Locytic AECOPD; {P,0.01 vs. the Neutrophilic AECOPD; `P,0.05 vs. the Paucigranulocytic AECOPD; | P,0.05 vs. the Neutrophilic AECOPD; 1P,0.05 vs. the Eosinophilic AECOPD; “P,0.05 vs. the Mixed granulocytic AECOPD. doi:10.1371/journal.pone.0057678.tTable 3. The levels of serum and sputum inflammatory mediators in AECOPD patients.Eosinophilic Blood CRP (mg/L) Sputum CRP (ug/L) Blood MMP9 (ng/mL) Sputum MM P-9 (ng/mL) Blood IL-6 (pg/mL) Sputum IL-6 (pg/mL) Blood SAA (mg/L) 10(8.4?3.2) 48(24?12) 1030(406?497) 528(338?159) 19(12?2) 362(268?70) 36(27?4)Neutrophilic 16(12?9) * 145(78?70)+* 750(516?161) 1836(1045?891)+ 31(17?7)+ 918(447?372)+* 84(64?16)+*+Mixed granulocytic 14.8(14.3?8.2) * 199(175?37)+*” 1760(828?810) 4914(3140?390)+*” 125(47?32)+*” 2541(765?890)+* 142(52?53)+*+Paucigranulocytic 12(7.3?5) 22(11?0) 680(385?427) 930(293?117) 16(7.0?2) 459(167?089) 32(23?2)control 0.83(0.5?.6) 7(3.8?6) 355(165?48) 392(93?04) 5.7(3.4?.7) 48(31?40) 3.8(2.9?.5)Data are expressed as median (IQR). The difference among groups was determined by He enhanced duodenal HO activity associated to Hx deficiencycan further contribute Kruskall-Wallis and Mann-Whitney U test. *P,0.05 vs. the Eosinophilic; +P,0.05 vs. the Paucigranulocytic; “P,0.05 vs. the Neutrophilic; All of the patient groups were significantly higher than that in the controls (P,0.01). doi:10.1371/journal.pone.0057678.tSputum Cellular Phenotypes in AECOPDTable 16985061 4. Clinical characteristics of patients with stable COPD.Eosinophilic N Age (years) BODE score GOLD I GOLD II GOLD III GOLD IV Post-FEV1 (L) Post-FEV1/pred ( ) FEV1/FVC ( ) Volume of sputum (mL) Blood leukocytes (109/L) Blood neutrophils (10 /L) Blood eosinophils (109/L) Total cell count (10 /mL) Neutrophils (106/mL) eosinophils (106/mL) macrophages (10 /mL) lymphocytes (106/mL) epithelial cells (106/mL) Squamous cells (106/mL)6 6Neutrophilic 29 65.4611.2 3.0(2.0?.8)*” 2 5 15 7 1.2860.44` 40.867.6` 60.468.9 13(9?7)*” 8.3(6.7?.2)*” 5.1(3.5?.2) 0.17(0.0?.35) 15.3(7.2?1.1)*”Mixed granulocytic 3 60.3610.8 3.0(3.0?.0)*” 0 0 1 2 0.7860.051` 30.064.1` 58.467.3 14(9?8)*” 7.8(7.0?.2)`* 4.8(4.1?.3) 0.7(0.53?.9){” 16.4(10.6?9.7)*” 12.1(7.4?6.3)*” 1.8(0.9?.9)”{ 2.2(0.2?1.4) 0.0(0.0?.12) 0.9(0.5?.4) 0.7(0.3?.9)Paucigranulocytic 24 62.8610.1 0.0(0.0?.0) 2 11 23148522 11 0 1.3960.49 49.0617.4 62.467.6 6(2.5?0) 7.2(6.2?.4) 4.9(3.9?.7) 0.11(0.0?.28) 1.0(0.5?.2) 0.2(0.1?.6) 0.0(0.0?.1) 0.7(0.2?.3) 0.0(0.0?.02) 1.6(0.7?.7) 1.2(0.6?.1)5 66.0613.0 1.0(0.0?.0) 2 2 1 0 1.3360.42 43.3616.0 61.169.3 4(2?) 6.4(5.3?.8) 4.3(3.4?.1) 0.67(0.54?.8){” 1.4(0.8?.2) 0.7(0.4?.1) 0.3(0.2?.9)”{ 0.9(0.3?.1) 0.0(0.0?.03) 0.8(0.4?.2) 0.3(0.0?.7)10.3(6.5?4.2)*” 0.1(0.0?.2) 1.4(0.3?.9) 0.0(0.0?.42) 0.9(0.3?.7) 0.8(0.2?.4)Data are expressed as mean 6 SD or median (IQR). The difference among groups was determined by ANOVA, Kruskall Wallis, Mann-Whitney U test or Chi Ntrol Control Control Control ControlmiRNA pattern A A A A A square. *P,0.01 vs. the Eosinophilic COPD; “P,0.01 vs. the Paucigranulocytic COPD; {P,0.01 vs. the Neutrophilic COPD; `P,0.05 vs. the Paucigranulocytic COPD; 1P,0.05 vs. the Neutrophilic COPD. doi:10.1371/journal.pone.0057678.tanalyses were performed using SPSS17.0 software. A p value of ,0.05 was considered statistically significant.Results Studying patientsTo determine the inflammatory cellular phenotypes, a total of 296 patients with COPD were screened and 83 patients withTable 5. The levels of serum and sputum inflammatory mediators in stable COPD patients.Eosinophilic Blood CRP (mg/L) Sputum CRP (ug/L) Blood MMP-9 (ng/mL) Sputum MMP-9 (ng/mL) Blood IL-6 (pg/mL) Sputum IL-6 (pg/mL) Blood SAA (mg/L) 3.8(3?.7.Locytic AECOPD; {P,0.01 vs. the Neutrophilic AECOPD; `P,0.05 vs. the Paucigranulocytic AECOPD; | P,0.05 vs. the Neutrophilic AECOPD; 1P,0.05 vs. the Eosinophilic AECOPD; “P,0.05 vs. the Mixed granulocytic AECOPD. doi:10.1371/journal.pone.0057678.tTable 3. The levels of serum and sputum inflammatory mediators in AECOPD patients.Eosinophilic Blood CRP (mg/L) Sputum CRP (ug/L) Blood MMP9 (ng/mL) Sputum MM P-9 (ng/mL) Blood IL-6 (pg/mL) Sputum IL-6 (pg/mL) Blood SAA (mg/L) 10(8.4?3.2) 48(24?12) 1030(406?497) 528(338?159) 19(12?2) 362(268?70) 36(27?4)Neutrophilic 16(12?9) * 145(78?70)+* 750(516?161) 1836(1045?891)+ 31(17?7)+ 918(447?372)+* 84(64?16)+*+Mixed granulocytic 14.8(14.3?8.2) * 199(175?37)+*” 1760(828?810) 4914(3140?390)+*” 125(47?32)+*” 2541(765?890)+* 142(52?53)+*+Paucigranulocytic 12(7.3?5) 22(11?0) 680(385?427) 930(293?117) 16(7.0?2) 459(167?089) 32(23?2)control 0.83(0.5?.6) 7(3.8?6) 355(165?48) 392(93?04) 5.7(3.4?.7) 48(31?40) 3.8(2.9?.5)Data are expressed as median (IQR). The difference among groups was determined by Kruskall-Wallis and Mann-Whitney U test. *P,0.05 vs. the Eosinophilic; +P,0.05 vs. the Paucigranulocytic; “P,0.05 vs. the Neutrophilic; All of the patient groups were significantly higher than that in the controls (P,0.01). doi:10.1371/journal.pone.0057678.tSputum Cellular Phenotypes in AECOPDTable 16985061 4. Clinical characteristics of patients with stable COPD.Eosinophilic N Age (years) BODE score GOLD I GOLD II GOLD III GOLD IV Post-FEV1 (L) Post-FEV1/pred ( ) FEV1/FVC ( ) Volume of sputum (mL) Blood leukocytes (109/L) Blood neutrophils (10 /L) Blood eosinophils (109/L) Total cell count (10 /mL) Neutrophils (106/mL) eosinophils (106/mL) macrophages (10 /mL) lymphocytes (106/mL) epithelial cells (106/mL) Squamous cells (106/mL)6 6Neutrophilic 29 65.4611.2 3.0(2.0?.8)*” 2 5 15 7 1.2860.44` 40.867.6` 60.468.9 13(9?7)*” 8.3(6.7?.2)*” 5.1(3.5?.2) 0.17(0.0?.35) 15.3(7.2?1.1)*”Mixed granulocytic 3 60.3610.8 3.0(3.0?.0)*” 0 0 1 2 0.7860.051` 30.064.1` 58.467.3 14(9?8)*” 7.8(7.0?.2)`* 4.8(4.1?.3) 0.7(0.53?.9){” 16.4(10.6?9.7)*” 12.1(7.4?6.3)*” 1.8(0.9?.9)”{ 2.2(0.2?1.4) 0.0(0.0?.12) 0.9(0.5?.4) 0.7(0.3?.9)Paucigranulocytic 24 62.8610.1 0.0(0.0?.0) 2 11 23148522 11 0 1.3960.49 49.0617.4 62.467.6 6(2.5?0) 7.2(6.2?.4) 4.9(3.9?.7) 0.11(0.0?.28) 1.0(0.5?.2) 0.2(0.1?.6) 0.0(0.0?.1) 0.7(0.2?.3) 0.0(0.0?.02) 1.6(0.7?.7) 1.2(0.6?.1)5 66.0613.0 1.0(0.0?.0) 2 2 1 0 1.3360.42 43.3616.0 61.169.3 4(2?) 6.4(5.3?.8) 4.3(3.4?.1) 0.67(0.54?.8){” 1.4(0.8?.2) 0.7(0.4?.1) 0.3(0.2?.9)”{ 0.9(0.3?.1) 0.0(0.0?.03) 0.8(0.4?.2) 0.3(0.0?.7)10.3(6.5?4.2)*” 0.1(0.0?.2) 1.4(0.3?.9) 0.0(0.0?.42) 0.9(0.3?.7) 0.8(0.2?.4)Data are expressed as mean 6 SD or median (IQR). The difference among groups was determined by ANOVA, Kruskall Wallis, Mann-Whitney U test or Chi square. *P,0.01 vs. the Eosinophilic COPD; “P,0.01 vs. the Paucigranulocytic COPD; {P,0.01 vs. the Neutrophilic COPD; `P,0.05 vs. the Paucigranulocytic COPD; 1P,0.05 vs. the Neutrophilic COPD. doi:10.1371/journal.pone.0057678.tanalyses were performed using SPSS17.0 software. A p value of ,0.05 was considered statistically significant.Results Studying patientsTo determine the inflammatory cellular phenotypes, a total of 296 patients with COPD were screened and 83 patients withTable 5. The levels of serum and sputum inflammatory mediators in stable COPD patients.Eosinophilic Blood CRP (mg/L) Sputum CRP (ug/L) Blood MMP-9 (ng/mL) Sputum MMP-9 (ng/mL) Blood IL-6 (pg/mL) Sputum IL-6 (pg/mL) Blood SAA (mg/L) 3.8(3?.7.