Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.

/pdf/international-ers-ats-guidelines-on-definition-evaluation-sedelwbk4v.pdf

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.12313

The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update.

A b s t r ac t The patients had a mean baseline FEV 1 of 62% of the predicted value; the mean age was 53 years. At 24 weeks, the mean (±SE) change in the peak FEV 1 from baseline was greater with tiotropium than with placebo in the two trials: a difference of 86±34 ml in trial 1 (P = 0.01) and 154±32 ml in trial 2 (P<0.001). The predose (trough) FEV 1 also improved in trials 1 and 2 with tiotropium, as compared with placebo: a difference of 88±31 ml (P = 0.01) and 111±30 ml (P<0.001), respectively. The addition of tiotropium increased the time to the first severe exacerbation (282 days vs. 226 days), with an overall reduction of 21% in the risk of a severe exacerba- tion (hazard ratio, 0.79; P = 0.03). No deaths occurred; adverse events were similar in the two groups. Conclusions In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov numbers, NCT00772538 and NCT00776984.)

/pdf/tiotropium-in-asthma-poorly-controlled-with-standard-4etfxc9ht9.pdf

Tiotropium in Asthma Poorly Controlled with Standard Combination Therapy

Asthma is a globally significant non-communicable disease with major public health consequences for both children and adults, including high morbidity, and mortality in severe cases. We have summarized the evidence on asthma trends, environmental determinants, and long-term impacts while comparing these epidemiological features across childhood asthma and adult asthma. While asthma incidence and prevalence are higher in children, morbidity, and mortality are higher in adults. Childhood asthma is more common in boys while adult asthma is more common in women, and the reversal of this sex difference in prevalence occurs around puberty suggesting sex hormones may play a role in the etiology of asthma. The global epidemic of asthma that has been observed in both children and adults is still continuing, especially in low to middle income countries, although it has subsided in some developed countries. As a heterogeneous disease, distinct asthma phenotypes, and endotypes need to be adequately characterized to develop more accurate and meaningful definitions for use in research and clinical settings. This may be facilitated by new clustering techniques such as latent class analysis, and computational phenotyping methods are being developed to retrieve information from electronic health records using natural language processing (NLP) algorithms to assist in the early diagnosis of asthma. While some important environmental determinants that trigger asthma are well-established, more work is needed to define the role of environmental exposures in the development of asthma in both children and adults. There is increasing evidence that investigation into possible gene-by-environment and environment-by-environment interactions may help to better uncover the determinants of asthma. Therefore, there is an urgent need to further investigate the interrelationship between environmental and genetic determinants to identify high risk groups and key modifiable exposures. For children, asthma may impair airway development and reduce maximally attained lung function, and these lung function deficits may persist into adulthood without additional progressive loss. Adult asthma may accelerate lung function decline and increase the risk of fixed airflow obstruction, with the effect of early onset asthma being greater than late onset asthma. Therefore, in managing asthma, our focus going forward should be firmly on improving not only short-term symptoms, but also the long-term respiratory and other health outcomes.

/pdf/epidemiology-of-asthma-in-children-and-adults-1mqpjjmvpb.pdf

Epidemiology of Asthma in Children and Adults.

Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably. A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide, although adaptation may be required in accordance with local conditions. A World Health Organization meeting was convened April 5-6, 2009, to propose a uniform definition of severe asthma. An article was written by a group of experts and reviewed by the Global Alliance against Chronic Respiratory Diseases review group. Severe asthma is defined by the level of current clinical control and risks as "Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)." Severe asthma includes 3 groups, each carrying different public health messages and challenges: (1) untreated severe asthma, (2) difficult-to-treat severe asthma, and (3) treatment-resistant severe asthma. The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment.

/pdf/uniform-definition-of-asthma-severity-control-and-2tp6r3xrdd.pdf

Christiaan van Weel

Papers

Uniform definition of asthma severity, control, and exacerbations: Document presented for the World Health Organization Consultation on Severe Asthma