Press Release

January 2008

Handling Pesticides Associated with Greater Asthma Risk in Farm Women

New research on farm women has shown that contact with some commonly used pesticides in farm work may increase their risk of allergic asthma.

“Farm women are an understudied occupational group,” said Jane Hoppin, Sc.D., of the National Institute of Environmental Health Sciences and lead author of the study. “More than half the women in our study applied pesticides, but there is very little known about the risks.”

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

The researchers assessed pesticide and other occupational exposures as risk factors for adult-onset asthma in more than 25,000 farmwomen in North Carolina and Iowa. They used self-reports of doctor-diagnosed adult asthma, and divided the women into groups of allergic (atopic) or non-allergic (non-atopic) asthma based on a history of eczema and/or hay fever.

They found an average increase of 50 percent in the prevalence of allergic asthma in all farm women who applied or mixed pesticides. Remarkably, although the association with pesticides was higher among women who grew up on farms, these women still had a lower overall risk of having allergic asthma compared to than those who did not grow up on farms, due to a protective effect that remains poorly understood.

"Growing up on a farm is such a huge protective effect it's pretty hard to overwhelm it," said Dr. Hoppin. "[But] about 40 percent of women who work on farms don't report spending their childhoods there. It is likely that the association with pesticides is masked in the general population due to a higher baseline rate of asthma."

Dr. Hoppin also found that most pesticides were associated only with allergic asthma, even though non-allergic asthma is generally more common in adults. “Asthma is a very heterogeneous disease,” said Dr. Hoppin. “This finding suggests that some of the agricultural risk factors for allergic and non-allergic asthma may differ.”

Some legal but rarely used compounds, such as parathion, were associated with almost a three-fold increase in allergic asthma. But even some commonly used pesticides were associated with a marked increase in allergic asthma prevalence. Malathion, for example, a widely used insecticide, was associated with a 60 percent increased prevalence of allergic asthma.

Of all the compounds examined, only permethrin, a commonly used insecticide that is used in consumer items such as insect-resistant clothing to anti-malaria bed-nets, was associated with both allergic and non-allergic asthma.

This is the first study to examine pesticides and asthma in farm women, and it points the way for future research to clarify the relationship. “At the end of the day, you have to remember that we’re looking at cross-sectional data, thus we cannot establish a temporal association between pesticide use and asthma,” cautions Dr. Hoppin. “There is a difference in asthma prevalence between women who did and did not use pesticides but whether it is causal or not remains to be seen.”

Dr. Hoppin and her colleagues are in the midst of planning a large scale prospective study that will better evaluate the links between pesticide exposures and asthma. “We want to characterize the clinical aspects of this disease, as well as lifetime exposures to agents that may either protect against asthma or increase risk,” said Dr. Hoppin. “We hope to start the study in 2008.”

New Therapy Reduces Mortality in Patients with Severe COPD

Patients with severe COPD may benefit more from therapy that combines salmeterol and fluticasone [SFC] than treatment with tiotropium, according to results from a long-term, multi-center study, “Investigating New Standards for Prophylaxis in Reducing Exacerbations” (INSPIRE) that directly compared the two therapies.

“Although we found no difference in the overall rate of exacerbations between treatment groups, SFC treatment was associated with better health status, fewer patient withdrawals, and a lower mortality rate than occurred during tiotropium therapy,” said lead author if the study, Jadwiga Wedzicha, M.D., of the Royal Free & University College Medical School in London

This was the first large-scale trial to directly compare the two different treatment approaches. The results appeared in the first issue for January of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

The researchers recruited 1,323 patients with severe COPD and randomized them to receive one of two treatments—either SFC or tiotropium—for two years. They analyzed number and type of exacerbations, health status as measured by the St. George’s Respiratory Questionnaire (SGRQ), lung function (post-dose forced expiratory volume in one second) and study withdrawal rate. The study was double-blinded and double-dummy controlled, and all patients underwent identical intensification of treatment before beginning the trial to standardize their clinical conditions.

While exacerbation rates between the two treatment groups were statistically indistinguishable, there were differences in the treatment that the exacerbations required. Oral corticosteroids were used more often to treat the tiotropium group, whereas patients on SFC required antibiotics more frequently.

“This finding provides indirect evidence that these treatments affect apparently similar patients in different ways that affect clinical judgment,” wrote Dr. Wedzicha in the article. “This difference warrants further study to determine the factors that affect therapeutic choice.”

There was also a small but statistically significant improvement in the SGRQ scores for patients on SFC. While this difference did not reach the standard of clinical significance, it did indicate that overall, SFC patients experienced a slightly higher overall quality of life and a post-hoc analysis revealed that more patients on SFC had a clinically significant improvement in health status than those on tiotropium therapy

Most strikingly, mortality was significantly lower in the SFC group during the study period, even though the trial was not powered to detect such a difference. There was more than a 50 percent reduction in the risk of on-therapy all-cause death at any time during the study period for the SFC patients. Patients undergoing SFC treatment were also significantly less likely to withdraw from the trial than others.

“Our study raises several important questions,” noted Dr. Wedzicha. “Why is there a difference between treatments? What is the biological basis of the differential effect on exacerbations, and is it related to the difference in mortality between the two treatments?”

