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Development of a screening protocol to identify persons who are responsive to wood smoke particle-induced airway inflammation with pilot assessment of GSTM1 genotype and asthma status as response modifiers.
Alexis, Neil E; Zhou, Laura Y; Burbank, Allison J; Almond, Martha; Hernandez, Michelle L; Mills, Katherine H; Noah, Terry L; Wells, Heather; Zhou, Haibo; Peden, David B.
Afiliação
  • Alexis NE; Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Zhou LY; Division of Allergy & Immunology, Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Burbank AJ; Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Almond M; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
  • Hernandez ML; Division of Allergy & Immunology, Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Mills KH; Children's Research Institute, Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Noah TL; Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Wells H; Division of Allergy & Immunology, Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Zhou H; Children's Research Institute, Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Peden DB; Division of Allergy & Immunology, Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Inhal Toxicol ; 34(11-12): 329-339, 2022.
Article em En | MEDLINE | ID: mdl-35968917
ABSTRACT

BACKGROUND:

We are currently screening human volunteers to determine their sputum polymorphonuclear neutrophil (PMN) response 6- and 24-hours following initiation of exposure to wood smoke particles (WSP). Inflammatory responders (≥10% increase in %PMN) are identified for their subsequent participation in mitigation studies against WSP-induced airways inflammation. In this report we compared responder status (<i>N</i> = 52) at both 6 and 24 hr time points to refine/expand its classification, assessed the impact of the GSTM1 genotype, asthma status and sex on responder status, and explored whether sputum soluble phase markers of inflammation correlate with PMN responsiveness to WSP.

RESULTS:

Six-hour responders tended to be 24-hour responders and vice versa, but 24-hour responders also had significantly increased IL-1beta, IL-6, IL-8 at 24 hours post WSP exposure. The GSTM1 null genotype significantly (<i>p</i> &lt; 0.05) enhanced the %PMN response by 24% in the 24-hour responders and not at all in the 6 hours responders. Asthma status enhanced the 24 hour %PMN response in the 6- and 24-hour responders. In the entire cohort (not stratified by responder status), we found a significant, but very small decrease in FVC and systolic blood pressure immediately following WSP exposure and sputum %PMNs were significantly increased and associated with sputum inflammatory markers (IL-1beta, IL-6, IL-8, and PMN/mg) at 24 but not 6 hours post exposure. Blood endpoints in the entire cohort showed a significant increase in %PMN and PMN/mg at 6 but not 24 hours. Sex had no effect on %PMN response.

CONCLUSIONS:

The 24-hour time point was more informative than the 6-hour time point in optimally and expansively defining airway inflammatory responsiveness to WSP exposure. GSTM1 and asthma status are significant effect modifiers of this response. These study design and subject parameters should be considered before enrolling volunteers for proof-of-concept WSP mitigation studies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Fumaça / Glutationa Transferase Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Humans Idioma: En Revista: Inhal Toxicol Assunto da revista: TOXICOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Fumaça / Glutationa Transferase Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Humans Idioma: En Revista: Inhal Toxicol Assunto da revista: TOXICOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos