Clinical Briefs by Louis Kuritzky, MD
Long-term Mortality Among Adults with Asthma
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.
Source: Ali Z, et al. Chest 2013;143: 1649-1655.
In the united states, approximately 5000 persons die each year from asthma. Counterintuitively, deaths in asthma are equally distributed among patients identified as mild, moderate, and severe. Studies of patients with near-fatal asthma have found a decreased sensitivity to hypoxia, hypercapnea, and resistance loading, suggesting that persons destined to succumb to asthma may not fully appreciate the severity of their symptoms, placing them at risk for unrecognized deterioration.
The long-term picture of causes of death in asthmatic adults was the subject of this report by Ali et al. The authors drew on a population of asthmatics enrolled from 1974-1990 in Denmark at their first visit for asthma to the Copenhagen Frederiksbergy Hospital Allergy and Chest Clinic, having been referred there by their general practitioners in the community. More than 75% of the enrollees were younger than 50 years of age at the time of enrollment.
Compared with age- and sex-matched control subjects, all-cause mortality in asthmatic subjects was essentially doubled over 25 years of follow-up. The excess risk for death was primarily due to obstructive airways disease, but was unrelated to smoking status (hence deaths were predominantly not related to chronic obstructive pulmonary disease). Degree of peripheral blood eosinophilia correlated with mortality, intimating that unmitigated atopy in asthmatics may contribute to adverse outcomes.
Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes
Source: The Look AHEAD Research Group. N Engl J Med 2013;369:145-154.
Type 2 diabetes (dm2) is characterized by increased risk for cardiovascular (CV) events, which are not only more frequent but also more severe than similar events in non-diabetics. Most DM2 patients in America are overweight or obese. Weight loss and exercise have been shown to improve glucose control, lipids, blood pressure, and progression from pre-diabetes to diabetes, but no large clinical trials have confirmed risk reduction for CV events attributable to lifestyle intervention.
The Look AHEAD trial randomized overweight or obese DM2 patients (n = 5145) to intensive lifestyle or control (the control group still received education and support in reference to care of their DM2). The goal of intensive lifestyle was to reduce weight by at least 7% and participate in at least 175 minutes/week of moderate-intensity physical activity.
The trial was originally intended to go on for 13.5 years, but was stopped early (at 9.6 years) because futility analysis demonstrated no likely possible benefit of the intensive intervention for CV events compared to controls, despite greater weight loss and improved glycemic control attained in the intensive lifestyle group.
Intensive lifestyle intervention in DM2 improves glycemic indices and body mass index, but does not appear to improve CV risk.
New Hope for Hepatitis C Patients
Source: Jacobson IM, et al. N Engl J Med 2013;368:1867-1877.
The centers for disease control and Prevention has recently advocated routine screening for hepatitis C (HEP-C) among all adults born from 1945-1965. These recommendations stem from the observation of the ever-growing burden of persons with HEP-C and its consequences who do not necessarily endorse traditionally recognized risk factors for HEP-C such as intravenous drug use, tattoos, etc. Early identification allows for potential cure of HEP-C, since as many as 80% of previously untreated individuals can achieve sustained virologic response with "standard" antiviral regimens (e.g., ribaviron plus interferon).
This does, however, leave a substantial minority of HEP-C patients (those who fail treatment, who are intolerant of treatment, or who have contraindications to it) at risk. Fortunately sofosbuvir, a new polymerase inhibitor, has demonstrated high efficacy in both untreated HEP-C and treatment failures.
Sofosbuvir was studied in two populations of HEP-C genotype 2 or 3: persons with contraindications to interferon and cases that had not responded to interferon therapy. Sustained virologic response was seen in 78% of subjects with interferon contraindications, and (at 16 weeks) 73% of interferon failures. Sofosbuvir was generally well tolerated, with a discontinuation rate of 1-2%.