Emphysema Severity Directly Linked to Coal Dust Exposure
Coal dust exposure is directly linked to severity of emphysema in smokers and nonsmokers alike, according to new research from the National Institute for Occupational Safety and Health (NIOSH).
“In this study we have shown that coal mine dust exposure is a significant predictor of emphysema severity,” said Eileen Kuempel, Ph.D., a senior scientist at NIOSH and lead author of the study.
The findings, which were reported in the August 1 issue of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine (AJRCCM), highlight a health problem related to a growing industry. In the past 25 years, coal production has nearly doubled worldwide.
Dr. Kuempel and colleagues compared lung autopsy results from 722 individuals, including 616 coal miners from West Virginia and 106 non-miners from West Virginia and Vermont. Those from West Virginia were collected from consecutive autopsies from 1957 and 1973 at the Beckley Southern Appalachian Regional Hospital as part of a black lung study. Those from Vermont were taken from consecutive autopsies performed at the University of Vermont between 1972 and 1978. Age at death, race, miner/non-miner status and smoking history were established where possible, and individual exposure to coal dust was estimated using work history data and job-specific dust exposure estimates.
Pathologists Francis Green, M.D., and Val Vallyathan, Ph.D., two of the coauthors on this study, examined sections of the lungs to determine the presence and extent of emphysema. A smaller subset of the study group had their lung tissue analyzed for dust content. Emphysema was graded for type and severity.
The researchers found that cumulative exposure to respirable coal mine dust was a highly significant predictor of emphysema severity after accounting for cigarette smoking, age at death, and race. Miners tended to be older at death than non-miners due to a higher proportion of accidental or other sudden deaths among the non-miners. Miners also smoked less on average, though differences were nonsignificant. However, emphysema in miners was significantly more severe than in non-miners among both smokers and never-smokers. Unsurprisingly, emphysema was also more severe among smokers than never smokers in both miners and non-miners. Coal mine dust exposure and cigarette smoking had similar, additive effects on emphysema severity in this study.
The lung tissue analysis corroborated these findings; the greater the concentration of coal dust in the lungs, the more severe the emphysema.
While the data were collected on miners who worked in the mines before the enforcement of the federal standard limiting legal coal dust concentrations to 2mg/m3 imposed in 1972, the study does have immediate relevance to current occupational safety standards. Even at the current federal standard, a full working lifetime’s exposure would produce a cumulative exposure similar to the levels found in the autopsied miners.
"Based on our findings, exposure to respirable coal mine dust for a full working lifetime at the current 2 mg/m3 standard would increase the emphysema severity index by 99 points on average. This provides additional evidence of the need to reduce dust exposures to 1 mg/m3 or less as NIOSH has recommended." said Dr. Kuempel. “Furthermore, miners in developing countries may be faced with exposure levels in excess of those reported here. Thus, the effects of dust that we report are relevant to current conditions in many countries, including the U.S.”
A 99-point increase on the 1000-point emphysema severity index scale is equivalent to an approximately 10 percent increase in diseased lung tissue. Previous studies have shown that a 99-point increase in emphysema severity could mean the difference between “normal” and “abnormal” lung function or the worsening of existing lung function.
Coal mine dust exposure is now generally accepted as a cause of COPD, but this study will provide the basis for improved recognition of dust-induced COPD, its relationship to cigarette smoking, and may enhance efforts at prevention, diagnosis and medical management of occupational dust-related lung diseases, according to Dr. Kuempel.
“Coal employs over 7 million people worldwide, 90 percent of whom are in developing countries. Coal production has almost doubled in the past 25 years,” notes Benoit Nemery, M.D., Ph.D., in an editorial in the same issue of the AJRCCM. “The environmental and climatic impacts of burning coal are, quite rightly, a source of concern. However, the direct consequences of extracting coal on the health of millions of coal miners must be an equal concern.”
“Improving disease surveillance and awareness among healthcare professionals about the occupational components of COPD including emphysema can increase the effective detection and management of these diseases,” said Dr. Kuempel.
Even Healthy Lungs Labor at Acceptable Ozone Levels
Ozone exposure, even at levels deemed safe by current clean air standards, can have a significant and negative effect on lung function, according to researchers at the University of California Davis.
