Age-Dependent Pulmonary Reactivity to House Dust Mite Allergen: A Model of Adult-Onset Asthma?

Details

• Personal Author:
  Ahn Y ; Castañeda AR ; Cho Y ; Fulgar C ; Mack S ; Peake J ; Pinkerton KE ; Shin J ; Zhang J
• Description:
  Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and onset age. The mouse model is widely used for studying the early life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous allergen house dust mite (HDM), 3- and 9-month-old (3mo & 9mo) female C57 Black/6 mice were randomized into two groups each and treated with HDM or phosphate buffered saline via intranasal instillation for sensitization and challenge phases. Twenty-four hours after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM. However, only 9mo, HDM-exposed mice demonstrated significant airway hyperresponsiveness compared to age-matched controls. These HDM-treated mice also had 1) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts; and 2) significantly increased extent of immunostaining compared to all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, peri-menopausal female phenotype. Findings suggest that lung function declines with age, and that the inflammatory profile of this adult subgroup is mixed, rather than a simple, atopic Th2 response. This model may enhance our understanding of how age influences the development of asthmatic-like symptoms in older subgroups. [Description provided by NIOSH]
• Subjects:
  Asthma Asthma, Occupational Dust Hypersensitivity Laboratories Lung Methacholine Compounds Occupational Health Phosphoric Acids Respiratory System Safety

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• Keywords:
  Allergens Atopy Author Keywords: Animal Model Bronchiolitis Dust Exposure Dusts Eosinophils Laboratory Animals Lung Function Methacholines Neutrophils Phosphates Pulmonary Function Sensitization

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• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  California ; Montana ; OSHA Region 8 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  316
• Issue:
  5
• NIOSHTIC Number:
  nn:20055281
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2019 May; 316(5):L757-L763
• Contact Point Address:
  S. Mack, One Shields Ave., Davis, CA 95616
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of California - Davis
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:76460f81c0aaefeda84b9748be83d353974a73fc3bd1660a2891aec55d5711e657fea6946a26b9ff23b35e2427e902ef52217c422a8e05f115591f951a12501e
• Download URL:
  https://stacks.cdc.gov/view/cdc/217622/cdc_217622_DS1.pdf
• File Type:
  [PDF - 554.72 KB ]