American Thoracic Society Journal news tips for July 2004 (second issue)

Researchers have revealed that patients with asthma, when compared to normal controls without the disease, had much lower levels of plasma arginine, an amino acid that produces nitric oxide (NO) through enzymatic activity in the body. Recently, investigators have come to believe that NO deficiency plays a significant role in the pathogenesis of asthma. The biomedical scientists in this study measured amino acid levels and nitric oxide metabolites in the blood of 26 patients with asthma who were in varying stages of disease exacerbation. They pointed out that NO is an important vasodilator of the bronchial circulation, with both bronchodilatory and anti-inflammatory properties. Moreover, today, exhaled NO is widely regarded as a marker of airway inflammation in both children and adults with asthma. In their study, the investigators revealed that reductions occurred in plasma levels of many amino acids in asthma patients with acute exacerbations. However, the greatest decrease came in plasma levels of arginine, which measured approximately one-half the amount found in normal control subjects. They believe that their findings have significant clinical relevance and represent a new focus for asthma research. The study appears in the second issue for July 2004 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.

RESPIRATORY VIRAL INFECTIONS OFFER DISTINCT RISK FOR LUNG TRANSPLANT PATIENTS

Lung transplant patients who develop community-acquired respiratory viral infections such as respiratory syncytial virus, parainfluenza, influenza, and adenovirus during the months after surgery had twice the risk of developing a potential killer syndrome called bronchiolitis obliterans. If the viral infection involved the lower respiratory tract, the risk was tripled. According to the researchers, the hazards from infection were distinct from those attributable to acute organ rejection. The investigators studied the records of 228 patients who underwent lung transplantation at their institution between January 1, 1996, and December 31, 2000. Data were accrued through July 1, 2002. Of this group, 21 patients suffered from various respiratory viral infections, and six patients died of bronchiolitis obliterans syndrome (BOS). (This complication, associated with fibrotic destruction of the small airways, constitutes the major long-term cause of mortality in lung transplant patients.) The authors said that the identification of community-acquired respiratory viral infections as a unique BOS risk factor has important clinical implications. It suggests that antiviral strategies aimed at preventing or treating viral infection might provide an approach that would either reduce the chance of onset or slow the progression of the syndrome. They point out that three of eight lung recipients who developed respiratory syncytial virus underwent treatment with ribavirin, and none of the three developed BOS, whereas four of the five untreated recipients developed the syndrome. The study appears in the second issue for July 2004 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.

UNIQUE LUNG CANCER SIGNATURES OFFER BIOMARKERS FOR HIGH- AND LOW-RISK PATIENT OUTCOMES

Researchers used lung tumor biopsies from 23 patients with proven lung cancer to identify unique tumor signatures that proved to be biomarkers for clinical outcome with an 87 percent accuracy rate. Utilizing residual material from lung biopsies, they identified a classifier set of 42 genes that were associated with risk of lung cancer death within 12 months. The group also identified genes with low-risk outcomes. (Lung cancer is the leading cause of death from cancer in the United States, with 187,000 cases and 165,000 deaths expected in 2004. Five-year survival rates for the disease run about 15 percent.) According to the authors, the potential role of lung biopsy gene expression profiling in the management of early-stage non-small cell cancer would be to identify patients with high-risk tumors who would be most likely to benefit from neoadjuvant systemic therapy. The potential utility of this approach has been demonstrated in breast carcinoma, where gene profiles obtained from breast tumors have been shown to predict short-term clinical response to the neoadjuvant docetaxel. The study appears in the second issue for July 2004 of the American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.

For the complete text of these articles, please see the American Thoracic Society Online Web Site at http://www.atsjournals.org. For either contact information or to request a complimentary journalist subscription to ATS journals online, or if you would like to add your name to the Society's twice monthly journal news e-mail list, contact Cathy Carlomagno.

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