Comparison of efficiency of inhaled and intravenous corticosteroid on pregnant women with COPD and the effects on the expression of PCT and hs-crp

Transcription

1 EXPERIMENTAL AND THERAPEUTIC MEDICINE 15: , 2018 Comprison of efficiency of inhled nd intrvenous corticosteroid on pregnnt women with COPD nd the effects on the expression of PCT nd hs-crp YULIANG ZHAO, FEI LI, YANGWEN LIU, YINGJUN SHI, ZHIHAI LI, GUANGKE CAO nd WANG ZHU Deprtment of Intensive Cre Union, The First People's Hospitl of Xuzhou, Xuzhou, Jingsu , P.R. Chin Received September 4, 2017; Accepted Jnury 19, 2018 DOI: /etm Abstrct. The efficiency of inhled nd systemic corticosteroids on pregnnt women with chronic obstructive pulmonry disese (COPD) ws investigted. The study lso compred the effects of the dministrtion on the expression of inflmmtory meditor proclcitonin (PCT) nd high-sensitivity C-rective protein (hs-crp). A totl of 120 pregnnt COPD ptients were recruited nd rndomly llocted into the following three groups: Intrvenous corticosteroid tretment group (n=42), inhled corticosteroid tretment group (n=38), nd control group (without ny corticosteroid tretment, n=40). Ptients of the ll three groups received symptomtic supportive tretments including oxygen therpy, nti-infection therpy, expectornt, nd bronchodiltor. The serum PCT nd hs-crp expression levels were mesured before tretment nd fter 7 dys of tretment. Moreover, the clinicl prmeters such s symptoms, blood gs nlysis prmeters, pulmonry function indexes, fsting blood glucose (FBG) nd dverse rections were recorded. The overll clinicl effective rtes of the group received budesonide inhltion nd the group receiving systemic methylprednisolone tretment were comprble. Both tretments were ble to reduce the levels of inflmmtory meditors, hs-crp nd PCT. On the other hnd, tretments incresed PO 2 of rteril blood gs while reducing PCO 2, thereby improving the lung function (FEV1% pred nd FEV1/FVC) (P>0.05). The study observed tht the FBG levels in COPD ptients receiving systemic corticosteroid tretment were significntly incresed, while budesonide inhltion did not significntly ffect the FBG levels. In ddition, rtes of dverse events (such s mouth dry, orl ulcers, horseness) of systemic corticosteroid tretment group were significntly higher thn those in inhled corticosteroid tretment group nd control group (38.1% vs. 17.5% vs. 5.0%, comprison Correspondence to: Dr Yuling Zho, Deprtment of Intensive Cre Union, The First People's Hospitl of Xuzhou, 19 Zhongshnbei Rod, Xuzhou, Jingsu , P.R. Chin E-mil: lwsd686@163.com Key words: chronic obstructive pulmonry disese, pregnncy, corticosteroid, inhltion, PCT, hs-crp between groups: P<0.05). In conclusion, inhled nd systemic use of corticosteroid both significntly improved dyspne nd other clinicl symptoms of pregnnt COPD ptients by incresing oxygen prtil pressure, correcting hypoxemi, nd enhncing lung function. Moreover, fewer dverse rections were observed with inhled corticosteroid tretment, suggesting tht inhled dministrtion is reltively good, sfe nd effective tretment for pregnnt COPD ptients. Introduction Chronic obstructive pulmonry disese (COPD) is chronic lung disese chrcterized with pthologicl fetures of inflmmtory chnges such s epithelil hyperplsi, hypertrophy of irwy mucos, nd clinicl mnifesttion of prtilly reversible irflow obstruction. The prime cuse of COPD is smoke either primry or secondry (1). Moreover, smoke in the environment is lso responsible to gret extent for the spred of COPD