After asthma: redefining airways diseases

Abstract

long-term treatment instituted, without any objective diagnostic measurements ever being made. Is there any other chronic disease for which objective diagnostic tests are readily available of which this can be said? Although the Commissioners differed in their views on the strength of evidence for diagnosis and management guided by biomarkers, particularly in children, there was a consensus that the incorporation of biomarkers into the diagnosis could only enhance the capacity to diagnose asthma responsive to ICS and lead to a paradigm shift from the current approach to diagnose the umbrella term asthma, to the diagnosis of asthma phenotypes that respond to specific treatments. New drug development Until recently we have not seen the developments in new drug discovery enjoyed by other specialty areas (table 2) 19. This area perhaps exposes the limitations of our current view of 'asthma' and airway disease most obviously. New asthma treatments are largely variants on the old; a browner inhaler, with more potent topical effects, despite increasing concerns about topical immunosuppression 103. When new treatments become available, they are widely prescribed to all comers despite being largely ineffective (Sodium Cromoglycate, Ketotifen) or effective only in subgroups of patients (Omalizumab, Mepolizumab). There has been, until recently, no concept of targeted treatment. Progress in new drug discovery has been slow, with relatively few molecules progressing from the laboratory to the clinic and a depressingly high rate of failure at the later stages of clinical development (table 2) 19. Mepolizumab, a humanised monoclonal antibody that was developed to inhibit eosinophilic airway inflammation by blocking interleukin (IL)-5, is a good example. Mepolizumab was found to be safe and effective at blocking IL-5 and reducing eosinophilic airway inflammation when tested with in vitro systems and in vivo models 104,105. A subsequent clinical trial was designed based around incorporating Mepolizumab into a step-up guideline-based paradigm 106. Within this paradigm, Mepolizumab was investigated in patients who remained symptomatic on current ICS therapy and the clinical trial focused on lung function and asthma symptoms as traditional outcome measures. Despite adequate power, this trial was unexpectedly negative. This led to much soul-searching and the near-abandonment of the drug 107. Investigators who were experienced with non-invasive measures of airway inflammation identified two important problems with this initial clinical trial: first, the heterogeneity of airway inflammation in severe asthma meant that a significant number of the trial participants would not have had eosinophilic airway inflammation and therefore would not be expected to respond; and second, the

Identifying Critical Errors: Addressing Inhaler Technique in the Context of Asthma Management

“…After decades of research, practice, and perceived knowledge, we find ourselves at crossroads in our understanding and management of airway diseases, such as asthma [1]. While asthma is an obstructive airways disease, which Pulm Ther (2018) 4:1-12 https://doi.org/10.1007/s41030-018-0051-0 to our current knowledge can neither be prevented nor cured, it is a disease that fluctuates in severity and 'control', is exacerbated by varying triggers, and its course over an individual's lifetime is essentially unpredictable [1].…”

“…While asthma is an obstructive airways disease, which Pulm Ther (2018) 4:1-12 https://doi.org/10.1007/s41030-018-0051-0 to our current knowledge can neither be prevented nor cured, it is a disease that fluctuates in severity and 'control', is exacerbated by varying triggers, and its course over an individual's lifetime is essentially unpredictable [1]. While the conversation about asthma and airways disease more broadly is not the focus of this review, it becomes particularly relevant in our consideration of the use of medications.…”

“…Given that asthma management is reliant on the use of medications [3], ensuring that patients use their medications correctly has become more than just a practical matter; it is a complex and critical issue. Correct medication use has become a fundamental step in our exploration and understanding of disease traits [1,2]: with careful and more precise evaluation of patient's response to treatment becoming integral to our understanding of disease endotypes and our evolution towards precision medicine [1,2]. For this reason, if for no other, it is now more important than ever that we address inhaler use, especially our knowledge of critical errors, which can 'cloud' our understanding of treatment success.…”

Recurrent lower respiratory tract infections in children

“…An isolated cough is not usually a manifestation of underlying asthma 20. The National Institute for Health and Care Excellence (NICE) guidelines on asthma21 stress the importance of objective measurements such as spirometry and measurement of exhaled nitric oxide to diagnose asthma, reiterated in the recent Lancet commission on airway diseases 22. Unfortunately, neglect of objective measurements leads to asthma being overdiagnosed 232425…”

‘We can’t diagnose asthma until <insert arbitrary age>’

“…However, reading the National Report on Asthma Deaths (NRAD)2 among other documents makes it very clear that progress has stalled. In response to this perception, a Lancet commission has recently been published 3. This annotation reviews some of the implications of that document for paediatrics.…”