News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2018)

The global health burden and mortality of asthma have plateaued since 2006, despite significant progress in the preceding decades, with one driver being a lack of implementation of novel diagnostic techniques and lack of drug discovery compared with other specialties. Because of this, Pavord et al (Lancet 2018;391:350-400; https://doi.org/10.1016/S0140-6736(1730879-6)) have published a Lancet Clinical Commission outlining current obstacles and next steps moving forward. The Commission argues that clinicians should deconstruct asthma into underlying component traits with biomarker testing, consider lifestyle and environmental factors on an individual basis, and provide patients with annual assessments and risk scores. The authors also propose a no-tolerance attitude toward asthma flares or exacerbations, which should be described using the term “attack” to emphasize that these events are unacceptable and require immediate action. Finally, they call for improved prevention and disease-modifying research, as well as a better understanding of the trajectory of asthma development from infancy to adulthood. The hope of the Commission is that widespread acceptance of this paradigm shift will improve asthma treatment and ultimately patient outcomes. Image used via Wikimedia Commons, created by user Тетяна Фіонік (own work; CC BY-SA 3.0; https://creativecommons.org/licenses/by-sa/3.0).This paradigm shift will improve asthma treatment This paradigm shift will improve asthma treatment We asked first author, Ian Pavord, DM, FRCP, of the University of Oxford, Oxford, United Kingdom, to comment on the study. He writes, “We hope this commission will shake us out of a rut, diverting us away from a diagnostic and therapeutic cul de sac and result in a better classification system for airway diseases that will be valuable in -epidemiologic and interventional studies and make it more likely that we unpick pathophysiology, develop new treatments, and achieve better outcomes for our patients. We hope it will add momentum to the recent encouraging progress in new drug discovery and, as did the first asthma guidelines 28 years ago, lead to a decade or more of improved outcomes.” Mucus plug formation causes significant airway obstruction in patients experiencing acute fatal asthma attacks. Because its role in patients with chronic severe asthma is unclear, Dunican et al (J Clin Invest 2018; https://doi.org/10.1172/JCI95693) used a newly developed scoring system to quantify pulmonary mucus plug burden through multidetector computed tomography in 146 asthmatic patients and 22 control subjects. Mucus plugs were detected in 58% of asthmatic patients and only 4.5% of control subjects (P < .01). Asthmatic patients with higher mucus scores were associated with worse lung function, as assessed based on FEV1, forced vital capacity, and FEV1/forced vital capacity ratio and were more likely to be resistant to treatment with β-adrenergic agonists and systemic corticosteroids. Higher mucus scores were also associated with increased sputum eosinophilia and eosinophil peroxidase (EPO) protein levels. Finally, in vitro mechanistic studies identified that EPO protein promotes mucus plug formation through oxidant generation. Overall, this study demonstrates that EPO promotes mucus plug formation, which likely contributes to airway obstruction and worsened lung function in patients with severe asthma. Collectively, these -results suggest that improved quantitation and treatment of airway mucus plugging might be of therapeutic benefit in patients with severe asthma. Image used via Wikimedia Commons, created by user ChumpusRex (CC-BY-SA-3.0; http://creativecommons.org/licenses/by-sa/3.0/)].Improved quantitation and treatment of airway mucus plugging might be of therapeutic benefit in patients with severe asthma Improved quantitation and treatment of airway mucus plugging might be of therapeutic benefit in patients with severe asthma Increasingly, it is appreciated that commensal microbiota at mucosal barrier surfaces are sensed by the immune system to regulate host immune functions, such as antimicrobial defense, although the underlying molecular mechanisms are not well understood. Linehan et al (Cell 2018;172:784-96, e18; https://doi.org/10.1016/j.cell.2017.12.033) identified that that the skin commensal bacterium Staphylococcus epidermidis induces proinflammatory CD8+ T-cell responses in the skin mediated by presentation of S epidermidis–derived N-formyl methionine peptides to the nonclassical MHC class I molecule H2-M3. Additionally, genome-wide RNA-sequencing analysis revealed that the cellular gene transcription program of these S epidermidis–induced CD8+ T cells was enriched in immunoregulatory and tissue repair genes compared with pathogen-specific T cells. Finally, these commensal-specific T cells improved skin wound repair in vivo. In total, these results demonstrate that commensal microbes promote antimicrobial defense and wound repair by inducing nonclassical adaptive immunity.Commensal microbes promote antimicrobial defense and wound repair by inducing nonclassical adaptive immunity Commensal microbes promote antimicrobial defense and wound repair by inducing nonclassical adaptive immunity Despite the high prevalence of episodes of virus-associated wheeze among pediatric populations, the efficacy of treatment with corticosteroids has been inconsistent, possibly because -previous studies did not ensure exclusion of patients with bronchiolitis. To clarify this, Foster et al (Lancet Respir Med 2018;6:97-106; https://doi.org/10.1016/S2213-2600(1830008-0)) performed a noninferiority, randomized, double-blind, placebo-controlled trial to compare the efficacy of oral prednisolone in children aged 2 to 6 years who presented to emergency departments with virus-associated wheeze. Six hundred five patients were randomized in a 1:1 fashion to receive 1 mg/kg/d oral prednisolone or placebo for 3 days. Treatment with prednisolone resulted in a lower median length of stay (370 vs 540 minutes, P = .0227), with the most dramatic effect occurring in patients with either severe wheeze or a prior history of asthma. Notably, this finding was independent of the virus that triggered the episode of wheeze. Overall, the authors conclude that oral prednisolone decreases length of stay in children presenting with virus-associated wheeze and propose its use early in the management of virus-associated wheeze in pediatric populations on presentation to the emergency department. Image used via Wikimedia Commons, created by user Bryan Derksen (own work using BKchem [public domain]). Oral prednisolone decreases length of stay in children presenting with virus-associated wheezeNews items were written by medical writer Jared Travers, PhD.Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com. Oral prednisolone decreases length of stay in children presenting with virus-associated wheeze News items were written by medical writer Jared Travers, PhD. Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com.