Publications

BACKGROUND

Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes.

METHODS

We utilized data from the placebo arm (n=126) of a clinical trial of patients with alpha1-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models.

RESULTS

At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV1 (p=0.03), FVC (p<0.001), carbon monoxide transfer factor (p=0.03), resting oxygen saturation (p=0.02), and ISWT distance walked (p=0.02) but were not associated with radiographic lung density or total lung capacity (TLC). In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p=0.04) and oxygen saturation (p<0.001). MMP-9 also predicted worsening lung density (p=0.003), increasing TLC (p=0.02), and more frequent COPD exacerbations over follow-up (p=0.003). Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes.

CONCLUSIONS

Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.

We report a case of a patient with idiopathic left ventricular tachycardia (VT) successfully ablated from the epicardial aspect of the left ventricle, after a previous failed endocardial ablation. The VT appeared to be catecholamine sensitive. An excellent epicardial pacemap was found in the midlateral region of the left ventricle, remote from vascular structures. Following ablation, the patient discontinued antiarrhythmic drug use and has not experienced any recurrence of VT for more than 2 1/2 years.

Malaria remains one of the leading health problems of the developing world, and Uganda bears a particularly large burden from the disease. Our understanding is limited by a lack of reliable data, but it is clear that the prevalence of malaria infection, incidence of disease, and mortality from severe malaria all remain very high. Uganda has made progress in implementing key malaria control measures, in particular distribution of insecticide-impregnated bednets, indoor residual spraying of insecticides, utilization of artemisinin-based combination therapy to treat uncomplicated malaria, and provision of intermittent preventive therapy for pregnant women. However, despite enthusiasm regarding the potential for the elimination of malaria in other areas, there is no convincing evidence that the burden of malaria has decreased in Uganda in recent years. Major challenges to malaria control in Uganda include very high malaria transmission intensity, inadequate health care resources, a weak health system, inadequate understanding of malaria epidemiology and the impact of control interventions, increasing resistance of parasites to drugs and of mosquitoes to insecticides, inappropriate case management, inadequate utilization of drugs to prevent malaria, and inadequate epidemic preparedness and response. Despite these challenges, prospects for the control of malaria have improved, and with attention to underlying challenges, progress toward the control of malaria in Uganda can be expected.