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Respiratory Disease Diagnosis and Testing Beyond COVID-19 Over the last year, the COVID-19 pandemic has placed healthcare for respiratory medicine firmly in the global spotlight. But even before this, over half a billion people worldwide1 were living with chronic respiratory illnesses such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). With an ever-increasing burden on healthcare systems, how can we advance the diagnosis and treatment of these conditions? In particular, how could non-invasive breath tests change our approach to respiratory care? Challenges in Respiratory Medicine The coronavirus pandemic has been the most significant global health crisis of modern times, affecting not just healthcare but every aspect of daily life. At time of writing, the SARS-CoV-2 virus has infected close to 150M people and been linked to over 3M deaths2. The pandemic has led to a dramatic increase in demand for respiratory care, with many severe cases requiring mechanical ventilation. For example, at the peak in the UK during January 2021, over 4000 COVID-19 patients had immediate access to mechanical ventilation3. What’s more, the emergence of socalled ‘long’ or ‘long-haul’ COVID, where symptoms persist beyond initial infection, is predicted to result in a marked increase in the demand for ongoing respiratory care.

Innovative solutions are needed to support chronic respiratory care as much as to detect acute infections. The critical challenge for diagnosing and treating chronic respiratory illnesses is that each condition is biologically complex and requires treatments to be suited to patient phenotypes. While the symptoms may be similar, the underlying mechanisms differ, and this has an impact on appropriate treatment and disease management. Current treatments are often found through trial and error, starting with affordable treatments that are most likely to succeed. This approach can take a long time to find an effective treatment and, during that time, a patient’s symptoms are poorly controlled5,6. When a treatment is found that the patient responds to, there’s also no certainty that it is the optimal solution for that patient.

Figure 2: Illustrating chronic inflammation phenotypes in respiratory diseases Chronic inflammatory airway diseases are often complex with a range of diverse phenotypes and overlapping symptoms. Underlying inflammation mechanisms can be a key distinguishing factor which can impact treatment, and being able to differentiate these subtypes could enable patient stratification and precision medicine. Finding biomarkers for these phenotypes could accelerate diagnosis and reduce the costs of treatment.

Figure 1: The impact of chronic respiratory diseases and COVID-19 A summary of key statistics around the number of cases and deaths associated with chronic respiratory diseases and COVID-19 infections as of May 2021. The number of deaths resulting from the pandemic is approximately equivalent to the annual number of deaths linked to COPD.1,2,4

While there is no denying the scale and impact of the pandemic, respiratory medicine faces many other challenges that existed before COVID-19 and will persist into the ‘new normal’. Current total COVID-19 statistics are comparable to annual numbers for common chronic inflammatory airway diseases. Most notably, statistics from the World Health Organisation estimate an annual 250M cases of COPD alone, leading to over 3M deaths per year4. In the last year, numerous efforts have been made to develop accessible diagnostic tests for COVID-19 and, thanks to unprecedented efforts, vaccines are now becoming widely available. Yet, diagnostics for asthma and COPD patients remain complex, unpleasant, and often unsuitable. 10 Journal for Clinical Studies

A key differentiator between chronic inflammatory airway disease phenotypes is the type of immune response responsible for causing inflammation7. These can include eosinophils, neutrophils, a combination of both, or sometimes neither. Treatments based on inhaled corticosteroids (ICS) are most often effective against eosinophilic cases, while the neutrophilic cases benefit more often from macrolide treatments. Another outstanding challenge for this area is predicting the onset, pattern, and recurrence of exacerbations, which present a significant and largely unpredictable risk for patients. Current Approaches for Respiratory Diagnostics There is currently no gold standard for diagnosing chronic inflammatory airway diseases. Traditional diagnostic approaches focus on the detection of symptoms such as wheezing, coughing and breathlessness, or on assessing lung function. Symptoms can Volume 13 Issue 4

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