Abstract
INTRODUCTION: Resistive breathing (RB) is the hallmark of diseases of airway obstruction, especially during exacerbations, resulting in significant mechanical stress on the lung. RB induces pulmonary inflammation and injury in previously healthy animals. Whether RB exerts additional injurious effects when superimposed on cigarette smoke (CS) exposure is unknown. METHODS: Adult mice were exposed to CS for 1 or 6 months, followed by RB for 24 h, induced through tracheal banding. Subsequently, respiratory system mechanics were assessed, bronchoalveolar lavage (BAL) was performed and cytokine levels were measured by ELISA in lung tissue samples. Surfactant protein D (SP-D) was measured in blood, and BAL and histology were performed. Emphysema was quantified by the mean linear intercept (Lm) and the destructive index (DI). RESULTS: CS exposure for 1 and 6 months increased BAL cellularity (∼8-fold and ∼1.9-fold to air, respectively, p<0.01). RB aggravated BAL cellularity at both time points (p=0.025 and p=0.002 to CS) and increased MCP-1 levels at 1 month (p=0.002 to control). Histology revealed augmented focal membrane thickening at 1 month following combination of RB with CS exposure (p=0.011), while at 6 months emphysema was more severe after RB in CS-exposed mice (p=0.001 to CS for both Lm and DI). CS increased Sp-D levels in BAL (p<0.01 at both time points), while RB caused increased levels in blood (p<0.01 to CS). RB decreased static compliance at 1 month of air exposure (p=0.007). CONCLUSION: Combining resistive breathing with cigarette smoke exposure results in augmented inflammatory responses, increased lung injury and augmented emphysema.