[Epub ahead of print])
Gender-based disparities, such as global environmental and sociocultural differences for women – environmental exposures (household air pollution in low- and middle-income countries, enhanced TB in women with HIV infection in resource-limited settings, increased asthma and COPD in developed countries, air pollution and biomass burning in low and middle-income countries), occupational and infectious scenarios, chemical exposures, and medical health beliefs and customs – as well as physiological differences (e.g., body size, ventilation patterns and hormonal levels), may be potential driving factors.
Pinkerton and others “have found the nonhuman primate provides an important, critical link to humans. Specific research at the CNPRC has afforded a number of observations in nonhuman primates to provide strong biological plausibility to a wide variety of conditions noted in humans, especially in women to explain gender-based health disparities in respiratory disease”. The nonhuman primate lung has been shown to have similar architectural, morphological, and developmental patterns to that of humans, providing an excellent animal model in lung development and aging processes.
“Our research represents highly innovative techniques to address questions of health status in low and middle income countries. I strongly believe the approach we are taking with this research will address questions in our own backyard as well.” Kent Pinkerton, CNPRC
A wide variety of studies performed at the CNPRC have demonstrated this disparity in male versus female lung health, and investigators are working to answer some of the questions discussed in the article. In addition to Dr. Pinkerton, CNPRC scientists Lisa Miller, PhD, Laura Van Winkle, PhD, Catherine VandeVoort, PhD, and Alice Tarantal, PhD are studying women’s health issues with nonhuman primates.
Understanding the mechanism(s) leading to the gender-differences in respiratory disease may provide therapeutic targets to treat pulmonary disorders. For example, recent CNPRC research has shown significant structural decrements associated with accelerated aging in the female rhesus macaque lung, which suggests women may be at higher risk for chronic lung disease compared to men.
The review by Pinkerton et al provides a broad and thorough review of sociocultural implications of pulmonary disease attributable to numerous causes, including biomass burning and infectious diseases among women in low- to middle-income countries, as well as disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided.
The development and progression of certain common respiratory diseases has been found to differ by sex. One such disease is COPD, now the third leading cause of death in the US. Traditionally more prevalent in men, women now account for over 50% of COPD deaths in the US. The increased prevalence of COPD in women is thought to be due to changing smoking patterns and women taking on more traditional male occupations. However, growing evidence supports significant sex-based differences in the disease. For example, of never-smokers that develop COPD, women are 1.5 times more likely to be diagnosed than men.
Many questions need to be answered to understand and manage women’s lung health and to develop effective therapeutics. The authors address certain mechanisms that may influence respiratory health.
- Do longer telomeres help women develop less pulmonary fibrosis than men?
- Does telomere shortening versus cigarette smoking affect the susceptibility of women to COPD?
- Is the susceptibility of women to pulmonary disease, such as COPD, influenced by women reacting differently to treatment of age-related pulmonary diseases compared to men?
- Does gender variation in respiratory disease arise from early life exposures that occur in a broad window of time extending from lung growth and maturation during the fetal period through young adulthood?
- How do stressors that can impact lung development and lung disease throughout a woman’s lifetime, such as indoor and outdoor air pollution, stress, access to healthcare, genetics and epigenetics, and diet affect lung health?
- How do lung hormone receptors that have been implicated in disease play a role in the maturation of the respiratory system in the postnatal period?
- How do interactions between exposures as well as cumulative effects from many exposures differ by sex and what are the long-term consequences?
Environmental toxins (naphthalene, smoke, vehicle exhaust related air pollution, and the ubiquitous component of plastics, bisphenol A (BPA)):
- How do everyday chemicals impact respiratory health?
- How do the primary routes of exposure to injurious compounds affect lung health: i.e., via inhalation and cardiac output and blood circulation?
- Early life exposure to BPA is linked to both allergic sensitization and decrements in lung function, including wheeze, in children and alterations in fetal lung maturation in nonhuman primate studies at the CNPRC. How does this early exposure to ubiquitous chemicals like BPA affect the pulmonary health of women later in life?
In the context of respiratory diseases, one global environmental exposure that has particular relevance for women is household air pollution (HAP) that results from indoor burning of solid fuels (biomass and coal) for cooking and heating. HAP exposure is associated with approximately 4 million deaths each year, predominantly from COPD, cardiovascular diseases, acute pneumonia in children under age 5 and lung cancer. The vast majority of HAP related deaths and disabilities occur in low- and middle-income countries among those households living in severe poverty, and women and children have the highest exposure to HAP due to their domestic roles.
Households typically have limited access to fuels, so wood, charcoal, animal dung, coal or crop residues are used for cooking using either open fires or traditional unvented stoves. These cooking fires have low combustion efficiencies resulting in excess emissions, such as black carbon or “soot,” into the households, blackening the interior walls. The daily breathing of air that exceeds WHO air quality standards by 10 to 100 fold has obvious health risks. Women often have the domestic responsibility for cooking and for childcare, and thus are, along with children, particularly exposed to very unhealthy air to breathe.
The good news is that cleaner cooking solutions, such as highly efficient cookstoves or effective ventilation of stoves by well-maintained chimneys, can significantly reduce household exposures and improve the health of women and children worldwide. There is also an increasing global awareness of the challenge ahead and the need to improve and implement cleaner cooking solutions that are accepted by households and communities in the very different social and cultural settings around the world. The scale of the problem is daunting, with a need to reach hundreds of millions of households and to find the best solutions and the best mechanisms to implement such strategies.
With the CNPRC’s extensive capabilities and resources, and a myriad of research projects under way, Dr. Pinkerton is well positioned to understand the mechanisms underlying respiratory disease and to develop new strategies to alleviate the detrimental health outcomes of pollutant exposures.
CNPRC scientists are optimistic for increased research opportunities with the recent National Institutes of Health implementation of reporting policies for balancing gender in preclinical studies. Different mechanisms underlying disease susceptibility in females and males may be uncovered more readily as future research addresses gender-based disparities in symptoms and diseases of the respiratory system.
This research was supported in part by the CNPRC NIH base grant P51 OD011107, NIH R21 ES021600, P30 ES023513, P42 ES04699, and R01 ES020867; CDC National Institute for Occupational Safety and Health OHO7550;, National Institute of Environmental Health Sciences R01 ES002710 and P42 ES004699; and the American Asthma Foundation.