Annual Meeting of the American Thoracic Society
Meeting: Toronto, Canada, May 16-21, 2008
The American Thoracic Society (ATS) held its annual meeting in Toronto, Canada, hosting over 16,000 physicians, scientists, and other respiratory healthcare providers from all over the world. There were no major or landmark studies presented at this meeting, but it was a very interesting update on research and clinical advances in respiratory diseases. Highlights from the meeting are presented below, and abstracts from the entire program can be viewed at the ATS website: https://www.thoracic.org.
Burden of Lung Disease Study
The very large and ambitious worldwide study, the Burden of Lung Disease (BOLD), on the prevalence of chronic obstructive pulmonary disease (COPD) was completed last year, and the main results were published in The Lancet in September 2007. The study measured lung function by spirometry in a representative sample of the population of every major country in the world, and using consistent definitions and measurements it objectively defined, for the first time, the prevalence of COPD by country worldwide.
There were many interesting sub-analyses of the BOLD study presented at this meeting. The variation in prevalence was quite surprising, from a high of 25% of the population in South Africa to a low of 5% in Mexico. In only four countries in the world, women had higher rates of COPD than men (USA, Austria, Iceland, and Australia), but the projected trends suggest that women worldwide are increasing in prevalence, so COPD can be added to the list of “women’s health issues.” Another interesting finding of the study was the higher than expected incidence of COPD in persons who had never smoked, about 15% of all COPD worldwide. COPD in non- smokers appears to be due to the genetic predisposition to the disease coupled with passive smoke or air pollution exposure. One of the most common pollution exposures in the developing world is the indoor pollution of heating and cooking with biomass fuels. There are an estimated 1.9 million excess deaths per year in China due to passive smoke and pollution exposure.
Reducing Acute Exacerbations in COPD
Several conference sessions and one evening seminar focused on the prevention of acute exacerbations (AEs) as the most important intermediate goal in managing COPD. Clinical guidelines for management of COPD list a number of therapeutic goals, including improving physical function and quality of life, reducing hospitalizations and emergency visits, and decreasing cost of care and mortality. Frequency of AEs is highly correlated with other adverse outcomes and appears to be the best predictor of the course of the disease. Pulmonary function measurements before and after AEs indicate that there is often an accelerated and permanent loss of lung parenchyma, and persons with COPD will often deteriorate in a stair-step fashion with each occurrence of an AE.
Patient education in COPD should include recognition of the signs of AE: (1) increased shortness of breath; (2) increased sputum production; and (3) change in sputum to a more purulent appearance. Early treatment of AEs with systemic corticosteroids and antibiotics if sputum is purulent can decrease the severity and recovery time from an AE.
Persons with COPD who have had AEs should be considered for preventive maintenance therapy using a combination of inhaled corticosteroids and a long-acting bronchodilator.
One clinical trial specifically targeted prevention of AEs in persons with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III COPD (FEV1 < 50% predicted) and a history of more than one AE in the previous year. It compared treatment with a bronchodilator alone, salmeterol (SAL) 50 mcg twice daily, versus the combination of salmeterol 50 mcg and fluticasone 250 mcg (SFC) twice daily. Subjects (N = 797) entered the study with a 4-week run-in period of combination SFC, treatment and then were randomized to a 1-year treatment with either SFC or SAL. The combination SFC treatment reduced moderate/severe exacerbations by 30% as compared to the SAL treatment alone (P < 0.001), and was also associated with better preservation of lung function as measured by FEV1 (P < 0.001). On the basis of this study and another that replicated these findings, the Food and Drug Administration has approved the combination of salmeterol 50 mcg and fluticasone 250 mcg for twice-daily use for the prevention of AEs.
Update on Tuberculosis
The epidemiology of tuberculosis (TB) is changing significantly. Global travel, immigrant populations, and the prevalence of human immune deficiency disease have all contributed to a new increase in TB cases. Of greater concern is the development of multidrug-resistant (MDR) strains of TB, and more recently, extensive drug-resistant (XDR) strains. Before the advent of effective antibiotics, the mortality rate from untreated TB was close to 50%, so the specter of widespread epidemics of MDR and XDR is a serious public health concern.
Part of the problem is the failure of primary treatment in many parts of the world. A retrospective study of persons treated for primary TB at a Brooklyn, NY, medical center found that only 44% of persons starting treatment completed at least 6 months of therapy, and only 15% of persons completed 6 months of therapy if they were residents of a homeless shelter. A World Health Organization report recommended that primary treatment guidelines should be re-evaluated in all countries where the incidence of MDR TB is greater than 3% of new cases. In those countries, mono-drug therapy is often inadequate, even with good compliance, because of the widespread primary drug resistance.
