Point-of-care precision medicine in patients with asthma

Asthma is a common chronic disease of the airways that affects people of all ages. The ‘chronic’ nature of the disease requires long-term and sometimes life-long treatments to help patients maintain an optimal quality of life. Unfortunately, there is still no cure for asthma, but there are effective medications that manage and control asthma by reducing daily symptoms and preventing asthma attacks. Despite being highly effective, not all patients respond the same to these medications and some might not benefit from the treatment at all.

Scientific efforts have made it evident that asthma has several subtypes with distinct underlying molecular mechanisms and disease processes which can demonstrate similar symptoms but require different treatment approaches. For example, patients with eosinophilic airway inflammation are responsive to inhaled or oral corticosteroids, whereas those with neutrophilic inflammation do not benefit from this medication. These findings have made asthma perfectly suitable for precision medicine since identifying subgroups of patients with similar clinical and biological features (‘phenotypes’) can enable tailored therapy to improve patients’ wellbeing. In fact, accumulated clinical evidence together with recent recommendations of clinical guidelines for treating each phenotype differently has started to facilitate precision medicine in health care especially in secondary and tertiary care centers [i].

Phenotyping in patients with asthma can be accomplished by blood or sputum analysis [ii]. However, these assessments do not provide results during actual patient consultations because they require laboratory procedures. As a result, most patients at the primary care are managed based on a trial-&-error approach. This often delays optimal disease control and increases risk of asthma attacks which can lead to emergency room visits or hospitalizations.

Exhaled breath analysis in patients with asthma

Hence efforts are ongoing to bring biological assessment to the point of care. If properly validated, molecular profiling of exhaled air may provide a noninvasive and rapid alternative for blood and sputum [iii]. Volatile Organic Compounds (VOCs) in the exhaled breath generate a characteristic “breath print” that is unique for each person. The complete VOC mixture reflects the current metabolic condition of the patient which can be captured by eNose technology [iv] [v]. Exhaled breath analysis in patients with asthma has shown that the technology not only can diagnose the disease [vi], but it can also identify its different phenotypes. In a study by de Vries et al, the eNose was able to identify 5 different clusters of patients with chronic airway diseases (e.g. asthma and COPD combined) that significantly differed in their clinical, demographic, and inflammatory features [vii]. For example, one of the clusters mainly included women with high Body Mass Index (BMI), severe symptoms but without airway inflammation. These “obese non-eosinophilic” patients are often overtreated with corticosteroids that are not helpful and may even cause metabolic changes and disorders [viii].

These findings suggest that a point-of-care eNose providing immediate feedback at the point-of-care, could help the GP to opt for the most suitable treatment for each patient at that moment. In fact, the results of this study have paved the way for a large multi-center, real-world clinical implementation study where the cloud-connected eNose, SpiroNose, will be used at primary care for clinical and inflammatory phenotyping of patients with asthma and COPD. This large project aims to take the final steps towards clinical implementation of the SpiroNose in combination with the online analysis platform, BreathBase, for diagnosis and phenotyping of asthma and COPD with the ultimate goal of improving health outcomes and general wellbeing of these individuals together with reducing health care costs. Thus, bringing precision medicine to the point-of-care.

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[i] Global Initiative for Asthma. Global strategy for asthma management and prevention 2020

[ii] Gonem S, Raj V, Wardlaw AJ, et al. Phenotyping airways disease: an A to E approach. Clin Exp Allergy 2012; 42: 1664–1683

[iii] Bos LD, Sterk PJ, Fowler SJ. Breathomics in the setting of asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol 2016; 138: 970–976

[v] Boots AW, Bos LD, van der Schee MP, et al. Exhaled molecular fingerprinting in diagnosis and monitoring: validating volatile promises. Trends Mol Med 2015; 21: 633–644

[vi] Montuschi P, Santonico M, Mondino C, et al. Diagnostic Performance of an Electronic Nose, Fractional Exhaled Nitric Oxide, and Lung Function Testing in Asthma. Chest 2010; 137(4): 790-796

[vii] de Vries R, Dagelet Y, Brinkman P, et al. Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label. European Respiratory Journal 2018; 51(1).

[viii] Suissa S, Kezouh A, Ernst P. et al, Inhaled Corticosteroids and the Risks of Diabetes Onset and Progression. The American Journal of Medicine 2010; 123(11): 1001-6