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Safety of bronchodilators and corticosteroids for asthma during pregnancy: what we know and what we need to do better.

 

Asthma is a common medical condition complicating pregnancy with potentially serious effects on pregnancy outcome.

The aim of this review is to provide an update on efficacy and safety of asthma medications, primarily bronchodilators and corticosteroids, used during pregnancy with focus on pregnancy outcome, and, furthermore, to discuss limitations of available studies and point to possible improvements in future studies. A planned series of systematic searches was conducted using the PubMed database. Use of short-acting β2-agonists has generally been established as safe, and the few studies stating otherwise appear to have, perhaps critical, methodological limitations.

The safety of long-acting β2-agonists remains to be further investigated, and the few available studies have methodological limitations and, therefore, provide no definite answers, although a very recent study supports the safety of add-on long-acting β2-agonists to inhaled corticosteroids. Inhaled corticosteroids are generally found to be safe, although further research is needed to investigate both the efficacy and safety of high dose therapy with inhaled corticosteroids. Studies have reported associations between the use of systemic corticosteroids and adverse perinatal outcomes, such as preterm birth, low birth weight, and pre-eclampsia. This must, however, be weighed against the potential serious impact of severe, uncontrolled asthma itself on pregnancy outcome.

The main obstacle to a valid interpretation of several of the available studies is the inadequate stratification for asthma severity and control.

Overall, asthma in itself and not just poor asthma control poses a greater risk to pregnancy outcomes than asthma medication. Nonetheless, more studies focusing on disentangling the effects of asthma alone and asthma medications are needed. Increased use of stratified risk assessments, taking the concept of asthma severity into greater consideration, is much warranted in future studies.

Vitamin D Status and Community-Acquired Pneumonia: Results from the Third National Health and Nutrition Examination Survey.

To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] level and history of community-acquired pneumonia (CAP).

PATIENTS AND METHODS: We identified 16,975 individuals (≥17 years) from the third National Health and Nutrition Examination Survey (NHANES III) with documented 25(OH)D levels. To investigate the association of 25(OH)D with history of CAP in these participants, we developed a multivariable logistic regression model, adjusting for demographic factors (age, sex, race, poverty-to-income ratio, and geographic location), clinical data (body mass index, smoking status, asthma, chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, stroke, chronic kidney disease, neutropenia, and alcohol consumption), and season. Locally weighted scatterplot smoothing (LOWESS) was used to depict the relationship between increasing 25(OH)D levels and the cumulative frequency of CAP in the study cohort.

RESULTS: The median [interquartile range (IQR)] serum 25(OH)D level was 24 (IQR 18-32) ng/mL. 2.1% [95% confidence interval (CI): 1.9-2.3] of participants reported experiencing a CAP within one year of their participation in the national survey. After adjusting for demographic factors, clinical data, and season, 25(OH)D levels <30 ng/mL were associated with 56% higher odds of CAP [odds ratio 1.56; 95% confidence interval: 1.17-2.07] compared to levels ≥30 ng/mL. LOWESS analysis revealed a near linear relationship between vitamin D status and the cumulative frequency of CAP up to 25(OH)D levels around 30 ng/mL.

CONCLUSION: Among 16,975 participants in NHANES III, 25(OH)D levels were inversely associated with history of CAP. Randomized controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of CAP.

Measuring and imaging small airways dysfunction in asthma.

Asthma is a chronic inflammatory disorder of the airways causing typical symptoms, and the diagnosis is supported by evidence of airflow obstruction which is variable, reversible or inducible. However, standard assessment of lung function with spirometry does not measure dysfunction in small airways which are < 2 mm in diameter towards the periphery of the lung.

These airways make only a small contribution to airway resistance under normal circumstances. Nevertheless, there is mounting evidence that pathology and dysfunction in these small airways are implicated in the pathogenesis and natural history of asthma. Using forced oscillation and the multibreath nitrogen washout techniques, uneven ventilation (ventilation heterogeneity) due to small airways dysfunction has been shown to be an important marker of asthma disease activity, even in the absence of abnormalities in standard spirometric measurements.

Recent advances in imaging research, particularly with hyperpolarised gas magnetic resonance imaging, have also given insights into the significance and dynamic nature of ventilation heterogeneity in asthma.

The challenge is to integrate these new physiological and imaging insights to further our understanding of asthma and facilitate potential new treatments.

Effects of nebulized high-dose budesonide on moderate-to-severe acute exacerbation of asthma in children: A randomized, double-blind, placebo-controlled study.

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Effects of nebulized high-dose budesonide on moderate-to-severe acute exacerbation of asthma in children: A randomized, double-blind, placebo-controlled study.

Respirology. 2013 Nov;18 Suppl 3:47-52

Authors: Chen AH, Zeng GQ, Chen RC, Zhan JY, Sun LH, Huang SK, Yang CZ, Zhong N

Abstract
BACKGROUND AND OBJECTIVE: The efficacy of inhaled corticosteroids (ICS) in asthma exacerbation are yet to be clarified. The aim of this study was to investigate the efficacy of nebulized ICS in children with moderate-to-severe acute exacerbation of asthma in an emergency room setting in order to elucidate the potential use of ICS as the first-line therapy in the management of acute exacerbation of asthma.
METHODS: This was a prospective, randomized, double-blind, placebo-controlled study. Paediatric patients with moderate-to-severe acute exacerbation of asthma in emergency room were randomized to receive nebulized salbutamol and ipratropium bromide, with the addition of nebulized high-dose budesonide (BUD group, n = 60) or normal saline (control group, n = 58), three doses in the first hour.
RESULTS: The improvement in forced expiratory volume in 1 s was similar in both groups at 0 h after three doses of nebulization, but there was significantly further improvement at 1 and 2 h in the BUD group (0.095 ± 0.062 L and 0.100 ± 0.120 L, respectively) compared with the control group (0.059 ± 0.082 L and 0.021 ± 0.128 L, respectively), P = 0.013 and 0.001, respectively. Complete remission rate was significantly higher (84.7% vs 46.3%, P = 0.004) and need for oral corticosteroids was significantly lower (16.9% vs 46.3%, P = 0.011) in BUD group than in control group.
CONCLUSION: On the basis of nebulized short-acting bronchodilators, addition of nebulized high-dose budesonide resulted in clinical improvement in children with moderate-to-severe acute exacerbation of asthma, suggesting that nebulized high-dose ICS can be used as first-line therapy for non-life-threatening acute exacerbation of asthma in children.

PMID: 24188203 [PubMed - in process]

Advances in antivirals for non-influenza respiratory virus infections.

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Advances in antivirals for non-influenza respiratory virus infections.

Influenza Other Respir Viruses. 2013 Nov;7 Suppl 3:36-43

Authors: Hayden FG

Abstract
Progress in the development of antivirals for non-influenza respiratory viruses has been slow with the result that many unmet medical needs and few approved agents currently exist. This commentary selectively reviews examples of where specific agents have provided promising clinical benefits in selected target populations and also considers potential therapeutics for emerging threats like the SARS and Middle East respiratory syndrome coronaviruses. Recent studies have provided encouraging results in treating respiratory syncytial virus infections in lung transplant recipients, serious parainfluenza virus and adenovirus infections in immunocompromised hosts, and rhinovirus colds in outpatient asthmatics. While additional studies are needed to confirm the efficacy and safety of the specific agents tested, these observations offer the opportunity to expand therapeutic studies to other patient populations.

PMID: 24215380 [PubMed - in process]

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