“The National Ambient Air Quality Standard (NAAQS) for ozone was recently revised to set lower limits for ozone concentrations. Our research indicates that the threshold for decrements in ozone-induced lung function in healthy young subjects is below this standard,” said Edward Schelegle, Ph.D., of the University of California Davis. “Specifically, we found that 6.6 hours exposure to mean ozone concentrations as low as 70 parts per billion have a significant negative effect on lung function, even though the current NAAQS standards allow ozone concentrations to be up to 75 parts per billion (ppb) over an eight-hour period.”
The results we published in the August 1 issue of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
To test whether mean ozone concentrations above and below the new standard induce lung function decrements and to further study the time-course of these decrements, Dr. Schelegle and colleagues recruited 31 healthy nonsmoking individuals to participate in 6.6-hour sessions during which they were exposed to ozone at 60, 70, 80 or 87 ppb or filtered air while undergoing six 50-minute bouts of moderate exercise followed by 10-minute breaks. A 35-minute lunch break separated the third and fourth bouts of exercise.
Lung function for each subject was assessed before, during and after exposure, and each individual answered a questionnaire evaluating their subjective symptoms. Of the four levels of ozone concentration tested, Dr. Schelegle and colleagues found significant decrements in both lung function and subjective respiratory symptoms at 70 ppb and above, beginning at 5.6 hours after exposure.
“These data tells us that even at levels currently below the air quality standard, healthy people may experience decreased lung function after just a few hours of moderate to light exercise such as bicycling or walking,” said Dr. Schelegle. “While these changes were fully reversible within several hours, these findings highlight the need to study susceptible individuals, such as asthmatics, at similar ozone concentrations and durations of exposure. These studies are needed to better understand the acute rise in hospitalizations that often occur in conjunction with high-ozone periods.”
The study also supports the previously reported smooth dose-response curve associated with ozone. That is, the higher the level of ozone, the greater the decrease in lung function. However, the healthy subjects in the study showed a marked individual variability in their responses to ozone, with a few exhibiting strong sensitivity to ozone concentrations. What causes some individuals to respond strongly while others do not is still unknown.
“Schelegle and colleagues do not, nor did they seek to explain the determinants of susceptibility in young, healthy adults,” noted James S. Brown, of the U.S. Environmental Protection Agency, in an accompanying editorial. “Only with continued research efforts will we be able to better characterize the susceptibility in some healthy individuals, to the effects of short-term ozone exposures.”
Dr. Schelegle also notes the need for further research to further elucidate the precise mechanisms that determine an individual’s ozone responsiveness in both healthy and susceptible populations. “Understanding how these mechanisms change with repeated daily exposures is critical, especially as ambient ozone levels are often elevated several days in a row,” Dr. Schelegle said.
Lung Volume Reduction Surgery Shown to Prolong and Improve Life for Some Emphysema Patients
Lung volume reduction surgery (LVRS) can have a significantly beneficial effect in patients with severe emphysema, according to the first ever study to randomize emphysema patients to receive either LVRS or non-surgical medical care.
“We found lung reduction surgery is good treatment alternative for selected emphysema patients since it not only improves survival but also meaningfully improves quality of life for a period of at least five years after the operation,” said lead author of the study, Roberto Benzo, M.D., MSc. of the Mayo Clinic. “Patients who underwent LVRS, with the exception of those who had non-upper-lobe-predominant emphysema, had both a survival and quality of life benefit when compared to similar patients undergoing medical treatment only.”
The results of the National Emphysema Treatment Trial (NETT) study were reported in the August 1 issue of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
The NETT group recruited 1,218 patients with severe emphysema and randomized them to either undergo LVRS or non-surgical medical treatment, which generally consisted of customized use of medication, oxygen support, smoking cessation and pulmonary rehabilitation. LVRS consists of removing a portion of emphysematous lung tissue in the patient. While removing lung tissue in patients whose breathing is compromised may seem counterintuitive, severe emphysema causes “air trapping”, where the patient can inhale, but is unable to force the air back out of the lung. This is one of the main causes of shortness of breath in patients with emphysema.
“By removing the section of lung that is primarily affected with severe emphysema, we can decrease air trapping and consequently the shortness of breath, which can thereby improve the patient’s perceived quality of life,” explained Dr. Benzo.
