Ashtma-Chronic obstructive pulmonary disease overlap syndrome (ACOS): current evidence and future research directions (Free Full text from 2017 COPD Research and Practice)

Chronic obstructive pulmonary disease and asthma are the most frequent chronic respiratory diseases that affect the general population. For a long period of time these two conditions were considered to be separate diseases. However, it became evident that some patients share symptoms and clinical findings from both diseases. 

These patients are considered to represent a distinct phenotype, called asthma-COPD overlap syndrome (ACOS). However, since approximately the one third of the asthmatics smoke the ACOS may primarily define those patients. This is a relatively newly defined clinical syndrome whose underlying mechanisms and most appropriate management remain to be confirmed. In this review, we summarize current knowledge on this syndrome, aiming to update clinicians and help their daily practice.

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https://copdrp.biomedcentral.com/articles/10.1186/s40749-017-0025-x

Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma (free full text from 2017 NEJM)

Many patients with severe asthma rely on oral glucocorticoids to manage their disease. We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid–sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.

In a 28-week randomized, controlled trial, we assessed the effects of benralizumab (at a dose of 30 mg administered subcutaneously either every 4 weeks or every 8 weeks [with the first three doses administered every 4 weeks]) versus placebo on the reduction in the oral glucocorticoid dose while asthma control was maintained in adult patients with severe asthma. The primary end point was the percentage change in the oral glucocorticoid dose from baseline to week 28. Annual asthma exacerbation rates, lung function, symptoms, and safety were assessed.

Results

Of 369 patients enrolled, 220 underwent randomization and started receiving benralizumab or placebo. The two benralizumab dosing regimens significantly reduced the median final oral glucocorticoid doses from baseline by 75%, as compared with a reduction of 25% in the oral glucocorticoid doses in the placebo group (P<0.001 for both comparisons). The odds of a reduction in the oral glucocorticoid dose were more than 4 times as high with benralizumab as with placebo. Among the secondary outcomes, benralizumab administered every 4 weeks resulted in an annual exacerbation rate that was 55% lower than the rate with placebo (marginal rate, 0.83 vs. 1.83, P=0.003), and benralizumab administered every 8 weeks resulted in an annual exacerbation rate that was 70% lower than the rate with placebo (marginal rate, 0.54 vs. 1.83, P<0.001). At 28 weeks, there was no significant effect of either benralizumab regimen on the forced expiratory volume in 1 second (FEV₁), as compared with placebo. The effects on various measures of asthma symptoms were mixed, with some showing significant changes in favor of benralizumab and others not showing significant changes. Frequencies of adverse events were similar between each benralizumab group and the placebo group.

Conclusions

Benralizumab showed significant, clinically relevant benefits, as compared with placebo, on oral glucocorticoid use and exacerbation rates. These effects occurred without a sustained effect on the FEV₁.

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http://www.nejm.org/doi/full/10.1056/NEJMoa1703501#Top

World Asthma Day 2017: read article on Asthma research in Europe from ERJ (Free full text)

Asthma is highly prevalent, often starting in infancy and persisting throughout life, and is associated with high morbidity and burden. It is a major global health challenge with growing impact, affecting more than 300 million people worldwide and at least 10% of all Europeans. Furthermore, it is the most prevalent long-term condition in children. Approximately 5–10% of asthma cases are so severe that current treatments do not work, and over five million people in the European Union (EU) fall into this category.

People with asthma live at risk of life-threatening asthma attacks, leading to at least 500 000 hospitalisations worldwide each year. A European study estimated that unscheduled care and rescue medication accounted for 47% of the total cost-per-patient in infants, 45% in children and 56% in adults. This results in high socio-economic impact, estimated at more than €70 billion annually. This includes the costs of direct primary and hospital healthcare (estimated to be close to €20 billion per annum), costs due to lost productivity (€14 billion), and the monetised value of disability-adjusted life-years (DALYs) lost (over €38 billion). Close to 1 million DALYs are lost due to asthma in Europe every year.

Despite the fact that the direct and indirect costs of asthma are substantial and continue to rise, asthma remains under-prioritised in the EU research agenda. Only 0.5% of the Seventh Framework Programme (FP7) health research budget was devoted to asthma and chronic obstructive pulmonary disease (COPD) (€30 million). In comparison, some 5.4 times this amount (over €163 million) was spent on cardiovascular conditions and some 20.6 times (over €618 million) on brain research.

Asthma, with its high global prevalence and an associated multi-billion global market for treatments, plus its historical underfunding and the demand for new treatments and diagnostics, represents an enormous opportunity to drive substantial economic growth. This paper sets out how the EU may capitalise on this via investment in research with high commercial potential that can radically improve the EUs research agenda and public health.

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http://erj.ersjournals.com/content/49/5/1602294

ERS Guidelines 2017: exhaled biomarkers in lung disease

Breath tests cover the fraction of nitric oxide in expired gas (F_eNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for F_eNO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and F_eNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.

Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.

Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.

Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

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http://erj.ersjournals.com/content/49/4/1600965

Relationship of Allergy with Asthma: There Are More Than the Allergy “Eggs” in the Asthma “Basket” (Free full text from 2017 Frontiers in Pediatrics)

Asthma and allergy share a similar and very close course, especially through childhood. Considerable research effort has been put in untangling these associations; however, it is now becoming obvious that this is an exceedingly difficult task. In fact, each research breakthrough further perplexes this picture, as we are steadily moving toward the era of personalized medicine and we begin to appreciate that what we thought to be a single disease, asthma, is in fact an accumulation of distinct entities. In the context of this “syndrome,” which is characterized by several, as of yet poorly defined endotypes and phenotypes, the question of the link of “asthma” with allergy probably becomes non-relevant. In this review, we will revisit this question while putting the emphasis on the multifaceted nature of asthma.

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http://journal.frontiersin.org/article/10.3389/fped.2017.00092/full

Pauci-granulocytic stable asthma (Article from Allergy 2017)

Read new article on hot topic paucigranulocytic asthma in comparison with another inflammatory asthma phenotypes! The emergence and increasing availability of validated, feasible non-invasive methods of assessment of inflammation has led to a greater understanding of inflammatory phenotypes in asthma. Two distinct and apparently stable sputum inflammatory phenotypes have been described, eosinophilic and non-eosinophilic, which have a differential treatment response, particularly to glucocorticosteroids. The classification has been further revised:  eosinophilic, neutrophilic, mixed granulocytic (raised eosinophils and neutrophils) and paucigranulocytic (normal levels of eosinophils and neutrophils).

http://onlinelibrary.wiley.com/doi/10.1111/all.13184/abstract

Background

According to induced sputum cell count, four different asthma phenotypes have been recognised(eosinophilic, neutrophilic, mixed and pauci-granulocytic). The aim of the present study was to detect functional and inflammatory characteristics of patients with pauci-granulocytic asthma.

Methods

240 asthmatic patients were categorised in the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of FeNO. The levels of IL-8, IL-13, and ECP were also measured in sputum supernatant. Treatment, asthma control and the presence of Severe Refractory Asthma(SRA) were also recorded.

Results

Patients were categorized in the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and pauci-granulocytic (47.9%). Although ACT did not differ between groups (p=0.288) patients with pauci-granulocytic asthma had better lung function (FEV₁%pred) (median (IQR):71.5(59.0-88.75) vs 69.0(59.0-77.6) vs 68.0(60.0-85.5) vs 80.5(69.7-95.0), p=0.009] for eosinophilic, mixed, neutrophilic and pauci-granulocytic asthma respectively, p=0.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7% respectively) and less frequently in the neutrophilic and pauci-granulocytic phenotype (25% and 21.7% respectively, p=0.01). FeNO, ECP and IL-8 were all low in the pauci-granulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma(p<0.001 for all comparisons). Interestingly, 14.8% of patients with pauci-granulocytic asthma had poor asthma control.

Conclusion

Pauci-granulocytic asthma most likely represents a “benign” asthma phenotype, related to a good response to treatment, rather than a “true” phenotype of asthma. However, pauci-granulocytic patients that remain not-well-controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.

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http://onlinelibrary.wiley.com/doi/10.1111/all.13184/abstract

Interventions to improve inhaler technique for people with asthma (Free fulltext from 2017 The Cochrane Library)

Background to the question

Many asthma drugs are taken by an inhaler, which deposits the drug directly into the lungs. It is important that the inhaler is taken properly, so the patient gets the most benefit. Taken properly, asthma drugs can improve symptoms and reduce attacks.

Lots of people do not use their devices correctly. This means that the drug is not delivered properly to the lungs, and as a result, asthma may not be as well controlled as it should be. People also tell us that they can have more than one type of inhaler, so it is confusing to know what to do.

We wanted to find out whether teaching people with asthma how to use their inhalers works, and whether this leads to better control of symptoms and fewer attacks. It may seem obvious, but it is important that doctors and nurses know how best to help people with asthma.

Study characteristics

We found 29 studies involving 2210 people with asthma. Studies lasted between 2 and 26 weeks. Studies reported inhaler technique on a range of different checklists.

We grouped studies into three types: studies testing enhanced face-to-face training session(s), studies using multi-media to deliver inhaler training (e.g. a video, computer app or game) and studies testing devices that give people visual or audio feedback about technique.

Studies tested different types of training and used different measures to gauge success, meaning that we could not bring data together. This was particularly true when we tried to assess effects on asthma attacks, adverse events, visits to a healthcare provider and absences from work or school.

Key results

Both face-to-face and multi-media inhaler training improved inhaler technique in most studies, although results varied depending on how and when each technique was assessed.

Some studies reported the number of people who had correct or 'good enough' technique. More people had correct or 'good enough' technique after face-to-face training and with feedback devices. But the benefit of multi-media training for adults was uncertain.

Interventions that provide inhaler training may bring some benefit for quality of life and asthma control among adults and children, but results were varied and studies were small.

Children may receive some benefit but results tended to be less clear for children because fewer and smaller studies have included children as participants.

Quality of the evidence

For studies like these, it is not possible to blind people to their assigned group. This may bias how people behave or respond to questionnaires, which reduced our confidence in the findings. We were uncertain about other results because studies did not provide enough data to show clear benefit.

Conclusions

We cannot say for sure what is the best way to help people learn how to use their inhaler properly. It is important that patients understand how their inhaler works, so they should ask their doctor or nurse for help.

We also use Cochrane Reviews to make suggestions for future research. We suggest that trials should last longer than six months and should report adherence information. The most useful information reported was the number of people who had 'good enough' inhaler technique, so we urge future trials to report this as well.

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