveys we prospectively studied 19,349 twins, 12–41 years of age, from the nationwide Danish Twin Registry.

Results : The eight-year incidence of asthma was 4.3%. After adjustment for sex, age, BMI, physical activity, educational level and smoking, the risk of new-onset asthma was significantly related to overall alcohol intake in a U-shaped manner with the lowest risk observed in the group with a moderate weekly intake of alcohol (1–6 units/week),p = 0.006. The highest risk of asthma was observed in rare/never drinkers (<1 unit/month), OR = 1.59 (1.25–2.02),p = 0.000, whereas the risk of asthma in heavy daily drinkers (≥4 units/day) was also increased, however not statistically significant, OR = 1.13 (0.54–2.36),p = 0.747. The risk of new-onset asthma was lower for subjects with wine preference (3.3%) compared with beer preference (4.3%) or no preference (4.4%). After multivariable adjustment, wine preference was inversely related to incident asthma compared with beer preference. However, this finding was not statistically significant, OR = 0.87 (0.51–1.46),p = 0.590.

Conclusion : Alcohol intake is associated with new-onset asthma in adults with a U-shaped association between amount of alcohol intake and the risk of asthma.

A better response in exercise capacity after pulmonary rehabilitation in more severe COPD patients

Pulmonary rehabilitation (PR) has positive effects on exercise capacity in Chronic Obstructive Pulmonary Disease (COPD). However, not all COPD patients benefit from PR to the same extent. We investigated whether there is a patient profile, which is associated with the improvement in endurance exercise capacity.

Methods : In this observational study, we included 102 COPD patients who followed PR (age 60 ± 10 (mean ± SD) years, FEV1%predicted 44 ± 16%, 54 men). Lung function, maximal incremental cycle testing (Wpeak, VO2peak, Δlactate), quadriceps force and incremental and endurance shuttle walk test (ISWT/ESWT) were performed at the start of PR. The ESWT was repeated after 7 weeks of PR.

Results : Mean change in ESWT (ΔESWT) was 100 ± 154%. Four variables showed a statistically significant negative correlation with ΔESWT: FEV1%pred. (ρ = −0.20), Wpeak (ρ = −0.24), Δlactate (ρ = −0.33) and incremental shuttle walk test (ISWT) (ρ = −0.31). A cluster analysis identified two patient profiles: A profile with high ΔESWT, TLC and RV and low FEV1, VO2peak, quadriceps force, Δlactate, HRpeak%pred. and ISWT distance and a profile with low ΔESWT, TLC and RV and high FEV1, VO2peak, quadriceps force, Δlactate, HRpeak%pred. and ISWT distance.

Conclusions : Single variables from lung function or exercise testing at baseline have limited predictive value for response to exercise training.However, patients with worse disease status (i.e. a combination of lower FEV1, more hyperinflation, lower exercise capacity and worse quadriceps force) improve more in endurance exercise capacity.

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