Suppression of neural activity of bronchial irritant receptors by surface-active phospholipid in comparison with topical drugs commonly prescribed for asthma.
BACKGROUND
Much indirect evidence has been put forward previously in support of the concept that surface-active phospholipid (SAPL) normally masks irritant receptors in the lungs and upper respiratory tract; but this physical barrier is deficient in asthmatics, imparting hyperresponsiveness of the bronchoconstrictor reflex.


OBJECTIVE
To determine whether exogenous SAPL applied to bronchial mucosa reduces the sensitivity of irritant receptors to a standard challenge used clinically to diagnose asthma and to compare the effects with those of corticosteroids and beta-stimulation.


METHODS
Nerve fibres in the vagi were monitored to record action potentials from irritant receptors identified in the upper airways of rat lungs in response to a methacholine challenge. SAPL in the form of dipalmitoyl phosphatidylcholine (PC) and phosphatidylglycerol (PG) - 7 : 3 PC:PG - was applied as a fine dry powder to enhance surface activity and, hence, chemisorption to epithelium. Comparison was also made with clinical doses of i.v. hydrocortisone and instilled salbutamol together with liquid or solid controls, as appropriate.


RESULTS
Neural activity of irritant receptors was found to be significantly (P = 0.0018) decreased by topical SAPL by 35.8% in response to a methacholine challenge in contrast to an increase of 11.2% in response to a solid (lactose) control. Instilled salbutamol and i.v. hydrocortisone also decreased responses to the same challenge by 43.4% and 14.7%, respectively, in contrast to a liquid (saline) control which increased by 24.5%.


CONCLUSIONS
Surface-active phospholipid has an appreciable effect upon irritant receptors in rat airways, reducing neural response to a methacholine challenge by an amount comparable to that of Salbutamol. These results support the concept of SAPL masking bronchial irritant receptors and warrant placebo-controlled clinical trials of this dry powder as a means of controlling asthma without the side-effects of current medication. Other possible roles discussed for the SAPL epithelial barrier include the exclusion of viruses and allergens.
Hills
B A
BA
Paediatric Respiratory Research Centre, Mater Children's Hospital, Brisbane, Australia.
Chen
Y
Y
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000420:Albuterol / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001980:Bronchi / Q000166:cytology; D001985:Bronchial Provocation Tests; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D006854:Hydrocortisone / Q000627:therapeutic use; D008297:Male; D016210:Methacholine Chloride; D010743:Phospholipids / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000502:physiology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000187:drug effects / Q000503:physiopathology*; D014630:Vagus Nerve / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D010743:Phospholipids; D011663:Pulmonary Surfactants; D016210:Methacholine Chloride; D000420:Albuterol; D006854:Hydrocortisone