Inclusion Criteria:

• - Inclusion Criteria for Probable Idiopathic Pulmonary Fibrosis (IPF) - Adult male or female patients aged 40 to 85 years.

• - Women of childbearing age should not be pregnant, planning to get pregnant or breast-feeding.

• - Command of the English language to be able to give informed consent.

• - Probable IPF requiring bronchoscopy to confirm the diagnosis, agreed within the local multi-disciplinary team (MDT).

,according to the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/ American Latin Thoracic Association (ATS/ERS/JRS/ALAT) guidelines (2018)

• (3) - IPF disease diagnosis within the past 5 years.

• - Usual Interstitial Pneumonia (UIP) on HRCT scan.

• - Recent lung function criteria: - Forced vital capacity (FVC) >40% of predicted value.

• - Carbon monoxide diffusing lung capacity (DLco) corrected for haemoglobin >30% of predicted value.

Inclusion criteria for Sarcoidosis.

• - Adult male or female patients aged 18 years and over.

• - Women of childbearing age should not be pregnant, planning to get pregnant or breast-feeding.

• - Clinical symptoms, CT scan and biopsy diagnosis of sarcoidosis.

• - Patients with lung parenchymal disease and pulmonary stage II or more.

• - Recent lung function criteria.

• - FVC>50% predicted.

• - DLCO >40% predicted.

Inclusion criteria for Healthy Volunteers.

• - Age between 40 to 85 years, age and sex to match the group with IPF.

• - Healthy subjects without any diseases that may cause inflammation.

• - Women of childbearing age should not be pregnant, planning to get pregnant or breast-feeding.

• - Currently non-smokers: see exclusion criteria.

Exclusion Criteria:

Exclusion Criteria for probable IPF and Sarcoidosis Patients. Respiratory Conditions other than IPF or sarcoidosis:

• - Confirmed diagnosis of occupational lung disease.

• - Drug-induced lung disease or hypersensitivity pneumonitis.

• - Lung and systemic autoimmune disease including connective tissue disease.

Patients with an auto-immune profile considered diagnostic for a specific connective tissue disease will be excluded, even in the absence of systemic symptoms. Non-specific rises in auto antibodies e.g. rheumatoid factor; anti-nuclear antibody etc. will not be used to exclude individuals from the study.

• - Asbestosis or other asbestos related disease (pleural plaques, mesothelioma, asbestos pleural effusions) - Granulomatous lung disease.

• - Pulmonary artery hypertension (PAH) requiring a specific treatment.

• - Predominant chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second /forced vital capacity (FEV1/FVC) <0.70.

• - Patients with active tuberculosis or incompletely treated latent tuberculosis infection.

• - Lung cancer.

• - Upper respiratory tract infections in the past 6 weeks.

Systemic Conditions.

• - History of vasculitis, autoimmune or connective tissue disease.

• - Known human immunodeficiency virus (HIV) or chronic viral hepatitis.

• - Clinically significant diseases (other than IPF or sarcoidosis) that may alter respiratory biomarkers: including other respiratory, gastrointestinal, endocrine, haematological, cardiovascular, genitourinary, skin or neurological diseases.

• - Recent or ongoing malignant diseases.

• - Significant nasal anatomical defects preventing nasal sampling: including hypertrophy of turbinates, major septum deviation, nasal polyposis or recurrent sinusitis and nasal mucosal defects.

Bronchoscopy Contraindications. Any contra-indication to bronchoscopy as set out in British Thoracic Society guidelines (34) Smoking. A detailed smoking history will be taken from all participants: to include total pack years, smoking in the past year, and smoking in the past 2 weeks. The history will include cigarettes, pipe smoking, cigars, vaping, and shisha. Any form of smoking is not permitted within 2 weeks of bronchoscopy. 5.4.2 Exclusion Criteria for Healthy Volunteers.

• - Current inflammatory/ immunological conditions.

Any clinically significant diseases that may alter respiratory biomarkers: including respiratory, gastrointestinal, endocrine, haematological, cardiovascular, genitourinary, skin or neurological diseases.

• - Recent or ongoing malignant diseases.

• - Significant nasal anatomical defects preventing nasal sampling: including hypertrophy of turbinates, major septum deviation, nasal polyposis or recurrent sinusitis and nasal mucosal defects.

• - Upper respiratory tract infections in the past 6 weeks.

• - Cigarette smoking: no cigarettes in the last 2 weeks not more than 10 cigarettes in the past year <10 year lifetime pack history of smoking.

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IPF is a progressive disease caused by irreversible scarring of the lung, and disease trajectory is not easily predicted based on clinical measurements. Biomarkers reflective of molecular pathways involved in IPF may help inform patient trajectory, but have been difficult to identify in circulation due to the disease manifesting in the lung. The study team will measure biomarkers from Probable IPF patients, sarcoidosis patients, and healthy volunteers using novel sampling methods involving absorption of upper and lower airway fluids. These novel sampling methods may enable less invasive and potentially more sensitive methods to detect disease activity and will be performed in IPF and sarcoidosis patients during a routine bronchoscopy procedure. The study team will compare the levels of biomarkers that have been shown to be predictive of disease course in airway fluids of probable IPF patients versus sarcoidosis and healthy controls. This study may help understand the molecular basis of IPF, and improve the understanding of diagnosis and treatment.

Arms

: Healthy Volunteers

These will be age matched healthy volunteers (n=15) who will not undergo bronchoscopy

: Probable Idiopathic Pulmonary Fibrosis

Patients with probable IPF, who will be having bronchoscopy as part of their clinical diagnostic work up

: Sarcoidosis,

Patients with sarcoidosis who will be having bronchoscopy as part of their clinical diagnostic work up

Interventions

Procedure: - Bronchoscopy for Probable Idiopathic Pulmonary Fibrosis and Sarcoidosis

Blood samples and Nasosorption sampling