Locytic AECOPD; {P,0.01 vs. the (-)-Calyculin A chemical Eliglustat site information 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.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.
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