Airway Dimensions in Fatal Asthma and Fatal COPD: Overlap in Older Patients

Figures & data

Figure 1.  Large airway of an asthmatic patient stained with Movatｴs pentachrome. With this staining, cartilage and mucous cells stain in blue, muscle in red, elastin in black/purple and connective tissue in yellow. The analyzed airway compartments were: inner wall (iw), airway smooth muscle (asm), submucosal glands area (sm) and outer wall (ow). Basement membrane = bm. Cartilage = c. Scale bar = 250 μm.

Table 1.  Clinical characteristics of asthma and COPD patients

	YFA (n = 12)	OFA (n = 15)	COPD (n = 14)
Gender (M/F, n)	2/10	4/11	8/6
Age (yr)	32 ± 3^a	65 ± 1	71 ± 1
Duration of disease (yr)	23 ± 4	28 ± 5	ND
Age of disease onset (yr)	8 ± 2	33 ± 5^b	ND
Early/late onset asthma (n)	7/5	1/11 (3 NA)	–
Oral corticosteroids	16.7%	40%	64.3%^c
Inhaled corticosteroids	8.3%^d	13.3%^d	100%
LABA	0	13.3%	100%
Methylxanthines	41.7%	53.3%
Regular SABA	92%	100%	100%
Previous hospital admission (%)	33%	53.3%	ND
Previous ICU admission	16.7%	20%	ND
Medical follow-up (%)	33%^d	40%^e	100%
FEV1 % pred	ND	ND	32.31 ± 3.81
FEV1 (L)	ND	ND	0.81 ± 0.09
FEV1/FVC	ND	ND	40 ± 2.31
FVC % pred	ND	ND	54.69± 4.73
Smoking (pack-years)	0	0	60 ± 3.4
Emphysema score^f	ND	ND	41.5 ± 8.2
DLCO %	ND	ND	42.17 ± 8.83


Definition of abbreviations: COPD, chronic obstructive pulmonary disease; DLCO, carbon monoxide diffusing capacity; F, female; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity, ICU, intensive care unit; L, liters; LABA, Long-Acting Beta-Agonist; M, male; NA, not available; ND, not determined; OFA, older fatal asthma; SABA, Short-Acting Beta-Agonist; YFA, younger fatal asthma.

Data presented as mean ± SEM, unless stated otherwise.

^ap < 0.001 in relation to OFA and COPD.

^bp = 0.001 in relation to YFA.

^cp = 0.02 in relation to YFA.

^dp < 0.001 in relation to COPD.

^ep = 0.001 in relation to COPD.

^fEmphysema score determined using ref 5.

Figure 2.  Histological examples of large and small airways of patients with asthma (A, B), with COPD (C, D) and a control patient (E, F). Observe the prominent airway smooth muscle layer (asm) in large and small airways of the asthmatic patient. Cartilage = c, airway smooth muscle = asm, submucosal gland = sm, ep = epithelium. H&E staining. Scale bar = 250 μm in A, C and E. Scale bar = 100 μm in B, D and F.

Table 2.  Characteristics of control patients

	YCTRL (n = 10)	OCTRL (n = 9)
Gender (M/F, n)	6/4	6/3
Age (yr) Cause of death (n)	49 ± 1	63 ± 1
Cardiovascular disease	10	5
Uterine cancer	–	1
Prostate cancer	–	1
Amyotrophic lateral sclerosis	–	1
Pancreatitis	–	1

Definition of abbreviations: F, female; M, male; OCTRL, older controls; YCTRL, younger controls. Age presented as mean ± SEM.

Table 3.  Airway dimensions in fatal asthma, severe fatal COPD and controls

	YFA	YCTRL	p^a	OFA	OCTRL	COPD	p^b	p^c
BM	9.37 ± 0.71^d	7.35 ± 0.37	0.02	7.88 ± 0.45	7.37 ± 0.38	6.77 ± 0.42	0.25	0.40
LA-IW	159.96/108.85	71.50/21.91	0.01	188.17/163.60	72.60/60.41	132.34/73.95	0.007	0.01
LA-ASM	124.05/100.69^e	58.51/28.69	< 0.001	100.29/95.23^f	54.36/43.60	20.23/29.97	0.20	0.003
LA-OW	668.85/523.35^g	290.15/126.98	0.001	711.09/1209.30^h	181.96/187.52	292.78/255.10	0.067	0.69
Glands	21.00/71.80	42.05/45.6^i	0.54	114.55/181.91	103.39/110.40	29.41/62.31	0.83	0.01
SA-IW	74.06/29.76	60.83/43.67	0.40	72.76/44.59	32.26/35.42	56.54/56.03	0.058	0.06
SA-ASM	69.28/61.95^j	34.42/28.72	0.02	37.59/38.62	29.60/7.69	11.87/12.26	0.08	0.007
SA-OW	273.59/233.58^k	186.08/122.75	0.06	157.72/207.16	159.70/124.36	109.12/139.29	1.00	0.22

