Data Analysis
We recorded data on-line using a MINC computer (Digital Equipment Company) for subsequent off-line analysis. The significance of differences was assessed by paired t test using the Bonferroni correction for multiple comparisons. Values are given as mean ± SEM.
Results
Histamine Challenge

The PC20 to histamine ranged from 0.05 to 3.4 mg/ dl (mean, 0.8 mg/dl). On average the FEV, fell by 37 ± 11 percent (Table 1), associated with a significant fall in ear oxygen saturation (Fig 1). This hypoxemia was not associated with a significant change in tidal volume (0.1>p>0.05), but there was a significant prolongation of Ttot (Fig 2) caused by prolongation of both inspiratory time (Ti; p<0.04) and of expiratory time (Te; p<0.02; Fig 3 and 4). The VT/Ttot fell significantly following histamine inhalation. However, there was no significant change in either Ti/Ttot or Vi/Ti (Table 1). Following inhalation of salbutamol, there was a significant rise in FEV! (p<0.02) associated with a rise in oxygen saturation (p<0.002). There was also a significant shortening of Te following salbutamol administration (p<0.02), and Ttot also tended to fall (Table 1). canadian pharmacy

Methacholine Challenge
The PC20 to methacholine ranged from 0.04 to 2.5 mg/dl (mean 0.6 mg/dl). The FEVi fall after methacholine challenge (an average of 34 ± 11 percent) was similar to that after histamine challenge associated with a significant fall in oxygen saturation (p<0.02) (Fig 1). However, there were no significant changes in the breathing pattern following the methacholine challenge (Table 1). Salbutamol inhalation again returned FEVj to around the control level, and the ear oxygen saturation also rose after salbutamol administration (p<0.02). However, salbutamol produced no significant change in the breathing pattern following methacholine challenge.
Table 1 — Ear Oxygen Saturation and Breathing Patterns Following Histamine or Methacholine Bronchial Challenge

Measurement Histamine Challenge Methacholine Challenge
Control Histamine Salbutamol Control Methacholine Salbutamol
FEV,, L 2.43±0.25 1.55±0.18t 2.66±0.19t 2.47 ±0.22 1.65 ±0.14$ 2.26±0.21t
SaOa, % 95.0±0.4 91.7±0.8t 95.0±0.4t 95.0±0.5 92.5±0.8t 95.0 ±0.5$
Ti, s 1.62±0.2 2.0±0.2§ 1.8±0.2 1.6±0.2 2.2±0.5 2.2±0.4
Te, s 2.4±0.2 3.1±0.2§ 2.2±0.2§ 2.7±0.4 2.7±0.3 2.4±0.2
Ttot, s 4.06±0.29 4.94±0.37§ 3.96±0.24 4.27±0.50 4.79 ±0.56 4.60 ±0.44
Ti/Ttot 40±3 41 ±3 45±3 40±2 44±4 45±4
Vt, ( ) 0.40 ±0.04 0.44 ±0.03 0.39 ±0.04 0.42 ±0.04 0.45 ±0.05 0.42 ±0.05
Vr/Ttot, /min 6.12±0.53 5.37±0.55§ 5.78 ±0.50 6.25±0.53 5.67 ±0.38 5.59 ±0.35
Vr/Ti,/min 16.7±2.0 15.5±2.2 14.8± 1.8 17.0± 1.8 15.3± 1.7 14.1± 1.4

 

Figure 1. Fall in ear oxygen saturation (SaO*) in ten stable asthmatic patients following inhaled histamine (left) and methacholine (right) administration.

Figure 1. Fall in ear oxygen saturation (SaO*) in ten stable asthmatic patients following inhaled histamine (left) and methacholine (right) administration.

Figure 2. Frequency histograms of the distribution of breath period (Ttot) of each breath before (H) and at maximal bronehoconstriction (□) induced by administration of either histamine (upper) or methacholine (lower) and after an inhaled (32-agonist (□) in two patients. In patient 1, FEV, fell from 3.61 to 2.41 L after receiving histamine and from 3.61 to 2.01 L after receiving methacholine. Inhaled salbutamol then increased FEV, to 3.2 L when given after histamine and to 3.0 L after methacholine challenges. In patient 2, FEV, fell from 1.91 to 1.41 L after histamine and from 1.9 to 1.6 L after methacholine administration. Salbutamol increased FEV, to 2.31 L when given after histamine and to 2.11 after methacholine administration.

Figure 2. Frequency histograms of the distribution of breath period (Ttot) of each breath before (H) and at maximal bronehoconstriction (□) induced by administration of either histamine (upper) or methacholine (lower) and after an inhaled (32-agonist (□) in two patients. In patient 1, FEV, fell from 3.61 to 2.41 L after receiving histamine and from 3.61 to 2.01 L after receiving methacholine. Inhaled salbutamol then increased FEV, to 3.2 L when given after histamine and to 3.0 L after methacholine challenges. In patient 2, FEV, fell from 1.91 to 1.41 L after histamine and from 1.9 to 1.6 L after methacholine administration. Salbutamol increased FEV, to 2.31 L when given after histamine and to 2.11 after methacholine administration.

Figure 3. Increase in expiratory time (Te) in ten patients following histamine challenge (left) and the subsequent decrease in Te after inhalation of the agonist. In contrast, methacholine inhalation produced no significant change in Te.

Figure 3. Increase in expiratory time (Te) in ten patients following histamine challenge (left) and the subsequent decrease in Te after inhalation of the agonist. In contrast, methacholine inhalation produced no significant change in Te.

Figure 4. Frequency histograms of the distribution of expiratory time (Te) of each breath before (■), at maximal bronchoconstriction (0) induced by histamine (upper) or methacholine (lower), and after administration of the 02-agonist (□) for the same two patients shown in Figure 2.

Figure 4. Frequency histograms of the distribution of expiratory time (Te) of each breath before (■), at maximal bronchoconstriction (0) induced by histamine (upper) or methacholine (lower), and after administration of the 02-agonist (□) for the same two patients shown in Figure 2.