The online version of this article (doi:10.1186/1465-9921-15-42) contains supplementary material, which is available to authorized users.
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.
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.
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.
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.
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.
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.
Additional file 1: An expanded Materials and Methods section is available for additional information regarding many of the models and techniques employed in this study.(DOC 89 KB)
Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007, 176: 532-555. 10.1164/rccm.200703-456SO. PubMedCrossRef
Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, Macnee W, Make BJ, Rabe KF, Rennard SI, Sciurba FC, Silverman EK, Vestbo J, Washko GR, Wouters EF, Martinez FJ: Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010, 182: 598-604. 10.1164/rccm.200912-1843CC. PubMedCrossRef
Jogi J, Ekberg M, Jonson B, Bozovic G, Bajc M: Ventilation/perfusion SPECT in chronic obstructive pulmonary disease: an evaluation by reference to symptoms, spirometric lung function and emphysema, as assessed with HRCT. Eur J Nucl Med Mol Imaging. 2011, 38: 1344-1352. 10.1007/s00259-011-1757-5. PubMedCrossRef
Wright JL, Sun JP: Effect of smoking cessation on pulmonary and cardiovascular function and structure: analysis of guinea pig model. J Appl Physiol. 1994, 76: 2163-2168. PubMed
Kirby M, Mathew L, Wheatley A, Santyr GE, McCormack DG, Parraga G: Chronic obstructive pulmonary disease: longitudinal hyperpolarized (3)He MR imaging. Radiol. 2010, 256: 280-289. 10.1148/radiol.10091937. CrossRef
Petersson J, Sanchez-Crespo A, Rohdin M, Montmerle S, Nyren S, Jacobsson H, Larsson SA, Lindahl SG, Linnarsson D, Glenny RW, Mure M: Physiological evaluation of a new quantitative SPECT method measuring regional ventilation and perfusion. J Appl Physiol. 2004, 96: 1127-1136. 10.1063/1.1763000. PubMedCrossRef
- Impact of inflammation, emphysema, and smoking cessation on V/Q in mouse models of lung obstruction
Brian N Jobse
Cory AJR McCurry
Mathieu C Morissette
Rod G Rhem
Martin R Stämpfli
Nancy Renée Labiris
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II