especilly in femles (2). Cliniclly, COPD ptients often experience continuous deteriortion due to the recurrence of re-infection symptoms, which hs become n importnt reson for incresed mortlity (3,4). Corticosteroid used s nti-inflmmtory gent nd vsoconstrictor of smll rteries could reduce inflmmtory exudtion nd reduce irwy obstruction, enbling its wide ppliction in COPD tretment. However, long-term systemic therpy is likely to pose severe dverse effects on humn body. Chnges in physiologicl nd endocrine structure ccompnied with suppression of cellulr immune function during pregnncy further increse the susceptibility to infection. According to the Globl Inititive for Chronic Obstructive Pulmonry Disese (GOLD, version 2009), inhled steroid medicines re recommended for AECOPD (cute excerbtions of chronic obstructive pulmonry disese) ptients filed to chieve stisfctory outcomes with bronchodiltors or hospitlized AECOPD ptients (5). In the present study, 120 pregnnt women with COPD dmitted to the Deprtment of Intensive Cre Union, of The First People's Hospitl of Xuzhou (Xuzhou, Chin) from April, 2015 to My, 2016 were recruited to compre the clinicl efficiency nd dverse events during tretment with systemic corticosteroids nd topicl inhled corticosteroids. The bove tsks were performed by evluting the effects of different pproches on inflmmtory fctors such s proclcitonin (PCT) nd high-sensitivity C-rective

2 4718 ZHAO et l: EFFICIENCY OF INHALED AND INTRAVENOUS CORTICOSTEROID ON PREGNANT WOMEN WITH COPD protein (hs-crp), so s to provide more pproprite, sfe nd effective tretment pln for pregnnt COPD ptients. Mterils nd methods Generl mterils. One hundred nd twenty pregnnt women with COPD ged yers were recruited. Ptients were dmitted to the Obstetrics nd Gynecology Deprtment of The First People's Hospitl of Xuzhou from April 2015 to My 2016 nd signed written informed consent before initiliztion of the study. Further, the Ethics Committee of The First People's Hospitl of Xuzhou provided ethicl clernce for the present study. COPD ws dignosed with the FEV1/FVC rtio (the rtio of the forced expirtory volume in the first one second to the forced vitl cpcity of the lungs) fter inhltion of bronchodiltor <70% (6). Ptients with one or more conditions listed in the exclusion criteri were excluded (7): Severe hert filure nd heptic nd renl dysfunction; other existing lung diseses; metbolic disorders nd consumptive diseses, such s hyperthyroidism, cncer, dibetes mellitus, nd ctive tuberculosis; impired consciousness. Experimentl methods. Recruited ptients conforming to the inclusion criteri were rndomly llocted into three groups: Intrvenous corticosteroid tretment group (n=42), treted with methylprednisolone (ct. no. MB0668; Phrmci nd Upjohn Co., Pfizer, NY, USA) 40 mg, OD, for 7 dys; inhled corticosteroid tretment group (n=38), treted with budesonide erosol (ct. no. H ; AstrZenec AB, Södertälje, Sweden), 2 mg, tid, for 7 dys; nd control group receiving no corticosteroid tretment. Ptients in ll groups received routine symptomtic supportive cre, including continuous low flow oxygen inhltion, nticholinergic medictions nd theophylline bronchodiltor, nd ntibiotics tretment. Gesttionl weeks nd ges were comprble mong ptients in the three groups. Prmeter detection. The serum PCT nd hs-crp expression levels were mesured before tretment nd fter 7 dys of tretment. Further, the clinicl prmeters such s symptoms, blood gs nlysis prmeters, pulmonry function indexes, fsting blood glucose (FBG) nd