Contributions of Age and Sex to Heterogeneity of Symptoms and Effectiveness of Secondary Prevention Strategies in Asthma as Modeled in the Guinea Pig

Figures & data

TABLE 1 Experimental groups of guinea pigs for cellular infiltration and airway hyperresponsiveness

		Sensitization		Challenge
Group	n	Age, days	Body weight, g	Age, days	Body weight, g	Sensitization/challenge interval, days
Young/Young (Y/Y)
Female	53	9–11	141.6 ± 3.5	29–31	307.6 ± 4.0	20–21
Male	54	9–11	152.3 ± 3.6	29–31	334.0 ± 5.1	20–21
Young/Adult (Y/A)
Female	32	9–10	141.4 ± 4.3	77–78	603.7 ± 13.6	67–69
Male	33	9–11	142.2 ± 4.8	105–108	854.4 ± 12.1	96–99
Adult/Adult (A/A)
Female	50	56–57	501.4 ± 8.1	77–78	614.9 ± 8.1	21–22
Male	61	84	762.7 ± 9.7	105–112	858.8 ± 10.5	21–28

Values represent the mean ± SE.

FIG. 1 Methacholine-induced changes in airway resistance (Rn) in male (M) and female (F) guinea pigs sensitized with 0.5 mg/kg OVA IP and challenged intratracheally with either saline (NSS) or 400 μ g/kg OVA. Responsiveness to vehicle (Veh; PBS/heparin) and two successive doses of IV methacholine was determined 24 hr after challenge. Details of treatment groups are shown in Table 1. Values represent the geometric mean ± SE. * p < 0.05, significant overall OVA effect with repeated measures ANOVA. #p < 0.05, the change in resistance to either 1 or 3.3 μ g/kg methacholine compared to its respective control in animals challenged with OVA is greater than animals challenged with NSS.

FIG. 2 Methacholine-induced changes in tissue damping (G) in male (M) and female (F) guinea pigs sensitized with 0.5 mg/kg OVA IP and challenged intratracheally with either saline (NSS) or 400 μ g/kg OVA. Responsiveness to vehicle (Veh; PBS/heparin) and two successive doses of IV methacholine was determined 24 hr after challenge. Details of treatment groups are shown in Table 1. Values represent the geometric mean ± SE. * p < 0.05, significant overall OVA effect with repeated measures ANOVA. #p < 0.05, the change in tissue damping to either 1 or 3.3 μ g/kg methacholine compared to its respective control in animals challenged with OVA is greater than animals challenged with NSS.

FIG. 3 Methacholine-induced changes in tissue elastance (H) in male (M) and female (F) guinea pigs sensitized with 0.5 mg/kg OVA IP and challenged intratracheally with either saline (NSS) or 400 μ g/kg OVA. Responsiveness to vehicle (Veh; PBS/heparin) and two successive doses of IV methacholine was determined 24 hr after challenge. Details of treatment groups are shown in Table 1. Values represent the geometric mean ± SE. * p < 0.05, significant overall OVA effect with repeated measures ANOVA. #p < 0.05, the change in tissue elastance to either 1 or 3.3 μ g/kg methacholine compared to its respective control in animals challenged with OVA is greater than animals challenged with NSS.

FIG. 4 Eosinophils in lung and BAL of male (M) and female (F) guinea pigs sensitized with 0.5 mg/kg OVA IP and challenged with either water vehicle (Veh) or varying doses of OVA intratracheally. Eosinophils were determined 24 hr after challenge. Details of treatment groups are shown in Table 1. Values represent the geometric mean ± SE. * p < 0.05 for the indicated comparisons.

FIG. 5 Neutrophils in lung and BAL of male (M) and female (F) guinea pigs sensitized with 0.5 mg/kg OVA IP and challenged with either water vehicle (Veh) or varying doses of OVA intratracheally. Neutrophils were determined 24 hr after challenge. Details of treatment groups are shown in Table 1. Values represent the geometric mean ± SE. * p < 0.05 for the indicated comparisons.

FIG. 6 RBC in BAL and protein in BAL supernatant of male (M) and female (F) guinea pigs sensitized with 0.5 mg/kg OVA IP and challenged with either water vehicle (Veh) or varying doses of OVA intratracheally. Values were determined 24 hr after challenge. Details of treatment groups are shown in Table 1. Values represent the geometric mean ± SE. * p < 0.05 for the indicated comparisons.

TABLE 2 ANOVA of data in Figures 4, 5, and 6

	Eosinophils		Neutrophils
Statistical comparison	Lung	BAL	Lung	BAL	Protein BAL	RBC BAL
OVA dose	*	*	*	*	*	*
Sex	*	*	*
Treatment (Y/Y, Y/A, A/A)	*		*		*	*
OVA dose*Treatment interaction	*
Sex*Treatment interaction		*	*
Sex*OVA dose interaction
Sex*Treatment*OVA dose interaction

* p < 0.05

TABLE 3 Statistical analysis of data in Figures 4, 5

	Eosinophils		Neutrophils
	Lung	BAL	Lung	BAL
Change from vehicle to 0.4 μ g/kg OVA
Female A/A	*
Female Y/A	*	*		*
Female Y/Y
Male A/A	*	*
Male Y/A	*			*
Male Y/Y	*
Change from vehicle to 4 μ g/kg OVA
A/A vs Y/Y
Y/Y vs Y/A				*
A/A vs Y/A	*

* p < 0.05

FIG. 7 OVA-specific IgG₁ antibody in the serum. All animals were sensitized with 0.5 mg/kg OVA and challenged with 0.4–400 μ g/kg OVA intratracheally. Serum was obtained 24 hr after challenge. Details of treatment groups are shown in Table 1. Values represent the geometric mean ± SE. *p < 0.05 for ANOVA analysis comparing A/A to Y/Y and Y/A to Y/Y. A/A was not different from Y/A.