From Statin Therapy to Vitamin C

From the American College of Chest Physicians New Options for Patients with Lung Disease

SALT LAKE CITY, Utah—Reports presented at the international scientific assembly of the American College of Chest Physicians included results from a range of studies that have important implications for physicians treating patients with pulmonary disorders. Major presentations highlighted the role of statins in slowing progression of lung damage in smokers and reducing cardiovascular events and all-cause death in severe carotid artery disease; the increased risk for pulmonary hypertension in black, not white women as was thought before; and the benefits of combination therapy in patients with chronic obstructive pulmonary disease (COPD).

Statins Slow Lung Damage in Smokers

Promising results were reported from a study that found statins could slow smoking-induced lung damage. Notably, current and former smokers who used statins had less rapid lung function decline than those not using statins, regardless of whether they continued or stopped smoking.

“Until now, no medication has shown to slow smoking-induced lung damage,” said lead investigator Walid G. Younis, MD, of the University of Oklahoma Medical Center. “Our study is the first to show that statins may decrease the decline in lung function in smokers and former smokers and therefore prevent millions from developing debilitating diseases that could eventually lead to death.”

The study included a review of the records of all patients (n = 485; mean age, 66.1 years; 480 men, 5 women) seen at the Oklahoma City VA hospital in 2005 who had at least 2 pulmonary function tests (PFTs) conducted at least 6 months apart. A total of 182 of the patients were current smokers, and 303 were former smokers. Based on their initial PFT results, the patients were categorized by their level of lung impairment: 319 had obstructive lung disease, 99 had restrictive lung disease, and 67 had normal lung function. Some 238 patients were receiving statin therapy for an average of 2.7 years, most of whom (n = 196) were taking simvastatin (Zocor). Those who did not use a statin constituted the control group.

The decline in forced expiratory volume in 1 second between the first and second PFTs was 12.8% in the control group and 2.5% in the statin group. Comparable declines in forced vital capacity were 10.3% and 2.5%. The beneficial effects of statins remained significant, regardless of type of lung disease and whether or not the patient continued or stopped smoking. In addition, statin use in patients with obstructive lung disease reduced the rate of respiratory-related emergency department visits and hospitalizations by 35%.

“It is conceivable that long-term statin therapy could be used in smokers and former smokers to prevent and slow the progression of lung diseases,” said Dr Younis. “Even though statins may help with lung function, they have no effect on preventing a patient from the major smoking-related killer, which is lung cancer. Therefore, smokers should never lose their incentive to quit smoking.”

Statins Improve Carotid Artery Disease

Statins can significantly reduce the risk of myocardial infraction (MI), stroke, or all-cause death in patients with severe carotid artery disease who have not undergone a revascularization procedure, findings presented at the meeting show.

“Our study focuses on statin use in patients with severe carotid artery disease, and our data favor the use of statins in order to reduce the incidence of stroke, MI, and all-cause mortality in this population,” said lead investigator Gautham Ravipati, MD, of New York Medical College, Valhalla.

This study, which was conducted from January 2001 to December 2005, involved an analysis of the charts of 449 patients (mean age, 72 years; 59% men) with carotid artery disease. Of these, 298 patients were treated with statins, and 151 were not. Follow-up lasted a mean of 26 months for the statin group and 21 months for the control group.

All of the statin users and 96% of the non-statin users had hypercholesterolemia. There were no significant differences in age, gender, smoking status, or prevalence of hypertension, diabetes, stroke, or MI between the 2 groups. All patients had narrowing of 1 or 2 carotid arteries, and none had undergone revascularization.

The incidence of MI, stroke, or death in statin-treated patients was 15% compared with 68% in the controls. Statins were found to be effective in patients with severe carotid artery disease, whether or not they had diabetes.

“Research like this, involving these types of incidences on these types of patients, has not previously been published, and what it supports is that all patients with carotid artery disease and hypercholesterolemia should be treated with statins, unless there is an absolute contraindication,” said Dr Ravipati.

Pulmonary Hypertension Death Rates Highest in Black Women

Black women are at greatest risk of dying from idiopathic pulmonary arterial hypertension, results of a new study have demonstrated.

“Idiopathic pulmonary arterial hypertension, by definition, means that there is no clear attributable cause for this disease,” said lead investigator Kala Davis, MD, of Stanford University School of Medicine, California. “What has become apparent from this and other studies is that we have been operating with a very limited understanding of the epidemiology of idiopathic pulmonary arterial hypertension, and that understanding is now changing.”

