Spontaneous Breathing Through Increased Airway Resistance Augments Elastase-Induced Pulmonary Emphysema

Abstract

Dimitrios Toumpanakis,1,2 Eleftheria Mizi,1 Vyronia Vassilakopoulou,1 Maria Dettoraki,1 Athanasia Chatzianastasiou,1 Fotis Perlikos,1 Georgia Giatra,2 Marina Moscholaki,1 Stamatios Theocharis,3 Theodoros Vassilakopoulos1,2 1“Marianthi Simou” Applied Biomedical Research and Training Center, Medical School, University of Athens, Evangelismos Hospital, Athens, Greece; 2 3rd Department of Critical Care Medicine, Evgenideio Hospital, Medical School, University of Athens, Athens, Greece; 3Department of Pathology, Medical School, University of Athens, Athens, GreeceCorrespondence: Theodoros Vassilakopoulos 3rd Department of Critical Care Medicine, Evgenideio Hospital, Medical School, University of Athens, Athens, GreeceEmail [email protected]: Resistive breathing (RB), the pathophysiologic hallmark of chronic obstructive pulmonary disease (COPD), especially during exacerbations, is associated with significant inflammation and mechanical stress on the lung. Mechanical forces are implicated in the progression of emphysema that is a major pathologic feature of COPD. We hypothesized that resistive breathing exacerbates emphysema.Methods: C57BL/6 mice were exposed to 0.75 units of pancreatic porcine elastase intratracheally to develop emphysema. Resistive breathing was applied by suturing a nylon band around the trachea to reduce surface area to half for the last 24 or 72 hours of a 21-day time period after elastase treatment in total. Following RB (24 or 72 hours), lung mechanics were measured and bronchoalveolar lavage (BAL) was performed. Emphysema was quantified by the mean linear intercept (Lm) and the destructive index (DI) in lung tissue sections.Results: Following 21 days of intratracheal elastase exposure, Lm and DI increased in lung tissue sections [Lm (μm), control 39.09± 0.76, elastase 62.05± 2.19, p=0.003 and DI, ctr 30.95± 2.75, elastase 73.12± 1.75, p< 0.001]. RB for 72 hours further increased Lm by 64% and DI by 19%, compared to elastase alone (p< 0.001 and p=0.02, respectively). RB induced BAL neutrophilia in elastase-treated mice. Static compliance (Cst) increased in elastase-treated mice [Cst (mL/cmH2O), control 0.067± 0.001, elastase 0.109± 0.006, p< 0.001], but superimposed RB decreased Cst, compared to elastase alone [Cst (mL/cmH2O), elastase+RB24h 0.090± 0.004, p=0.006 to elastase, elastase+RB72h 0.090± 0.005, p=0.006 to elastase].Conclusion: Resistive breathing augments pulmonary inflammation and emphysema in an elastase-induced emphysema mouse model.Keywords: resistive breathing, elastase, emphysema, mechanical forces

Keywords

• resistive breathing
• elastase
• emphysema
• mechanical forces