The contribution of neurogenic reflexes to hypertonic saline-induced bronchoconstriction in asthma.
BACKGROUND
Hypertonic saline induces bronchoconstriction in most patients with asthma; however, the mechanisms involved are not clearly understood. We have investigated the role of neurogenic mechanisms in hypertonic saline-induced bronchoconstriction.


METHODS
The effect of pretreatment with the anticholinergic drugs atropine and ipratropium bromide and the local anesthetic drug lidocaine on hypertonic saline responsiveness was studied in 11 subjects with asthma. Ultrasonically nebulized hypertonic saline challenge was given in a dose-response manner to determine the provocative dose of hypertonic saline-laden air required to produce a fall in forced expiratory volume in 1 second (FEV1) of 20% or greater (PD20HS). A control PD20HS with no pretreatment was measured before randomization, and on the next three visits PD20HS was determined after pretreatment with each of the following: intramuscularly administered atropine, inhaled ipratropium bromide, and inhaled lidocaine.


RESULTS
The baseline mean FEV1 values increased by 3.5% and 4% 30 minutes after administration of atropine and ipratropium bromide, respectively, and decreased by 5.8% at 10 minutes after inhalation of lidocaine. These changes in the baseline FEV1 were not significant and did not have any effect on the PD20HS response. Premedication with atropine, ipratropium bromide, and lidocaine resulted in increases of 2.5, 2.0, and 2.6 times in mean PD20HS, respectively.


CONCLUSIONS
The protection afforded by the drugs was variable in the individual subjects and not related to age, sex, baseline FEV1, provocative concentration of histamine causing a 20% fall in FEV1 or use of the inhaled corticosteroids. The protection afforded by anticholinergic and local anesthetic drugs suggests the contribution of neurogenic reflexes in the pathogenesis of hypertonic saline-induced bronchoconstriction in asthma.
Makker
H K
HK
Immunopharmacology Group, University of Southampton, Southampton General Hospital, England.
Holgate
S T
ST
D000328:Adult; D000704:Analysis of Variance; D001250:Asthma, Exercise-Induced / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D001285:Atropine / Q000008:administration & dosage; D001985:Bronchial Provocation Tests / Q000379:methods / Q000706:statistics & numerical data; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage; D008012:Lidocaine / Q000008:administration & dosage; D008297:Male; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D012044:Regression Analysis; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D012462:Saline Solution, Hypertonic; D001285:Atropine; D006632:Histamine; D008012:Lidocaine; D009241:Ipratropium