Definition of abbreviations: ASM, airway smooth muscle; BM, basement membrane; COPD, chronic obstructive pulmonary disease; CTRL, controls; FA, fatal asthma; Glands, submucosal gland area; IW, inner wall area; LA, large airways; O, older; OW, outer wall area; Y, younger; SA, small airways. Data presented as mean ± SEM or median/IQR.

^aYFA vs YCTRL.

^bOFA vs OCTRL.

^cOCTRL vs COPD.

^dYFA vs COPD, p = 0.002.

^eYFA vs COPD, p < 0.001.

^fOFA vs COPD, p = 0.004.

^gYFA vs COPD, p ≤ 0.01.

^hOFA vs COPD, p = 0.01.

ⁱYCTRL vs OCTRL, p = 0.036.

^jYFA vs COPD, p = 0.004.

^kYFA vs COPD, p = 0.01.

Figure 3.  Longitudinal sections of a large airway of patients with asthma (A), COPD (B) and a control patient (C). The basement membrane (bm) in A is thicker than in B and C, and has an hyaline eosinophilic aspect. Observe the thick airway smooth muscle (asm) bundle in A. Submucosal gland = sm, cartilage = c. H&E staining. Scale bar = 50 μm.

Figure 4.  Large airways basement membrane thickness (μm) in younger adult fatal asthmatics (YFA), older adult fatal asthmatics (OFA) and in patients with severe Chronic Obstructive Pulmonary Disease (COPD). Data presented as mean ± SEM.

Figure 5.  Large airway dimensions in younger adult fatal asthmatics (YFA), older adult fatal asthmatics (OFA) and in patients with severe Chronic Obstructive Pulmonary Disease (COPD). Areas were normalized by basement membrane perimeter (μm2/μm). Each bar indicates the median and the whiskers represent the interquartile range. IW = inner wall, ASM = airway smooth muscle, OW = outer wall, gland = submucosal glands area.

Figure 6.  Small airway dimensions in younger adult fatal asthmatics (YFA), older adult fatal asthmatics (OFA) and in patients with severe Chronic Obstructive Pulmonary Disease (COPD). Areas were normalized by basement membrane perimeter (μm2/μm). Each bar indicates the median and the whiskers represent the interquartile range. IW = inner wall, ASM = airway smooth muscle, OW = outer wall.

Figure 7.  Curve estimation plots of parameters associated with age in regression analyses. Fit lines represent quadratic curves. ASM, airway smooth muscle; COPD, chronic obstructive pulmonary disease; OCTRL, older controls; OFA, older fatal asthma; YCTRL, younger controls; YFA, younger fatal asthma. Age presented in years, basement membrane thickness presented in μm, ASM and outer wall areas presented in μm2/μm.

Figure 8.  Large airways inflammation in the inner wall (IW) and outer wall (OW) in younger adult fatal asthmatics (YFA), older adult fatal asthmatics (OFA), patients with severe Chronic Obstructive Pulmonary Disease (COPD), younger controls (YCTRL) and older controls (OCTRL) based on a semi-quantitative score (0 = no inflammation, 1 = mild inflammation, 2 = moderate inflammation, 3 = intense inflammation). Data presented as median/IQR. *p ≤ 0.01 vs. COPD. †p < 0.001 vs. YCTRL and OCTRL. §p < 0.01 vs. YCTRL and OCTRL.

Figure 9.  Small airways inflammation in the inner wall (IW) and outer wall (OW) in younger adult fatal asthmatics (YFA), older adult fatal asthmatics (OFA), patients with severe Chronic Obstructive Pulmonary Disease (COPD), younger controls (YCTRL) and older controls (OCTRL) based on a semi-quantitative score (0 = no inflammation, 1 = mild inflammation, 2 = moderate inflammation, 3 = intense inflammation). Data presented as median/IQR. *p ≤ 0.001 vs. YCTRL. †p = 0.002 vs. OCTRL. §p ≤ 0.001 vs. OCTRL. ‡p < 0.001 vs. COPD. **p = 0.04 vs. COPD. §§p = 0.004 vs.OCTRL.