Disparity Between Proximal and Distal Airway Reactivity During Methacholine Challenge

Figures & data

Table 1.  Baseline data (n = 185)

Age	45 [36–52]
Gender (Male%)	44
BMI	27 [24–31]
Smoking History (%)
Never	74.1
Past	23.2
Current	2.7
Spirometry
FEV1/FVC	0.80 [0.77–0.84]
FEV1 (% predicted)	98 [89–105]
FVC (% predicted)	102 [92–110]
Oscillometry
R5 (cmH2O/L/s)	3.97 [3.21–5.14]
R20 (cmH2O/L/s)	3.38 [2.67–4.11]
R5–20 (cmH2O/L/s)	0.69 [0.33–1.13]
AX (cmH2O/L)	3.92 [1.97–7.77]

Note: Data expressed as Median [IQR] unless otherwise specified.

Figure 1.  Left panel illustrates data for baseline R₅ (median and IQR) obtained in all subjects prior to methacholine administration. Right panel illustrates the bronchodilator response of R₅ assessed on a prior day in 117/185 subjects. Baseline R₅ and bronchodilator response did not relate to the degree of BHR (p = ns).

Figure 2.  Relationship between degree of BHR and changes in oscillometric parameters during MCT. The top panel illustrates that the change in total airway resistance as assessed by R₅ was significantly larger in the positive and borderline BHR groups compared with the negative BHR group (p = 0.025). The bottom two panels illustrate minimal change in R₂₀ during MCT while there was a larger change in distal airway mechanics as assessed by R_5–20 (p<0.001 for comparison of R_5–20 between positive and borderline vs. negative BHR groups).

Figure 3.  Relationship between change in FEV₁ obtained after the highest dose of methacholine with the simultaneous change in R₅. Although many of the subjects demonstrated concordant changes in spirometric and oscillometric parameters during MCT, there was disparity between change in FEV₁ and change in R₅ (r = 0.17, p = 0.019).

Figure 4.  Relationship between the change in R₅ during methacholine administration to changes in R₂₀ and frequency dependence of resistance between 5–20 Hz. Analysis of the slopes of these relationships indicated that R₂₀ increased only 0.3 cmH₂O/L/s for every 1 cmH₂O/L/s change in R₅. In contrast, R_5–20 increased 0.7 cmH₂O/L/s for every 1 cmH₂O/L/s change in R₅ indicating that the effect of methacholine on resistance at 5Hz was predominantly driven by increased frequency dependence of resistance.

Figure 5.  The effect of methacholine on resistance at 5Hz was tightly correlated with the frequency dependence of reactance as assessed by the change in AX.

Figure 6.  Relationship between onset of respiratory symptoms to changes in airflow and changes in R₅. Data are illustrated for the 9/33 subjects who developed symptoms with minimal change in FEV₁ (mean change = -3.4%, left panel). The mean increase in R₅ was 42% from the baseline value in these subjects (right panel).