American Thoracic Society 2010 International Conference
The 2010 International Conference of the American Thoracic Society (ATS) was held in New Orleans, LA, May 14-19, with an international attendance of over 15,000 persons. This annual meeting of respiratory health researchers and clinicians took on additional significance since 2010 has been designated the “Year of the Lung” by hundreds of international organizations focusing on the importance of lung health and lung disease. The campaign is aimed at educating the public, elected officials, and the media about the global importance of respiratory health and the quality of the air that we breathe.
An international task group has been formed with members representing the major respiratory societies and health organizations, including the World Health Organization (WHO). The website www.2010yearofthelung.org describes how the campaign was developed and how individuals or organizations can become partners. One of the major efforts of the campaign is to get every country to ratify the WHO Framework Convention on Tobacco Control, already signed by more than 160 countries around the world. Ratifying countries agree to adopt such measures as a ban on tobacco advertising, warnings on tobacco products, initiatives to protect nonsmokers from tobacco products, and taxes to reduce tobacco consumption. Clearly, a major focus of the campaign is targeted at reducing tobacco consumption and improving air quality, but there are also major advocacy efforts directed at improving asthma care, eliminating tuberculosis, treating sleep disorders, and many other important lung health problems. Coincidently, another campaign has been launched this year in this country, the “Drive4COPD” program (www.drive4copd.com), sponsored by Boehringer Ingelheim Pharmaceuticals, Inc., the COPD Foundation, NASCAR, the American Lung Association, and other public and private organizations targeting earlier awareness and treatment of chronic obstructive pulmonary disease (COPD). It is especially focused on the “missing millions,” the estimated 12 million persons in the United States who have COPD but are not aware of it.
Smoking is a known major risk factor for respiratory disease as well as a number of other health problems, so a half-day session at the ATS meeting focused on understanding barriers to quitting and strategies to improve smoking cessation outcomes. A multicentered, multinational, controlled trial (N = 598) reported significantly better quit rates at the end of 12 weeks of treatment (53.59% vs 18.69%; P < 0.0001; odds ratio [OR], 5.76) using varenicline versus placebo with both groups receiving counseling at each visit. The quit rate was sustained better to 24 weeks in the treatment group (39.74% vs 13.13%; P < 0.001; OR, 4.78), and the treatment was well tolerated, with only a 4.1% dropout rate due to treatment-emergent side effects versus 1.5% in the placebo group.
For many persons, especially women, a significant barrier to smoking cessation is the weight gain that ensues with quitting. Researchers from Greece hypothesized that the appetite suppressant effect of nicotine could be at least partially maintained using the nicotine receptor agonist varenicline as an aid in smoking cessation. In a small study (N = 15), they demonstrated that persons using varenicline had an average weight gain of 4.18 pounds versus a weight gain of 8.8 pounds in a control group when measured four weeks after successful smoking cessation in both groups.
Another study jointly conducted by Japanese and U.S. researchers (Cincinnati, OH) compared spontaneous smoking cessation rates in two groups of smokers who were seen for annual check-ups at a health clinic. Both groups had spirometry done as a part of their examination, and one group (N = 1034) was given their spirometry results plus a calculated “lung age.” The control group (N = 988) was simply given their spirometry results as a percentage of predicted values. Lung age is calculated from a nomogram (some spirometers give it automatically as part of the spirometry results) that converts a person’s actual FEV1 to the age for which that would be the normal or predicted FEV1. A person with significant obstructive lung disease will have a “lung age” that is substantially older than his/her chronological age. With no other intervention than the lung age information, that group had an eight times greater smoking quit rate (1.64% vs 0.2%) than the control group when contacted by questionnaire one year later. Even though the quit rates were low in both groups, the researchers felt that using lung age as an additional motivator may improve outcomes in smoking cessation programs.
Asthma, in addition to COPD, is another major lung disease that is not well managed in many patients. Asthma does not have “missing millions” of undiagnosed persons like COPD, but many asthma patients are undertreated and rely too much on rescue medication (albuterol) for symptom relief. In a session on asthma, data were reviewed from a national asthma survey that indicated that 41% of persons responding to a screening questionaire (Asthma Control Test) were not in good control with respect to frequency/severity of symptoms and impact of symptoms on daily life. Monitoring albuterol use is recommended as one of the best indicators of asthma control. One canister of albuterol has 200 puffs or 100 doses, and good asthma control is defined as two or fewer doses of rescue medication per week. Therefore, one canister should last at least 50 weeks or approximately one year. Patients calling for refills of albuterol more often than once a year should be evaluated for better control. Doses of albuterol that are used as prophylaxis for exercise-induced asthma are not considered rescue use and would be an exception to the use of more than one canister per year.
