Airways Disease

Bronchi are the tubes that conduct air to air sacs (alveoli) where gas exchange occurs in the lungs.  We are investigating a range of chronic inflammatory airways diseases, including asthma, rhinitis, chronic obstructive pulmonary disease (COPD), primary ciliary dyskinesia (PCD) and cystic fibrosis, using relevant lung-derived samples which can be used outside the body (ex vivo) as models of disease in which the underlying mechanisms and novel drugs can be studied.

Airways diseases are characterized by the presence of persistent inflammation, which may be driven by a variety of mechanisms (eg. allergens, environmental pollutants or persistent infections) depending on the disease. They are usually also associated with alterations in tissue architecture, termed remodelling (link to tissue injury and remodelling page), leading to impaired lung function and reduced quality of life. A major unmet need in these diseases is prevention of exacerbations (worsening of symptoms) which can often result in hospital admission or even death. Our research spans many aspects of these diseases, but we place a particular emphasis on those areas of unmet need, especially acute exacerbations invfolving viral and bacterial infections (link to infection page) and chronic or severe disease that is resistant to current therapies.  The respiratory group is also a leader in the identification and validation of biomarkers of airways disease, having co-founded UBIOPRED , a €22m programme in severe asthma funded in collaboration by public funding from the EU and several pharmaceutical companies.

Oxygen enters the blood in the alveoli where it is exchanged for CO ₂ which is then removed in the exhaled air. Within the alveoli, lung surfactant plays a critical role to stabilize the air sacs and prevent their collapse and to maintain them in a sterile and non-inflamed state. We are exploiting the properties of the hydrophilic surfactant proteins A and D (SP-A and SP-D) in regulating inflammation in the lung after exposure to infectious or allergic agents and are developing artificial forms of surfactant to treat inflammation in asthma, lung infections, cystic fibrosis, neonatal chronic lung disease and adult emphysema. We are also studying the biochemistry of phospholipids and dynamic lipidomics in health and disease.

A particular strength of the respiratory group is the close link between paediatric  and adult research in the lung, providing a distinctive life-course perspective of disease development and progression.  Our work is recognised internationally for its translational approach ranging from epidemiology and genetics, cell and molecular biology, biochemistry, pathology, therapeutic target discovery, biomarker discovery and validation, lung imaging, early proof of pharmacological efficacy, to phase I-III clinical trials. This seamless interface between basic and clinical research is facilitated by our NIHR-funded Respiratory Biomedical Research Unit .

Research into airways diseases is conducted by following investigators :

Asthma across the life-course
( Stephen Holgate , Donna Davies , Ratko Djukanovic , Peter Howarth , Hasan Arshad , Graham Roberts , John Holloway , Judith Holloway , Andrew Walls , Tony Sampson , Jane Collins , Tilman Sanchez-Elsner , Tony Postle , Pandurangan Vijayanand ).

COPD
( Ratko Djukanovic , Peter Howarth , Donna Davies , Tom Wilkinson , Jane Warner , Clark , Simon Bourne )

Rhinosinusitis and paediatric ENT infection
( Peter Howarth , Rami Salib , Saul Faust , Luanne Hall-Stoodley , Howard Clark )

PCD
( Jane Lucas , Peter Lackie )

Lung and airway infection including Cystic Fibrosis
( Saul Faust, Howard Clark , Janet Carroll, Julian Legg, Rami Salib , Jane Lucas , Gary Connett, Luanne Hall-Stoodley, Sonia Quaratino )

Neonatal lung injury
( Howard Clark , Tony Postle , Jens Madsen , Alan Hunt )

Acute lung injury and adult critical care
( Michael Grocott, Tony Postle )

Pulmonary sarcoidosis
(Marshall and Kate O'Reilly )

Exacerbations of COPD and cognitive function
( Clive Holmes , Hugh Perry , Jessica Teeling, Ratko Djukanovic )