Four-week prospective single centre exploratory study in adults with bronchiectasis suffering a pulmonary exacerbation (defined as a change in one or more of the following: cough; sputum amount; sputum colour; breathlessness; fevers; and malaise).

The study will recruit ten adult subjects (male and female) who attend the Cambridge Centre for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United Kingdom. The study will include individuals with a known diagnosis of bronchiectasis suffering a current pulmonary exacerbation. Participants seen during their usual clinic review with an exacerbation will be invited to participate and enrolled to commence the study that same day (day 0). Participants enrolled will undergo clinical review and a series of standard-of-care testing including sputum culture, lung function tests and blood analysis. Additional to these standard investigations, participants will also undertake a series of patient reported outcomes via validated respiratory questionnaires (Quality of Life - Bronchiectasis - QOL-B; & Leicester Cough Questionnaire - LCQ) and functional respiratory imaging (FRI). FRI consists of low dose high-resolution CT at full inspiration and expiration, combined with computational fluid dynamic testing.

Participants will be treated without delay according to standard of care treatment as per current international guidelines. Participants may be treated as either an inpatient or outpatient determined by the treating respiratory physician.

Follow up will occur on day 7, 14 and 28 post enrolment with serial CT imaging on days 0, 14 and 28. No scheduled follow up testing will be required beyond the day 28 visit, however all participants will receive a follow-up phone call at day 35.

The investigators hypothesize that changes in FRI parameters will be seen pre and post exacerbation treatment and will correlate with changes in lung function and patient reported outcomes. This will confirm FRI as a surrogate biomarker for assessing therapeutic response in future clinical trials in bronchiectasis.

Four-week prospective single centre exploratory study in adults with bronchiectasis suffering a pulmonary exacerbation.

The study will endeavour to recruit ten adult subjects (male and female) who attend the Cambridge Centre for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United Kingdom. The study will include individuals with a known diagnosis of bronchiectasis (defined as symptoms of chronic or recurrent bronchial infection with radiological evidence of abnormal and permanent dilation of bronchi) not from cystic fibrosis; and a current pulmonary exacerbation (defined as a 'deterioration in three or more of the following key symptoms for at least 48h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND that a clinician determines a change in bronchiectasis treatment is required).

In order to maximise subject recruitment and understanding of the study, all CCLI patients with bronchiectasis that are known to suffer frequent exacerbations (>2 per year) will be sent details of the trial including the Patient Information and Consent Form at the time of study commencement, prior to their individual enrolment. Subjects then seen during their usual clinic review with a pulmonary exacerbation will be invited to participate and enrolled to commence the study that same day (day 0). Participants enrolled will undergo clinical review and a series of standard testing including pulmonary function tests and blood analysis. Additional to these standard investigations, participants will also undertake a series of patient reported outcomes via validated respiratory questionnaires (Quality of Life - Bronchiectasis - QOL-B; & Leicester Cough Questionnaire - LCQ) and functional respiratory imaging (FRI). FRI consists of low dose high-resolution CT at total lung capacity (TLC) and functional residual capacity (FRC), combined with computational fluid dynamic testing (CFD).

Participants will be treated without delay according to standard usual care as per the current European Respiratory Society (ERS) and British Thoracic Society (BTS) Bronchiectasis Guidelines. Participants may be treated as either an inpatient or outpatient determined by the treating consultant respiratory physician.

Follow up will occur on day 7, 14 and 28 post enrolment. Participants will undergo clinical review and repeat testing according to the below schedule. No scheduled follow up testing will be required beyond the day 28 visit, however all participants will receive a follow up phone call at day 35.

Day 0: Initial consultation - presentation with a pulmonary exacerbation

• Recruitment, consent and enrolment
• History and clinical examination
• Bloods (WCC; neutrophil count; CRP)
• Pregnancy test (urine dipstick) - if appropriate
• Lung function testing (FEV1; FVC; TLC)
• Sputum collection
• Functional respiratory imaging (HRCT at TLC and FRC; may occur + 48 hours of enrolment)
• Patient reported outcomes / questionnaires (QOL-B; LCQ)
• Usual treatment commencement (as per current bronchiectasis guidelines)

Day 7: Mid-treatment follow up (as per usual standard of care)

• History and clinical review
• Bloods (WCC, neutrophil count; CRP)

Day 14: End of treatment follow up

• History and clinical examination
• Bloods (WCC; neutrophil count; CRP)
• Pregnancy test (urine dipstick) - if appropriate
• Lung function testing (FEV1; FVC; TLC)
• Functional respiratory imaging (HRCT at TLC and FRC; may occur +/- 48 hours of day 14)
• Patient reported outcomes / questionnaires (QOL-B; LCQ)

Day 28: Completion of study testing

• History and clinical examination
• Bloods (WCC; neutrophil count; CRP)
• Pregnancy test (urine dipstick) - if appropriate
• Lung function testing (FEV1; FVC; TLC)
• Functional respiratory imaging (HRCT at TLC and FRC; may occur +/- 48 hours of day 28)
• Patient reported outcomes (QOL-B; LCQ)

Day 35: Phone call by research team member

- No scheduled investigations

No scheduled follow up testing will be required beyond the day 28 visit other then a follow up phone call at day 35 (see above).

The investigators hypothesize that changes in FRI parameters will be seen pre and post exacerbation treatment and will correlate well with changes in lung function and patient reported outcomes. This will confirm FRI as a surrogate biomarker for assessing therapeutic response in future clinical trials in bronchiectasis.

Inclusion Criteria:

• Adult male and females ≥18 years and ≤ 80 years
• Current diagnosis of bronchiectasis (see above definition)
• Current pulmonary exacerbation (see above definition)

Exclusion Criteria:

• Severe obstructive airways disease (defined as FEV1 < 30%; FEV1/FVC < 70%)
• Diagnosis of other active chronic lung disease (asthma; ABPA; COPD; pulmonary fibrosis)
• Currently treated non-tuberculous mycobacterial disease
• Acute congestive cardiac failure
• Contra-indication or unable to perform HRCT imaging, including pregnancy
• Contra-indication or unable to perform pulmonary function testing
• Active lung malignancy

The study will endeavour to recruit ten adult subjects (male and female) who attend the Cambridge Centre for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United Kingdom. The study will include individuals with a known diagnosis of bronchiectasis (defined as symptoms of chronic or recurrent bronchial infection with radiological evidence of abnormal and permanent dilation of bronchi) not from cystic fibrosis; and a current pulmonary exacerbation (defined as a 'deterioration in three or more of the following key symptoms for at least 48h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND that a clinician determines a change in bronchiectasis treatment is required).