dverse rections were recorded. Mesurement of rteril blood gs prmeter oxygen prtil pressure (PO 2 ) nd prtil pressure of crbon dioxide (PCO 2 ): The rteril blood gs nlysis ws performed with blood gs nlyzer I-STST1 (300) mode (Abbott Phrmceuticl Co. Ltd., Lke Bluff, IL, USA). Pulmonry function test: Spirometry (BTL-08, BTL Group Ltd., London, UK) ws pplied to mesure the FEV1% pred (predicted % forced expirtory volume in 1 min) nd FEV1/FVC. PCT nd hs-crp mesurement: PCT ws mesured using double ntibody sndwich immunochromtogrphy Lumt LB 9507 PCT-Anlyzer (Berthold Technologies GmbH & Co. KG, Bd wildbd, Germny); nd hs-crp ws mesured with turbidimetric immunossy (QuikRed, Espoo, Finlnd). Determintion of clinicl efficiency. The clinicl efficiency ws mesured s ineffective, effective, nd significntly Figure 1. PCT level chnge of vrying groups before nd fter tretment. The hs-crp levels of ll three groups re significntly decresed compred with pre-therpy conditions (P<0.05). The downregultion of inhled nd intrvenous corticosteroid tretment groups is significnt compred to the control group (P<0.05). However, compring inhled nd intrvenous corticosteroid tretment groups no significnt difference ws observed. effective bsed on the frequency of coughs, the mount of sputum, the degree of dyspne, nd the usculttion of the lungs (8). The overll efficiency rte ws clculted with the following formul: (significntly effective cses + effective cses)/totl number of cses x 100%. Sttisticl nlysis. SPSS 18.0 softwre (SPSS, Inc., Chicgo, IL, USA) ws used to nlyze the dt. Quntittive dt were described s men ± stndrd devition, nd ssessed using F-test. Enumertion dt were expressed s percentges (%) nd performed with Chi-squre test to compre the difference. P<0.05 ws considered to indicte sttisticlly significnt difference. Results No sttisticlly significnt differences were observed by compring prmeters including ge, gesttionl weeks, lung function, blood gs nlysis, inflmmtory fctors (PCT, hs-crp) nd FBG mong different groups. Results of blood gs nlysis. The rtes of improvement of blood gs nlysis (ph, PO 2, PCO 2 ) of the inhled corticosteroid tretment group nd intrvenous corticosteroid tretment group were both significntly higher thn those in the control group (P<0.05; Tble I). Pulmonry function indictors. The pulmonry function indictors (FEV1% pred, FEV1/FVC) of inhltion tretment group nd intrvenous tretment group incresed from (42.42±3.29, 47.49±3.55) nd (42.22±3.57, 47.35±3.68) to (50.65±3.57, 54.79±3.44) nd (49.47±3.37, 53.76±3.15), respectively. Both were significntly higher thn tht of the control group (P<0.05; Tble II). Chnge in PCT levels. The PCT vlues before nd fter tretment of the control group, intrvenous tretment group nd inhltion tretment were 3.64±2.37 vs. 1.10±0.35 ng/ml,

3 EXPERIMENTAL AND THERAPEUTIC MEDICINE 15: , Tble I. Blood gs nlysis mong the three groups of ptients (men ± SD). Prmeters (n=40) group (n=42) group (n=38) F/χ 2 vlue P-vlue PCO 2 (mmhg) Before tretment 42.98± ± ± After tretment 40.44±2.86,c 37.96±2.96,b 38.83±3.55 c PO 2 (mmhg) Before tretment 60.68± ± ± After tretment 63.62±3.48,c 66.83±3.14,b 66.55±3.36,b ph Before tretment 7.30± ± ± After tretment 7.36±0.03,c 7.38±0.04,b 7.40±0.03 c P<0.05, b P<0.05, nd c P<0.05 correspond to comprison with pre-therpy vlue of the sme group, comprison with post-therpy vlue of the control group, nd comprison with post-therpy vlue of intrvenous tretment group. Tble II. Comprison of pulmonry function indictors mong ptients of three groups (men ± SD). Prmeters (n=40) group (n=42) group (n=38) F/χ 2 vlue P-vlue FEV1% (pred) Before tretment 42.41± ± ± After tretment 44.35±2.65,c 49.47±3.37,b 50.65±3.57,b FEV1/FVC (%) Before tretment 47.8± ± ± After tretment 50.43±3.02,c 53.76±3.15,b 54.79±3.44,b P<0.05, b P<0.05, nd c P<0.05 correspond to comprison with pre-therpy vlue of the sme group, comprison with post-therpy vlue of the control group, nd comprison with post-therpy vlue of intrvenous tretment group. 