Pulmonary Arterial Hypertension

PAH is often diagnosed late. Early detection is critical to improve clinical outcomes.

Pulmonary Arterial Hypertension Diagram

Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease characterized by extensive occlusion of small to mid-sized pulmonary arterioles. The gradual increase in arterial pressure leads to the development of high resistance, leading eventually to right-sided heart failure and death. PAH is considered to be a heterogeneous group of conditions including forms of the disease with unknown causes, known as idiopathic PAH (IPAH).

PAH is often diagnosed in its advanced stages, reducing the effectiveness of available treatments. The complex pathological mechanisms involved in PAH could be a source of VOCs in breath or urine, present at earlier stages of the disease (Figure 1). The excessive cell proliferation associated with local hypoxia promotes glycolysis as an energy source, which results in production of ketones and alcohols.

Additionally, increased cholesterol metabolism causes higher levels of isoprene, and reactive oxygen species (ROS) from inflammatory oxidize proteins and fatty acids, releasing various hydrocarbons. These VOC biomarkers offer a potential route to earlier diagnosis, which could improve survival rates and clinical outcomes.

PAH Case Study - Hypothetical schema of possible VOC sources in PAH
Figure 1. Hypothetical schema of possible VOC sources in PAH. Adapted from Nakhleh et al. 2017 [1]

Breath Biopsy® has been developed to provide robust, reliable and detection and validation of non-invasive VOC biomarkers on breath. The Breath Biopsy Collection Station enables reproducible sample collection that is easy to store and transport. We also provide offline sample analysis using GC-Oribtrap mass spectrometry through Breath Biopsy Services. You can choose between focused or global biomarker discovery pipelines and select from a range of reporting and interpretation options to support your needs.

Our expert team is on hand to help you get started planning your next PAH study:

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Read on to see how our FAIMS technology and expertise has already been deployed in this area.

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Detecting IPAH with the Lonestar VOC Analyzer

Owlstone Medical performed a pilot study to assess the ability of the Lonestar VOC Analyzer to distinguish between IPAH patient and control urine samples. The ATLAS headspace sampler was used to analyze urine samples (10 IPAH and 10 Controls) in a randomized sequence.

Multiple features were found to be present in FAIMS spectra for IPAH and control subjects’ urine. The 3 dimensional raw data acquired from the Lonestar was transformed and multivariate data analysis was performed using SIMCA (Sartorius Stedim, Sweden).

A supervised approach Partial Least Squares - Discriminant Analysis (PLS-DA) showed a clear separation between the two groups of urine samples, indicating differences in the raw data which are detectable by the Lonestar (Figure 2)

Figure 3 shows an example box plot for one of the discriminant features, demonstrating the difference across the two groups.

Control vs IPAH Patients

PAH vs Control Graph 1
Figure 2. Partial Least Squares - Discriminant Analysis (PLS-DA) of control vs IPAH patients.

PAH vs Control Graph 2
Figure 3. Example box plot for one of the discriminant features.

References

[1] Nakhleh et al., Volatolomics of breath as an emerging frontier in pulmonary arterial hypertension, Eur. Resp. J., 49: 1601897, (2017). http://dx.doi.org/10.1183/13993003.01897-2016

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