The Role of Viral Infections on Severe Asthma Exacerbations: Present and Future

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Biologics in Asthma: Don’t Let the Magic Bullets Sink the Boat / Biológicos en asma: que las balas mágicas no hundan el barco

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Treatment of moderate-severe asthma: an alternative strategy to the guideline recommendations / Estrategia para el tratamiento del asma moderada-grave: una alternativa a la recomendada por las guías

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The long road to biologic therapies for asthma in pediatric patients / El largo camino al tratamiento con biológicos del asma en pediatría

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Want to Work on Asthma Genetics?

Twins, data and emails. Some of the words that first come to mind when I think of Nick. Lots of twins. With lots of data. And short single-finger-typed emails. And great wine. Well, it works, there is no doubt. That's how I ended up in Australia, working on asthma genetics.

Living with asthma in 19th-century France: The doctor, Armand Trousseau, and the patient, Emile Pereire.

Major advances in the French medical system following the French Revolution have stimulated a rich historiography of which Michel Foucault's Naissance de la clinique: une archéologie du regard médical (1963) and Erwin H. Ackerknecht's Medicine at the Paris Hospital, 1794-1848 (1967) are of lasting significance. Changes in the organisation and structure of hospitals accompanied the development and availability of new medical technologies and procedures and encouraged a more intense study of the aetiology and pathology of disease. Theories about asthma and its treatment profited from this dynamic environment as Classical Greek doctrines about the effect of the humours on bodily imbalance gave way to an increasingly more precise understanding of the nature and cause of asthma. The clinician and teacher, Armand Trousseau (1801-1867), who held the chair of Clinical Medicine at the Hôtel-Dieu in Paris and was himself an asthmatic, promoted new theories about the illness and developed innovative ways of dealing with its effects. Among his patients was the banker and financier, Emile Pereire (1800-1875), a lifelong asthmatic. Based on the Pereire Family Archives (hereafter AFP), the case of Emile Pereire provides a preface to the later case of that other, more famous, asthmatic, Marcel Proust.

Genetic susceptibility to severe childhood asthma and rhinovirus-C maintained by balancing selection in humans for 150 000 years.

Selective pressures imposed by pathogens have varied among human populations throughout their evolution, leading to marked inter-population differences at some genes mediating susceptibility to infectious and immune-related diseases. Here, we investigated the evolutionary history of a common polymorphism resulting in a Y529 versus C529 change in the cadherin related family member 3 (CDHR3) receptor which underlies variable susceptibility to rhinovirus-C infection and is associated with severe childhood asthma. The protective variant is the derived allele and is found at high frequency worldwide (69-95%). We detected genome-wide significant signatures of natural selection consistent with a rapid increase of the haplotypes carrying the allele, suggesting that non-neutral processes have acted on this locus across all human populations. However, the allele has not fixed in any population despite multiple lines of evidence suggesting that the mutation predates human migrations out of Africa. Using an approximate Bayesian computation method, we estimate the age of the mutation while explicitly accounting for past demography and positive or frequency-dependent balancing selection. Our analyses indicate a single emergence of the mutation in anatomically modern humans ~150 000 years ago and indicate that balancing selection has maintained the beneficial allele at high equilibrium frequencies worldwide. Apart from the well-known cases of the MHC and ABO genes, this study provides the first evidence that negative frequency-dependent selection plausibly acted on a human disease susceptibility locus, a form of balancing selection compatible with typical transmission dynamics of communicable respiratory viruses that might exploit CDHR3.

Caelius Aurelianus' textbook on medicine of the fifth century: rhythm in asthma, pain, and drug effects.

Caelius Aurelianus was a Greek-Roman physician in the fifth century. He translated the work of Soranus from Ephesus into Latin and extended the medical knowledge of his time in several textbooks. His book "De Morbis acutis et chronicis" was reprinted many times up to the 19th century and served as the handbook for physicians. Aurelianus aready described in detail the rhythmic pattern - daily and seasonally - of asthma. Tooth pain was also first described by Caelius Aurelianus to peak at night and that drugs were not able to fully suppress the pain, a first indication of chronopharmacology.

Changes in the prevalence of asthma and respiratory symptoms in western Sweden between 2008 and 2016.