A total of 608 patients underwent LVRS and 610 received standard medical care. The patients were followed for five years or until they died. All endpoints except death were measured at six-month intervals. The primary outcome was a composite endpoint consisting of death or an “unquestionable and meaningful deterioration” in quality of life, defined as an 8-point or greater drop on the Saint George’s Respiratory Questionnaire, a widely used standardized measure of quality of life in patients with respiratory disease.
In the total sample, the average time until a “composite event”—either death or a serious decline in quality of life— was one year for medically treated patients and two years for patients who had undergone LVRS. Patients whose emphysema was predominantly found in the upper lobes of their lungs—about 65 percent of emphysema patients— also showed quality of life and survival benefits greater than survival benefits alone, suggesting that they lived longer and better.
However, LVRS has a small but inherent danger of perioperative mortality.
“LVRS has risks that patients need to understand and acknowledge,” said Dr. Benzo. “In NETT, close to five percent of the patients undergoing lung reduction died in the post-operative period. However, once the post operative period is over, the quality of life benefit comes right away.”
“NETT was landmark study: randomization was necessary at that point as we did not know the true benefits of the surgery,” said Dr. Benzo. “We now know the individuals that benefit from it. Randomization would be unethical now in the group of individuals that we now know get benefit. This study shed light on the palliative (overall well-being) benefits of the surgery, which many patients consider as important as the survival benefit.
Doctors’ Opinions Not Always Welcome in Life Support Decisions
Some caregivers of critical care patients prefer doctors to keep their opinions on life support decisions to themselves, according to new research that challenges long-held beliefs in the critical care community.
The research, an article to be published in the August 15 issue of the American Journal of Respiratory and Critical Care Medicine, found that surrogates are virtually split when it comes to how much guidance they want to receive from physicians in making end-of-life medical choices on behalf of critically ill patients, according to lead author of the paper, Douglas B. White, of the University of Pittsburgh Medical Center.
“In fact, what we found was that, while a slight majority did prefer doctors to help them make those difficult decisions, many felt that it was a decision they wanted to make without guiding input from doctors other than an explanation of the options,” said Dr. White.
At the end of life, critically ill patients frequently require surrogates to make their medical decisions for them, who, in the absence of advance directives from the patient, must rely on what they believe would have been the patients’ desires. “This puts an enormous emotional burden on surrogates; not only are they losing a loved one, they also may feel burdened by guilt about allowing the patient to die.” said Dr. White. “It was therefore assumed by some in the medical community that a doctor’s dispassionate advice could reduce some of that burden and help surrogates make a good decision with less second-guessing themselves. However, there was little or no research to support this assumption.”
Dr. White and colleagues set out to test that assumption, recently formalized as a recommendation by a number of critical care societies, by asking surrogates of critical care patients to watch and respond to two videos. The videos depicted a hypothetical ICU “family conference” in which surrogates must decide whether to continue or withdraw life support from a loved one who has a small chance of survival with continued intervention, but a high likelihood of severe functional impairment in the long-term, including dependence on a ventilator. Both videos were identical in all ways except one: in one version, the doctor says that the most important thing is for the surrogate to “make the choice that’s consistent with [the patient’s] values,” but states that only the surrogate could make that decision; in the alternate version, the doctor offers his opinion that the patient would likely not have wanted to continue aggressive treatment given the likely outcome.
A total of 169 surrogates who were recruited from four ICUs at the University of California San Francisco Medical Center to watch the films in randomized order and respond to it. The researchers used a multi-method analysis to code the responses and validated their analyses with the surrogates themselves to ensure an accurate and complete qualitative assessment of the data.
To their surprise, Dr. White and colleagues found that only a slight majority, 56 percent, of surrogates expressed a preference for the version in which the physician offered an opinion to limit life support. A slight minority, 42 percent, preferred no recommendation, and the final two percent had no preference.
“This is an important article that has changed my clinical practice,” said J. Randall Curtis, M.PH., M.D., president of the American Thoracic Society and Professor of Medicine Pulmonary and Critical Care Medicine Section Head, Harborview Medical Center in Seattle, WA“I had previously assumed that almost all families would want physicians’ recommendations, but these findings indicate that there is no such consensus among surrogates. I suspect that physicians can do more harm by withholding a recommendation that is desired than by providing a recommendation that is not desired, but this study suggests we should ask rather than assume.”
