Prevention of Allergy, Asthma & Chronic Respiratory Morbidity

Lack demonstrated that cutaneous exposure to peanut allergen is a risk factor for developing peanut allergy. This has resulted in a number of manufacturers removing peanut and other nut oils from their topical products. Early oral exposure to peanut is associated with the development of tolerance to peanut, raising the possibility that current guidelines that promote peanut avoidance during the first three years of life may actually promote development of peanut and nut allergies.

Greenough demonstrated that RSV and other viral infections increase the risk of chronic respiratory morbidity/asthma in infants born prematurely. This resulted in changes in the recommendations by the Joint Committee of Vaccines and Immunisations regarding RSV prophylaxis. She also showed that the majority of very prematurely born infants develop bronchopulmonary dysplasia (BPD), require frequent hospital admissions and anti-asthma medication. She demonstrated prophylactic high frequency oscillation did not impact favourably on BPD or lung function at one year.

She developed novel techniques of neonatal respiratory support. This research has been central to Cochrane reviews and national and international evidence based guidelines. Her critical assessment of the respiratory outcome of infants and children has informed changes in practice regarding antenatal diagnostic and therapeutic interventions. The Foundation for Sudden Infant Death Syndrome has requested that she drafts recommendations for the safe sleeping position for prematurely born infants with the hope of reducing sudden infant death in this high risk population, as a direct result of her discoveries on position of sleep in prematurely born infants.

She discovered that in children with sickle cell syndrome (SCD) both in Jamaica and the UK asthma may predispose to episodes sickle cell crises and that atopic asthma leads to recurrent crises, important causes of mortality and morbidity in SCD patients.

Moxham was the first to demonstrate that non-invasive ventilation (NIV) was helpful in acute exacerbations of COPD. NIV is now standard practice in the management of acute exacerbations in COPD. He also demonstrated that pulmonary rehabilitation immediately following an exacerbation of COPD improves quality of life, increases exercise capacity and reduces use of healthcare resources. Ventilatory load is reflected by central respiratory drive, which can be accurately recorded in terms of the diaphragm EMG using a new multielectrode catheter which he invented. He demonstrated that muscular weakness in COPD is likely to be due to inactivity rather than a systemic inflammatory process as suggested by others. Patients with severe obstructive airways diseases may have secondary pulmonary hypertension. Ward and Aaronson demonstrated that the oxygen sensor linked to the elevation of calcium during hypoxic pulmonary vasoconstriction (HPV) involves complex III of the mitochondrial electron transport chain and is due to an increased reactive O2 species. They also defined the role of the endothelium as a critical component of sustained HPV, mediated via potentiation of Rho kinase mediated calcium sensitisation. These findings suggest new opportunities for intervention to reduce morbidity.

Lack will be conducting a 7-year NIH-funded interventional study to induce oral tolerance to peanuts by feeding peanut proteins to atopic infants. If the approach is successful it may introduce a completely new paradigm in the way that food allergy is managed in clinical practice and will have important implications for public health policy worldwide.

These studies will use unique physiological techniques that Greenough and Rafferty have developed to assess lung function and bronchial hyperresponsiveness in children. Greenough and Rafferty will identify whether prematurely born infants with premorbid lung function abnormalities or with certain genetic predispositions are at increased risk of developing severe RSV disease and subsequent asthma and hence inform criteria for administering prophylactic therapies. Greenough will follow up her unique large cohort of very prematurely born children and determine whether at school age respiratory outcome has been influenced by neonatal ventilation mode. She will determine whether anti-asthma medication reduces the devastating pulmonary morbidity of SCD patients.

Ward and Aaronson will ascertain the molecular identity, expression, and signalling pathways of channels underlying Ca2+ entry and protein kinases regulating Ca2+ sensitivity and thus contraction of pulmonary artery and human airway smooth muscle and small bronchioles. A key goal is to characterise the functional consequences of changes in expression and/or function of these pathways that are associated with asthma and chronic hypoxic lung diseases, thereby providing insight on new targets for therapeutic intervention.

Moxham will extend his studies of early pulmonary rehabilitation in patients with COPD exacerbations including analysis of quadriceps biopsies in collaboration with Prof Herridge. Recent work suggests overlap in mechanisms of COPD and severe asthma. As Moxham is already developing better measures of disease outcomes in COPD, we are poised to test them in severe asthma.