Despite no difference in the overall rate of exacerbations between treatment groups, SFC treatment was associated with better health status, fewer patient withdrawals, and a lower mortality rate than occurred during tiotropium therapy and this may have important implications for the clinical management of COPD.

Mothers’ Stress May Increase Children’s Asthma

Children whose mothers are chronically stressed during their early years have a higher asthma rate than their peers, regardless of their income, gender or other known asthma risk factors.

“It is increasingly clear that traditional environmental risk factors do not fully explain the origins of asthma,” said lead investigator, Anita Kozyrskyj, Ph.D., Associate Professor in the Faculty of Pharmacy at the University of Manitoba, Canada. “Evidence is emerging that exposure to maternal distress in early life plays a causal role in the development of childhood asthma. In a cohort of children born in 1995, we found that maternal distress which persists beyond the postpartum period is associated with an increased risk of asthma at school-age.”

The findings appeared in the second issue for January of the American Journal or Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Dr. Kozyrskyj and her colleagues analyzed the medical records of nearly 14,000 children born in Manitoba in 1995 who were continuously registered with Manitoba Health Services until 2003. They determined whether the children had current asthma at age seven by analyzing records of doctor visits, hospitalizations and medications in the year of the child’s seventh birthday, and related it to maternal distress as defined by doctor visits, hospitalizations and medication for depression and anxiety. Maternal distress was categorized according to onset and duration into four categories: no distress, postpartum distress only, short-term distress and long-term distress.

“Unlike existing studies that have measured maternal stress during the first few years only, the longitudinal nature of our health care study enabled us to characterize maternal distress over time to identify whether it continued,” said Dr. Kozyrskyj.

Even after controlling for the known risk factors of male gender, maternal asthma, urban location and total health care visits, long-term maternal stress was associated with an increase of nearly a third in the prevalence childhood asthma. This is the first study of a non-high-risk cohort of children to report an association with childhood asthma.

The study also found that the risk of asthma associated with maternal stress was intensified under specific home environments: children of mothers with chronic distress who were living in high-income households or who had more than one sibling were more at risk of developing asthma than others whose mothers showed distress.

The mechanisms for how maternal distress causes asthma are not well understood. Depressed mothers are more likely to smoke and less likely to breastfeed—actions which are associated with the development of asthma. However, research has also suggested that depressed mothers are also less likely to interact with their infants. Animal studies indicate that decreased attentiveness from the mother affects the infant’s stress and immune response, but the same effect in humans has not yet been definitively demonstrated.

“Our maternal distress measure captured women who sought health care for their depression and anxiety, and thus, our findings may be limited to more severe depression and anxiety,” said Dr. Kozyrskyj. “We plan to further explore the role of postpartum distress by doing a similar study which will link health care records with public health nurse assessments of depression and anxiety from a provincial postnatal screening program. This will enable us to assess the effects of less severe depression and anxiety during the postpartum period.”

Smoking Belies Milder Disease but Worse Prognosis for IPF Patients

Smokers and ex-smokers with idiopathic pulmonary fibrosis (IPF), an untreatable progressive lung disease that usually leads to death within a few years of diagnosis, have a worse prognosis than non-smokers, according to research from London.

Previous research had counter-intuitively suggested that current smokers with IPF might livelonger than ex-smokers, but the new study establishes that the data likely reflected a healthy smoker effect.

The study appears in the second issue for January of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

“Smoking is associated with a higher mortality in IPF, and an earlier finding, suggesting the contrary, was almost certainly due to the fact that smokers tend to stop smoking when disease becomes more severe—and so current smoking is linked to milder disease,” said Athol U. Wells, M.D., of the Interstitial Lung Disease Unit at the Royal Brompton Hospital in London, who headed the research.

The investigators studied the medical records of 249 patients with IPF, and analyzed the extent and severity of their disease, smoking history and survival. Their initial findings, unadjusted for disease severity, were similar to the earlier study— namely that smokers had longer survival times than ex-smokers. But when they adjusted their data to reflect the extent and severity of the disease at presentation, their findings shed a new light on the previous finding.

“We established that current smokers live longer, but this is mostly because they have much milder disease. Clearly, many patients stop smoking precisely because their disease is getting worse. This is the ‘healthy smoker’ effect: that current smoking is a marker for milder disease because advancing disease causes smoking cessation,” said Dr. Wells. “Symptomatic patients with more severe disease may be more likely to stop smoking for perceived health reasons. It can, therefore, be argued that current smoking might be a marker of less severe disease, associated with better survival.”

Using the composite physiologic index (CPI), an index of disease severity that takes into account lung function and diffusion capacity as well as the confounding functional effects of concurrent emphysema, they found that survival was better in non-smokers than in the two smoking groups.

“We speculate as to whether this reflects disease co-morbidity—that is, excess mortality from non-pulmonary disease ascribable to smoking— or an effect of smoking in driving progression of lung disease,” said Dr. Wells.

The researchers have several ongoing studies to determine the precise linkage between smoking damage such as smoking-related emphysema, IPF and other forms of fibrotic lung disease.

“The next step is to pursue the idea that mechanisms linked to smoking cause progression of pulmonary fibrosis,” says Dr. Wells. “If we can then understand these mechanisms better, this may give us new treatment options.”