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Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease

The leukotriene pathway has been associated with an increased cardiovascular risk. However, the effects of the antileukotriene treatment used in asthmatic patients on cardiovascular outcomes have remained largely unexplored.

Objective: We sought to examine a potential protective role of the leukotriene receptor antagonist montelukast on future risk of incident and recurrent myocardial infarction and ischemic stroke.

Methods: A nationwide population-based cohort of approximately 7 million persons integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational, and Emigration Registers was followed from July 1, 2005, to December 31, 2008. Analyses were performed in the whole population after exclusion of subjects with a prior cardiovascular diagnosis (incident events; sample size, n = 6,910,923 for myocardial infarction and n = 6,932,578 for stroke) and in subjects with a prior diagnosis (recurrent events; n = 153,937 and n = 132,291 for stroke and myocardial infarction, respectively).

Results: Cox proportional hazard ratios (HRs) did not reveal an association of montelukast use with incident events. In contrast to these findings, montelukast use was associated with a lower risk for recurrent stroke (HR, 0.62; 95% CI, 0.38-0.99) accounting for age, sex, education level, and yearly income. Adjusting the latter finding also for respiratory and cardiovascular medications and diagnoses revealed similar point estimates (HR, 0.62; 95% CI, 0.39-1.0). Post hoc analyses revealed a significant association of montelukast use with a lower risk for recurrent myocardial infarction in male subjects (HR, 0.65; 95% CI, 0.43-0.99).

Conclusion: These data provide a first indication for a potential role of the antiasthma drug montelukast for secondary prevention of cardiovascular disease.

Pneumococcal polysaccharide vaccine at 12 months of age produces functional immune responses

Background: Infections with Streptococcus pneumoniae (pneumococcus) are a cause of significant child mortality. Pneumococcal glycoconjugate vaccines are expensive and provide limited serotype coverage. The 23-valent pneumococcal polysaccharide vaccine (Pneumovax) might provide wider serotype coverage but is reported to be weakly immunogenic in children less than 2 years of age.

We have previously reported that Pneumovax administered to healthy 12-month-old Fijian infants elicits significant serotype-specific IgG responses. However, the functional capacity of these responses in 12-month-old infants is not known.

Objective: We sought to assess the functional, serotype-specific immune response of 12-month-old infants after immunization with Pneumovax.

Methods: Functional responses of 12-month-old infants were assessed by using the opsonophagocytic and antibody avidity assay against 8 serotypes and 23 serotypes, respectively.

Results: Seventy-one percent of infants produced strong opsonophagocytic activity against 4 of 8 serotypes, and 30% produced high-avidity serotype-specific IgG antibodies to 10 of 23 serotypes at 2 weeks after Pneumovax. Responses were protective for most serotypes that cause disease in Western countries, whereas responses to most of the epidemiologically relevant serotypes for developing countries were low.

Conclusion: This is the first comprehensive study evaluating the functional antibody response to Pneumovax in 12-month-old infants. Pneumovax induced functional antibody responses to several serotypes causing disease in Western countries but induced poorer responses to serotypes that are responsible for the majority of disease in developing countries. Pneumovax might be of benefit in some populations, but further studies are required before this can be recommended in developing countries.

High prevalence of asthma in HIV-infected adults: New insights

Over the past decade, many new insights into asthma pathophysiology have been reported in the Journal and elsewhere complemented by reports of increasingly sophisticated therapeutic approaches. Disturbingly, however, the Centers for Disease Control and Prevention continues to report increasing rates of asthma prevalence and incidence (http://www.cdc.gov/vitalsigns/Asthma/).

Consequently, asthma is now the most common chronic disease of children in the United States and many other nations and is one of the most common chronic disorders of adulthood. The ineffable reality of asthma is that despite such progress on the research side, it remains a disease without a clear immune pathogenesis, prognostic tools, and certainly not even the remote possibility of a cure. Only by viewing asthma from as many different research perspectives as possible do we stand the greatest possibility of making the key unique insight or insights that are genuinely needed to improve clinical management and alter short- and long-term outcomes.

Advances in upper airway diseases and allergen immunotherapy in 2011

The purpose of this review is to highlight recently published important articles on upper airway diseases and allergen immunotherapy.

We review articles on rhinitis, sinusitis, conjunctivitis, and immunotherapy. New insights into epidemiology, pathophysiology, diagnosis, and therapy are described for each of the above diseases.

Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity

Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known.

Objectives: We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD.

Methods: In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less −950 Hounsfield units).

Results: Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity.

Conclusions: Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.

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