For patients with sarcoidosis:

Inclusion Criteria:

• - Suspected pulmonary sarcoidosis (as determined by referring physician) - Requires bronchoscopy, EBUS and BAL (as determined by ILD team at Royal Papworth or Addenbrooke's Hospitals).

• - Male or female ≥ 30 years with a BMI of 17-35kg/m2.

• - Consents to additional bronchoscopic evaluation during NHS mandated bronchoscopy, EBUS and BAL.

Exclusion Criteria:

• - Inability to provide Informed Consent.

• - A cardiovascular event in the last 6 months (i.e. acute coronary syndrome, unstable angina, CABG, PCI, stroke, MI, carotid endarterectomy).

• - Patients with known clinically significant pulmonary diagnoses of COPD, lung fibrosis, interstitial lung disease, or α1-antitrypsin deficiency.

• - Active smoking during the last 5 years.

• - Patients with known chronic infections such as HIV or known active tuberculosis.

• - Patients with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease).

• - Known diabetes mellitus or known impaired glucose tolerance.

• - Participation in a previous research trial in the last three years which involved exposure to significant ionising radiation (i.e. cumulative research radiation dose >10 mSv) - Pregnancy.

• - Women of childbearing potential [i.e. either postmenopausal or documented hysterectomy and/or bilateral oophorectomy - tubal ligation is not sufficient].

• - Use of systemic steroids (oral or intravenous) at a dose > 10mg od of prednisolone or equivalent and/or antibiotics 4 weeks prior to PET/CT scan.

• - Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the subject ineligible for inclusion because of a safety concern.

For healthy volunteers:

Inclusion criteria:

• - Age/gender-matched group (Part A only): Male or female ≥ 30 years with a BMI of 17-35kg/m2 inclusive.

• - LPS/saline challenge group (Part B only): Male or female ≥ 50 years with a BMI of 17-35kg/m2 inclusive.

• - No smoking history.

• - Normal predicted spirometry values: FEV1/FVC > 0.7 and FEV1 > 80% predicted.

• - Healthy as determined by clinical history & examination by the investigator.

Exclusion criteria:

• - Inability to provide informed consent.

• - Pregnancy.

• - Patients with known chronic inflammation conditions such as rheumatoid arthritis, connective tissue disorders and inflammatory bowel disease.

• - A significant cardiovascular event in the last 6 months.

• - Insulin dependent diabetes mellitus or known impaired glucose tolerance.

• - Participation in previous research trial in the last three years which involves exposure to significant ionising radiation (cumulative dose >10mSv) - Use of systemic steroids (oral or intravenous) at a dose > 10mg od of prednisolone or equivalent and/or antibiotics 4 weeks prior to PET/CT scan.

• - Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the subject ineligible for inclusion because of a safety concern.

• - Women of childbearing potential.

• - Patients with known chronic infections such as HIV or known active tuberculosis.

• - Active smoking history (defined as > than 1 cigarette per day on a regular basis) over lifetime.

- Known lung and/or respiratory disease or associated symptoms (e.g. dyspnoea, wheeze)

Inflammation plays an important role in a myriad of human diseases. Interstitial Lung Diseases (ILDs) are characterised by widespread inflammation and represent a major burden to the health sector. Imaging offers a method of assessing lung inflammation which is non-invasive and may help facilitate the development of new therapeutic drugs. Positron Emission Tomography (PET) is a sensitive imaging modality that uses radioactive material to highlight areas of disease. 18F-FDG is the most common radioactive tracer; it accumulates in cells with an increased metabolic rate. Previous studies have shown that inflammatory cells have an increased metabolic rate, thus PET imaging could highlight inflammation. 18F-FDG PET has been used in many studies exploring lung diseases; the concentration of tracer is thought to relate to the severity of inflammation. There is currently no standardised method to analyse FDG-PET scans to assess the concentration of tracer in the lung (and therefore inflammation). A major challenge is providing corrections to ensure that the image only represents tracer in the lung tissue. Such corrections are non-trivial and affect how images are interpreted. A robust validation is needed to ensure that the analysis methods used in FDG-PET images truly represent the degree of lung inflammation. Part A of this study aims to validate and compare the different analysis methods. Pulmonary sarcoidosis is a disease characterised by widespread lung inflammation. In Part A of the study the investigators will recruit patients with this condition, as well as age and gender matched (wherever possible) healthy volunteers. All Part A participants will receive one dynamic 18F-FDG PET/CT scan. The investigators will assess the uptake of 18FDG from PET images from patients with sarcoidosis versus those taken from healthy volunteers to validate and assess the reliability of the analysis method. For Part B of the study the investigators will recruit healthy volunteers aged 50 or more. If sarcoidosis patients in Part A are 50 years old or more, the age-matched HV will be recruited in to Part B instead, thus potentially minimising the number of HVs that might need to be recruited in to Part A of the study. The aims of this research study are: i) To compare FDG-PET derived tissue inflammation measures against measures of inflammation from BAL samples. ii) To compare different models of 18F-FDG lung analysis in patients with pulmonary sarcoidosis. iii) To identify whether FDG PET is sensitive enough to detect a change in inflammation induced in healthy volunteers.

Arms

: Participants with sarcoidosis

Bronchoscopy, BAL collection, and PFTs* [SoC] *if required Screening, research and safety bloods Dynamic 18F-FDG PET/CT scan

: Healthy volunteers

Part A: PFTs Screening, research and safety bloods Dynamic 18F-FDG PET/CT scan Part B: PFTs Screening, research and safety bloods Baseline and post challenge Dynamic 18F-FDG PET/CT scans LPS/saline challenge

Interventions

Radiation: - PET/CT scan

PET/CT will be performed at Cambridge University Hospital's PET-CT unit, Cambridge. Participants in Part A of the study (sarcoidosis and HVs) will receive one PET/CT scan. A Cine-CT scan will be performed immediately prior to the 18F-FDG PET/CT scan. Settings for the CT scans will be determined by clinical protocols, radiation dose will be kept as low as reasonably practicable (ALARP) consistent with UK legislation. After 6 hours of fasting and if blood glucose concentration is ≤11mmol/L participants will proceed to undergo an 18FDG PET/CT scan. 18F-FDG will be administered intravenously at a dose of approximately 200 MBq. Positron emission scanning will involve a 60-minute dynamic acquisition from the lungs.

Other: - LPS Challenge

In Part B, eight healthy volunteers will undergo an LPS challenge whereby each participant is injected with the challenge agent, Lipopolysaccharide (LPS), to invoke temporary mild lung inflammation. Each participant will have a PET/CT scan before and after the administration of LPS and the images will be assessed to determine whether these methods are able to detect true lung inflammation.

Other: - Saline Challenge

In Part B, four healthy volunteers will undergo a saline challenge as outlined above for the LPS challenge. Pre- and post-challenge scans will provide control data for the study.

Diagnostic Test: - Blood and urine sampling

For women whose post-menopausal status and/or pregnancy status is uncertain at screening, a blood sample will be collected to test for pregnancy and menopausal status (hormone profiling) before enrolling them on to the study. If pregnancy status is still uncertain at study visits, participants will have a urine pregnancy test before undergoing any PET/CT scans to ensure it is safe for them to continue in the study.