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Edgbaston, United Kingdom

Stockley R.A.,Queen Elizabeth Hospital Birmingham | Turner A.M.,University of Birmingham
Trends in Molecular Medicine | Year: 2014

The recognition of α-1-antitrypsin deficiency, its function, and its role in predisposition to the development of severe emphysema was a watershed in our understanding of the pathophysiology of the condition. This led to the concept and development of intravenous replacement therapy used worldwide to protect against lung damage induced by neutrophil elastase. Nevertheless, much remained unknown about the deficiency and its impact, although in recent years the genetic and clinical variations in manifestation have provided new insights into assessing impact, efficacy of therapy, and development of new therapeutic strategies, including gene therapy, and outcome measures, such as biomarkers and computed tomography. The current article reviews this progress over the preceding 50 years. © 2013 Elsevier Ltd.

World M.J.,Queen Elizabeth Hospital Birmingham
Journal of the Royal Army Medical Corps | Year: 2013

Objectives A review of 26 years of British military renal pathology showed the commonest diagnosis to be immunoglobulin A (IgA) nephropathy affecting 115/346 (33%) of cases. It was possible to follow-up 50/115 military patients with this condition with the primary objective to determine whether initial observations enabled a confident prediction of prognosis. Additionally, unpublished observations have shown that the incidence of glomerulonephritis in an Indo-Asian British military racial group was fourfold that in the majority Caucasians although the nature of pathology (IgA vs non-IgA nephropathy) was not statistically significantly different. The present study secondarily sought to determine if prognosis of IgA nephropathy was different in this Indo- Asian military group. Finally, some conclusions concerning the traditionally restrictive policy towards applicants for military service with evidence of active nephritis were attempted. Methods An archive of military renal patients covering 1985-2011 was reviewed and clinical details of cases of IgA nephropathy were extracted and analysed. Results 95 cases (80 Caucasian, 15 Indo-Asian) were reviewed. There was no racial difference (p=0.2) in initial median estimated glomerular filtration rate (eGFR, 86 vs 83 ml/min/1.73 m2). Altogether, initial median of mean arterial pressure (MAP) was 96 mm Hg (IQR=87- 103) and median proteinuria was 485 mg/24 h (IQR=195-925). There was an inverse correlation between initial eGFR and both MAP (p=0.0008) and proteinuria (p=0.0006). In the 50 patients who were followed up, the change in eGFR with time (ΔeGFR) was calculated. 10 of the 44 Caucasians and 3/6 Indo-Asians showed significant changes in eGFR but population proportions were not significantly different (p=0.2). Altogether, 11/50 (22%) showed deteriorating eGFR despite therapeutic interventions, compared with those without deterioration; this was not due to different duration of observation (p=0.08), initial MAP (p=0.23) or initial proteinuria (p=0.07). There was no statistically significant correlation between ΔeGFR and initial MAP (p=0.6) or proteinuria (p=0.7). Conclusions The proportion of military cases of IgA nephropathy with deteriorating renal function (22%) was not different from that described in civilians, suggesting that military medical management (including operational restriction where necessary) was appropriate. Initial clinical observations, including racial group, did not permit confident prediction of prognosis thus mandating followup for all military cases. Relaxing current enlistment policy would be inadvisable given the inability to confidently predict prognosis in individual cases.

Carter R.I.,University of Birmingham | Stockley R.A.,Queen Elizabeth Hospital Birmingham
COPD: Journal of Chronic Obstructive Pulmonary Disease | Year: 2014

It is increasingly recognised that new measures of disease 'activity' for COPD are required, however the relationship between markers of disease 'activity', 'severity' and 'impact' though closely linked, is poorly understood. Additionally, while change in markers of disease 'severity' (e.g. change in FEV1) may be considered a marker of disease 'activity', these quantify a single aspect of disease 'activity' in COPD rather than measuring the overall disease process and this has stimulated the search for new biomarkers of COPD that reflect the 'activity' of the disease process. The ideal biomarker of disease 'activity' would be stable with respect to time since measurement at any time point would then relate to subsequent disease progression. This would allow the influence of a therapeutic intervention to be assessed early, facilitating both phase 2 and 3 clinical trials. Although a number of potential biomarkers of COPD disease 'activity' have been studied, to date none have been shown to conclusively relate to disease progression and the stability of underlying disease 'activity' therefore requires further consideration. Interestingly, while the variability of disease 'activity' of COPD is rarely mentioned in the current literature, and there is uncertainty whether 'activity' is constant or highly variable, there are clues from available data as discussed in the current article. Finally we consider how markers of disease 'activity', 'severity' and 'impact' may relate, which is of utmost importance in the ongoing search for new biomarkers in COPD and a greater understanding of the pathogenesis of the disease process. © 2014 Informa Healthcare USA, Inc.

Stockley R.A.,Queen Elizabeth Hospital Birmingham
International Journal of COPD | Year: 2014

The field of biomarker research has almost reached unmanageable proportions in chronic obstructive pulmonary disease (COPD). The developments of new technology platforms have generated a huge information data base, both cross sectionally and increasingly, longitudinally. The knowledge emerging provides an enormous potential for understanding the disease pathophysiology, for developing markers specific for long-term outcomes, and for developing new therapeutic strategies. However, the excitement must be tempered with an understanding of the limitations of the data collection techniques, and of the variations in disease state, activity, impact, and progression. Nevertheless, the most crucial aspect in interpreting the current literature is the recognition of the relatively superficial characterization of what is a complex group of pathological processes with a common end point of airflow limitation. The current review explores some of these issues together with those areas where real progress appears to have been made, and provides caution on interpretation. © 2014 Stockley.

Wyrko Z.,Queen Elizabeth Hospital Birmingham
Clinical Medicine, Journal of the Royal College of Physicians of London | Year: 2015

Significant numbers of older people attending hospital can be considered to be frail or living with frailty. This is a multicomponent syndrome with many manifestations that leads to poorer outcomes in terms of mortality, morbidity and institutionalisation. Recognition and management of frailty can be challenging, and requires a true multidisciplinary approach, but appropriate assessment and subsequent intervention have been proven to be beneficial. This article discusses the background to frailty, and a number of validated frailty scores which can be applied by non-specialists in the acute environment. It highlights other resources which are available to help with the management of this complex group of patients, and discusses potential local and national service developments in this area. © Royal College of Physicians 2015. All rights reserved.

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