The importance and impact of real-world studies in breathomics

Currently, the SpiroNose, a cloud-connected electronic nose (eNose), is included in more than 30 clinical studies investigating the accuracy of exhaled breath analysis for e.g. (early) diagnosis and phenotyping of diseases ranging from respiratory diseases, different types of cancer to neurological and sleep disorders.

What most of these studies have in common is that eNose measurements are merely added to standard diagnostic procedures during day to day visits of the patients to the e.g. clinic, hospital, or diagnostic centers. This is a great advantage and means that there are no extra preparations, nor changes to routine and standard clinical care of the study participants. The first and foremost aim of this approach is to ensure the patient’s comfort and the health care provider’s convenience. Additionally, there are no restrictions for participants regarding eating, drinking, smoking or medication usage prior to the breath test. Instead, by collecting this information from each participant, the influence of different factors on breath profiles is rigorously and continuously assessed which in return will increase the applicability of the findings. This is in contrast with approaches, in which strict restrictions are implied on patients and their behaviors in order to create an ideal and controlled world that is in fact far from real-world conditions. As a result, findings from such studies cannot be readily and directly translated into routine clinical practice as the study population does not represent the general patient population [i] [ii].

”The first and foremost aim of this approach is to ensure the patient’s comfort and the health care provider’s convenience”

 

Additionally, in most studies, especially in clinical trials, young children, elderly and those with comorbidities are often excluded. Thus, diagnostic models are developed based on information from patients with more similar characteristics, and with less severe disease and thereby, cannot be directly applied to the real-world patient populations. The non-invasiveness of exhaled breath analysis, as well as fast and easy-to-perform measurement maneuver of the SpiroNose, make it particularly suitable for these vulnerable populations. For this reason, real-world studies of SpiroNose consist of patients of all ages, with and without comorbidities to ensure clinical applicability of the exhaled breath analysis to everyone.

Another critical point is that, in daily clinical practice, one of the most difficult tasks is to distinguish between diseases that often demonstrate similar symptoms but require different treatment approaches. The correct diagnosis of most diseases becomes apparent after performing specific tests and laboratory procedures, that are not commonly and easily available at the General Practitioners’ (GPs) office, where most patients are managed. This leads to treatment strategies based on a trial and error approach, which subsequently results in suboptimal disease control. To ensure clinical value and relevance of exhaled breath analysis in real-world, clinical studies of SpiroNose investigate and compare breath profiles of patients that present with similar symptoms but require a different clinical diagnosis.

For example, asthma or Chronic Obstructive Pulmonary Disease (COPD) are two chronic airway diseases that often present with shortness of breath and cough. Exhaled breath analysis of combined samples of asthma and COPD patients using the SpiroNose has not only showed its high accuracy in distinguishing the two diseases [iii] but has also led to identifying subgroups of patients that are more likely to benefit from tailored treatment approaches [iv]. This is in line with the current concept of “treatable traits” that focuses on specific subtypes (“phenotypes”) of disease and their underlying molecular and cellular mechanism rather than using traditional diagnostic labels such as asthma or COPD. Notably, the same holds for subphenotyping lung cancer patients in relation to their responsiveness to novel immunotherapy. In patients with non-small cell lung cancer (NSCLC), eNose has shown to accurately distinguish between responders and non-responders to anti-PD-1 (pembrolizumab and nivolumab). The results indicated that in 24% of the patients, ineffective therapy could potentially be stopped, without withholding anyone effective treatment [v].

Improving healthcare by understanding patients’ preferences

The importance of these “real-world studies” where study conditions are representative of everyday clinical practice is becoming more evident day by day. One of the most important and only recently acknowledged factors in clinical research is considering patients’ needs and preferences when conducting clinical studies. Real-world studies provide the opportunity to assess several health outcomes (e.g. disease symptoms, quality of life, etc.) simultaneously including those that are highly important to patients. By taking real-world conditions as well as patient and health care providers’ needs into account, we are steadily moving towards clinical implementation of exhaled breath analysis by eNose while maximizing its benefits and applicability for a wide range of diseases affecting both old and young.

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[i] Cohen AT, Goto S, Schreiber K, et al. Why do we need observational studies of everyday patients in the real-life setting? European Heart Journal Supplements. 2015.

[ii] Price D, Brusselle G, Roche N. Real-world research and its importance in respiratory medicine. Breathe 2015.

[iii] R de Vries, P Brinkman, M P van der Schee, N Fens, E Dijkers, S K Bootsma, F H C de Jongh and P J Sterk. Integration of electronic nose technology with spirometry: validation of a new approach for exhaled breath analysis. J Breath Res. 2015.

[iv] R de Vries, Peter J Sterk et al. Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label. ERJ. 2018.

[v] R de Vries , Muller M, Prediction of response to anti-PD-1 therapy in patients with non-small-cell lung cancer by electronic nose analysis of exhaled breath. Annals of Oncology. 2019.