Nocturnal thoracoabdominal asynchrony in house dust mite-sensitive nonhuman primates

Figures & data

Table 1 Characteristics of nonallergic and allergic groups

	Serum α-HDM-IgE (% allergic control)	Eosinophils in BAL (%)	Total cells in BAL compartment × 10^6	HDM concentration (AU/mL)	ΔRL (%)	ΔCdyn (%)
Nonallergic	15.8 ± 3.5	1 ± 0.4	9.58 ± 3.47	2500 ± 0	0.6 ± 5.3	−5.6 ± 4.9
Allergic	70.4 ± 5.1	35.1 ± 4.7	13.65 ± 1.76	360 ± 120.7	103.4 ± 16.7	−47.6 ± 3.4
P value	<0.0001	<0.0001	0.236	<0.0001	<0.0001	<0.0001

Notes: Values are mean ± SE, nonallergic, n = 11, allergic, n = 21. Animals were exposed to increasing concentrations of HDM in sterile saline until the concentration presented in this table elicited the associated ΔR_L or ΔC_dyn during 15 minutes following the HDM challenge.

Abbreviations: BAL, in bronchoalveolar lavage; HDM, house dust mite; C_dyn, dynamic compliance; R_L, lung resistance; SE, standard error of measurement.

Table 2 Methacholine PC₅₀ of conventional respiratory indexes

	Methacholine PC50 (mg/mL)		Pvalue
	Mean	SE	RR	Cdyn	RL
RR	0.07	0.01	–	0.031	0.001
Cdyn	0.23	0.05	0.031	–	0.001
RL	0.63	0.09	0.001	0.001	–

Abbreviations: RR, respiratory rate; C_dyn, dynamic compliance; R_L, lung resistance; SE, standard error of measurement.

Figure 1 Responses to sequential exposure of aerosolized saline, maximum concentration of HDM extract, and albuterol. Shown are changes in (A) RR, (B) C_dyn, (C) R_L, (D) eBPRL, (E) ePhRL, and (F) PhAng. Responses to saline and HDM were recorded in 23 animals. Albuterol was administered to eight animals exhibiting severe and prolonged increases in airway resistance. The changes were expressed as a percentage of the baseline measurement recorded prior to saline delivery. Values are expressed as means ± SE.

Abbreviations: HDM, house dust mite; RR, respiratory rate; C_dyn, dynamic compliance; R_L, lung resistance; eBPRL, baseline effort phase relation; ePhRL, effort phase relation; PhAng, phase angle; SE, standard error of measurement.

Table 3 Multiple linear regression results of eBPRL, ePhRL, and PhAng recorded during the first 30 minutes following HDM challenge

Dependent variable	Independent variable	Regression coefficients		tbj	P
		Bj	SE sbj
eBPRL	Intercept	26.80	13.72	1.95	0.056
	Cdyn	−3.85	1.25	−3.08	0.003
	RL	1.65	0.41	4.08	<0.001
ePhRL	Intercept	30.15	13.99	2.16	0.035
	Cdyn	−4.43	1.27	−3.48	0.001
	RL	1.68	0.41	4.06	<0.001
PhAng	Intercept	98.62	25.20	3.91	<0.001
	Cdyn	−11.42	2.29	−4.98	<0.001
	RL	2.07	0.74	2.782	0.007

Note: The P value is a test of H₀: β_j = 0 against H_a: β_j ≠ 0.

Abbreviations: HDM, house dust mite; RR, respiratory rate; C_dyn, dynamic compliance; R_L, lung resistance; eBPRL, baseline effort phase relation; ePhRL, effort phase relation; PhAng, phase angle; SE, standard error or measurement.

Figure 2 Representative RIP recordings of one animal (ID: 8065) during both the early asthmatic response and the nocturnal asthmatic response. Excursions of the rib cage (RC) and the abdomen (AB), as well as corresponding eBPRL, ePhRL, and PhAng are shown for multiple breaths. Note the triangular RC and AB wave forms, and that eBPRL and ePhRL are better reflections of TAA than PhAng during the early asthmatic response peak and also are good reflections of TAA during the nocturnal asthmatic response peak. The Konno-Mead diagram (bottom of each vertical panel) shows the direction of RC movement (dRC) and the direction of AB movement (dAB) during inhalation and exhalation in three breaths.

Abbreviations: AB, abdomen; RC, rib cage; eBPRL, baseline effort phase relation; ePhRL, effort phase relation; PhAng, phase angle; TAA, thoracoabdominal asynchrony.

Figure 3 Long-term stability of nocturnal eBPRL and ePhRL. Plots of eBPRL and ePhRL (30-minute averages) starting at 10 pm and ending at 5 am next morning in 11 nonallergic animals. The changes were expressed as a percentage of the baseline measurement recorded during afternoon. Values are means ± SE at each time point.

Abbreviations: eBPRL, baseline effort phase relation; ePhRL, effort phase relation; SE, standard error or measurement.

Figure 4 Representative nocturnal eBPRL and ePhRL response of the same animal represented in Figure 2 (ID: 8065). Plot of eBPRL (filled circle) and ePhRL (open circle) (30-minute averages) starting at 1 pm and ending at 6 am next morning. AUC was started at 10 pm and ended at 5 am.

Abbreviations: eBPRL, baseline effort phase relation; ePhRL, effort phase relation; AUC, area under the curve.

Figure 5 Changes in (A) eBPRL and (B) ePhRL between 10 pm and 5 am for each individual animal in both the allergic group (n = 21) and the nonallergic group (n = 11). A and B the allergic group mean AUC for eBPRL and ePhRL were significantly greater than the nonallergic control group mean AUC. The arrow indicates values for animal ID: 8065 which is also represented in Figure 2 and 4. Dashed lines represent the upper limit of the 99% confidence interval for the nonallergic group.

Abbreviations: eBPRL, baseline effort phase relation; ePhRL, effort phase relation; AUC, area under the curve.

Figure 6 Reproducibility of the nocturnal response to HDM challenge. Eight animals were challenged with HDM on two different dates. AUC for (A) eBPRL and (B) ePhRL are shown. Symbols represent individual animals. Dash lines represent the upper limit of the 99% confidence intervals for the nonallergic group. The symbols above the dashed lines were classified as nocturnal asthmatic responses.

Abbreviations: eBPRL, baseline effort phase relation; ePhRL, effort phase relation; AUC, area under the curve; HDM, house dust mite.