The environment, epigenome, and asthma

Juan Carlos Ivancevich Saturday, 30 December 2017 21:49

Abstract

Asthma prevalence has been on the increase, especially in North America compared with other continents. However, the prevalence of asthma differs worldwide, and in many countries the prevalence is stable or decreasing. This highlights the influence of environmental exposures, such as allergens, air pollution, and the environmental microbiome, on disease etiology and pathogenesis. The epigenome might provide the unifying mechanism that translates the influence of environmental exposures to changes in gene expression, respiratory epithelial function, and immune cell skewing that are hallmarks of asthma. In this review we will introduce the concept of the environmental epigenome in asthmatic patients, summarize previous publications of relevance to this field, and discuss future directions.

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Evaluation of Potential Continuation Rules for Mepolizumab Treatment of Severe Eosinophilic Asthma

Juan Carlos Ivancevich Saturday, 30 December 2017 12:58
Background

Mepolizumab significantly reduces exacerbations in patients with severe eosinophilic asthma. The early identification of patients likely to receive long-term benefit from treatment could ensure effective resource allocation.

Objective

To assess potential continuation rules for mepolizumab in addition to initiation criteria defined as 2 or more exacerbations in the previous year and blood eosinophil counts of 150 cells/μL or more at initiation or 300 cells/μL or more in the previous year.

Methods

This post hoc analysis included data from 2 randomized, double-blind, placebo-controlled studies (NCT01000506 and NCT01691521) of mepolizumab in patients with severe eosinophilic asthma (N = 1,192). Rules based on blood eosinophils, physician-rated response to treatment, FEV1, Asthma Control Questionnaire (ACQ-5) score, and exacerbation reduction were assessed at week 16. To assess these rules, 2 key metrics accounting for the effects observed in the placebo arm were developed.

Results

Patients not meeting continuation rules based on physician-rated response, FEV1, and the ACQ-5 score still derived long-term benefit from mepolizumab. Nearly all patients failing to reduce blood eosinophils had counts of 150 cells/μL or less at baseline. For exacerbations, assessment after 16 weeks was potentially premature for predicting future exacerbations.

Conclusion

There was no evidence of a reliable physician-rated response, ACQ-5 score, or lung function–based continuation rule. The added value of changes in blood eosinophils at week 16 over baseline was marginal. Initiation criteria for mepolizumab treatment provide the best method for assessing patient benefit from mepolizumab treatment, and treatment continuation should be reviewed on the basis of a predefined reduction in long-term exacerbation frequency and/or oral corticosteroid dose.

 

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Lung ultrasonography to diagnose community-acquired pneumonia in children

Juan Carlos Ivancevich Wednesday, 20 December 2017 11:32
Nicola PrincipiAndrea EspositoCaterina Giannitto and Susanna Esposito

Abstract

Background

Early diagnosis of community-acquired pneumonia (CAP) is essential to reduce the total burden of this disease. Traditionally, chest radiography (CR) is used to identify true CAP. However, CR is not a perfect diagnostic test for CAP. The use of lung ultrasonography (LUS) has been suggested as an alternative to overcome the problems associated with CR and increase the feasibility and accuracy of CAP diagnosis. LUS has largely been used for the diagnosis of several lung problems, including CAP, in adult patients with satisfactory results. Experience with LUS in children has grown over recent years. The main aim of this paper is to discuss the advantages and limits of LUS in the diagnosis of paediatric CAP.

Discussion

The presence of a consolidation pattern during LUS may represent pneumonia or atelectasis, although this conclusion is operator dependent. An overall agreement between LUS and CR was observed in most of the studies that were examined. In most reports where a disagreement between the two methods was found, CR was not able to identify the cases that were correctly diagnosed by LUS, particularly when CR was performed only with postero-anterior/antero-posterior projection and consolidation was observed in lung areas that are poorly visualized by CR. However, the lack of standardized LUS methods is problematic. Finally, the real advantage of LUS for the diagnosis of CAP in children remains unclear.

Summary

LUS is an interesting diagnostic modality that appears a useful first imaging test in children with suspected CAP. However, the methods used to perform LUS in children are not precisely standardized, and the diagnosis of interstitial CAP is inaccurate. Further studies are needed before LUS can be routinely used in everyday paediatric practice.

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Add-on Therapy for Symptomatic Asthma despite Long-Acting Beta-Agonists/Inhaled Corticosteroid

Juan Carlos Ivancevich Tuesday, 26 December 2017 20:59

Tuberc Respir Dis. 2017;80:e18. English.
Published online Dec 13, 2017.  https://doi.org/10.4046/trd.2017.0102 

Michael Dreher, M.D. and Tobias Müller, M.D

 

Abstract

Asthma, remains symptomatic despite ongoing treatment with high doses of inhaled corticosteroids (ICS) in conjunction with long-acting beta-agonists (LABA), is classified as “severe” asthma. In the course of caring for those patients diagnosed with severe asthma, stepping up from ICS/LABA to more aggressive therapeutic measures would be justified, though several aspects have to be checked in advance (including inhaler technique, adherence to therapy, and possible associated comorbidities). That accomplished, it would be advisable to step up care in accordance with the Global Initiative for Asthma (GINA) recommendations. Possible strategies include the addition of a leukotriene receptor antagonist or tiotropium (to the treatment regimen). The latter has been shown to be effective in the management of several subgroups of asthma. Oral corticosteroids have commonly been used for the treatment of patients with severe asthma in the past; however, the use of oral corticosteroids is commonly associated with corticosteroid-related adverse events and comorbidities. Therefore, according to GINA 2017 these patients should be referred to experts who specialize in the treatment of severe asthma to check further therapeutic options including biologics before starting treatment with oral corticosteroids.

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Barriers and facilitators of effective self-management in asthma: systematic review and thematic synthesis of patient and healthcare professional views

Juan Carlos Ivancevich Saturday, 16 December 2017 15:33
 

Abstract

 Self-management is an established, effective approach to controlling asthma, recommended in guidelines. However, promotion, uptake and use among patients and health-care professionals remain low. Many barriers and facilitators to effective self-management have been reported, and views and beliefs of patients and health care professionals have been explored in qualitative studies. We conducted a systematic review and thematic synthesis of qualitative research into self-management in patients, carers and health care professionals regarding self-management of asthma, to identify perceived barriers and facilitators associated with reduced effectiveness of asthma self-management interventions. Electronic databases and guidelines were searched systematically for qualitative literature that explored factors relevant to facilitators and barriers to uptake, adherence, or outcomes of self-management in patients with asthma. Thematic synthesis of the 56 included studies identified 11 themes: (1) partnership between patient and health care professional; (2) issues around medication; (3) education about asthma and its management; (4) health beliefs; (5) self-management interventions; (6) co-morbidities (7) mood disorders and anxiety; (8) social support; (9) non-pharmacological methods; (10) access to healthcare; (11) professional factors. From this, perceived barriers and facilitators were identified at the level of individuals with asthma (and carers), and health-care professionals. Future work addressing the concerns and beliefs of adults, adolescents and children (and carers) with asthma, effective communication and partnership, tailored support and education (including for ethnic minorities and at risk groups), and telehealthcare may improve how self-management is recommended by professionals and used by patients. Ultimately, this may achieve better outcomes for people with asthma.
 

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Editor: Juan C. Ivancevich, MD

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