About Surfactant in Airway Disease

pulmonary surfactantAll over the world, asthma is treated with β2-adrenergic agonists. They cause smooth muscles to relax. They also cause pulmonary surfactant to be released from alveolar type II cells, which is a widely overlooked effect, since the importance of airway surfactant in asthma is not yet appreciated. Surfactant maintains the openness of alveoli and terminal conducting airways, and thereby promotes normal blood gas levels and low airway resistance. Excellent reviews of the ability of surfactant to maintain low airway resistance and its vital importance for asthma patients have been published. The present review includes a description of the physical properties of surfactant.

The importance of pulmonary surfactant was early recognized by neonatologists. The airway liquid of term infants contains surfactant, which is synthesized in alveolar type II cells. It consists mainly of saturated phospholipids, with dipalmitoyl-phosphatidylcholine dominating. The phospholipid molecules are amphi-pathic (ie, at one end, where the fatty acids are located, they are hydrophobic); whereas, the polar heads are hydrophilic. Air-liquid interfaces of expanded lungs constitute ideal locations for phospholipids. The fatty acids can avoid water by staying in air, while the polar heads remain in water. A film of shows how the pressure difference (AP) at the air-liquid interface is dependent on the surface tension of alveolar moisture (7) and the alveolar radius (R). Since the alveolus communicates with ambient air, AP is approximately equal to the negative pressure surrounding the alveolus. If 7 does not change during breathing, the law shows that during expiration AP would increase as R decreases. Consequently, small alveoli might not be surrounded by the suction they require to maintain expansion; they collapse. However, breathing does change 7. During expiration, surfactant phospholipids are forced to come closer, causing 7 to diminish, and, if diminishing more than R, AP will not increase; alveoli will not collapse. Treat asthma attacks with My Canadian Pharmacy’s remedies.

Plasma proteins are also amphipathic, but their hydrophobicity is weak, explaining why they are water soluble and evenly distributed in the airway moisture. Due to their weak hydrophobicity, they are not strongly attached to the air-liquid interfaces; during expiration, they will probably be squeezed out from the interface film. They prevent phospholipids from coming as close to each other as they normally do. For that reason, surface tension is not lowered the normal way, possibly causing alveolar collapse, these molecules, at least monomolecular, will spontaneously form at the air-liquid interfaces of lungs.

The law of Laplace as it applies to the spherical surface of an alveolus

Formule-1

The pulsating bubble surfactometer-5 (US patent 4,800,750; General Transco; Seminole, FL) is intended for an evaluation of alveolar pulmonary surfactant. It’s function is based on the law of Laplace. In a small chamber containing the liquid to be evaluated, a bubble is created. It breathingcommunicates with ambient air and simulates an alveolus during breathing. The bubble R shifts from 0.4 to 0.55 mm. By measuring the pressure around the bubble, AP is obtained, and, when correlated with R, 7 can be calculated and recorded.

The law of Laplace as it applies to the cylindrically shaped conducting airway,

Formule-2

shows how the AP between the moisture lining the airway and the air in its center is dependent on the surface tension of airway moisture (7) and the terminal airway radius (R). During expiration, when R is diminishing, phospholipids are forced to come closer, causing 7 to be lowered. If the 7 is reduced more than R, AP will diminish, and the liquid will not be sucked into the narrowest part of the airway (Fig 1). However, if the phospholipids are too few, absolutely or in relation to proteins, 7 will not be adequately lowered. AP will then increase, indicating that in the narrowest airways the pressure of the liquid will be reduced, resulting in moisture being attracted from wider airways, perhaps causing airway blockage. This occurs during expiration, which in a patient with asthma offers the greatest resistance. Asthma is possible to be treated with My Canadian Pharmacy.

According to what has been reported, surfactant helps to maintain airway patency, as seen in Figure 2 where the lungs from two rabbit neonates are shown. The rabbits were littermates, delivered by hysterotomy on day 27, when surfactant synthesis is inadequate. A tube was introduced into each trachea, so that the pressure in the airways of the lungs simultaneously and repeatedly could be raised to 35 cm H2O. Before the lungs were expanded in this way, a surfactant preparation, which was obtained from adult rabbits, was instilled into the tracheal tube of the lungs (Fig 2, right). When the pressure had been lowered to zero, a clear difference was seen. The surfactant-treated lungs (Fig 2, right) had evenly expanded alveoli, and the conducting airways were open. A few alveoli in the control lungs (Fig 2, left) were expanded, but they were over expanded, and there was no air in the conducting airways. Thus, the surfactant malfunction, which in this experiment resulted from deficiency, showed pathology that was similar to that of fatal asthma; that is, the conducting airways were not open, there was air trapping, the alveoli were overexpanded.