3.71±1.99 vs. 0.50±0.49 ng/ml, nd 3.58±2.20 vs. 0.56±0.49 ng/ml, respectively. It ws noted tht the inhibition of inflmmtory meditor PCT in corticosteroid-treted group ws remrkbly enhnced in comprison to tht of the control group (P<0.05; Fig. 1). Chnge in hs-crp level. The hs-crp levels before nd fter tretment of the control group, intrvenous tretment group, nd inhltion tretment were 70.12±36.68 vs ±6.66 mg/dl, 68.87±36.01 vs ±5.99 mg/dl, 73.68±37.96 vs ±5.78 mg/dl. The inhibition level of inflmmtory meditor hs-crp in corticosteroid-treted group ws remrkbly enhnced compred with tht of the control group (P<0.05; Fig. 2). Chnge in FBG level. Compred with the control group nd inhled corticosteroid tretment group, the FBG level of intrvenous corticosteroid tretment group incresed significntly (P<0.05) (Tble III). Comprisons of rtes of clinicl efficiency nd dverse events. The overll clinicl efficiency rtes of inhled nd intrvenous Figure 2. Hs-CRP level chnge of vrying groups before nd fter tretment. The hs-crp levels of ll three groups were significntly decresed compred with pre-therpy condition (P<0.05). The downregultion of inhled nd intrvenous corticosteroid tretment groups ws significnt compred to the control group (P<0.05). However, compring inhled nd intrvenous corticosteroid tretment groups no significnt difference ws observed. corticosteroid tretment groups were comprble (P>0.05), nd both were higher thn tht of the control group (P<0.05).

4 4720 ZHAO et l: EFFICIENCY OF INHALED AND INTRAVENOUS CORTICOSTEROID ON PREGNANT WOMEN WITH COPD Tble III. Comprison of fsting blood glucose mong three groups of ptients (men ± SD). Observtion index (n=40) group (n=42) group (n=38) F/χ 2 vlue P-vlue FBG (nnmol/l) Before tretment 4.92± ± ± After tretment 5.01±0.46 c 5.64±0.56,b 5.03±0.45 c P<0.05, b P<0.05, nd c P<0.05 correspond to comprison with pre-therpy vlue of the sme group, comprison with post-therpy vlue of the control group, nd comprison with post-therpy vlue of intrvenous tretment group. Tble IV. Comprisons of rtes of clinicl efficiency nd dverse events mong three groups of ptients. Observtion index (n=40) group (n=42) group (n=38) F/χ 2 vlue P-vlue Overll efficiency rte [n (%)] 26 (65.0) 38 (90.5) 35 (87.5) Adverse events [n (%)] 2 (5.0) b 16 (38.1) 7 (17.5),b P<0.05 nd b P<0.05 correspond to comprison with post-therpy vlue of the control group, nd comprison with post-therpy vlue of intrvenous tretment group. Overll rtes of dverse events of inhled nd intrvenous corticosteroid tretment group (such s mouth dry, orl ulcers, horseness) were significntly higher thn tht of the control group, nd the increse ws more pronounced in the intrvenous corticosteroid tretment group (P<0.05; Tble IV). Discussion Comprehensive tretment pproches for cute excerbtion of COPD (AECOPD) minly include bronchil diltion, nti inflmmtory therpy, nd use of corticosteroids to control irwy inflmmtion (9). Studies hve shown tht systemic corticosteroid tretment helps shorten the rehbilittion time, restored lung function