Devices, methods, and systems are provided for sealing a lung region. The target lung compartment is accessed and isolated via an isolation catheter. Fluid is delivered into the target lung compartment such that the target compartment is pressurized and the fluid flows through the collateral flow channel. A sealing agent is injected into the isolated lung compartment such that the agent is carried by the fluid to the collateral flow channel, thereby sealing the collateral flow channel. Variables of air flow may be measured or analyzed prior to injection of the sealing agent, or the sealing agent may be introduced into the region after a suitable time has elapsed.