Inhaled synthetic surfactant abolishes the early allergen-induced response in asthma

Abstract

Allergen-induced inhibition of pulmonary surfactant in asthma may promote airway oedema and consequently potentiate the severity of the asthmatic response. A randomised, single-blind, cross-over study of an inhaled synthetic phospholipid dry-powder surfactant (Pumactant) was conducted in atopic, asthmatic subjects with previously documented early and late asthmatic responses (EAR and LAR) to an inhaled allergen. This was conducted to evaluate the role of exogenous surfactant administration on EAR and LAR. A total of seven subjects had complete evaluable data and received the full dose of Pumactant.Asthmatic subjects inhaled two separate doses of 400 mg Pumactant prior to an allergen exposure. The first dose was administered 8 h in advance and the second dose 30 min in advance. The dosage occurred through a purpose-built administration device. This was followed by a standard bronchial-provocation test, and forced expiratory volume in one second (FEV1) was measured at regular intervals over a 10-h period.Pumactant was well tolerated and, surprisingly, abolished the EAR but not the LAR in all seven subjects. The mean area under the curve between 0-2 h (EAR) following bronchial provocation test was 0.08 for the Pumactant treatment group (PT) and 13.29 for the no treatment (NT) group. The maximum drop in FEV1 for EAR was 4.19% and 23.98% in the PT and the NT group, respectively.The demonstration of inhibition of the early asthmatic response by exogenous surfactant, provides the first evidence that pulmonary surfactant dysfunction may also contribute to the very early asthmatic response to allergen. Exogenous surfactant administration could serve as a useful adjunct in controlling the early allergen-induced symptoms in patients with allergic asthma.

Physiologic Dysfunction of the Asthmatic Lung: What's Going On Down There, Anyway?

“…This work has recently been extended by Hite and colleagues (29), who showed that surfactant aggregates in BAL from individuals with asthma were correlated to FEV 1 . Associations of polymorphisms in the genes that encode surfactant proteins to asthma (30) also strongly support a key role for surfactant dysfunction (31) and suggest a potential therapeutic role for surfactant replacement therapy (32). Further, it has recently become apparent that b-agonists, as well as relaxing smooth muscle, may also cause release of surfactant molecules into the air-liquid interface, thereby reducing surface tension within the lungs and stabilizing airways.…”

Novel dry powder inhalation system based on dispersion of lyophilisates

“…Among them are, for example, low molecular weight heparin [88], lung surfactant [89] and an NK1 receptor antagonist [90].…”

Influence of Natural Lung Surfactant Inhalations on Clinical Symptoms and Pulmonary Function Parameters in Patients with Bronchial Asthma. Communication 1

“…[12] Improvement of pulmonary function due to LS administration has also been shown in human patients with BA in several studies. Babu et al [13] demonstrated the feasibility of stopping early response to antigen provocation in atopic BA and increased FEV1 due to Pumactant inhalations. Kurashima et al, [14] in a doubleblind, placebo-controlled study of 12 patients with BA, registered a significant increase of FEV, FEV1 and MMF 20 minutes after administering 10 mg of surfactant formulation.…”

“…The patients were instructed how to use it at the first visit (V1) and then continued to use it on their own for inhalations at home. The surfactant was taken daily at the dose of 25 mg for the first 7 days of the study and then at Days 10,13,16,19,22,26,30,35 and 40 (a total of 16 inhalations), so that the intervals between inhalations were gradually increased. Patients were examined at 5 visits on Days 1(V1), 8(V2), 15(V3), 29(V4) and 41(V5).…”