The role of sex in particle-induced inflammation and injury

Our plain-English summary of The role of sex in particle-induced inflammation and injury, by J.L. Ray, P. Fletcher, R. Burmeister, et al (Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology, 2020).

The study

• Authors: J.L. Ray, P. Fletcher, R. Burmeister, A. Holian
• Journal: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
• Published: 2020;12(2):e1589
• Type of article: Review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The use of engineered nanomaterials within various applications such as medicine, electronics, and cosmetics has been steadily increasing; therefore, the rate of occupational and environmental exposures has also increased. Inhalation is an important route of exposure to nanomaterials and has been shown to cause various respiratory diseases in animal models. Human lung disease frequently presents with a sex/gender-bias in prevalence or severity, but investigation of potential sex-differences in the adverse health outcomes associated with nanoparticle inhalation is greatly lacking. Only ~20% of basic research in the general sciences use both male and female animals and a substantial percentage of these do not address differences between sexes within their analyses. This has prevented researchers from fully understanding the impact of sex-based variables on health and disease, particularly the pathologies resulting from the inhalation of particles. The mechanisms responsible for sex-differences in respiratory disease remain unclear, but could be related to a number of variables including sex-differences in hormone signaling, lung physiology, or respiratory immune function. By incorporating sex-based analysis into respiratory nanotoxicology and utilizing human data from other relevant particles (e.g., asbestos, silica, particulate matter), we can improve our understanding of sex as a biological variable in nanoparticle exposures. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

© 2019 Wiley Periodicals, Inc.

In plain English

This article is a review, not a new study. The authors summarized published research on whether males and females respond differently to inhaled particles. It mainly covered engineered nanoparticles: carbon nanotubes, silver, gold and metal oxides. Because human data on nanoparticles are scarce, it also covered asbestos, crystalline silica and fine air pollution. The authors noted that malignant mesothelioma is much more common in men. It is unclear whether this reflects greater susceptibility or more high-level exposure in male-dominated jobs. Cited studies of non-work exposure gave mixed results by fiber type. Two Australian studies (crocidolite and amosite) reported more mesothelioma in men at the same exposure, but a steeper dose-response in women. A Turkish study linked tremolite to an 88.3 times higher mesothelioma risk in men but 799 times in women. A Libby, Montana study found more asbestosis and COPD among winchite-exposed women. The authors cautioned that occupational studies may be biased and that animal studies of sex and asbestos are hard to find. They concluded that the research is limited but compelling and warrants further investigation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published animal and human studies on sex differences in responses to inhaled particles
• Who was studied: Published studies, mostly in rats and mice plus some human studies, on engineered nanoparticles. Because nanoparticle data are scarce, it also covered human and animal studies of three non-nano particles: asbestos, crystalline silica and PM2.5 air pollution.
• Exposure: Inhaled engineered nanomaterials (carbon-based nanomaterials, silver, gold, metal oxide nanoparticles), plus asbestos (serpentine chrysotile and amphiboles; the cited epidemiology covered crocidolite, amosite, tremolite and winchite), crystalline silica and PM2.5/diesel exhaust particles
• Main results:
  • The authors reported that malignant mesothelioma is much more common in men than in women. They said it is unclear whether this is due to greater male susceptibility or to more high-level exposure in male-dominated jobs.
  • Studies cited by the authors proposed that the share of pleural mesothelioma attributable to asbestos is 58–88% in men but only 23% in women.
  • Two Australian studies cited in the review found residential exposure to crocidolite (Reid et al., 2007) and amosite (Korda et al., 2017) linked to a greater incidence of mesothelioma in men than women at the same level of exposure. Women had a steeper dose-response curve.
  • A cited study in rural Turkey (Metintas et al., 2002) associated naturally occurring tremolite with an 88.3 times higher risk of mesothelioma in men and a 799 times greater risk in women.
  • A cited case-control study in New Caledonia (Luce et al., 2000) found similar pleural mesothelioma risk for men and women exposed to tremolite whitewash ('pö'). For squamous cell carcinoma, the odds ratio was 6.49 in women and 0.77 in men.
  • A cited study in Libby, Montana (Naik et al., 2017) found asbestosis and COPD more common in women than men among people with non-work exposure to winchite.
  • Cited rat studies of an asbestos-like multi-walled carbon nanotube (Mitsui-7) reported more granulomatous changes and lung cancer in male rats than in females.
  • In the one cited asbestos animal study involving sex (Levis et al., 2008), female mice given male bone marrow had less acute inflammation after asbestos than mice that were not irradiated. The authors noted this is hard to interpret without sex-matched control groups.
  • From cited mouse studies of crystalline silica, the authors concluded that males appear more susceptible to silica-related lung disease.
• The authors' conclusion: The authors concluded that basic research on sex differences after nanoparticle inhalation is limited but compelling and warrants further mechanistic investigation. They also said conclusions about sex differences in asbestos disease must specify asbestos type, exposure level and duration, and disease endpoint.
• Limitations the authors state:
  • Occupational asbestos studies may be biased because high-level exposures occur mostly in jobs dominated by one sex, such as mining and construction.
  • Studies of environmental asbestos exposure may also be biased because non-work exposures are incompletely characterized.
  • Animal studies of sex differences in asbestos disease are scarce.
  • Nanomaterials vary so much in their physical and chemical properties that comparing separate studies to draw conclusions about sex differences is difficult.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Environmental Exposure.

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