The role of surfactant in asthma - Respiratory Research

Airway surfactant reduces surface tension at the air-liquid interface of conducting airways. This decreases the tendency of airway liquid to form bridges in the more narrow airway lumen (film collapse). In addition, a low surface tension minimizes the amount of negative pressure in the airway wall and its adjacent liquid layer, which in turn decreases the tendency for airway wall ('compliant') collapse. According to the law of LaPlace that applies to cylinders (P= γ/r, where p is transmural pressure, γ is surface tension, and r is airway radius), it becomes obvious that the smaller the airways become, the higher the pressure would rise if surface-active material lowering the value of γ were absent. Surface tension in the conducting airways has been shown to be in the range 25–30 mN/m [12,17]. This causes transmural pressures of less than 1 cmH2O whereby the patency of airways is maintained. By preventing both film collapse and compliant collapse, airway surfactant secures airway architecture and its openness.

Capillary surfactometer

A simple method to estimate surfactant function, as it applies to the cylindrical surface of a narrow conducting airway, is the capillary surfactometer. This instrument simulates the morphology and function of a terminal conducting airway with a glass capillary that in a short section is particularly narrow with an inner diameter of 0.2 mm [18,19,20]. It utilizes a very small volume (0.5 μl) of surfactant. By raising the pressure, the liquid is extruded from the narrow section. Pressure is zero if the capillary is open for free airflow, but there is an increase in pressure when the liquid returns to block the narrow section. Well functioning pulmonary surfactant will keep the capillary open 100%, showing an excellent ability to maintain airway patency, whereas when surfactant functions very poorly, the value of 'open in %' will be zero.

Airway models

Liu et al. [18] found that surfactant-containing fluid allowed a free airflow through the tube whereas saline led to spontaneous refilling of the capillary. The ability of surfactant to maintain free airflow was lost with the addition of albumin or fibrinogen (two potent surfactant inhibitors). In a recent study, we demonstrated that surfactant dysfunction by proteins was further disturbed by cooling [21]. This may explain the finding of increased airway resistance in patients with exercise-induced asthma where airway surfactant with sufficient surface activity becomes seriously inactivated due to cooling during exercise with hyperventilation of cold air. The principal findings of surfactant function and dysfunction in the rigid airway model using the capillary surfactometer have been confirmed using an elegant approach to study conducting airway function in excised isolated rat lungs [22].

Other functions

Surfactant also contributes to the regulation of airway fluid balance, improves bronchial clearance and sets up a barrier to inhaled agents. Firstly, the high surface pressure (low surface tension) of surfactant counteracts fluid influx into the airway lumen. Loss of surface activity would result in additional inward forces that cause fluid accumulation in the airway lumen. The influence of surfactant on airway liquid balance also includes prevention of desiccation. Secondly, surfactant improves bronchial clearance by optimizing transport of particles and bacteria from the peripheral to the more central airways. Moreover, surfactant has been shown to enhance mucociliary clearance [23], partly by increasing ciliary beat frequency [24]. Thirdly, several studies have suggested that surfactant sets up a barrier to the diffusion of inhaled agents, including bacteria, allergens and drugs [25,26]. For example, depletion of the surfactant layer by lung lavage leads to augmented responses to drugs and allergens [27,28]. Interestingly, exogenous surfactant treatment lessens the airway response to inhaled, but not systemically given, bronchoconstrictor stimuli in rats, suggesting an airway barrier to drug diffusion [29]. In addition, it has recently been shown that treatment of rats with exogenous phospholipids suppresses the neural activity of bronchial irritant receptors [30]. This may support the view of a possible link between airway hyper-responsiveness and airway surfactant balance.