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Updated: Apr 28, 2026

Methodology for Sputum Induction and Laboratory Processing
Published on: December 17, 2017
Association of COPD exacerbation frequency with gene expression of pattern recognition receptors in inflammatory
Daisuke Kinose1, Emiko Ogawa2, Megumi Kudo1
1Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Background:
Bacteria and viruses are major causes of chronic obstructive pulmonary disease (COPD) exacerbations. Molecular components of these pathogens are recognized by pattern-recognition receptors (PRRs) expressed by various cells in the airway, which leads to initiation of inflammatory processes. Expression levels of PRRs in airway inflammatory cells are expected to affect susceptibility to COPD exacerbation.
Aims:
This prospective observational study was conducted to detect any association between exacerbation and PRR expression.
Methods:
Thirty-one male COPD patients were recruited. At baseline, clinical history, lung function measurements, peripheral blood samples and induced sputum were obtained. Using sputum samples, we performed gene expression analysis of TLR2, TLR3, TLR4, NOD1, NOD2, RIG-I and MDA-5 by quantitative reverse transcription-polymerase chain reaction in addition to quantitative bacterial culture. COPD exacerbations were assessed based on Anthonisen's criteria using symptom diaries for the following 1-year period.
Results:
During 1-year follow-up period, 13 patients experienced at least one exacerbation, but 18 patients did not. Those with exacerbations tended to be more severe COPD and showed larger neutrophil fraction in their induced sputum. Among PRRs, only TLR3 gene expression was increased in COPD patients with exacerbation compared with those without exacerbations. Multivariate logistic regression analysis including neutrophil fraction and TLR3 gene expression as predictor variables demonstrated that only an increase of neutrophil fraction, but not TLR3 gene expression, was a significant predictor for COPD exacerbation.
Conclusion:
TLR3 expression in inflammatory cells might affect the susceptibility to COPD exacerbation.
Insights
In chronic obstructive pulmonary disease (COPD) patients, increased neutrophil fraction, not Toll-like receptor 3 (TLR3) expression, predicted exacerbations. This finding impacts understanding COPD exacerbation triggers.
Area of Science:
- Respiratory Medicine
- Immunology
- Molecular Biology
Background:
- Bacteria and viruses trigger chronic obstructive pulmonary disease (COPD) exacerbations via pattern-recognition receptors (PRRs) on airway cells, initiating inflammation.
- PRR expression levels in airway inflammatory cells may influence COPD exacerbation susceptibility.
Purpose of the Study:
- To investigate the association between exacerbations in COPD patients and the expression of specific pattern-recognition receptors (PRRs).
Main Methods:
- A prospective observational study involved 31 male COPD patients.
- Gene expression of TLR2, TLR3, TLR4, NOD1, NOD2, RIG-I, and MDA-5 was analyzed in sputum using quantitative reverse transcription-polymerase chain reaction.
- COPD exacerbations were tracked for one year using symptom diaries and Anthonisen's criteria.
Main Results:
- Thirteen patients experienced exacerbations; 18 did not. Exacerbated patients had more severe COPD and higher sputum neutrophil fractions.
- Toll-like receptor 3 (TLR3) gene expression was elevated in COPD patients with exacerbations compared to those without.
- Multivariate analysis revealed that only increased neutrophil fraction, not TLR3 expression, significantly predicted COPD exacerbation.
Conclusions:
- While TLR3 expression may play a role, increased neutrophil fraction is a significant predictor of COPD exacerbation.
- Further research is needed to fully elucidate the role of PRRs, including TLR3, in COPD exacerbation pathogenesis.
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