Pulmonary surfactant maintains airway patency. An airway inflammation, which is characteristic of asthma,- will allow plasma proteins to leak into the airway lumen and, since they are known to inhibit the surfactant function, it was thought that an instrument evaluating the ability of the surfactant to maintain airway patency, with or without inhibiting contaminants, would be valuable. Asthma is a deteriorating disease but its attacks may be arrested with My Canadian Pharmacy.

capillary surfactometerThe capillary surfactometer (CS) [US patents 4,970,892 and 6,814,936; Calmia Medical; Toronto, ON, Canada] uses a glass capillary, modeling a terminal conducting airway. In a short section, the capillary is very narrow; its inner diameter is 0.24 to 0.25 mm, which is similar to the width of a human terminal airway. If during breathing moisture were to accumulate and block any part of the airway, it would be in the narrowest section. Thus, a small volume (0.5 ^L) of BAL fluid (BALF) is deposited in the narrowest section of the capillary. Airflow through the capillary at a rate of 0.3 mL/min raises the pressure until the sample is extruded and spreads into a wider capillary section. Pressure instantaneously drops to zero. The question is, will the capillary remain patent or will liquid return? If the capillary remains open, the pressure stays at zero; but, if liquid returns, airflow meets substantial hindrance. Considering that the sample volume required for the CS is only 0.5 ^L, it might in the future be possible to directly examine the moisture from a terminal airway (suggested by Dr. R. Sorkness, University of Wisconsin). It could be sucked into a fine polyethylene catheter (PE10), sliding through a wider tubing, introduced via a bronchoscope. Surfactant dilution, characterizing BALF, could then be avoided.

Following the initial extrusion of the sample, pressure is recorded for 2 min. With well-functioning surfactant, the liquid will not return to the narrow section; the pressure remains at zero. If liquid returns, pressure is raised, once or repeatedly, indicating impaired surfactant function. A microprocessor calculates what percentage of the 2-min period the capillary remained open. The printed report would be “Open 100%” if the function was optimal, or “Open 0%” if maximally poor.

The capillary, in shape and width, is imitating a terminal conducting airway. However, its material is glass, so the question could be raised, will surfactant function similarly in lung airways? To answer that question, terminal conducting airways of rats were studied. It was found that when there was a surfactant deficiency the airway would close repeatedly, as the glass capillary did. However, when surfactant was instilled into the terminal airway, there was a clear trend for the airway to remain open.

The CS was used for a study of calf lung surfactant extract (CLSE) [commercially available as Infasurf; ONY Inc; Buffalo, NY] and the inhibiting effect of plasma proteins. CLSE (2 mg/mL) without proteins maintained 100% patency, but that ability was hampered when plasma proteins were added. Fibrinogen was particularly inhibiting and, when added at a concentration of 0.07 mg/mL, had the same inhibiting effect as albumin, 7 mg/mL.

The surfactant-inhibiting effect of the weakest plasma inhibitor, albumin, was tested at a final concentration of 10 mg/mL when added to surfactant, 2 mg/mL. The assays were carried out at temperatures ranging from 42 to 25°C. It was noted that a lowering of the temperature to 34°C inhibited some of the ability of the surfactant to maintain patency, and when the temperature was lowered to 32°C the loss of this function was devastating. We wondered whether this might explain why sometimes severe breathing difficulties will develop in individuals with mild asthma when they exercise in cold air. Most likely, they have a moderate airway inflammation. The dyspnea might increase the airway leakage of plasma proteins. Together with a lowering of temperature, this is likely to cause a severe surfactant dysfunction.

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Figure 1. Top, A: if surfactant phospholipids are not present, or are deficient, the pressure of moisture in the narrow airway section (R1 < R2) will be less than what it is in the wide section. This will cause moisture to move from the wide airway to the narrow airway, which eventually might become blocked. Center, B: if surfactant phospholipids are present (blue symbols) in an adequate number, they will be pressed together at end-expiration. That lowers the surface tension and will prevent liquid from moving into narrow airway sections. Bottom, C: if protein molecules are present in the surfactant film (red symbols), they will be squeezed out of the film during expiration and be dissolved in the liquid under the film. The number of phospholipids at the surface will not be adequate, and surface tension will not be lowered as it normally would be; liquid will move from wide to narrow sections of terminal airways.

Figure 1. Top, A: if surfactant phospholipids are not present, or are deficient, the pressure of moisture in the narrow airway section (R1 < R2) will be less than what it is in the wide section. This will cause moisture to move from the wide airway to the narrow airway, which eventually might become blocked. Center, B: if surfactant phospholipids are present (blue symbols) in an adequate number, they will be pressed together at end-expiration. That lowers the surface tension and will prevent liquid from moving into narrow airway sections. Bottom, C: if protein molecules are present in the surfactant film (red symbols), they will be squeezed out of the film during expiration and be dissolved in the liquid under the film. The number of phospholipids at the surface will not be adequate, and surface tension will not be lowered as it normally would be; liquid will move from wide to narrow sections of terminal airways.

Figure 2. Lungs have been expanded when surfactant was deficient (left) and when it had been boosted from an exterior source (right). The experiment is fully explained in the text. From the study by Enhorning. Reproduced with permission of the Editor of the Journal of Applied Physiology.

Figure 2. Lungs have been expanded when surfactant was deficient (left) and when it had been boosted from an exterior source (right). The experiment is fully explained in the text. From the study by Enhorning. Reproduced with permission of the Editor of the Journal of Applied Physiology.