Eicosanoids and Eosinophilic Inflammation of Airways in Stable COPD

Figures & data

Table 1 Clinical Characteristics of the COPD Cohort

Variables	COPD (n=76)	HC (n=37)	P
Male/female subjects, n (%)	54 (71)/22 (29)	23 (62)/14 (38)	NS
BMI, mean (min–max)	28.7 (17.7–45.8)	23.4 (19,3–31,5)	0.007
Age (y), mean±SD	66.8±8.3	62.5±11.7	NS
Age at COPD diagnosis (years), mean±SD	56.2±11.7	–
Post-bronchodilator FEV1% of predicted value, mean (min–max)	61 (29–124)	94 (75–115)	<0.001
Smoking status: current/ex/passive-smoker (%)	19 (25)/52 (68)/5 (7)	4 (10.8)/0/0	<0.001
Pack years, median (25th–75th pc)	30 (15–48)	–
CAT, median (25th–75th pc)	18 (11–24)	–
mMRC, median (25th–75th pc)	2 (1–3)	–
No. of exacerbations per year, median (min–max)	1 (0–12)	–
GOLD categories A/B/C/D (%)	11 (14)/40 (53)/5 (7)/20 (26)	–
ACO diagnosis, n (%)	17 (22%)	–
Blood eosinophil count, cells/µL, median (25th–75th pc)	297.6 (130–380)	140 (100–210)	0.01
Sputum eosinophilia,%, median (25th–75th pc)	1.25 (0.3–5.5)	0.27 (0–0.57)	<0.001
Sputum cell pattern, no. (%)			<0.001
Eosinophilic	21 (28)	2 (5)	0.005
Neutrohilic	25 (33)	7/19	NS
Mixed	6 (8)	1 (3)	NS
Paucigranulocytic	24 (32)	27 (73)	<0.001
Treatment of COPD, n (%)
ICS	37 (49)	–
LAMA	70 (92)	–
LABA	58 (76)	–

Abbreviations: NS, not significant; BMI, body mass index; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; CAT, COPD Assessment Test; mMRC, modified Medical Research Council, ACO, asthma-COPD overlap, LAMA, long-acting muscarinic antagonists; LABA, long-acting beta agonists; ICS, inhaled corticosteroids.

Table 2 Concentrations of Eicosanoids in Induced Sputum in COPD and Healthy Controls

Metabolite [pg/mL] Median (IQR) Method LLOQ	COPD (n=76)	HC (n=37)	P
LTE4 HPLC-MS/MS 3.22	49.4 (20.5–102.2)	6.3 (3.2–10.5)	<0.001
LTD4 HPLC-MS/MS 2.85	18.9 (6.7–56.1)	8.2 (3.1–16.9)	0.003
LTB4 HPLC-MS/MS 2.96	300.1 (81–896.3)	348.5 (117.2–1269)	NS
PGE2 GC-MS 1.62	92 (33.8–252.9)	46.2 (34–64.8)	0.002
Tetranor-PGE-M HPLC-MS/MS 1.45	4.4 (3.2–6.1)	31.4 (27–34.3)	<0.001
PGA2 HPLC-MS/MS 12	13.8 (7.9–23)	14.4 (9.4–17.7)	NS
PGD2 GC-MS 2.09	37.9 (19.3–77.2)	19.4 (10.3–33)	<0.001
Tetranor-PGD-M HPLC-MS/MS 1.55	1.8 (1.3–2.5)	6.2 (10.3–33)	<0.001
8-izo-PGE2 GC-MS 1.65	18.5 (11.9–36.9)	9.6 (6.1–13.7)	<0.001
8-izo-PGF2a GC-MS 0.63	17.8 (6.6–50)	9.4 (5.5–15)	0.006
5-HETE HPLC-MS/MS 0.82	493.6 (150.6–1039.7)	245.6 (42.2–1127.5)	NS
5-oxo-ETE HPLC-MS/MS 5.3	198.3 (138.4–279.7)	114.1 (62.1–252.4)	0.006
12-HETE HPLC-MS/MS 0.63	1241.8 (690–2240)	1652.2 (995.3–2.744.7)	NS
12-oxo-ETE HPLC-MS/MS 10	212.9 (90.7–511.9)	61.6 (34.1–86.9)	<0.001
15-HETE HPLC-MS/MS 2.16	481.7 (690–2240.8)	495.6 (155.2–922.7)	NS
15-oxo-ETE HPLC-MS/MS 5	126.1 (30.5–323.7)	215 (56.2–330.8)	NS
11-dehydro-TBX2 HPLC-MS/MS 1.84	26.7 (14–48.6)	19.3 (15–23.3)	0.043

Abbreviations: NS, not significant; COPD, chronic obstructive pulmonary disease; HC, healthy controls; GC-MS, gas chromatography/mass spectrometry; HPLC-MS/MS, high-performance liquid chromatography/tandem mass spectrometry; LLOQ, lowest limit of quantification; LTE4, leukotriene E₄; LTD₄, leukotriene D₄; LTB₄, leukotriene B₄; PGE₂, prostaglandin E₂; PGD₂, prostaglandin D₂; PGA₂, prostaglandin A₂; tetranor-PGE-M, tetranor-prostaglandin E metabolite; tetranor-PGD-M, tetranor-prostaglandin D metabolite; 8-iso-PGE₂, 8-iso-prostaglandin E₂; 8-iso-PGF_2a, 8-iso-prostaglandin F_2a, 5-HETE, 5-hydroxyeicosatetraenoic acid; 5-oxo-ETE, 5-oxo-eicosatetraenoic acid; 12-HETE, 12-hydroxyeicosatetraenoic acid; 12-oxo-ETE, 12-oxo-eicosatetraenoic acid; 15-HETE, 15-hydroxyeicosatetraenoic acid; 15-oxo-ETE, 15-oxo-eicosatetraenoic acid; 11-dehydro-TBX₂, 11-dehydro-thromboxane B_2.

Figure 1 Heat map presenting concentrations of selected eicosanoids.

Notes: (A) Healthy controls, (B) COPD subjects with noneosinophilic airway inflammation, (C) COPD subjects with eosinophilic airway inflammation.

Figure 2 Correlations between PGD₂ and sputum eosinophilia (A) and post-bronchodilator FEV1 (B).