An interesting study with relevance to eating habits and food choices of persons with asthma was reported by researchers from Newcastle, Australia. They recruited 40 subjects with persistant asthma and randomized them to a “food challenge” of either a high-fat, high-energy 1000-calorie meal (fast food burgers and hash browns, 52% calories from fat), or a low-fat, low-energy 200-calorie meal (reduced-fat yogurt, 13% calories from fat). Sputum samples were collected before the meal and four hours later and were analyzed for inflammatory markers. Persons with the high-fat meal challenge had a marked increase in airway neutrophils and toll-like receptor 4 (TLR4) messenger ribonucleic acid (mRNA) expression. TLR4 is a cell surface receptor and is activated by nutritional fatty acids. TLR4 “senses” the presence of saturated fatty acids and prompts the cell to respond as if they were an invading pathogen, releasing inflammatory mediators. In addition to increased neutrophils in the airways, the inflammatory cytokine interleukin-8 and the protease neutrophil elastase were increased in the sputum of the high-fat challenge group. A surprise finding from pre-/post-challenge spirometry measures indicated a significantly impaired bronchodilator reponse to albuterol in the high-fat group. These researchers are planning further studies to explore these findings, but they suggest that fat consumption may have an impact on asthma control, and strategies to manage fat intake may be important in the clinical mangement of some persons with asthma.
There have been observations from cohort studies and from clinical practice that women with asthma tend to have increased symptoms and exacerbations during the low estrogen phase of the menstrual cycle and after menopause if they do not have hormone replacement. Researchers from the Mayo Clinic (Rochester, MN) hypothesized that this may be due to the effect of estrogen on intracellular calcium levels. They designed an in vitro experiment using smooth muscle tissue from surgical specimens. They found that acute (15 min) exposure to estradiol at physiologic concentrations decreased intracellular calcium in airway smooth muscle cells. Furthermore, small amounts of estradiol significantly decreased force production in smooth muscle cells when stimulated by bronchoconstrictors, suggesting a bronchodilator effect. To further evaluate the bronchodilator effect, they tested a combination of estradiol and the beta-agonist isoproterenol, as well as each agent individually, on airway smooth muscle cells. They found that the combination had a synergistic effect on decreasing intracellular calcium and contraction force more than either agent alone. They acknowledged that more research is needed to understand the in vivo effects and chronic use of agents, but these findings may have implications for hormone replacement in postmenopausal asthma management, and perhaps could even lead to an inhaled combination estrogen/beta-agonist agent for women with asthma.
Management of COPD has been increasingly focused on preventing and reducing severity of acute exacerbations. Many exacerbations are caused by bacterial infection with hemophilus, pneumococcus, moraxella, or pseudomonas. Attempts to reduce bacterial infections using chronic antibiotic therapy have been less than successful due to side effects and the tendency for these organisms to develop resistance. Inhalation therapy with antibiotics (tobramycin) in patients with cystic fibrosis and bronchiectasis has been shown to have some success in reducing colonization with pseudomonas. This has led researchers to explore the inhalation mode of antibiotic therapy for persons with COPD and frequent exacerbations. For an inhaled antibiotic to be useful in COPD it must: (1) have efficacy against the four common bacterial organisms; (2) not itself cause lung irritation; (3) be deliverable to the bronchiole levels of the lung (ie, 5-8 micron particle size); and (4) not cause significant systemic side effects or bacterial resistance. The fluoroquinolones have a good spectrum of coverage for these organisms, and researchers have been successful in designing a levofloxacin molecule that is well tolerated in the lung and reaches the bronchiole level of the pulmonary tree. Pulmonary tissue levels of this inhaled antibiotic are ten times higher than those achieved with oral dosing, and the systemic blood levels are quite low, with levels less than one hundredth of that in the lung. Pilot studies with inhaled levofloxacin suggest that it might be most successful when used as “pulse therapy,” several days of treatment every 2-4 weeks. The tissue levels are so high in the lung that it is very effective at eliminating those pathogenic bacteria quickly with less chance of resistance developing, and the pulsing of therapy minimizes side effects and resistance as well. Long-term safety trials are under way.
Statins and Thromboembolic Disease
Statin therapy has been observed to have clinical benefits beyond the management of dyslipidemias. One such area has been the antithrombotic benefits of statin therapy presumably due to anti-inflammatory effects. Researchers from the University of Connecticut conducted an impressive meta-analysis of all of the major statin clinical trials to try to quantitate the antithrombotic benefit of statin therapy. They found ten trials totaling more than 900,000 subjects who met their meta-analysis criteria. They found that statin therapy reduced the risk of deep vein thrombophlebitis by 41% (OR, 0.59; confidence interval [CI], 0.43-0.82) and reduced the risk of pulmonary embolus by 30% (OR, 0.70; CI, 0.53-0.94). The researchers concluded that patients at serious risk for thromboembolic disease might warrant statin therapy prophylactically.
Dr. Keenan is a retired professor from the Department of Family Medicine, University of Minnesota, Minneapolis.