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Mast Cell Infiltration Discriminates Between Histopathological Phenotypes of Chronic Obstructive Pulmonary Disease.

COPD is a complex disease with heterogeneous manifestations. Attempts are been made to define different phenotypes that could guide toward better disease understanding. We described before that smokers can develop either panlobular (PLE) or centrilobular emphysema (CLE). The latter has worse small airways remodeling and narrowing which account for the airflow obstruction similarly to asthma.

Objective. Because of the small airways involvement in CLE similarly to asthma, we hypothesized a role for mast cells (MCs) in CLE but not in PLE. Hence we investigated MCs infiltration, along with overall inflammation, and their relation with hyperreactivity and emphysema type in COPD.

Methods. We studied lung function, emphysema type, MCs and overall inflammation in small airways and alveolar walls, along with alveolar wall thickening in 67 subjects undergoing lung resection (59 smokers, 8 nonsmokers).

Results. 27 smokers had CLE, 24 PLE, and 8 no emphysema. MCs were significantly increased in CLE compared to PLE and controls. Especially relevant was the MCs increase in airway smooth muscle in CLE, which related significantly to airway hyperreactivity. CD4+T-cells, neutrophils and macrophages but not eosinophils and CD8+T-cells, were significantly higher in CLE than PLE. Alveolar wall thickness was increased in all smokers, but significantly more in CLE.

Conclusion. The pathological phenotypes of COPD CLE and PLE show important differences in their overall inflammation with a protagonism of mast cells, which are related to airway reactivity. These findings highlight the distinctness of these COPD phenotypes and the role of mast cells in the pathophysiology of COPD.

A Year in Review: New Drugs for Older Adults in 2011.

New drugs approved by the Food and Drug Administration (FDA) may offer tremendous clinical advances by providing health care providers with new treatment strategies. However, additional care must be taken for safe and effective use of these new agents by older adults.

OBJECTIVE: Our objective was to identify FDA-approved medications in 2011 most likely to be prescribed to older adults, and to describe medication characteristics that may require special attention in this population.

METHODS: The FDA Web site was reviewed for new drug approvals from January through December 2011. Approved labeling for each drug was obtained from the manufacturer's Web site and PubMed was searched for primary literature published between 1967 and 2012.

RESULTS: Rivaroxaban, an oral factor Xa inhibitor, is approved for once-daily use in treatment of nonvalvular atrial fibrillation and deep vein thrombosis prophylaxis after replacement of a hip or knee. Drug interactions and renal function must be considered when prescribing this drug to older adults. Fidaxomicin is an oral anti-infective approved for the treatment of Clostridium difficile-associated diarrhea. It has minimal oral absorption or side effects, no relevant drug interactions, but a very high cost. It is a treatment option after failure of oral metronidazole and oral vancomycin. Roflumilast is a selective inhibitor of phosphodiesterase 4 and is approved to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD and a history of exacerbations. It is recommended as a second or alternative choice combined with a long-acting bronchodilator in patients at high risk for hospitalization. Indacaterol is an inhaled long-acting β-agonist approved for COPD maintenance. It is administered once daily, which may improve adherence in older adults compared with currently available twice-daily agents.

CONCLUSIONS: Four new drugs approved in 2011 applicable to the geriatric population are presented. Clinicians must consider the available evidence, cost, drug-drug interactions, renal function, pharmacokinetic/pharmacodynamic differences, and patient preferences when considering prescribing these agents to older adults.

Is there a role for bronchial thermoplasty in the treatment of asthma?

Is there a role for bronchial thermoplasty in the treatment of asthma?

Can Respir J. 2012 May;19(3):191-2

Authors: Boulet LP, Laviolette M

Abstract
Bronchial thermoplasty is a new technique proposed to improve control of moderate to severe asthma. It delivers thermal energy to the large airways during a bronchoscopy to decrease the amount of bronchial smooth muscle. This intervention has been shown to reduce asthma exacerbations, and improve asthma control and quality of life over a three-year period without significant complications up to a five-year period. It could be considered as another option in the treatment of selected patients requiring oral and⁄or high doses of inhaled corticosteroids to control asthma. It should, however, be performed in specialized centres in patients who understand the potential benefits and side-effects of this technique. The response to this treatment varies from one patient to another. Consequently, further studies are required to better define the role of this option in the treatment of asthma.

PMID: 22679610 [PubMed - in process]

[Prevalence and control of asthma in young children in France].

[Prevalence and control of asthma in young children in France].

Rev Mal Respir. 2012 May;29(5):688-96

Authors: Delmas MC, Guignon N, Leynaert B, Annesi-Maesano I, Com-Ruelle L, Gonzalez L, Fuhrman C

Abstract
INTRODUCTION: Few data on regional variations in asthma prevalence are available in France.
METHODS: The study was carried out during the academic year 2005-2006 in a random sample of around 20,000 children in the last year of nursery school. The lifetime prevalence of asthma and the preceding year prevalences of asthma-like symptoms and treatment for wheezing or asthma attacks were estimated by region.
RESULTS: Overall, the lifetime prevalence of asthma was 9.8 % and the past-year prevalence of wheezing was 10.7 %. An increasing trend in prevalence was observed from Eastern to Western France and in overseas territories. The regional variations in past-year prevalence of wheezing remained when adjusting for gender, family structure and the number of siblings. Among children who had wheezed or received a treatment in the past year, 42 % had experienced frequent or severe symptoms.
CONCLUSION: Large regional variations in asthma prevalence among young children in France exist.

PMID: 22682595 [PubMed - in process]

Motor vehicle air pollution and asthma in children: A meta-analysis.

Motor vehicle air pollution and asthma in children: A meta-analysis.

Environ Res. 2012 Jun 6;

Authors: Gasana J, Dillikar D, Mendy A, Forno E, Ramos Vieira E

Abstract
BACKGROUND: Asthma affects more than 17 million people in the United States;1/3 of these are children. Children are particularly vulnerable to airborne pollution because of their narrower airways and because they generally breathe more air per pound of body weight than adults, increasing their exposure to air pollutants. However, the results from previous studies on the association between motor vehicle emissions and the development of childhood wheeze and asthma are conflicting. Therefore, we conducted a meta-analysis to clarify their potential relationship. METHODS: MEDLINE, Highwire, and The Cochrane Library databases were searched for relevant studies. Adjusted odds ratio (OR) with corresponding 95% confidence interval (CI) for the association between traffic air pollutants and wheeze or asthma were retrieved from individual studies and pooled to generate summary effect estimates (meta-OR) in STATA 11.1. RESULTS: Nineteen studies were included in the meta-analysis. Exposure to nitrogen dioxide (meta-OR: 1.05, 95% CI: 1.00-1.11), nitrous oxide (meta-OR: 1.02, 95% CI: 1.00-1.04), and carbon monoxide (meta-OR: 1.06, 95% CI: 1.01-1.12) were positively associated with a higher prevalence of childhood asthma. Exposure to sulfur dioxide (meta-OR: 1.04, 95% CI: 1.01-1.07) was positively associated with a higher prevalence of wheeze in children. Exposure to nitrogen dioxide was positively associated with a higher incidence of childhood asthma (meta-OR: 1.14, 95% CI: 1.06-1.24), and exposures to particulate matter was positively associated with a higher incidence of wheeze in children (meta-OR: 1.05, 95% CI: 1.04-1.07). CONCLUSIONS: Living or attending schools near high traffic density roads exposes children to higher levels of motor vehicle air pollutants, and increases the incidence and prevalence of childhood asthma and wheeze.

PMID: 22683007 [PubMed - as supplied by publisher]

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