Inhaled synthetic surfactant abolishes the early allergen-induced response in asthma.
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.
Babu
K S
KS
Division of Infection, Inflammation and Repair, School of Medicine, Southampton General Hospital, Southampton, UK. ksb@soton.ac.uk
Woodcock
D A
DA
Smith
S E
SE
Staniforth
J N
JN
Holgate
S T
ST
Conway
J H
JH
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D018592:Cross-Over Studies; D005541:Forced Expiratory Volume; D006801:Humans; D010715:Phosphatidylglycerols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D011208:Powders; D011446:Prospective Studies; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D012130:Respiratory Hypersensitivity / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D016037:Single-Blind Method; D013997:Time Factors
D010715:Phosphatidylglycerols; D011208:Powders; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine