Breath Analysis in Patients With Suspected Sarcoidosis: The VOCs-IS Study

Sarcoidosis is chronic condition which can affect any organ within the body, however frequently involves the lungs and thoracic lymph nodes. The exact cause of the disease remains uncertain and it is thought that the immune system overreacts to a possible inhaled antigen in the environment. A role has been suggested for triggers such as certain types of infection.

The clinical course and prognosis of sarcoidosis is extremely variable. Some patients make a full recovery without the need for any specific treatment, however up to a third of patients may develop a more severe form of the disease which can lead to scarring and fibrosis of the lungs. As such, the treatment of sarcoidosis focuses on suppressing the immune system, however the evidence to support this remains weak. Furthermore, such treatment may place the patient at risk of long-term side effects.

At the present time, there is a lack of useful markers which not only help diagnose the condition, but also help to predict and identify those patients at risk of developing more severe disease or who may require treatment.

The purpose of this study is to use a technique which analyses breath samples to provide a profile of chemicals which are present in the exhaled breath of patients with sarcoidosis. It is important to know if this profile differs from healthy people, relates to infections or changes over time, particularly in response to treatment. As such, hopefully this technique will provide an alternative way of monitoring the disease or predicting progression.

This is an observational case-control study of patients with suspected sarcoidosis receiving standard care at two NHS hospitals over the course of 12 months. At baseline, if patients are undergoing a bronchoscopy or endobronchial ultrasound and lymph node biopsy as part of their routine clinical care an additional sample of bronchoalveolar lavage fluid will be collected and used for metagenomic sequencing to identify the presence of any infections such as bacterial, viruses or fungi. In addition, patients will also be invited to provide additional voluntary consent for an extra biopsy to be taken which would also be used for metagenomic sequencing. Alongside this a sample of breath would be collected using the ReCIVA device (Owlstone Medical, Cambridge, UK), as well as blood sampling and storage for biomarker analysis. Patients would also be asked to complete three questionnaires including the medical research council dyspnoea score (MRC) and King's Sarcoidosis Health Related Quality of Life Questionnaire (KSQ) relating to their employment, level of breathlessness, symptoms and quality of life. Additional voluntary consent would also be sought for an extra blood test to be taken at baseline and stored for future genetic analysis.

During the course of study, three further follow-up visits would then take place at 3, 6 and 12 months. During each visit a sputum sample would be collected (if the patient was able to expectorate spontaneously) as well as repeated blood and breath sampling and completion of the medical research council dyspnoea score and King's Sarcoidosis Questionnaire. Pulmonary function tests would be performed as part of routine clinical care. At the end of the study, a repeat high resolution computerised tomography (CT) scan of the chest would take place to look for any new changes related to sarcoidosis and assess the activity of the disease.

The study will aim to recruit a total of 80 patients presenting with suspected sarcoidosis across both sites. In a subset of 10 participants, repeated breath sampling will take place two weeks from baseline to assess for reproducibility.

Alongside patients with suspected sarcoidosis, 40 healthy volunteers (including partners or spouses) will be recruited for breath sampling at baseline.

The study is being undertaken as part of a PhD programme and is funded by a grant from British Lung Foundation. Ethical approval has been granted from the North West - Greater Manchester Central Research Ethics Committee (IRAS Number 241100).

Participants with Suspected Sarcoidosis:

Inclusion criteria

• Age >18 years
• Suspected pulmonary sarcoidosis undergoing investigations for diagnosis, staging and treatment consideration or discussion at a designated interstitial lung disease multidisciplinary meeting (this includes participants with stage I disease characterised by the presence of hilar or mediastinal lymphadenopathy)

Exclusion criteria

• Significant respiratory co-morbidity where the primary major respiratory diagnosis is not sarcoidosis
• Current smoker or ex-smoker (having ceased smoking <3 months duration)
• Extra-pulmonary sarcoidosis without any evidence of pulmonary involvement (characterised by normal pulmonary function tests and no radiological evidence of thoracic sarcoidosis on HRCT or chest radiography)
• Inability to provide written consent
• Self-reported lower respiratory tract infection, or treatment with antibiotics for a lower respiratory tract infection or any other infection within the previous 4 weeks

Healthy Volunteers:

Inclusion criteria

• Age >18 - 70 years
• Normal spirometry

Exclusion criteria

• Current smoker or ex-smoker (having ceased smoking <3 months duration)
• History of uncontrolled diabetes, respiratory, inflammatory gastroenterological, autoimmune or renal disease (characterised by an eGFR <30ml/min/1.73m2)
• Self-reported lower respiratory tract infection, or treatment with antibiotics for a lower respiratory tract infection or any other infection within the previous 4 weeks
• Inability to provide written consent