Press Release

October 2007

Treating Obstructive Sleep Apnea, Preventing Heart Attacks and Strokes

Researchers in Brazil have found that treating patients who suffer from obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) dramatically reduces early indications of atherosclerosis in just months, linking OSA directly to the hardening or narrowing of the arteries. Until now, no study has demonstrated such a direct relationship between the two.

“OSA is independently associated with increased risk of fatal cardiovascular events that can be reversed by treatment with CPAP,” wrote Luciano Drager, M.D., of the University of São Paulo Medical School in Brazil.

The research was published in the first issue of the American Journal of Respiratory and Critical Care Medicine for October of 2007, published by the American Thoracic Society.

The researchers selected 24 men with severe OSA and no other comorbidities and randomly assigned them to receive either CPAP therapy or no treatment. After establishing the baseline data for each subject, they then tracked several indicators of pre-clinical atherosclerosis, including carotid intima-media thickness (a measure of arterial plaque), pulse-wave velocity (a measure of arterial stiffness), carotid diameter, C-reactive protein (a marker of inflammation), and catecholamine level (a marker of physical stress) over the course of four months.

“[All markers] were similar across the study period in the control group,” wrote Dr. Drager. “In contrast, the group treated with CPAP had a significant decrease in carotid intima-media thickness, pulse-wave velocity, C-reactive protein, and catecholamines.”

While there is a known association between OSA and risk of myocardial infarctions and strokes, the causal connection between OSA and atherosclerosis as the principle mechanism behind those cardiovascular events has proven difficult to establish.

“The majority of patients with OSA share several risk factors for atherosclerosis, including obesity, hypertension, hypercholesterolemia, insulin resistance, and hyperglycemia,” explained T. Douglas Bradley, M.D., and Dai Yumino, M.D., both of the Sleep Research Laboratory at the Toronto Rehabilitation Institute at the Centre for Sleep Medicine and Circadian Biology at the University of Toronto, in an editorial in the same issue of the journal.

Furthermore, while non-randomized observational trials have suggested that the risk of adverse cardiovascular events is lower among patients who accept treatment by CPAP than in patients who do not accept CPAP therapy, it is possible that this difference may be due to better overall adherence to all prescribed treatments in patients who accept CPAP than in those who do not, as opposed to any direct benefit of CPAP itself.

“Whereas physiological studies suggest that OSA provides a substrate for the development of atherosclerosis, and epidemiological and observational studies suggest an association between OSA and odds of having atherosclerosis, there remains a gap between cause and effect yet to be filled,” wrote Drs. Yumino and Bradley. “Drager and colleagues provide evidence that begins to fill that gap.”

Indeed, after four months of CPAP therapy, carotid intima-media thickness declined by nine percent, which is remarkable in light of the fact that in a large-scale study, patients undergoing cholesterol-lowering pravastatin therapy saw carotid intima-media thickness decline by twelve percent after a full year. Other indicators showed similar magnitudes of improvement.

The researchers put forth a number of potential pathways whereby OSA could contribute to atherosclerosis progression, including inflammation, oxidative stress, lymphocyte activation, and high-density lipoprotein dysfunction. “CPAP treatment could reverse several of these pathways,” they wrote.

Still, the investigators caution that, while they are confident in the biological validity of their results, the rigid inclusion criteria makes it difficult to extrapolate their results to different populations, including women, patients with other co-morbidities and patients with mild to moderate OSA.

Acute Lung Injury Patients One-Third Less Likely to Die in “Closed” Model ICUs

Patients with acute lung injury (ALI) are nearly one-third less likely to die if they are treated at ICUs that require board-certified critical care physicians to oversee patient care, as compared to patients treated at ICUs that allow any attending physician to oversee admission and case management.

ALI is an inflammatory disorder of the lung often seen in patients with pneumonia or sepsis. Mortality rates are high—about 40 percent—and worsen with age and co-morbidities. Treatment generally involves addressing the underlying condition and providing protective low tidal volume mechanical ventilation and supportive therapy.

“ICUs that require patient transfer to an intensivist run team or mandate a co-attending intensivist are associated with reduced mortality in patients with ALI,” wrote Miriam Treggiari, M.D., M.P.H., of the Harborview Medical Center at the University of Washington, who led the study that appears in the first issue for October of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

The study is the first to use data from a population-based prospective cohort of patients to evaluate outcomes of different ICU organizational models. As part of the National Institutes of Health funded King County Lung Injury Project, all patients in Seattle area ICUs receiving mechanical ventilation were screened for ALI, between April 1999 and July 2000. Detailed data on co-morbidities, length of hospital stay and discharge information was collected. Questionnaires were sent to both the medical directors and/or attending physicians of the ICUs and the nurse managers to assess the organizational model and structure of the ICUs. The final study group included 1,075 patients in 22 ICUs across 16 hospitals.