nd improved hypoxemi. Further, it lso reduced hospitl sty nd erly recurrence rte. However, multiple dverse events could be induced by corticosteroid tretment. This included bnorml lipid metbolism, blood sugr disturbnce, nd infection secondry to immune function decline. Moreover, in few cses, ptients might lso experience respirtory filure (10,11). With locl dministrtion of corticosteroid vi inhltion, drugs re inhled through the irwy into the lveolr, where the highly concentrted locl drug deposition on the lesion surfce directly exerts the therpeutic effect. The heptic first-pss metbolism of systemic dministrtion cn be voided, thus significntly reducing the side effects. However, whether the inhled corticosteroid could replce the systemic dministrtion or existence of ny potentil difference when compred with systemic corticosteroid therpy remined mtter of concern. COPD ptients experience persistent irflow obstruction. Acid-bse nd electrolyte disorders could be detected on the bsis of blood gs nlysis (ph, PCO 2 nd PO 2 ), This helped to dignose potentil hypoxemi or hypercpni nd types of respirtory filure, nd predict the outcome. Around hlf of AECOPDs could be ttributed to bcteril infection-relevnt cuse (12). As n cute-phse protein incresing in positive proportion to infection severity in erly onset of infection, CRP level is insensitive to tretments such s corticosteroid, immunosuppressive gents, nd nti-inflmmtory drugs. This enbled CRP s mjor indictor for erly dignosis of COPD nd reflector of clinicl tretment outcome (13,14). PCT is the precursor of clcitonin nd significntly increses only during bcteril infection. It is currently considered tht the sensitivity nd specificity of serum PCT in the dignosis of bcteril inflmmtion re significntly better thn those of CRP (15,16). Recent findings showed tht tretment course of ptients with respirtory trct infection receiving PCT-bsed ntibiotic therpy is significntly reduced when compred with ptients receiving tretment guided otherwise. Further, 30-dys follow up did not show ny dverse event, suggesting tht PCT could be used s stisfctory supplementry evidence for dignosis of AECOPD (17,18). In the present study, under the sme tretment time, there ws no significnt difference in the overll rte of clinicl efficiency between the inhled budesonide tretment group nd the systemic methylprednisolone tretment group. Both resulted in the decrese of inflmmtory meditors (hs-crp nd PCT). The PCT levels before nd fter tretment of the control group, intrvenous corticosteroid tretment group nd inhled corticosteroid tretment group were 3.64±2.37 vs. 1.10±0.35 ng/ml, 3.71±1.99 vs. 0.50±0.49 ng/ml nd 58±2.20 vs. 0.56±0.49 ng/ml, nd ccordingly the hs-crp levels before nd fter tretment were 70.12±36.68 vs ±6.66 mg/dl, 68.87±36.01 vs ±5.99 mg/dl nd 73.68±37.96 vs ±5.78 mg/dl, respectively. Combintion of increse in rteril blood gs PO 2 nd decrese in PCO 2, in ddition to improvement of lung function indictors FEV1% pred nd FEV1/FVC suggested tht, locl inhltion nd intrvenous systemic corticosteroid tretment could help in the reduction of

