Airways Diseases

Principal Investigators

Chronic obstructive pulmonary disease (COPD) / Alpha-1-antitrypsin

COPD is caused by smoking or exposure to other environmental agents which cause inflammation of the lung, leading to persistent airflow limitation, chronic bronchitis, and emphysema.

John Hurst holds an NIHR Global Health Research Professorship and investigates COPD using translational methodology ranging from interventional drug trials to experimental clinical investigation and laboratory science. His focus is on exacerbations and cardiovascular co-morbidity, and case-finding in low- and middle-income countries.

Swapna Mandal leads research into the management of patients with chronic respiratory failure secondary to airways disease and novel techniques for diagnosis and monitoring of chronic respiratory diseases.

Alpha-1 antitrypsin deficiency is a genetic defect that significantly increases the chances that smoking will cause emphysema. David Lomas' group uses a range of cell and advanced structural biology techniques to characterise why alpha-1 antitrypsin deficiency causes emphysema and liver disease, and to identify new treatments.  Previously he helped define the genes that predispose smokers to COPD, and chaired the Respiratory Therapy Area Board at GlaxoSmithKline (2012-15) during which they developed mepolizumab (anti-IL5 monoclonal antibody) and the Trelegy Ellipta inhaler that are now widely used to treat asthma and COPD respectively.

Airway diseases cause specific changes in the structure of the lungs that can be increasingly accurately assessed and measured using CT scans. Joe Jacob uses complex computer analysis to evaluate the relationships between CT signs of airways diseases, disease severity and progression over time. In the future, this technique could predict which patients are most likely to develop severe disease and would benefit the most from early intervention.

Bronchiectasis

Irreversible widening of bronchi due to chronic inflammation or infection causes bronchiectasis. This results in chronic low grade lung infection and gradual loss of lung function. Jeremy Brown and John Hurst conduct clinical and translational research into bronchiectasis, including as part of the UK-wide multicentre BRONCH-UK bronchiectasis research study. Joe Jacob's group have developed computational tools to measure airway narrowing which will enable quantification of bronchiectasis and allow for early detection of early airway damage.

Obstructive sleep apnoea

Obstructive sleep apnoea affects airway function during sleep, causing temporary blockages that lead to disrupted breathing patterns, daytime fatigue, and an increased risk of cardiovascular disease. Swapna Mandal leads clinical trials investigating the optimum treatment and monitoring of patients with OSA.

Selected Publications

1. Siddharthan T, Pollard SL, Quaderi SA ... Hurst JR; GECo Study Investigators (2022). Discriminative Accuracy of Chronic Obstructive Pulmonary Disease Screening Instruments in 3 Low- and Middle-Income Country Settings. JAMA. 2022 Jan 11;327(2): 151-160.
2. Young AL, Bragman FJS, Rangelov B ... Hurst JR; COPDGene Investigators (2020). Disease Progression Modeling in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2020 Feb 1;201(3): 294-302.
3. Polverino E, De Soyza A, Dimakou K ... Brown JS, Hurst JR, et al (2024). The Association between Bronchiectasis and Chronic Obstructive Pulmonary Disease: Data from the European Bronchiectasis Registry (EMBARC). Am J Respir Crit Care Med. 2024 Jul 1;210(1): 119-127.
4. De Soyza A, Mawson P, Hill AT ... Brown J, Hurst JR, et al (2021). BronchUK: protocol for an observational cohort study and biobank in bronchiectasis. ERJ Open Res. 2021 Apr 19;7(2): 00775-2020.
5. Quan K, Tanno R, Shipley RJ, Brown JS, Jacob J, Hurst JR, Hawkes DJ (2019). Reproducibility of an airway tapering measurement in computed tomography with application to bronchiectasis. J Med Imaging (Bellingham). 2019 Jul;6(3): 034003.
6. Lomas DA, Irving JA, Arico-Muendel C, Belyanskaya S, et al (2021). Development of a small molecule that corrects misfolding and increases secretion of Z α1 -antitrypsin. EMBO Mol Med. 2021 Mar 5;13(3): e13167.
7. Faull SV, Elliston ELK, Gooptu B ... Lomas DA (2020). The structural basis for Z α1-antitrypsin polymerization in the liver. Sci Adv. 2020 Oct 21;6(43): eabc1370.
8. Kamuda K, Ronzoni R, Majumdar A, Guan FHX, Irving JA, Lomas DA (2024). A novel pathological mutant reveals the role of torsional flexibility in the serpin breach in adoption of an aggregation-prone intermediate. FEBS J. 2024 Jul;291(13): 2937-2954.
9. Mansell SK, Mandal S, et al (2024). Clinical impact of customised positive airway pressure (PAP) therapy interfaces versus usual care in the treatment of patients with sleep-disordered breathing (3DPiPPIn): a randomised controlled trial protocol. BMJ Open 2024;14:e087234.
10. Cheung WK, Pakzad A, Mogulkoc N ... Hurst JR, Jacob J (2023). Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis. Eur Radiol. 2023 Nov;33(11): 8228-8238.

Grants

Professor John Hurst
NIHR Global Health Research Professorship (2024-2029).
£1.78 million.

Professor John Hurst
NIHR HTA Award (2024-2027): "Rescue packs post-discharge in chronic obstructive pulmonary disease (The RAPID study)".

Professor John Hurst
AstraZeneca. Grant to support Clinical Research Studies in COPD (2023-2026).
£600,000.

Professor David Lomas, J Christodoulou and J Irving.
MRC Programme Grant. Structural and cellular basis of alpha-1-antitrypsin (AT) deficiency and the serpinopathies MR/V034243/1 (2021-2026).
£1.6 million.

Professor David Lomas, K Thalassinos, J Irving
Alpha-1 Foundation (US). Cellular effects of A1AT Aggregation with Single-Cell and Crosslinking Proteomics (2025-2027).
£134,050.

Dr Joe Jacob
Wellcome Career Development Fellowship. "Enhancing the characterisation of early respiratory disease to improve population health" (2024-2032)
£2.86 million.

Dr Joe Jacob
Chan Zuckerberg Institute. "Developing a three-dimensional computed tomography foundational model to transform diagnosis of early disease in lung cancer screening populations" (2024-2027).
$3.8 million.

Dr Joe Jacob
Rosetrees Trust. Quantifying the functional effects of vascular and airway changes in lung fibrosis and cystic fibrosis to evaluate disease progression and treatment response (2024-2027)
£210,000

Dr Swapna Mandal
HTA grant. Exacerbation Prevention in COPD/OSA overlap syndrome
£2.4 million.

Facilities / Techniques

1. BRONCH UK – a multicentre UK consortium investigating bronchiectasis. and providing a platform for therapeutic and other clinical trials (eg CLEAR trial of hypertonic saline).
2. Clinical Trials in COPD and alpha-1 antitrypsin deficiency through the NIHR Clinical Research Facility at the Royal Free Hospital.
3. Alpha-1-antitrypsin deficiency: cryo-electron microscopy, NMR, mass spectrometry, protein biochemistry and cell biology.
4. Clinical trials in OSA ): device studies, wearable technology for diagnosis and mornitoring using non-linear analysis.
5. Advanced computational image analysis tools for lung CT scan quantification.
6. Development of hyperpolarised MRI techniques to improve the characterisation of lung disease.

AI, Smartphones and Lung Health: Breathless with Excitement

Over 600 million people worldwide live with long-term lung health problems such as asthma and COPD. We urgently need better ways to diagnose and treat them. Prof. John Hurst and Dr Luke Hale review how artificial intelligence can improve the care of those living with asthma and COPD, including a smartphone platform under development for patients with these conditions.