Two-thirds of the patients were treated at “closed” ICUs—units that require cases to be managed by board-certified critical care physicians or that mandate intensivists to co-manage on all patients. The remaining third received care at “open” ICUs, where cases could be managed by any attending physicians with admitting privileges, and pulmonary consultations were optional. According to the American College of Chest Physicians, only 25 percent of ICUs nationwide follow the closed model.

There were no significant differences in the degree of illness between patients who were cared for in closed versus open ICUs as measured by Acute Physiological and Chronic Health Evaluation III (APACHE III) scores, but patients at closed ICUs were younger and more likely to be male.

“Patients cared for in a closed ICU had statistically significantly lower mortality than patients cared for in open ICUs,” the researchers reported. Interestingly, the effect remained significant after adjusting for a number of variables in the analysis. While 77 percent of patients in closed ICUs were seen by a pulmonary consultant, consults alone did not have a significant effect on mortality. Similarly, adjusting for nurse-to-patient ratio and hospital volume of mechanically ventilated patients had no effect on mortality. Of patients treated in open ICUs, 45 percent died; in closed ICUs there was 35 percent mortality.

The investigators noted that because of the small sample size of hospitals and the date of the data collection, it would be difficult to extrapolate their results to a general trend among ICUs in the United States. Noting that the use of low tidal volume mechanical ventilation differed between closed and open ICUs, the researchers remarked that other unrecognized differences in patient care could exist, but that their results add support for the positive effect of a closed ICU model on patient outcome.

“These findings add to the evidence of the important role of intensivist staffing in caring for critically ill patients, and support the recommendations to implement closed-model ICUs in the United States,” said Dr. Treggiari. “Further studies will need to investigate if the beneficial effects of closed ICU derive from higher degree of staffing that could facilitate earlier recognition of critical/deteriorating conditions or greater expertise in the specific management aspects of critical care patients.”

Dysfunctional Families and Bad Neighborhoods May Worsen Asthma in Children and Adolescents

A lack of family support and problems in one’s neighborhood are associated with greater asthma symptoms in children and adolescents, according to researchers in Vancouver, Canada.

Social environment has long been thought to be an important factor in asthma manifestations in youth, but few studies have empirically tested social factors at the family, peer and neighborhood levels and their implications for childhood asthma.

Edith Chen, Ph.D., of the University of British Columbia, and other researchers set out to determine whether, and to what extent, social factors influence asthma symptoms and lung function. They reported their results in the first issue for October in the American Journal of Respiratory and critical care Medicine, published by the American Thoracic Society.

The researchers hypothesized that greater neighborhood problems and a lack of peer and family support would all relate to greater asthma morbidity. Furthermore, they hypothesized that social factors would work by altering either biological systems, such as inflammation, or behaviors, such as smoking.

They recruited 78 children who had physician-diagnosed asthma without other chronic illnesses, and assessed the extent to which youth perceived support from family, support from peers and problems in their neighborhood, such as crime and violence. They measured their lung function using standardized spirometry techniques, and assessed their asthma symptoms based on interviews and daily diaries that the subjects kept. They also assessed behaviors, including smoking and compliance with medications, and evaluated biological markers of inflammation including IgE, eosinophil count and IL-4 production.

The investigators found a correlation between social environment and asthma symptoms and lung function. Asthma symptoms were greater among children who reported less family support and lived in worse neighborhoods; lung function also was poorer among children who reported less family support.

To determine possible reasons for these associations, the researchers performed statistical analyses of pathways linking family support and neighborhood problems to asthma symptoms and lung function. They found that family support and asthma outcomes were linked via inflammation, but not behaviors. That is, low levels of family support were associated with greater inflammation, and, in turn, greater inflammation was associated with poorer asthma outcomes. In contrast, family support did not appear to change children’s behaviors.

Neighborhood problems and asthma symptoms were linked through behavioral pathways, but not through inflammation. The more problematic neighborhoods were associated with greater rates of child smoking and exposure to smoke. In turn, smoking was associated with poorer asthma outcomes. In contrast, neighborhood characteristics did not appear to change children’s inflammatory profiles.

“Poor family relations may foster psychological experiences with direct physiologic consequences, whereas problematic neighborhoods may operate by providing role models for maladaptive behaviors,” wrote Dr. Chen.

