Nasal, Tracheal and Bronchial Mucosal Lining Fluid(MLF) Sampling From Patients With Respiratory Diseases
Nasal, Tracheal and Bronchial Mucosal Lining Fluid(MLF) Sampling From Patients With Respiratory Diseases
Nasal, tracheal and bronchial sampling of MLF in patients with idiopathic pulmonary
 fibrosis(IPF), sarcoidosis, tuberculosis(TB), asthma and COPD. Similar sampling from healthy
 controls for comparative data.

 Aim: To characterise the molecular basis of the upper and lower airway mucosa inflammatory
 response in different respiratory diseases. To assess molecular biomarkers and signatures to
 see if these can aid diagnosis, stratification of these respiratory diseases. To direct
 personalised medicine and rationalise therapy.

 Outcome measures:Measurement of levels of inflammation, coagulation, complement activation
 and fibrosis in MLF, transcriptomics from nasal curettage and airway brushings and to assess
 the tolerability of absorption procedures in these patients.
Aim- To define the diagnosis, stratification and monitoring of IPF, sarcoidosis and TB,
 providing targets and biomarkers for new therapy. The investigators will study asthma and
 COPD patients with inflammation of the airways, and to compare with healthy control subjects.
 Characterising inflammation using upper airway sampling may eventually remove the requirement
 for invasive diagnostic bronchoscopy in these patients. The investigators shall assess the
 presence of cytokines, chemokines, together with complement, coagulation and fibrosis. The
 investigators propose to obtain opportunistic nasal, bronchial and tracheal mucosal samples
 from patients with IPF, sarcoidosis and TB. The investigators will compare these samples with
 healthy controls and with patients with asthma and COPD.

 Objectives: Determining biomarkers and molecular signatures in terms of cytokines and
 chemokines, coagulation, complement activation and fibrosis in the MLF from the range of lung
 diseases Study design: This is a pilot study and the investigators shall obtain our study
 group from patients attending the bronchoscopy suite, specialist respiratory clinics and
 those being admitted to the wards at St Mary's Hospital under the Respiratory team. The
 investigators shall recruit patients with asthma and COPD,as well as age/ sex- matched
 healthy volunteers.

 IPF, sarcoid and TB patients are usually undergoing bronchoscopy or endobronchial
 ultrasound(EBUS) and transbronchial needle aspiration(TBNA) for diagnostic purposes. Their
 diagnosis may only be confirmed after sampling is done after the bronchoscopy.

 The patients included in the study will represent the following groups:

 IPF at least 12 subjects Sarcoidosis at least 12 subjects TB at least 12 subjects COPD at
 least 12 subjects Asthma at least 12 subjects Healthy at least 12 subjects Study visits:
 Having identified patients suitable for this study, the study involves a single bronchoscopy,
 during which all airway sampling takes place. The investigators will recruit patients with
 asthma, COPD and healthy volunteers and they will be reimbursed for their participation,
 since bronchoscopy is not routinely part of their normal clinical care. They will be
 recruited by advertisements to the general public. They will be given relevant participant
 information sheet regarding this study by email or post.

 Participants with confirmed or suspected IPF, sarcoidosis and TB who are due for a
 bronchoscopy will be identified during their routine clinical care and as part of their
 diagnostic work-up, and will not receive compensation.
Inclusion criteria for all participants-

 -  Women of childbearing age should not be pregnant, planning to get pregnant or
 breastfeeding.

 -  Participants should have no upper respiratory tract infections in past 6 weeks.

 -  Participants should have no significant cardiovascular disease.

 -  Body mass index (BMI) should be between 18 and 39.

 -  Participants with signs or symptoms of significant nasal anatomical defects including
 hypertrophy of turbinates, major septum deviation, nasal polyposis or recurrent
 sinusitis and nasal mucosal defects, injury, ulceration will not undergo nasal
 sampling.

 -  All participants will have to be able to provide informed consent.

 Inclusion Criteria:

 -  Healthy volunteer- no history of lung disease, age 18-65, BMI 18-39, PEF >90%, no
 reversibility, no atopy, non smoker/ ex smoker with >10PYH.

 -  Asthma- diagnosis of asthma, age 18-65, BMI 18-39, GINA mild, PEF >70%, reversibility
 with salbutamol or positive with histamine, well controlled on asthma
 questionnaire(ACQ <0.75), non smoker/ex smoker with <10PYH.

 -  IPF- HRCT suggestive ofILD/IPF, age 45-80, BMI 18-39, FVC >50%, DLCO 30-90%.

 -  Sarcoidosis- HRCT suggestive of sarcoidosis, age 18-95, BMI 18-39, FVC>50%, DLC0>30%.

 -  TB- same as sarcoidosis, including clinical history and/ or CT evidence of TB, age
 18-65.

 -  COPD- diagnosis of COPD, age 45-65, age 18-39, gold stage 2, post bronchodilator FEV1
 50-79%, FEV1/FVC ratio <70%,TLCO 60-80% or emphysema on HRCT,Smoker/ex smoker with
 >10PYH.

 Exclusion Criteria:

 -  Healthy volunteer- use of anti-inflammatory meds including statins, antihistamines,
 NSAIDs, salicylates, anti-rheumatics, use of any OTC medications, URTI within the last
 six weeks, chronic inflammatory illness or CVS/ Resp disease/ systemic disease.

 -  Asthma- Use of inhaled corticosteroids in the last 4 weeks, use of oral steroids in
 the last 6 months, use of anti- inflammatory meds including statins, antihistamines,
 NSAIDs, salicylates, anti-rheumatics, use of any OTC medications, exacerbation
 requiring hospitalisation the last year, URTI within the last six months, significant
 CVS or inflammatory disease.

 -  IPF- Use of anti- inflammatory meds including statins, antihistamines, NSAIDs,
 salicylates, anti-rheumatics, use of oral steroids for 6 months, use of anti-fibrotic
 therapy( pirfendidone, nintedanib) for 6 months, FVC < 50%, baseline spO2 < 90%, use
 of any OTC medications, URTI within the last 6 weeks, significant CVS disease.

 -  Sarcoidosis- Same as IPF, including use of methotrexate for 6 months.

 -  COPD- Same as asthma volunteers and includes atopy.

 -  TB- Same as IPF, including use of anti-TB drugs.