Data from the US National Center for Health Statistics were reviewed to identify all deaths with idiopathic pulmonary arterial hypertension reported as the underlying cause. Information regarding the age, gender, race, and state of residence of the deceased patients was extracted, and specific tabulations of deaths related to these categories were aggregated into 9 geographic regions. Average, annual, age-adjusted, and region/race/gender-specific rates were then calculated.

A total of 10,053 pulmonary hypertension–related deaths were reported during the study period (1994-1998). Although more white women were diagnosed with the disease, black women with this condition had the highest mortality rate. Patients at both extremes of the age spectrum were also at increased risk of death.

“Race, gender, and age have become defining factors in assessing the risk of death in idiopathic pulmonary arterial hypertension,” said Dr Davis. “Clinicians must therefore be cognizant of this emerging demographic profile, which contrasts with the classic description of the condition as being a disease of middle-aged Caucasian women.”

World Trade Center and Rapid Lung Function Decline

A rare genetic disorder, alpha-1 anti-trypsin (A1AT) deficiency, may predispose patients to lung disease, and a new rapid test might be able to identify those with the deficiency before significant lung damage has occurred, data presented at the meeting show.

A study of rescue workers at the World Trade Center (WTC) site found that those who were deficient in the A1AT protein had more rapid declines in lung function than those who had normal levels of the protein.

“A1AT deficiency is a genetic defect with variable penetrance,” said lead investigator Gisela Banauch, MD, of Montefiore Medical Center, New York City. “Some with the defect will develop emphysema early, even without cigarette smoking. Others with less penetrance may need to be exposed to additional environmental irritants in order to develop emphysema and other forms of obstructive airway disease.”

The study included 151 workers from the WTC site who were followed from October 2001 through 2005; all underwent annual lung function testing. In September 2005, all workers were offered A1AT testing; 90 workers accepted. Severe or moderate A1AT deficiency was identified in 11 workers; the remainder had normal A1AT levels.

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Those with A1AT deficiency had significantly faster post-WTC lung function declines compared with normal/moderately deficient workers ( = .003). Those with moderate A1AT deficiency had lung function declines between severely deficient and normal workers ( = .003). Before the WTC disaster, A1AT-deficient individuals showed no signs of accelerated lung function decline.

Vitamin C for COPD, Pneumonia?

Serum vitamin C levels are significantly decreased, and serum inflammatory markers are markedly increased in patients with acute pneumonia or with exacerbations of COPD who have not yet received treatment, according to results of a new study presented at the meeting.

A total of 60 patients, all nonsmokers, were divided into 3 groups according to their conditions: (1) 20 patients with acute pneumonia; (2) 20 with stable COPD; and (3) 20 with exacerbations of COPD.

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Laboratory testing showed that in groups 1 and 3, serum vitamin C concentrations were decreased and serum inflammatory markers were increased before therapy compared with vitamin C levels after therapy ( <.01 for both groups). Vitamin C values for group 2 were normal before and after therapy.

These results, the researchers said, suggest that serum vitamin C concentration may be a good predictor of worsening disease and may also chart new directions for therapy.

Combination Therapy for COPD

Combination therapy with the agent that contains the 2 common medications inhaled salmeterol and fluticasone propionate (Advair Diskus) may help prolong the lives of patients with COPD.

&#8220;The combination therapy of salmeterol and fluticasone is the first intervention since oxygen therapy or smoking cessation to show improved survival in patients with COPD,&#8221; said lead investigator Bartolome R. Celli, MD, FCCP, of Caritas-St. Elizabeth&#8217;s Medical Center, Boston.

The double-blind study, Towards a Revolution in COPD Health (TORCH), included 6112 patients (mean age, 65 years; 76% men) from 42 countries who had moderate or severe COPD. Investigators randomized 1534 to fluticasone (Flonase), 1521 to salmeterol (Serevent Diskus), 1533 to the combination of both agents (Advair Diskus), and the remainder to placebo.

The combination therapy reduced the risk of dying at any time by 18% compared with placebo during the 3-year study period, with an absolute risk reduction of 15.2% compared with 12.6% for placebo. A trend was also reported toward reduced COPD-related mortality with the combination agent compared with placebo (6.0% vs 4.7%, respectively).

Overall, survival was better with the combination agent than with either agent alone, but the difference was only statistically significant when compared with fluticasone monotherapy.