Interestingly, peer group support had no significant effects on asthma symptoms or lung function. These findings suggest that among children with asthma, family and one’s neighborhood play a more important role in asthma morbidity than do peers.

Dr. Chen noted that the study group was small and that the cross-sectional design of the study precluded drawing a direct causal relationship, stressing that more research is necessary before drawing any definitive conclusions. If these findings are confirmed in future research, however, they could have important implications for asthma interventions. For example, interventions that target family interaction patterns may help improve children’s asthma by altering biological profiles. The neighborhood effects suggest the potential utility of making community-wide changes that could help shape the health behaviors of children with asthma.

“To test these implications, future research is needed that investigates the effects of experimental manipulations of social factors on childhood asthma morbidity,” said Dr. Chen.

Even Occasional Use of Spray Cleaners May Cause Asthma in Adults

Using household cleaning sprays and air fresheners as little as once a week can raise the risk of developing asthma in adults, say researchers in Europe. Such products have been associated with increased asthma rates in cleaning professionals, but a similar effect in nonprofessional users has never before been shown.

“Frequent use of household cleaning sprays may be an important risk factor for adult asthma,” wrote lead author Jan-Paul Zock, Ph.D., of the Centre for Research in Environmental Epidemiology at the Municipal Institute of Medical Research in Barcelona, Spain.

The epidemiological study, the first to investigate the effects of cleaning products on occasional users rather than occupational users, appeared in the second issue for October of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

The investigators used baseline data from the first phase of the European Community Respiratory Health Survey (ECRHS I), one of the world's largest epidemiologic studies of airway disease, and interviews conducted in the follow-up phase, ECRHS II. Altogether, the study included more than 3,500 subjects across 22 centers in 10 European countries. Subjects were assessed for current asthma, current wheeze, physician-diagnosed asthma and allergy at follow-up, which took place an average of nine years after their first assessment. They were also asked to report the number of times per week they used cleaning products.

Two-thirds of the study population who reported doing the bulk of cleaning were women, about six percent of whom had asthma at the time of follow-up. Fewer than ten percent of them were full-time homemakers.

The risk of developing asthma increased with frequency of cleaning and number of different sprays used, but on average was about thirty to fifty percent higher in people regularly exposed to cleaning sprays than in others. The researchers found that cleaning sprays, especially air fresheners, furniture cleaners and glass-cleaners, had a particularly strong effect.

“Our findings are consistent with occupational epidemiological studies in which increased asthma risk was related to professional use of sprays among both domestic and non-domestic cleaning women,” wrote Dr. Zock. “This indicates a relevant contribution of spray use to the burden of asthma in adults who do the cleaning in their homes.”

The design of the study was not intended to determine the biological mechanism behind the increase in asthma with exposure to cleaning sprays, but Dr. Zock and colleagues propose a number of hypotheses, including the possibility that asthma is partially irritant-induced, that sprays contain sensitizers that are specific to asthma, and/or that an inflammatory response is involved in asthma development. “There is a need for researchers to conduct further studies to elucidate both the extent and mechanism of the respiratory toxicity associated with such products,” noted Dr. Zock.

Despite the uncertainty of the biological mechanism, the findings have important clinical relevance. “Clinicians should be aware of the potential for cleaning products used in the home to cause respiratory symptoms and possibly asthma,” wrote Kenneth D. Rosenman, M.D., professor at Michigan State University, in an editorial in the same issue of the journal.

The research may have also significant implications for public health. “The relative risk rates of developing adult asthma in relation to exposure to cleaning products could account for as much as 15 percent, or one in seven of adult asthma cases,” wrote Dr. Zock.

Statins Reduce Loss of Function, Keeping Old Lungs Young—Even in Smokers

Statins are known to be good for lowering cholesterol and maybe even fighting dementia, and now they have another reported benefit: they appear to slow decline in lung function in the elderly— even in those who smoke. According to researchers in Boston, it may be statins’ anti-inflammatory and antioxidant properties that help achieve this effect.

Their findings were published in the second issue for October in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

“We hypothesized that statins would have a protective effect on decline in lung function,” wrote Dr. Joel Schwartz, Ph.D., professor of environmental epidemiology at Harvard School of Public Health, a lead researcher on the study, the first to examine the relationships between statins and lung function decline.

“The link between lung function and mortality and the reduced levels of lung function in the elderly indicates the importance of a possibility of reducing the rate of decline,” wrote Dr. Schwartz.

To investigate whether statins had an effect of loss of lung function, the researchers used data from the ongoing and longitudinal Veterans Administration Normative Aging Study, which began in 1963. They analyzed 803 subjects who had had their lung function measured at least twice between January 1995 and June 2005. Both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured. The study subjects also completed questionnaires on pulmonary disorders, smoking and medication usage.

