Addressing unmet needs in understanding asthma mechanisms: From the European Asthma Research and Innovation Partnership (EARIP) Work Package (WP)2 collaborators.

Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European productivity. There is a wide spectrum of disease severity and control. Therapeutic advances have been slow despite greater understanding of basic mechanisms and the lack of satisfactory preventative and disease modifying management for asthma constitutes a significant unmet clinical need. Preventing, treating and ultimately curing asthma requires co-ordinated research and innovation across Europe. The European Asthma Research and Innovation Partnership (EARIP) is an FP7-funded programme which has taken a co-ordinated and integrated approach to analysing the future of asthma research and development. This report aims to identify the mechanistic areas in which investment is required to bring about significant improvements in asthma outcomes.

Eosinophilic esophagitis: asthma of the esophagus?

The question whether eosinophilic esophagitis (EoE) might be an 'asthma of the esophagus' is reasonable. There are a number of similarities between the two diseases: EoE and asthma, as well as other atopic diseases, are frequently associated and have a number of similarities in their pathogenesis. Thus, investigating differences and similarities between the diseases might be a worthwhile endeavor. Both EoE and asthma are chronic immune-mediated conditions characterized by inflammatory changes in the mucosa and submucosa with a characteristic and diagnostic infiltration of eosinophils. They result in organ dysfunction with considerable morbidity and (in the case of asthma) even mortality. Asthma and EoE affect all ages, but frequently start in childhood or adolescence. While asthma has seen a large increase in its prevalence in the past 50 years, EoE was first described in the 1970s. Since then the frequency of the diagnosis of EoE has increased significantly. The prevalence for both diseases seems to be highest in the Western world. In contrast to asthma, where females are more often affected, EoE is more frequent in males. Asthma in children, however, is also more common in boys, but this changes after puberty. EoE is frequently associated with asthma, and up to 80% of patients with EoE are atopic, similar to childhood asthma. Adult-onset asthma is not necessarily associated with atopy (termed intrinsic asthma) and similar observations have been made for EoE. Endoscopically, asthmatic airway mucosa as well as esophageal mucosa in EoE can appear normal, and biopsies are required for diagnosis. Long-standing disease in asthma has been associated with 'remodeling' compared to predominantly reversible inflammatory changes early in the course of the disease. Similar observations have been made in EoE. Toxic proteins derived from eosinophils such as major basic protein, eosinophil-derived neurotoxin and eosinophil cationic protein can be found in the mucosa of both diseases, which are also characterized by a thickening of the lamina propria or basement membrane, respectively. Despite these histologic and immunochemistry findings, asthma as well as EoE remain clinical diagnoses, and diagnosing either condition can be challenging. Therapeutically, both diseases respond well to corticosteroids. Ironically, corticosteroids for inhalation are deliberately swallowed in EoE to reach the esophageal mucosa. Allergen/food avoidance can improve symptoms in asthma and EoE. Taken together, allergic asthma and EoE have a number of common features which make a common pathogenesis manifested in different organs for reasons not yet fully understood likely. Combining allergological research with gastroenterologic and pneumologic expertise with a focus on similarities between these diseases might be a way forward.

COVID-19 mortality rates in the European Union, Switzerland, and the UK: effect of timeliness, lockdown rigidity, and population density.

BACKGROUND: To date, the European experience with COVID-19 mortality has been different to that observed in China and Asia. We aimed to forecast mortality trends in the 27 countries of the European Union (EU), plus Switzerland and the UK, where lockdown dates and confinement interventions have been heterogeneous, and to explore its determinants. METHODS: We have adapted our predictive model of COVID-19-related mortality, which rested on the observed mortality within the first weeks of the outbreak and the date of the respective lockdown in each country. It was applied in a training set of three countries (Italy, Germany and Spain), and then applied to the EU plus the UK and Switzerland. In addition, we explored the effects of timeliness and rigidity of the lockdown (on a five-step scale) and population density in our forecasts. We report r2, and percent variation of expected versus observed deaths, all following TRIPOD guidance. RESULTS: We identified a homogeneous distribution of deaths, and found a median of 24 days after lockdown adoption to reach the maximum daily deaths. Strikingly, cumulative deaths up to April 25th, 2020 observed in Europe separated countries in three waves, according to the time lockdown measures were adopted following the onset of the outbreak: after a week, within a week, or even prior to the outbreak (r2=0.876). In contrast, no correlation neither with lockdown rigidity nor population density were observed. CONCLUSIONS: The European experience confirms that early, effective interventions of lockdown are fundamental to minimizing the COVID-19 death toll.