The role of pulmonary surfactant in obstructive airways disease

Abstract

Pulmonary surfactant research has an increasing impact on treatment considerations in adult respiratory disorders, above all acute respiratory distress syndrome (ARDS). Obstructive airways diseases have only been sporadically addressed in this respect. In the last decade, direct and circumstantial evidence for surfactant as a contributing factor in the regulation of airway calibre has emerged.Morphologically, a bronchiolar surfactant layer has been demonstrated, whereby the airways are mostly supplied by alveolar surfactant components via the mucociliary escalator. Functionally, prevention of airway film collapse and collapse of the airway walls are important surfactant properties in maintaining airway stability. In addition to its surface activity, airway surfactant improves bronchial clearance and regulates airway liquid balance, thus indirectly modulating airway wall thickness and airway diameter. Surfactant has furthermore been shown to modulate the function of respiratory inflammatory cells. Its immunomodulatory activity includes suppression of cytokine secretion and transcription factor activation. This may be of importance in the inflammatory network of asthma.Thus, dysfunction of surfactant in obstructive lung disease might be one of the mechanisms leading to increased airway resistance, which is commonly thought to be due to narrowing of airways under humoral and nervous control. In animal models of asthma, surfactant dysfunction was demonstrated, which was possibly due to protein inhibition. Furthermore, surfactant therapy seems to be capable of preventing allergen-induced bronchoconstriction. Human studies on surfactant impairment in obstructive airways diseases are still scarce but the data available are consistent with animal studies.Antiobstructive pharmacotherapy, mainly with corticosteroids, might influence and improve airway surfactant balance, but the exact mechanisms and the overall effect of pharmacotherapy on surfactant function in obstructive airways disease has to be further elucidated. Our knowledge about the role of pulmonary surfactant in obstructive airways disease is still limited, but there is convincing evidence that pulmonary surfactant plays a role in keeping the airways open.

Lung Surfactant and Its Use in Lung Diseases

“…В течение последних лет появились сведения о том, что бронхообструкция, вызываемая сокраще нием гладкой мускулатуры бронхов, отек слизистой и повы шенная секреция жидкости в просвет бронхов могут быть час тично обусловлены нарушениями в системе ЛС [53,54,112,113]. Обнаружены изменения в составе ЛС, выделенного из БАЛ больных бронхиальной астмой, и показано, что он обла дает меньшей способностью снижать ПН [22].…”

“…Экспериментальные исследования убеждают в обосно ванности попыток сурфактант терапии бронхиальной астмы, однако пока клинические исследования ограничены [23,53,112,165]. S. B. Oetomo и соавт.…”

“…Особую роль при этом играют САБ, они действуют в качестве первой линии защиты против некоторых микроорганизмов и вирусов. Показано, что САБ связывают некоторые полютанты и аллергены, а сам ЛС участ вует в обеспечении нормального просвета бронхов, поэтому нарушения в системе ЛС могут вносить существенный вклад в патогенез бронхиальной астмы [53,54].…”

Physiological basis of improvement after lung volume reduction surgery for severe emphysema: where are we?

“…These findings may be due to the inability of the P-V curve to account for complex locoregional heterogeneity in mechanical and airway properties. Conversely, it may be suggested that LVRS, as does bullectomy, allows the decompression of relatively more normal lung areas, and thereby leads to: 1) a recruitment of effective lung volume; 2) a modification of airway geometry that may reduceairway obstruction; and3)an improvement ofsurfactant synthesis in the better inflated, formerly compressed zones, which may also concur with better airway patency [79].…”

Pulmonary Surfactant Protein-A (SP-A) Restores the Surface Properties of Surfactant after Oxidation by a Mechanism That Requires the Cys6 Interchain Disulfide Bond and the Phospholipid Binding Domain

“…Whereas unsaturated PL species are essential to the fluidity of surfactant, the initial formation of the surface film, and the reincorporation of material into the film during expansion in the breathing cycle (1,2,8), they are also distinctively susceptible to oxidation. Surfactant oxidation and dysfunction likely contributes to the pathophysiology of several diseases including adult respiratory distress syndrome (10,11), asthma (12,13), chronic obstructive pulmonary disease (12), and infections (10). In addition to direct effects on the surface properties of surfactant, lipid peroxidation products can inhibit the synthesis and secretion of new surfactant (14) and reduce the viability of alveolar macrophages, and type II pneumocytes (15).…”