Predicting Balb/c and B6C3F₁ Mouse Sensitivity to Inhaled Methacholine: Impact of Calculating Lung-Airway Dimension and Airflow Distribution

Figures & data

TABLE 1 Lobar distribution of distal lung volume (as % of total; mean ± SE; n = 3 lungs): comparison between mice (B6C3F₁ and Balb/c)

Airway lobe	Entrance airway code	Distal volume B6C3F1 (%)	Distal volume Balb/c (%)
Left apical (LA)	122	11.8 ± 3.1	7.5 ± 0.3
Left diaphragmatic (LD)	121	15.4 ± 4.0	20.1 ± 1.9
Right apical (RA)	112	17.7 ± 2.0	16.2 ± 0.6
Right medial (RM)	1112	9.1 ± 2.2	16.8 ± 0.9
Right diaphragmatic (RD)	11111	33.3 ± 3.1	28.5 ± 2.3
Right caudal (RC)	11112	12.8 ± 1.6	10.9 ± 1.3
TB		# TB (used to calculate % distal volume)
# TB in whole lung (mean ± SE)		1,418 ± 48	1,198 ± 22
Note: SE, standard error.

FIG. 1 Surface area per airway generation (mean ± SE; n = 3). For airway generations 1–6, comparison of surface area between mice (B6C3F₁ or Balb/c) and between method of calculating airway surface area (based on average airway dimensions or based on individual airway dimensions). White columns represent surface area from average airway dimensions of B6C3F₁ mice; light-grey columns represent area from individual airway dimensions of B6C3F₁ mice; grey columns represent area from average airway dimension of Balb/c mice; and dark-grey columns represent area from individual airway dimensions of Balb/c mice.

TABLE 2 Mass deposited in airway generations 1–6 (mean ± SE): Comparison between mice (B6C3F₁ and Balb/c), deposition model (typical path, TP; individual airway, IA; or none, M_Ch), and method of calculating airflow (cross-sectional area, xA; distal volume, dV)

Dosimetry model	B6C3F1 (μg)	Balb/c (μg)
M_Ch_2002	—– ± —–	—– ± —–
TP_xA_2006	13.80 ± 3.18	3.80 ± 0.90
TP_xA(current)	12.69 ± 2.92	2.42 ± 0.58
IA_xA(current)	2.12 ± 0.40	0.85 ± 0.16
IA_dV(current)	4.38 ± 0.93	0.63 ± 0.12

FIG. 2 Relative impact on response to methacholine: Comparison of dose-response-factor (DRF) ratios [DRF(Balb/c) vs. DRF(B6C3F₁; mean ± SE)] of three DRFs [airway surface dose (vertical bar filled with tight stipple of small dots); airway physiology (relating airway circumference with pressure drop; vertical bar filled with open stipple of parallel 45-degree lines); and bio-sensitivity (vertical bar filled with open stipple of large dots)] as calculated by five dosimetry models: M_Ch_2002; TP_xA_2006; TP_xA(current); IA_xA(current); and IA_dV(current).