Meeting Report

AMERICAN THORACIC SOCIETY • MAY 20-25, 2005 • SAN DIEGO, CA

The American Thoracic Society celebrated its 100th anniversary at this year’s annual meeting in San Diego, CA, May 20-25. There were interesting retrospectives on progress in the understanding and treatment of respiratory diseases over this period of time, as well as even more interesting predictions of future advances.

Advances in the application of genetics to the understanding of the epidemiology, pathogenesis, and treatment of disease hold the most potential for major future breakthroughs in health care in general, but especially so in respiratory diseases. These areas of research still appear to be years, if not decades, away from actual practical application. However, there already have been significant transgenic and gene knockout successes in animal models.

A new jargon has evolved to describe these investigations. Genomics involves the searching of the entire genome for candidate genes linked to disease processes, and often involves working backwards from the genetic clusters found in groups of individuals with the disease in question. It also may mean studying genetic patterns in animal models that have natural or transgenic forms of the disease.

Proteonomics involves studying the specific gene location or locations associated with production or failure of production of target proteins linked to a disease. Pulmonomics is a neologism that includes both of the above processes in investigating respiratory diseases.

It is already evident that breakthroughs in the understanding of disease in one system (ie, the lungs) can have a major impact on the understanding of disease processes in other physiological systems. For example, advances in the understanding of inflammatory processes associated with asthma and chronic obstructive pulmonary disease (COPD) appear to have parallel processes involved in rheumatoid arthritis, gingivitis, atrophic gastritis, diabetes mellitus, and even heart disease. Furthermore, it is increasingly recognized that the cytokines and other messaging proteins associated with a respiratory disease like COPD can have systemic effects on muscle, bone, blood vessels, appetite, and even mood. It was observed at a symposium on management of COPD that while aggressive management of moderate-to-severe COPD prolongs life expectancy, the gain appears to be mostly in the reduction of cardiovascular death in these patients rather than the prevention of respiratory death. Thus, the benefit of treatment may be primarily a systemic rather than a pulmonary effect.

UPDATE ON COPD

One of the most interesting areas of meeting content was the discussion of advances in the understanding and treatment of COPD. Unfortunately, COPD remains one of the more poorly managed of the major chronic diseases in the United States. It is estimated that approximately 24 million persons have COPD, and over half of them are undiagnosed, and therefore untreated. Smoking accounts for more than 95% of COPD in the United States and remains the prime target for intervention at any stage of the disease. Age also is a risk factor for COPD. As more persons survive other diseases and live longer, they are at increased risk of developing COPD, due to the compounding of other risk factors and the effects of aging on the lung. This fact is sometimes overlooked in geriatric patient care; chronic cough or shortness of breath can be misinterpreted as chronic asthma or heart-related symptoms. Chronic active asthma and passive smoke exposure increase the incidence of COPD in nonsmoking persons. Thus, even in the absence of a smoking history, pulmonary functions tests may be indicated to check for COPD if respiratory symptoms exist.

The comorbid conditions associated with COPD also may be more likely to be present or aggravated in the geriatric population. Heart failure can be caused or worsened by hypoxia, pulmonary hypertension, or the elevated hematocrit associated with COPD. Depression, sexual dysfunction, and generalized muscle and tissue wasting is common in COPD, all of which can be mis-attributed to “old age.” The secondary effects on bone metabolism are especially prevalent in COPD. One presenter cited a study that showed that 99% of persons with COPD had either osteopenia or osteoporosis when evaluated by DEXA scan. Virtually every person with the diagnosis of COPD would benefit from active intervention to improve bone health. The recurring theme of these symposia was that COPD is a treatable disease, and that early and active management can reduce morbidity and mortality and improve quality of life for these patients.

Treatment of COPD remains primarily smoking cessation. However, active treatment including immunizations (flu, pneumovax), education, and medications is indicated even in the face of continued smoking. Bronchodilators should be initiated for mild-to-moderate disease, and inhaled corticosteroids (ICS) should be considered for more severe disease or if there are frequent exacerbations of bronchitis. Traditional bronchodilators, such as the short- and long-acting beta-agonists and anticholinergics including ipatropium, are useful.

The new long-acting anticholinergic agent, tiotropium, which was approved this past year by the FDA, appears to be the agent of choice because of its 24-hour coverage with once-a-day dosing. Research has shown that airway inflammation is the driving factor in the pathogenesis of the disease, and it produces both direct obstruction from secretions and inflammation as well as actual airway destruction.

Unfortunately, the inflammation associated with COPD, unlike asthma, is quite resistant to anti-inflammatory therapy and requires higher doses of ICS for effect. There was mention at the meeting of a large 3-year study, Towards a Revolution in COPD Health (TORCH), which will be completed in November 2005, that was specifically designed to assess the effect of high-dose ICS on the morbidity and mortality of COPD. Stay tuned.

Recent research has shown that in susceptible persons, the inhalation of smoke stimulates overproduction of phosphodiesterases in the airways. These compounds have multiple deleterious effects causing active promotion of inflammatory reaction in the airway tissues, impairment of the body’s natural ability to regulate or modulate the inflammatory response, and impairment of the ability of anti-inflammatory therapy such as ICS to be effective. This has led to promising research in the area of pharmacologic agents that are selective anti-phosphodiesterase agents that significantly reduce the inflammatory process in COPD. Theophylline and other xanthine derivatives have anti-phosphodiesterase activity, but due to their lack of selectivity they are associated with side effects that limit their usefulness. The first generation of newer agents have had some of the same problems as theophylline, but more selective agents are in the pipeline.

UPDATE ON OBSTRUCTIVE SLEEP APNEA

It is well known that aging is a risk factor for disordered sleep, and specifically for obstructive sleep apnea (OSA). There were a number of papers and abstracts on recent research on OSA indicating its association with significant systemic problems beyond the known risks for hypertension and cardiovascular disease.

Persons with OSA have been shown to have higher levels of circulating catecholamines. This has been shown to raise insulin levels, and on a chronic basis may be linked to insulin resistance and impaired glucose tolerance. Persons with OSA and metabolic syndrome or type II diabetes have been shown to improve glucose tolerance, insulin sensitivity, and glycated hemoglobin levels with appropriate continuous positive airway pressure (CPAP ) therapy. The fatigue and drowsiness associated with OSA can also cause significant changes in mental function and may be mistaken for clinical depression, or even early dementia. CPAP therapy in OSA has been shown to significantly improve mental and emotional functioning. Although CPAP is the treatment of choice for OSA, some persons still have poor sleep structure even with CPAP, and these individuals may benefit from the new drug modafinil, which can improve daytime wakefulness.

The snoring that is associated with OSA may also be more than an annoyance to the person’s bed or room partner. The loudness of snoring has been measured as high as 80 decibels. That level of noise exposure in the workplace would require an ear protector, and some partners may be at risk of acoustic trauma from this exposure. The loud snoring also creates vibration in the local tissues of the throat and neck, which appears to be a source of significant inflammation. Several studies reported increased levels of circulating cytokines and C reactive protein associated with OSA, suggesting that this may be another source of systemic effects of the disease. One investigator even reported an association between the intensity of snoring and the risk of stroke, and he postulated the possibility that the vibrations in the neck may be sufficient to “shake loose” pieces of plaque in the carotid arteries.

Perhaps the most sobering statistic regarding sleep apnea is that it is estimated that up to 80% of persons with this disorder are undiagnosed, and therefore untreated. Aging and obesity are both risk factors, so we should certainly be aware of the potential for this disorder in overweight elderly persons.