On lung nerves and neurogenic injury

Information accumulated in recent years has begun to unveil a previously unsuspected complexity in the innervation of the lungs. We know now that the conducting airways receive a highly redundant supply of vagal motor and sensory fibers; that many of these fibers cross over from the contralateral side of the brain to reach distant portions of the lung, thereby assuring the symmetry and simultaneity of the bronchomotor responses; and that, perhaps in recognition of the different functions and properties of proximal and distal airways, vagal motor fibers have a distinctive segmental distribution. Both sensory and motor neurons serve as the input and output elements of a complex brain stem neuronal network, which integrates the regulation of airway smooth muscle tone into the control of ventilation. This network has a local counterpart in the airway walls, where a heterogeneous population of intrinsic neurons may act not only as a relay for cholinergic stimuli, but also as a local mechanism of inflammatory modulation. The interruption of the nerve supply to the lungs (for instance after lung transplantation) abolishes the integration of bronchomotor and ventilatory activities, and, by increasing airway deformation, may initiate fibroproliferative responses in the airway walls. In addition, the destruction of vagal motor and sensory fibers leaves behind a surviving population of denervated intrinsic neurons, which may act as a disregulated mechanism of inflammatory amplification.