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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Respiratory Research 1/2014

Impact of inflammation, emphysema, and smoking cessation on V/Q in mouse models of lung obstruction

Zeitschrift:
Respiratory Research > Ausgabe 1/2014
Autoren:
Brian N Jobse, Cory AJR McCurry, Mathieu C Morissette, Rod G Rhem, Martin R Stämpfli, Nancy Renée Labiris
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1465-9921-15-42) contains supplementary material, which is available to authorized users.

Competing interests

Financial Support: Firestone Institute of Respiratory Health – AstraZeneca Collaboration Unrestricted Grant; The Canadian Institutes of Health Research; N.R. Labiris holds an internal Department of Medicine Career Award.

Authors’ contributions

BNJ was involved in concept and design, experimentation and collection of biological and imaging data, analysis, drafting and review of the manuscript. CAJRM was involved in experimentation and collection of biological and imaging data. MCM was involved in experimentation and collection of biological data as well as review of the manuscript. RGR was involved in collection and analysis of imaging data. MRS contributed to concept and design and review of the manuscript. NRL contributed to concept and design and review/editing of the manuscript. All authors read and approved the final manuscript.

Abstract

Background

Chronic obstructive pulmonary disease (COPD) is known to greatly affect ventilation (V) and perfusion (Q) of the lung through pathologies such as inflammation and emphysema. However, there is little direct evidence regarding how these pathologies contribute to the V/Q mismatch observed in COPD and models thereof. Also, little is known regarding how smoking cessation affects V/Q relationships after inflammation and airspace enlargement have become established. To this end, we have quantified V/Q on a per-voxel basis using single photon emission computed tomography (SPECT) in mouse models of COPD and lung obstruction.

Methods

Three distinct murine models were used to investigate the impact of different pathologies on V/Q, as measured by SPECT. Lipopolysaccharide (LPS) was used to produce neutrophilic inflammation, porcine pancreatic elastase (PPE) was used to produce emphysema, and long-term cigarette smoke (CS) exposure and cessation were used to investigate the combination of these pathologies.

Results

CS exposure resulted in an increase in mononuclear cells and neutrophils, an increase in airspace enlargement, and an increase in V/Q mismatching. The inflammation produced by LPS was more robust and predominantly neutrophilic, compared to that of cigarette smoke; nevertheless, inflammation alone caused V/Q mismatching similar to that seen with long-term CS exposure. The emphysematous lesions caused by PPE administration were also capable of causing V/Q mismatch in the absence of inflammation. Following CS cessation, inflammatory cell levels returned to those of controls and, similarly, V/Q measures returned to normal despite evidence of persistent mild airspace enlargement.

Conclusions

Both robust inflammation and extensive airspace enlargement, on their own, were capable of producing V/Q mismatch. As CS cessation resulted in a return of V/Q mismatching and inflammatory cell counts to control levels, lung inflammation is likely a major contributor to V/Q mismatch observed in the cigarette smoke exposure model as well as in COPD patients. This return of V/Q mismatching to control values also took place in the presence of mild airspace enlargement, indicating that emphysematous lesions must be of a larger volume before affecting the lung significantly. Early smoking cessation is therefore critical before emphysema has an irreversible impact on gas exchange.
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