5 EXPERIMENTAL AND THERAPEUTIC MEDICINE 15: , the inflmmtory response, hypoxi, nd effectively improve lung function. Corticosteroid tretment during COPD cute excerbtion could improve rte of clinicl efficiency nd reduce hospitl sty by improving FEV1 nd incresing PO 2 (10,19,20). Budesonide given with oxygen-driven tomiztion device enters lung vi irwy nd cts on lung tissue cells nd exerts locl nti-inflmmtory nd ntillergic effect with high selectivity. However, some ptients might experience dverse events including dry mouth, throt soreness, horseness nd orl cndidisis. Corticosteroid provides efficiency by generting ctive complex by binding with cytoplsm nd hormone receptor on the cell membrne to promote poptosis of inflmmtory cells. It hs been reported to reduce irwy hyperresponsiveness, nd relieve bronchospsm nd improve dyspne (21). In the present study, we found tht the fsting blood glucose (FBG) level of COPD ptients receiving systemic corticosteroid tretment ws significntly incresed, while inhled budesonide did not ffect FBG. In ddition, we observed tht incidence of dverse events such s dry mouth, orl ulcers, nd horseness of systemic corticosteroid tretment group ws higher thn locl erosol inhltion tretment group nd control group. The difference might be ttributed to the fct tht inhled corticosteroid generted high locl concentrtion of drugs, leving low mount of drugs into systemic circultion. Therefore no obvious systemic biologicl effect ws observed without increse of blood sugr levels due to liver glycogen gluconeogenesis, nd the dverse events were reltively relieved s well. The pproch, dosge nd course of clinicl ppliction of corticosteroid should be determined by selecting individulized protocol bsed on vrying ptient popultion nd disese condition. Considering tht the recruited ptients in the study were pregnnt women, the side effects secondry to systemic corticosteroid use might exceed the therpeutic effectiveness. Therefore, in summry, topicl erosol inhltion is n idel dministrtion pproch, which might be more suitble for pregnnt COPD ptients. Acknowledgements Not pplicble. Funding No funding ws received. Avilbility of dt nd mterils The dtsets used nd/or nlyzed during the current study re vilble from the corresponding uthor on resonble request. Authors' contributions YZ contributed significntly to writing the mnuscript nd detectin serum PCT nd hs-crp expression levels. FL nd YL nlyzed nd interpreted clinicl prmeters.ys mesured rteril blood gs prmeter. ZL nd GC performed clinicl efficiency. WZ provided sttisticl nlysis. All uthors red nd pproved the finl mnuscript. Ethics pprovl nd consent to prticipte The study ws pproved by the Ethics Committee of The First People's Hospitl of Xuzhou (Xuzhou, Chin). Written informed consents were signed by the ptients nd/or gurdins. Consent for publiction Not pplicble. Competing interests The uthors declre tht they hve no competing interests. References 1. Ukw S, Tmkoshi A, Ytsuy H, Ymgishi K, Ando M nd Iso H; JACC Study Group: Pssive smoking nd chronic obstructive pulmonry disese mortlity: Findings from the Jpn collbortive cohort study. Int J Public Helth 62: , DeVries R, Kriebel D, Sm S: Outdoor ir pollution nd COPD relted emergency deprtment visits, hospitl dmissions, nd mortlity: A met-nlysis. COPD 14: , Ohno Y, Koym H, Yoshikw T, Mtsumoto K, Aoym N, Onishi Y, Tkenk D, Mtsumoto S, Nishimur Y nd Sugimur K: Comprison of cpbility of dynmic O 2 -enhnced MRI nd quntittive thin-section MDCT to ssess COPD in smokers. Eur J Rdiol 81: , Diz-Guzmn E nd Mnnino DM: Epidemiology nd prevlence of chronic obstructive pulmonry disese. Clin Chest Med 35: 7-16, Rbe KF, Hurd S, Anzueto A, Brnes PJ, Buist SA, Clverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, vn Weel C nd Zielinski J; Globl Inititive for Chronic Obstructive Lung Disese: Globl strtegy for the dignosis, mngement, nd prevention of chronic obstructive pulmonry disese: