The Capillary Surfactometer (CS) is an essential new tool in the study of pulmonary surfactants and what effect inhibitors have on its ability to rapidly adsorb, spread, and reform a monolayer in the dynamic conditions of the respiratory cycle. Most often samples will be obtained from Broncho-Alveolar Lavage Fluid (BALF) or possibly from sputum. The fluid needs to be concentrated to a phospholipid concentration of 0.5 to 2 mg/ml. Inhibitors, such as albumin or other proteins which leak into the conducting airways during an asthma attack or allergens can be incorporated to determine what effect they have on the performance of the samples.
Also, the CS is an invaluable tool when investigating the quality and consistency of surfactant preparations in the treatment of RDS and ARDS and in determining what influences inhibitors have on its function. The CS can be used in many applications.
Surfactant is a mixture of lung-specific proteins and fats produced in the lungs. Surfactant enables narrow terminal airways and alveoli to remain expanded at end of expiration.
The worthiness of surfactants and their effects by various inhibitors are studied by instilling an extremely small sample into a very narrow glass capillary. By using this model which mimics the terminal airways, it creates a better understanding of surfactants role in maintaining patency (openness) of narrow terminal airways. This enables investigators to also evaluate its function in other pulmonary diseases such as asthma, COPD, MAS, pneumonia and cystic fibrosis. The CS’s ability to quickly evaluate samples of very small volumes (0.5 ul) is of great importance. Each assay is completed in less than three minutes.
The CS was developed by Dr. Goran Enhorning, who has been instrumental in promoting the principle that neonatal RDS can be prevented and treated by exogenously supplied pulmonary surfactant. Essential for that work was the invention of the Pulsating Bubble Surfactometer (PBS). Studies with that instrument led to the development of the CS. The CS is the only tool available that enables the investigator to study the pulmonary surfactant function under conditions simulating those in terminal conducting airways.
If the surfactant is not functioning adequately because its concentration is too low, its composition is abnormal, or because plasma proteins or other agents inhibit it, then liquid lining the airway will accumulate to the most narrow section. Extensive accumulation may result in the formation of a blocking liquid column. Extra force is required to move such a liquid column and if many airways are affected the airway resistance will thus be increased and this will lead to a lowering of FEV1 (Forced Expiratory Volume in one second). It is likely that this mechanism is part of the reason for the breathing problems affecting patients with asthma, RDS (Respiratory Distress Syndrome), ARDS (Acute Respiratory Distress Syndrome), COPD (chronic obstructive pulmonary disease), pneumonia and cystic fibrosis
Animal studies have shown that an exposure to ozone1,2 or an infection with respiratory syncytial virus3,4 will lead to breathing difficulty and surfactant dysfunction. Since a leakage of plasma proteins into the airways was shown to cause a surfactant inhibition, this would be the most likely reason for its dysfunction.
Two recent studies in patients with mild asthma have shown5,6 that Broncho-Alveolar Lavage (BAL) fluid obtained after a segmental challenge with an antigen had a disturbed surfactant function, and there was an increased leakage of plasma proteins into the airways.
The surfactant function of humans can be studied in BAL fluid. Also, sputum samples from asthmatic patients, collected during an attack, have been used for evaluation of the surfactant function7. If surfactant can be evaluated with sputum samples it will be possible to follow the surfactant status of patients with asthma and determine the effect of various types of treatment.
The principle of the patented Capillary Surfactometer is to simulate terminal human airways. The sample to be evaluated has a volume of only 0.5 ml. It is introduced into the narrow section of a glass capillary, where the ID is 0.25 mm, similar to that of a terminal human airway.
At one end the capillary is connected to a bellows and a pressure transducer. When the bellows is slowly compressed, pressure is raised and recorded. The increasing pressure causes the sample to be extruded from the narrow section of the capillary.
As air gets through, pressure is abruptly lowered. If the sample contains well functioning pulmonary surfactant the sample liquid will not return to the narrow section. The steady airflow obtained by the continuous compression of the bellows will meet no resistance and the pressure recorded will be zero. If on the other hand the sample did not contain well functioning pulmonary surfactant the sample liquid will return repeatedly.
Results from studying the preparation of Calf Lung Surfactant Extract (CLSE) when it is functioning well and when it is inhibited by the addition of albumin are seen in the figure below.
Each time the liquid blocks the capillary lumen pressure is raised. The airflow continues 120 seconds following the initial extrusion of the liquid sample and a computer calculates the percentage of the 120-second period that the capillary was open.