A study of new cases of TB by researchers in Monterey, Mexico, showed that 15.6% of these cases of TB were resistant to at least one of the primary drugs (isoniazid, rifampin, ethambutol, or streptomycin), and 2.9 % of new cases were MDR to all of the primary drugs.
Another paper from Korea reported that better outcomes and survival were obtained when MDR TB was treated aggressively using a combination of four effective drugs plus surgical resection of the infected area of lung. Fluoroquinolones have remained one of the better second-line drugs for MDR and XDR TB, but widespread use of these drugs for urinary tract and respiratory infections has public health officials concerned that they could lose their effectiveness. A report presented by the Tennessee Department of Public Health, which has monitored this concern over the past five years, was reassuring, indicating that resistance to fluoroquinolones has remained stable at about 3% of new cases of TB.
Several studies underscored the importance of testing for latent TB in any persons undergoing immune-suppressive therapy. Persons already on an immune-suppressive agent, such as methotrexate for rheumatoid arthritis, who may be under consideration for additional therapy such as anti-tumor necrosis factor-alpha, may be anergic to the standard Mantoux type skin test. A new gamma interferon in-vitro assay (T-spot, Oxford Immunotec, UK) can be useful in looking for latent TB in such cases, especially in areas that are endemic for TB.
Procalcitonin (PCT) levels have been shown to be useful in identifying bacterial infections, especially in differentiating bacterial from viral pneumonias. A study from Utrecht, Netherlands, reported that PCT is also useful in differentiating bacterial pneumonia from active pulmonary TB. PCT levels were elevated in 17 of 28 patients who presented to the emergency department with a non-TB cause of respiratory symptoms and infiltrate/consolidation seen on chest x-ray. However, none of 15 persons with proven TB causing the respiratory symptoms and infiltrate/consolidation on x-ray had elevated levels of PCT. Since sputum smears can be unreliable in identifying TB, and TB cultures take a long time, PCT levels can be very helpful in clinical decision-making in the acute setting.
Lung Cancer Treatment in Older Persons
Lung cancer is primarily a disease of older persons, and older persons with cancer are sometimes treated less aggressively than younger persons because of comorbidities or concern that treatment will not significantly extend survival. A large retrospective study (N = 27,859) reported by the Mount Sinai School of Medicine, NY, sought to determine whether older persons with stage I, non-small-cell lung cancer treated with surgery or radiation therapy had similar survival benefits to those achieved by younger patients. The patients were divided into four groups by age (< 60 yr, 61-69 yr, 70-79 yr, and > 80 yr) and two groups by treatment (surgery or radiation alone). The outcome of interest was 5-year survival rates as compared to age- and sex-matched survival of the general U.S. population. The findings indicated that for men treated with surgery there was a 69% 5-year survival rate for persons younger than age 60 years as compared to a 64% 5-year survival rate for persons older than age 80 years; for women treated with surgery there was a 79% 5-year survival rate for persons younger than age 60 years as compared to a 78% 5-year survival rate for persons older than age 80 years. For persons treated with radiation there was no difference between age groups or between men and women in 5-year survival rate. The study researchers concluded that women with stage I, non-small-cell lung cancer benefit from surgery regardless of their age, and that older men are only slightly less likely to benefit from surgery than younger patients. These data indicate that older persons should receive aggressive treatment for lung cancer unless there are specific contraindications for surgery or radiation treatment.
Rapid Response Teams and Quality of Death
Hospitals have developed rapid response teams (RRTs) with the intention of improving resuscitation efforts, decreasing in-patient mortality, decreasing length of stay, and decreasing utilization of critical care resources. Researchers at Yale Medical Center, New Haven, CT, postulated that RRTs might also identify appropriate candidates for palliative care, and thereby provide a previously unexpected benefit to patient care. They used a case control methodology to study quality-of-death measures in patients who died (N = 73) during a 4-month period prior to deployment of their RRT versus a similar 4-month period (N = 52) after the deployment. Fifty-two percent of patients who died pre-RRT received palliative care as compared to 76% post-RRT (P < 0.01). Family members were present for 70% of the deaths pre-RRT as compared to 89% post-RRT (P = 0.01). Fifty-five percent received opiates pre-RRT as compared to 77% post-RRT (P = 0.01). The average maximum pain during the 24-hour period before death was 3/10 pre-RRT as compared to 1.8/10 post-RRT (P = 0.01). A chaplain attended the bedside in 81% of deaths pre-RRT as compared to 94% post-RRT. The investigators concluded that deployment of the RRT was associated with improved quality of death.
