Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients

Figures & data

Table 1 Flowchart describing visits and tests

Weeks	−2	0	12	24
Visit	1	2	5	8
	Screening	Baseline start treatment A	Stop treatment A, start treatment B	End of treatment
Informed consent	X
Inclusion/exclusion criteria	X
Physical examination	X			X
Monitoring current therapy	X
Medical history	X
Spirometry	X	X	X	X
NO		X	X	X
Body plethysmography		X	X	X
Diffusion		X	X	X
ABG		X	X	X
EBC		X	X	X
Low-dose multislice CT thorax		X	X	X
Blood collection and vital signs		X	X	X
AGRQ		X	X	X

Abbreviations: SGRQ, St George’s Respiratory Questionnaire; ABG, arterial blood gas; EBC, exhaled breath condensate; CT, computed tomography; NO, nitric oxide.

Table 2 Patient characteristics at baseline

	Age, years	Height (cm)	Pack-years	FEV1 (L)	FEV1 (% predicted)	FEV1/FVC (%)	TLC (% predicted)	RV (% predicted)
Males (n = 9)	66.0 ± 10.0	172.7 ± 8.8	62.5 ± 35.2	2.0 ± 0.3	66.0 ± 8.0	57.0 ± 6.2	97.8 ± 13.3	118.8 ± 30.7
Females (n = 3)	62.0 ± 9.5	166.7 ± 4.7	37.1 ± 18.4	1.6 ± 0.3	63.5 ± 4.1	56.4 ± 11.0	114.0 ± 14.5	147.3 ± 22.1

Abbreviations: TLC, total lung capacity; FEV, forced expiratory volume in one second; FVC, forced vital capacity; RV, residual volume.

Figure 1 Changes in iRaw and iVaw for all patients.

Abbreviations: iRaw, image-based resistance; iVaw, image-based volume.

Figure 2 Changes in iRaw after 3 months of treatment with NAC (top) and placebo (bottom) in iRaw responders.

Abbreviations: NAC, N-acetylcysteine; iRaw, image-based resistance.

Figure 3 Changes in iRaw after 3 months of treatment with NAC (top) and placebo (bottom) in an iRaw nonresponder.

Abbreviations: NAC, N-acetylcysteine; iRaw, image-based resistance.

Figure 4 Significant correlation between change in computational fluid dynamics-based resistance of the central airways, iRaw_cent, and glutathione levels after NAC treatment.

Abbreviations: iRaw, image-based resistance; GSH, glutathione; NAC, N-acetylcysteine.

Figure 5 Significant correlation between change in computational fluid dynamics-based resistance of the distal airways iRaw_dist and level of GPx at baseline (top) and after placebo (bottom).

Abbreviations: iRaw, image-based resistance; GPx, glutathione peroxidase.

Figure 6 Glutathione after NAC treatment was significantly different for patients who experienced a decrease in iRaw_cent (top) and an increase in iVaw_cent (bottom).

Abbreviations: iRaw, image-based resistance; GSH, glutathione; iVaw, image-based volume.

Figure 7 Significant difference in change in GPx between responders and nonresponders in terms of iRaw_tot (top) and no significant difference in change in GPx between responders and nonresponders in terms of FEV₁ (bottom).

Abbreviations: iRaw, image-based resistance; GPx, glutathione peroxidase; FEV₁, forced expiratory volume in one second.

Table 3 Lobar inspiratory capacity decreased significantly after placebo and increased after treatment with NAC in patients with a reduction in iRaw_dist < 0.002 kPa/L

	Baseline	After placebo	After NAC
Inspiratory capacity (L) on lobe level (TLC-FRC)	0.63 ± 0.27	0.59 ± 0.26	0.65 ± 0.28
Mann–Whitney U test with baseline, P-value	–	0.011	0.028
Mann–Whitney U test with placebo, P-value	0.011	–	0.011

Abbreviations: NAC, N-acetylcysteine; TLC, total lung capacity; FRC, functional residual capacity; iRaw, image-based resistance.

Figure 8 Significant difference in reduction of hyperinflation (lobar FRC volumes) between responders and nonresponders in terms of iRaw_dist.

Abbreviations: iRaw, image-based resistance; FRC, forced residual capacity.