The investigators found that subjects taking statins experienced a markedly slower annual decline in lung function. In FEV1, statin users lost 10.9 ml on average, whereas nonusers lost an average of 23.9 ml each year—more than twice that of the statin group. Similarly, statin users lost an average of 14 ml a year in FVC, whereas nonusers lost an average of 36.2 ml.

To determine whether smoking status modified that effect, the researchers also divided their subjects into four smoking groups: never-smokers, long-ago quitters, recent quitters and current smokers. “Within each smoking group, those not taking statins were estimated to experience faster declines in FEV1 and FVC than those taking statins,” wrote Dr. Schwartz, noting that the size of the effect varied a bit with smoking status.

“Our results suggest (weakly) that long-term quitters and recent quitters may be able to benefit more from statin use than other groups,” Dr. Schwartz wrote.

But because of overlap between groups and the lack of randomization and controls in this study, the researchers point out that further data is needed before any definitive conclusions are drawn. Their findings do, however, support the hypothesis that statins reduce the annual loss of lung function that occurs with age.

The researchers suggest that the observed effect may be attributable to statins’ ability to reduce inflammation and smoking-induced injury in the lung, as well as their capacity to reduce serum levels of C-reactive protein, which relates to systemic inflammation, and to protect against oxidative damage.

The research adds to a growing body of knowledge indicating the positive effects of statin use beyond its cholesterol lowering properties.

COPD Rates, Higher than Expected in China, Will Continue to Grow

In China, chronic obstructive pulmonary disease (COPD) in people over the age of 40 is much more prevalent than previously thought, according to researchers in Guangdong.

Their findings appear in the second issue for October of the American Journal of Respiratory and Critical care Medicine, published by the American Thoracic Society. The investigators administered spirometric tests and questionnaires to a cross-sectional population in seven provinces/cities in China. Of the more than 20,000 who completed these materials, 8.2 percent of respondents over 40 met the criteria for having COPD.

Men were more than twice as likely to have COPD as women. But while smoking was, and is, a significant risk factor for COPD in China, only 24 percent of the females with COPD were smokers, as opposed to nearly 82 percent of males, suggesting that women’s risk might be more strongly associated with the use of biomass fuels, especially for cooking in poorly ventilated areas.

“Although China has experienced remarkable modernization over the past two decades, in many rural areas residents continue to use wood, charcoal or coal for fuel, leading to significant biomass exposure, especially in women, who perform most of the cooking duties,” wrote Don D. Sin, M.D., and Wan Tan, M.D., of the University of British Columbia in Vancouver, Canada, in an editorial in the same issue of the journal.

“To the best of our knowledge, this is the first large-scale, population-based epidemiologic study on COPD prevalence in China,” wrote Nanshan Zhong, M.D., of the Guangzhou Institute of Respiratory Diseases at The First Affiliated Hospital in Guangzhou Medical College, and lead researcher.

According to an estimation by the World Health Organization, COPD ranks first among the burdens of diseases in China and accounts for one million deaths and five million disabilities each year.

The researchers selected provinces and cities from a wide range of geographic areas within China, and then selected an urban and a rural area within each province/city. They then used randomized cluster sampling from a randomly selected street or township, and attempted to recruit all individuals older than 40. About 79 percent of attempted were successfully contacted. They completed questionnaires and underwent spirometric testing for obstructive and restrictive lung disease.

While the overall rate of COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was higher than expected, there were some notable differences among the population.

“Multivariate logistic regression analyses showed that smoking, pulmonary problems in childhood, family history of respiratory diseases, male sex, low education level, aging, lower body mass index, poor ventilation in the kitchen, and exposure to biomass and occupational dust/gases/fumes are associated with COPD,” wrote Dr. Zhong.

Importantly, more than a third of the subjects who had COPD were asymptomatic, and nearly two-thirds had never been diagnosed, suggesting that diagnosis of COPD on symptoms alone is not sufficient.

“Even among subjects with GOLD stages 3 and 4 of the disease, fewer than 10 percent have ever received spirometry,” noted Drs. Sin and Tan. “The gross underutilization of spirometry represents a ‘Great Wall,’ a huge barrier to good care for patients with COPD in China.”

Dr. Zhong and colleagues’ findings present a dark picture of COPD in China, which is expected to grow worse before it gets better due to an aging population and rising smoking rates, especially in women.

“Our results highlight COPD as a major public health problem in China and call for more research to be directed toward preventative measures and efforts,” wrote Dr. Zhong.