Methacholine versus histamine: paradoxical response of spirometry and ventilation distribution.
We investigated the differential effect of histamine and methacholine on spirometry and ventilation distribution (where indexes S(cond) and S(acin) represent conductive and acinar ventilation heterogeneity; Verbanck S, Schuermans D, Van Muylem A, Noppen M, Paiva M, and Vincken W. J Appl Physiol 83: 1807-1816, 1997). Thirty normal subjects were challenged with cumulative doses of 6.52 micromol histamine and, on a separate day, with either 6.67 micromol methacholine (equal-dose group; n = 15) or 13.3 micromol methacholine (double-dose group; n = 15). Largest average forced expiratory volume in 1 s (FEV(1)) decreases or S(cond) increases obtained in either group were -9% and +286%, respectively; S(acin) remained unaffected at all times. In the equal-dose group, a smaller FEV(1) decline (P = 0.002) after methacholine was paralleled by a smaller S(cond) increase (P = 0.041) than with histamine. However, in the double-dose group, methacholine maintained a smaller FEV(1) decline (P = 0.009) while inducing a larger S(cond) increase (P = 0.006) than did histamine. The differential action of histamine and methacholine is confined to the conductive airways, where histamine likely causes the greatest overall airway narrowing and methacholine induces the largest parallel heterogeneity in airway narrowing, probably at the level of the large and small conductive airways, respectively. The observed ventilation heterogeneities predict a risk for dissociation between ventilation-perfusion mismatch and spirometry, particularly after methacholine challenge.
Verbanck
S
S
Respiratory Division, Academic Hospital, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. sylvia.verbanck@az.vub.ac.be
Schuermans
D
D
Noppen
M
M
Vincken
W
W
Paiva
M
M
D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008450:Maximal Midexpiratory Flow Rate / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology*; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D013147:Spirometry
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D006632:Histamine