Shafi, NT; (2013) Pulmonary Involvement in Anderson Fabry Disease. Doctoral thesis , UCL (University College London).

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Abstract

Aim: To investigate the clinical, physiological, radiological and pathological changes which occur in the lungs in Anderson Fabry Disease (AFD) Methods: In this study we have used lung function testing, high resolution CT scanning and induced sputum examination to investigate the lung. We have measured sputum enzyme activity using fluorometric assays, cell populations using flow cytometry and cytokines using enzyme linked immunosorbent assays. We have compared investigation findings from AFD subjects with those from patient’s with airways disease in the form of chronic obstructive pulmonary disease (COPD) and healthy controls Results: We have shown that respiratory symptoms are common, and airway involvement is widespread though mild in AFD. Pulmonary involvement is more common in males, in subjects with worse overall disease as measured by Mainz Severity Score Index, and is independent of smoking. No significant radiological changes were evident on CT chest imaging in AFD. We have presented novel data on α-galactosidase A activity from lung derived samples, which demonstrate low sputum enzyme activity in AFD males compared to controls and AFD females, and consistently higher enzyme activity in sputum derived leucocytes compared to those derived from peripheral blood. We did not find any detectable differences in blood or sputum α-galactosidase A activity in subjects on enzyme replacement therapy. Cell populations from induced sputum in AFD subjects demonstrated a predominance of monocytes/macrophages, similar to the COPD subjects, and there was the suggestion of an increased T cell population in AFD subjects with airway obstruction compared to those without. Elevated concentrations of sputum IL-8 were seen in the sputum of AFD subjects compared to controls. Conclusion: There is demonstrable and clinically relevant involvement of the lungs in AFD, which appears to occur as a result of deficient α-galactosidase A in the lungs and subsequent inflammatory processes.

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