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Incidence and risk factors for exacerbations of asthma during pregnancy.

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Incidence and risk factors for exacerbations of asthma during pregnancy.

J Asthma Allergy. 2013;6:53-60

Authors: Ali Z, Ulrik CS

Abstract
BACKGROUND: Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma during pregnancy.
METHODS: A narrative literature review was carried out using the PubMed database.
RESULTS: During pregnancy, up to 6% of women with asthma are hospitalized for an acute exacerbation. The maternal immune system is characterized by a very high T-helper-2:T-helper-1 cytokine ratio during pregnancy and thereby provides an environment essential for fetal survival but one that may aggravate asthma. Cells of the innate immune system such as monocytes and neutrophils are also increased during pregnancy, and this too can exacerbate maternal asthma. Severe or difficult-to-control asthma appears to be the major risk factor for exacerbations during pregnancy, but studies also suggest that nonadherence with controller medication and viral infections are important triggers of exacerbations during pregnancy. So far, inconsistent findings have been reported regarding the effect of fetal sex on exacerbations during pregnancy. Other risk factors for exacerbation during pregnancy include obesity, ethnicity, and reflux, whereas atopy does not appear to be a risk factor.
DISCUSSION: The incidence of asthma exacerbations during pregnancy is disturbingly high. Severe asthma - better described as difficult-to-control asthma - nonadherence with controller therapy, viral infections, obesity, and ethnicity are likely to be important risk factors for exacerbations of asthma during pregnancy, whereas inconsistent findings have been reported with regard to the importance of sex of the fetus.

PMID: 23671393 [PubMed]

Perception of bronchoconstriction: a complementary disease marker in children with asthma.

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Perception of bronchoconstriction: a complementary disease marker in children with asthma.

J Asthma. 2013 May 15;

Authors: Nuijsink M, Hop WC, de Jongste JC, Sterk PJ, Duiverman EJ, on behalf of the CATO Study Group

Abstract
Introduction Asthma guidelines use symptoms as the most important aspect of asthma control. Symptom perception varies widely between individuals. Over-perception as well as underperception of bronchoconstriction could have a negative effect on asthma management. We hypothesized that perception of bronchoconstriction in childhood asthma is not related to common measures of disease control. For that reason we examined the clinical determinants of the perception of bronchoconstriction and the repeatability of perception measurements. Patients and methods In school-age children with moderately severe atopic asthma we measured perception of bronchoconstriction (decrease in forced expiratory volume in 1 second (FEV1)) during methacholine bronchoprovocation challenges. The perception of bronchoconstriction was assessed as the slope of the relation between FEV1 and Borg score, and as the Borg score at 20% decrease in FEV1 from baseline during the provocation test (PS20). Data from subjects who had a 20% or more decrease in FEV1 (n=112) were used for analysis. Fifty-four children repeated the test after 3 months. Symptoms, use of rescue medication and peak expiratory flows were scored in diaries during 2 weeks before testing. Results Symptom perception was significantly better in children without (PD20 > 1570 μg, n=28) than in children with airway hyperresponsiveness (PD20 = 1570 μg, n=112), slope 0.22 versus 0.13 respectively (p<0.001). Borg scores correlated with PD20 (p=0.01), baseline FEV1 (only for slope, p=0.04) and use of rescue beta agonist (p=0.01), but not with other aspects of asthma control. Repeatability of Borg scores was good (slope: R=0.59, PS20: R=0.52) Conclusion Poorer symptom perception in asthmatic children correlated with hyperresponsiveness, and was associated with lower baseline FEV1 and less use of rescue bronchodilators. This suggests that measurement of symptom perception should be taken into account in individual management plans for children with asthma.

PMID: 23672570 [PubMed - as supplied by publisher]

Theophylline.

Theophylline (dimethyxanthine) has been used to treat airway diseases for over 80 years. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more widely used. More recently it has been shown to have anti-inflammatory effects in asthma and COPD at lower concentrations.

The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3, but the anti-inflammatory effect may be due to inhibition of PDE4 and histone deacetylase(HDAC)-2 activation, resulting in switching off of activated inflammatory genes. Through this mechanism theophylline also reverses corticosteroid resistance and this may be of particular value in severe asthma and COPD where HDAC2 activity is reduced. Theophylline is given systemically (orally as slow-release preparations for chronic treatment and intravenously for acute exacerbations of asthma). Efficacy is related to blood concentrations, which are determined mainly by hepatic metabolism that may be increased or decreased in several diseases and by concomitant drug therapy. Theophylline is now usually used as an add-on therapy in asthma patients not well controlled on inhaled corticosteroids with or without long-acting β2-agonists and in COPD patients with severe disease not controlled by bronchodilator therapy. Side effects are related to plasma concentrations and include nausea, vomiting and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism.

In the future low dose theophylline may be useful in reversing corticosteroid-resistance in COPD and severe asthma.

Airway inflammation and oxidative potential of air pollutant particles in a pediatric asthma panel.

Airborne particulate matter (PM) components from fossil fuel combustion can induce oxidative stress initiated by reactive oxygen species (ROS). Reported associations between worsening asthma and PM2.5 mass could be related to PM oxidative potential to induce airway oxidative stress and inflammation (hallmarks of asthma pathology).

We followed 45 schoolchildren with persistent asthma in their southern California homes daily over 10 days with offline fractional exhaled nitric oxide (FENO), a biomarker of airway inflammation. Ambient exposures included daily average PM2.5, PM2.5 elemental and organic carbon (EC, OC), NO2, O3, and endotoxin. We assessed PM2.5 oxidative potential using both an abiotic and an in vitro bioassay on aqueous extracts of daily particle filters: (1) dithiothreitol (DTT) assay (abiotic), representing chemically produced ROS; and (2) ROS generated intracellularly in a rat alveolar macrophage model using the fluorescent probe 2'7'-dicholorohidroflourescin diacetate.

We analyzed relations of FENO to air pollutants in mixed linear regression models. FENO was significantly positively associated with lag 1-day and 2-day averages of traffic-related markers (EC, OC, and NO2), DTT and macrophage ROS, but not PM2.5 mass. DTT associations were nearly twice as strong as other exposures per interquartile range: median FENO increased 8.7-9.9% per 0.43 nmole/min/m(3) DTT.

Findings suggest that future research in oxidative stress-related illnesses such as asthma and PM exposure would benefit from assessments of PM oxidative potential and composition.

The Coexistence of Asthma and Chronic Obstructive Pulmonary Disease (COPD): Prevalence and Risk Factors in Young, Middle-aged and Elderly People from the General Population.

The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described. This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors.

METHODS: A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study.

RESULTS: A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65-84 years respectively. Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%). The prevalence of the overlap of asthma and COPD was 1.6% (1.3%-2.0%), 2.1% (1.5%-2.8%) and 4.5% (3.2%-5.9%) in the 20-44, 45-64 and 65-84 age groups. Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01). Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions.

CONCLUSION: Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects. The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research.

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