GOLD executive summry. Am J Respir Crit Cre Med 176: , Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Brnes PJ, Fbbri LM, Mrtinez FJ, Nishimur M, et l: Globl strtegy for the dignosis, mngement, nd prevention of chronic obstructive pulmonry disese: GOLD executive summry. Am J Respir Crit Cre Med 187: , Gupt D, Agrwl R, Aggrwl AN, Mturu VN, Dhoori S, Prsd KT, Sehgl IS, Yenge LB, Jindl A, Singh N, Jindl SK, et l; for the COPD Guidelines Working Group: Guidelines for dignosis nd mngement of chronic obstructive pulmonry disese: Joint ICS/NCCP (I) recommendtions. Lung Indi 30: , Buer TT, Nilius G, Grüning W nd Rsche K: Dignosis nd therpy of COPD excerbtion. Med Klin Intensivmed Notfmed 107: , 2012 (In Germn). 9. Alí I, de l Cl MA, Estebn A, Abell A, Ferrer R, Molin FJ, Torres A, Gordo F, Elizlde JJ, de Pblo R, et l: Efficcy of corticosteroid therpy in ptients with n cute excerbtion of chronic obstructive pulmonry disese receiving ventiltory support. Arch Intern Med 171: , Gude GS nd Ndgoud S: Nebulized corticosteroids in the mngement of cute excerbtion of COPD. Lung Indi 27: , Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, Brnes PJ, Fbbri LM, Mrtinez FJ, Nishimur M, et l: Globl strtegy for the dignosis, mngement, nd prevention of chronic obstructive pulmonry disese: GOLD executive summry. Am J Respir Crit Cre Med 187: , Rutschmnn OT, Cornuz J, Poletti PA, Bridevux PO, Hugli OW, Qndli SD nd Perrier A: Should pulmonry embolism be suspected in excerbtion of chronic obstructive pulmonry disese? Thorx 62: , Arújo JP, Lourenço P, Azevedo A, Friões F, Roch-Gonçlves F, Ferreir A nd Bettencourt P: Prognostic vlue of high-sensitivity C-rective protein in hert filure: A systemtic review. J Crd Fil 15: , 2009.

6 4722 ZHAO et l: EFFICIENCY OF INHALED AND INTRAVENOUS CORTICOSTEROID ON PREGNANT WOMEN WITH COPD 14. Lcom A1, Prt C, Andreo F, Lores L, Ruiz-Mnzno J, Ausin V nd Domínguez J: Vlue of proclcitonin, C-rective protein, nd neopterin in excerbtions of chronic obstructive pulmonry disese. Int J Chron Obstruct Pulmn Dis 6: , Hur M, Moon HW, Yun YM, Kim KH, Kim HS nd Lee KM: Comprison of dignostic utility between proclcitonin nd C-rective protein for the ptients with blood culture-positive sepsis. Koren J Lb Med 29: , 2009 (In Koren). 16. Lee JY, Hwng SJ, Shim JW, Jung HL, Prk MS, Woo HY nd Shim JY: Clinicl significnce of serum proclcitonin in ptients with community-cquired lobr pneumoni. Koren J Lb Med 30: , Flsey AR, Becker KL, Swinburne AJ, Nylen ES, Snider RH, Formic MA, Hennessey PA, Criddle MM, Peterson DR nd Wlsh EE: Utility of serum proclcitonin vlues in ptients with cute excerbtions of chronic obstructive pulmonry disese: cutionry note. Int J Chron Obstruct Pulmon Dis 7: , Albrich WC, Dusemund F, Bucher B, Meyer S, Thomnn R, Kühn F, Bssetti S, Sprenger M, Bchli E, Sigrist T, et l; ProREAL Study Tem: Effectiveness nd sfety of proclcitoninguided ntibiotic therpy in lower respirtory trct infections in rel life : An interntionl, multicenter poststudy survey (ProREAL). Arch Intern Med 172: , Siddiqui S, Hollins F, Sh S nd Brightling CE: Inflmmtory cell microloclistion nd irwy dysfunction: Cuse nd effect? Eur Respir J 30: , Mikhk Z: Dose-response studies of fluticsone propionte nd budesonide: Clssifiction bsed on sthm severity. Allergy Asthm Proc 27: , Alngri AA: Genomic nd non-genomic ctions of glucocorticoids in sthm. Ann Thorc Med 5: , This work is licensed under Cretive Commons Attribution-NonCommercil-NoDerivtives 4.0 Interntionl (CC BY-NC-ND 4.0) License.