Just over half (51 percent) of the surrogates expressing a preference for receiving their doctors’ advice believed that it was the doctor’s role to provide that opinion, whereas nearly four of five (79 percent) who preferred not to receive the advice saw it as overstepping.
“A very important part of American bioethics is respecting patient’s choices,” said Dr. White. “The family’s most important job when acting as a surrogate decision maker is to give voice to the patient’s values. I think our research highlights that the physician’s job is to be flexible enough and insightful enough to respond to the surrogate’s individual needs for guidance.
“It is rare that a research paper changes clinical practice, and I think this one will,” said Dr. Curtis.
Misuse of Common Antibiotic is Creating Resistant TB
Use of a common antibiotic may be undercutting its utility as a first-line defense against drug-resistant tuberculosis (TB). Fluoroquinolones are the most commonly prescribed class of antibiotics in the U.S. and are used to fight a number of different infections such as sinusitis and pneumonia. They are also an effective first line of defense against TB infections that show drug resistance. New research shows, however, that widespread general use of fluoroquinolones may be creating a strain of fluoroquinolone-resistant TB.
The results are published in the August 15 issue of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
“While fluoroquinolone resistance in TB strains has been reported since the mid 1990’s, to our knowledge no one had investigated the direct causes of it,” said Dr. We wanted to determine whether and to what extent clinical practices were having an effect of creating that resistance,” said Rose A. Devasia, M.D., M.P.H., clinical instructor of Vanderbilt University.
To investigate the causes of the small but growing proportion of fluoroquinolone-resistant TB cases, Dr. Devasia and colleagues performed a retrospective case-control study using data from the Tennessee Department of Health. They analyzed the records of every newly diagnosed patient with culture-confirmed TB who was also enrolled in Tennessee’s Medicaid program, TennCare between January 2002 and December 2006. Using the TennCare pharmacy database, they were able to obtain information on the patients’ use of fluoroquinolone for the 12 months prior to their TB diagnosis. They used M. tuberculosis isolates taken from each patient to test for fluoroquinolone resistance in each case.
After excluding those who were not enrolled in TennCare or whose culture were either unavailable or unusable, the researchers analyzed data for 640 patients. Age, race and other demographic factors were not significantly associated with resistance, but when researchers further analyzed the data they found a linear association between previous fluoroquinolone exposure and fluoroquinolone resistance.
Overall, patients who had used fluoroquinolones within 12 months of diagnosis were almost five times as likely to have a fluoroquinolone-resistant strain of TB than those who had not used fluoroquinolones, and there was a linear association between length of fluoroquinolone use and fluoroquinolone resistance.
“Patients who had undergone shorter treatment (less than 10 days) had a relatively low rate of resistance of only 1.6 percent,” said Dr. Devasia. “[But] for every additional 10 days of fluoroquinolone use, we found that patients had a 50 percent increase in the likelihood of having resistant TB. Of the116 people who had taken fluoroquinolones, 13 percent had fluorquinolone- resistant TB.”
Interestingly, Devasia and colleagues found that fluoroquinolone resistance was highest among those who had undergone treatment more than 60 days prior to TB diagnosis. “Exposure to fluoroquinolones early in the course of disease may select for and allow a fluoroquinolone-resistant strain to predominate,” explained Dr. Devasia.
John Bernardo, M.D., of Boston University School of Medicine and Wing Wei Yew, M.B., of Grantham Hospital in Hong Kong, noted that pressure on doctors, particularly in settings such as emergency rooms, to inappropriately prescribe antibiotics may contribute to this growing problem. “For now, we all need to be more careful when considering the use of these drugs un the community setting and limit the use of prolonged or repeated courses of fluoroquinolones, or even avoid them altogether, in patients who are risk of having active TB,” they wrote in an accompanying editorial in the same issue of the journal.
“These findings underscore the importance of considering TB in people with symptoms consistent with it and to limit the use of fluoroquinolone in those patients until TB can be definitively ruled out and that repeated courses of fluoroquinolones for the same clinical symptoms may be an indication that TB is the real problem,” said Dr. Devasia.