BACKGROUND: Asthma is a common chronic inflammatory disease of the airways, with a noticeable increase in prevalence during the second half of the 20th century. Recent studies assessing the prevalence trends among adults have been inconsistent. We investigated the changes in the prevalence of asthma, respiratory symptoms, and risk factors between 2008 and 2016 in western Sweden. METHODS: The West Sweden Asthma Study (WSAS) is a population-based study which started in 2008 (WSAS I) and then repeated in 2016 (WSAS II) in western Sweden. Randomly selected individuals aged 16-75 years (N = 18 087 in 2008 and N = 24 534 in 2016) completed a questionnaire regarding obstructive lung diseases, respiratory symptoms, potential risk factors, and also questions from the GA2 LEN survey. RESULTS: The prevalence of reported ever asthma, physician-diagnosed asthma, use of asthma medication, and current asthma increased significantly from 9.6% to 11%, 8.3% to 10%, 8.6% to 9.8%, and 8.1% to 9.1%, respectively, between 2008 and 2016. There were also increases in the prevalence of respiratory symptoms during the same period. The greatest increase occurred in young adults aged 16-25 years. Female gender, allergic rhinitis, obesity, and family history of asthma remained the strongest risk factors for asthma in 2016 as it was in 2008. CONCLUSION: There were moderate increases in asthma and respiratory symptoms in adults in western Sweden between 2008 and 2016, the greatest increase occurring in younger adults. The potential risk factors for asthma remained the same during the study period.

Allergic sensitization and clinical outcomes in urban children with asthma, 2013-2016.

BACKGROUND: The aim of this study was to examine if food and/or aeroallergen sensitization was associated with worse asthma, pulmonary function tests (PFT), and laboratory markers. METHODS: At our institution, 386 children with asthma were divided into allergic and nonallergic groups based on allergen-specific immunoglobulin E (IgE) testing classes 1-6 versus 0. Asthma severity and/or control, IgE level, eosinophil counts and/or percentages, forced vital capacity (FVC), forced expiratory volume in the first second of expiration (FEV1), and FEV1/FVC, were compared by using bivariate, regression, and subgroup analyses for children who were highly allergic (≥4 allergens). RESULTS: A total of 291 subjects with asthma were allergic, significantly older, and had higher mean IgE levels and eosinophil counts and percentages (all p < 0.001). A total of 203 subjects who were highly allergic had worse obstruction on PFTs. Increasing age predicted allergen sensitization after confounder adjustment, odds ratio (OR) 1.54 (95% confidence interval [CI], 1.18-2.02). Similarly, PFT obstruction was associated with multiple allergen sensitization (OR 0.97 [95% CI, 0.93-1.02]). CONCLUSION: Increasing age predicted allergic sensitization and multiple allergen sensitization. Worse obstruction on PFT also predicted multiple allergen sensitization. Continued surveillance of aeroallergen sensitization and PFT results may be beneficial in asthma management, particularly in older urban children.

Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine.

The mushroom Amanita muscaria (fly agaric) is widely distributed throughout continental Europe and the UK. Its common name suggests that it had been used to kill flies, until superseded by arsenic. The bioactive compounds occurring in the mushroom remained a mystery for long periods of time, but eventually four hallucinogens were isolated from the fungus: muscarine, muscimol, muscazone and ibotenic acid. The shamans of Eastern Siberia used the mushroom as an inebriant and a hallucinogen. In 1912, Henry Dale suggested that muscarine (or a closely related substance) was the transmitter at the parasympathetic nerve endings, where it would produce lacrimation, salivation, sweating, bronchoconstriction and increased intestinal motility. He and Otto Loewi eventually isolated the transmitter and showed that it was not muscarine but acetylcholine. The receptor is now known variously as cholinergic or muscarinic. From this basic knowledge, drugs such as pilocarpine (cholinergic) and ipratropium (anticholinergic) have been shown to be of value in glaucoma and diseases of the lungs, respectively.

The 100 most influential publications in asthma from 1960 to 2017: A bibliometric analysis.

BACKGROUND: The area of asthma medicine has produced a large volume of important clinical and scientific papers that can be found in those most influential journals. The purpose of our study was to identify the 100 most cited papers in asthma research and to analyze their characteristics. METHODS: We used the Institute for Scientific Information Web of Knowledge Database to identify the most frequently cited articles published from 1960 to December 2017. Original articles and reviews were included in the study. The 100 top-cited articles were then analyzed with regard to number of citations, publication year, journals, institution, research type and field, authors and countries of authors of publications. RESULTS: The 100 top-cited articles in asthma were published between 1960 and 2011 with a median of 933 citations per article (range, 701-2947). The number of citations per article was greatest for articles published in the 1990s. The United States of America contributed most of the classic articles, followed by England. The leading institutions were Imperial College London, McMaster University, Erasmus University Rotterdam. The 100 top-cited articles were published in twenty-five journals, led by The New England Journal of Medicine (21 articles), followed by American Journal of Respiratory and Critical Care Medicine (19 articles), Lancet (11 articles), respectively. Among the 100 classics, 50% articles were clinical research articles. CONCLUSIONS: Our study provides a historical perspective on the progress of research on asthma. Studies conducted in well-developed European countries and North America, published in high-impact journals had the highest citations.