{'fraction_non_alphanumeric': 0.019149751053236307, 'fraction_numerical': 0.0007659900421294523, 'mean_word_length': 5.5863808322824715, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 1, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Severe asthma: We can fix it? We can try!

For decades, a small proportion of individuals with asthma, the 3–10% with severe disease, have suffered the consequences of treatment refractoriness, toxicity from add-on therapies and misdiagnosis. This has resulted in severe quality of life impairment, unacceptable asthma mortality and major economic costs to patients and their families, the health care system and society. Clinicians and patients have been left unarmed in the battle to achieve the therapeutic goals of management. However, with an era of precisionbased medicine, now comes renewed hope for severe asthma management, for patients and clinicians alike. This review series ‘Seeking Innovative Solutions in Severe Asthma’ is therefore timely. There is a need to prioritize severe asthma research and we hope that this review series has promoted ideas and challenged thinking. For the series, we set the goal of highlighting important and contemporary issues such as the complexity of severe asthma disease mechanisms, considerations for management and gaps for knowledge transfer and implementation. Global leaders were invited to contribute to the series. We take the opportunity to thank all of the authors and acknowledge their outstanding contributions, which have made this series a valuable resource to guide and inform the clinical and research community. What were the common themes that emerged during this review series? It is clear that in both paediatric and adult populations, assessment and diagnosis of severe asthma are difficult. Effective management requires systematic, multidimensional, multidisciplinary and targeted approaches. There have been many notable advances in targeted therapies, supported by an improved understanding of disease mechanisms in clinical population and animal models. However, knowledge gaps remain in relation to disease pathophysiology, approaches to assess inflammatory phenotypes, mechanisms and what components are required for multidisciplinary assessment (MDA). Furthermore, implementation gaps exist on how to integrate new knowledge into the clinic and how to address disease complexity. The first manuscript of the review series reported the proceedings of roundtable discussions that were hosted by the Centre of Excellence in Severe Asthma and focused on two key areas: models of care for severe asthma and targeted therapies. The discussions of multidisciplinary experts from around Australia noted the variability in severe asthma definitions used and in approaches to clinical practice. McDonald et al. highlighted proposed recommendations to improve the quality and consistency of care and areas for future research. The need to identify and address access barriers to new targeted therapies and to develop better ways of determining treatment response were acknowledged as priority areas. The Centre of Excellence in Severe Asthma is progressing this area and has developed and made available clinical recommendations for the use of biological agents in practice, which is available at http://www.severeasthma.org.au/toolsresources/toolkits/. Improving asthma treatment and reducing disease burden requires an understanding of disease pathophysiology. King et al. discuss the structural, mechanical and inflammatory abnormalities relevant to severe asthma. King et al. eloquently describe how our understanding of the pathogenesis of severe asthma has been limited by the heterogeneity and complexity of disease processes and the difficulty performing studies in relevant clinical populations. Biomarkers are key to phenotyping patients and selecting those most likely to respond to individualized therapies. Fricker et al. painted an insightful view of the use of biomarkers, as an approach to assess and characterize underlying disease mechanisms. Novel ways to use existing biomarkers to objectively assess adherence to corticosteroids and to identify patients likely to respond to targeted therapies were described. They also recognized that limited biomarkers are available for other disease subsets, such as non-type-2 inflammation, and that future research needs to be focused here. As more biomarkers are reported, consensus is required on which to measure and how to use test results to inform clinical decision-making. Dynamic model systems are essential tools to characterize disease mechanisms and for preclinical studies of novel therapeutics. Maltby et al. provide an update on mouse models relevant to severe asthma. New approaches are providing insight into mechanisms underlying steroid resistance, tissue remodelling and disease exacerbations. Translation of findings from these models will require further careful characterization in clinical population. Bush et al. provide insight into severe asthma in children, highlighting the differences between paediatric and adult diseases. They discuss the difficulty in differentiating between ‘difficult asthma’, ‘asthma plus comorbidities’ and ‘severe treatment-refractory asthma’. Similar to the approaches proposed in the management of adult severe asthma, management in the paediatric population requires approaches that recognize and address multiple factors that affect asthma