508085
research-article2013
AOPXXX10.1177/1060028013508085Annals of PharmacotherapySammons and Doligalski
Review Article-Drug Information Rounds
Utility of Procalcitonin as a Biomarker for Rejection and Differentiation of Infectious Complications in Lung Transplant Recipients
Annals of Pharmacotherapy 2014, Vol. 48(1) 116–122 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013508085 aop.sagepub.com
Chelsea Sammons, PharmD1 and Christina T. Doligalski, PharmD, BCPS1
Abstract Objective: To evaluate the utility of procalcitonin (PCT) as a biomarker for rejection and differentiation of infectious complications in lung transplant recipients. Data Sources: An English-language literature search was conducted using MEDLINE (1966-September 2013) using the terms procalcitonin, transplantation, and lung transplantation. Additional articles were identified through a manual search of reference lists of the articles obtained. Study Selection and Data Extraction: All articles evaluating PCT use in lung transplant recipients, including those where lung transplant patients were a subgroup of immunocompromised patients, were included. Data Synthesis: Infection and rejection are leading causes of mortality in lung transplant recipients, with similar clinical presentations; PCT could be a valuable biomarker to differentiate between these complications. Five prospective and 2 retrospective single-center observational evaluations were reviewed. Study populations were diverse, with only 3 focused solely on lung transplant recipients. PCT levels were not elevated during episodes of rejection and viral infections, whereas elevations were seen with bacterial infections. The effect of colonization or fungal infection on PCT varied. Conclusions: Current data suggest that PCT can be used to differentiate bacterial infections from rejection in lung transplant recipients, with unclear utility in colonization or fungal infection. It is reasonable to conclude that PCT values more than 8.18 ng/mL and PCT area under receiver operating curve greater than 0.97 indicate bacterial infection in this population, and PCT trends may increase predictive value. Because of the lack of randomized controlled trials, PCT should only be utilized in conjunction with standard tests for infection and rejection diagnosis. Keywords procalcitonin, clinical biomarker, lung transplantation, infection, rejection
Request Is procalcitonin (PCT) a useful biomarker to differentiate between rejection and infectious complications in lung transplant recipients?
Response Background Infection and rejection remain the two most common complications following solid organ transplantation and are associated with significant morbidity and mortality.1 Lung transplant recipients are at an increased risk for these complications because of the unique situation of contact of the graft with the outside environment and subsequent need for higher immunosuppression as compared with other allografts.1 Additionally, the newly transplanted lungs have an impaired cough reflex and decreased mucociliary
clearance that further increases infectious risk.2 Bacterial infections are the second most common cause of death in the first 30 days after lung transplantation and the leading cause of death in the first year. Furthermore, 35% of lung transplant recipients will be diagnosed with acute rejection in the first year following transplant.1 Unfortunately, clinical manifestations of infection and rejection are similar, including decreased lung function, increased sputum production, and cough. Due to these similarities, clinicians often struggle to arrive at a prompt and accurate diagnosis. The search for an accurate and specific biomarker of infection has yielded many candidates, including leukocyte 1
Tampa General Hospital, Tampa, FL, USA
Corresponding Author: Christina Doligalski, Pharmacy Department, Tampa General Hospital, 1 Tampa General Circle, Tampa, FL 33611, USA. Email: [email protected]
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Sammons and Doligalski counts (white blood cell [WBCs]), C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor, each with advantages and limitations. The most common limitation of these biomarkers is lack of sensitivity and specificity for infection. Serum PCT has shown promise as a more specific and sensitive biomarker of bacterial infections in intensive care as well as emergency room settings.3,4 PCT, along with immature calcitonin and katacalcin, are initial by-products of preprocalcitnonin.5-7 Under normal physiological conditions, PCT is converted to calcitonin in the neuroendocrine parafollicular cells of the thyroid (C-cells),5-7 and serum levels of PCT are less than 0.5 ng/ mL.8 The half-life of PCT is approximately 24 hours; although some evidence suggests renal elimination of PCT, studies of PCT trends in renal failure patients fail to demonstrate “false positives” or a prolonged half-life when compared with those in patients with normal renal function.9 The exact physiological function of PCT remains unclear as it does not appear to play a role in calcium homeostasis or regulation of the parathyroid hormone. However, in response to stress events causing cytokine release such as sepsis, shock, trauma, major surgery, and most importantly, bacterial infection, other organs, including the liver, lung, pancreas, and colon will produce PCT leading to its serum elevation.5,7 Under stress conditions, PCT rises quickly, typically peaking within 6 hours of insult.10 To measure serum PCT, several assays are available, none of which directly measure PCT but rather the other by-products ofpreprocalcitonin: katacalcin, or immature calcitonin. A more detailed review of available assays has previously been reported.5 A commonly used assay is the immunoluminometric quantitative assay, which uses antikatacalcin antibodies linked to fluorescent tracers to indirectly quantify the elevation of PCT, with a relatively quick test result time (less than 1 hour). Newer assays utilizing time-resolved amplified cryptate emission technology appear to be more sensitive and quick (less than 30 minutes) but are more expensive. Although most assays report the same standard reference ranges, test sensitivity may impair direct comparison between assays.5 The major advantages of PCT over other clinical biomarkers such as CRP, ILs, and WBCs include its rapid rise following an inciting physiological insult (6-hour peak), relatively short half-life (24 hours), and ability to predict etiology of the infection. Additionally, serial PCT tends to mirror clinical course; severe systemic infections will cause a larger release of cytokines and, therefore, a higher PCT concentration compared with less-severe localized infections, and untreated infections will result in persistently elevated PCT values. However, as appropriate antibiotic therapy begins to attenuate the cytokine release, PCT levels will decrease in response.5,6 Recently, the utility of PCT has been evaluated in more diverse patient populations, including lung transplant
recipients; however, its role in this unique subset of patients is not well established. Specific to the transplant population, PCT concentrations peak between postoperative day (POD) 0 and 1 because of the stress of surgery, and if no complications arise, these levels steadily decline to normal in the first week.5 PCT levels will increase up to 10-fold in response to muromonab and antithymocyte globulin induction therapy but is unaffected by routine maintenance immunosuppression.11,12 If PCT can demonstrate utility in differentiating between posttransplant complications, such as rejection and infection, it could be a key tool in increasing the accuracy and timeliness of diagnosis and treatment.
Literature Review An English-language literature search was conducted using MEDLINE (1966-September 2013) using the terms procalcitonin, transplantation, and lung transplantation. Additional articles were identified through a manual search of the reference lists of the articles obtained. In all, 9 publications and one abstract representing 7 distinct patient populations were reviewed and are included below; all evaluations were observational and single center in nature, with 2 retrospective and 5 prospective evaluations (Table 1). Only 3 evaluated lung transplant recipients alone; 3 included a variety of solid organ transplant recipients, and one assessed an immunocompromised population. Of note, all studies utilized immunoluminometric assays for PCT quantification except one, which used a time-resolved amplified cryptate emission assay. PCT Values in Rejection Versus Infection. Four retrospective, observational publications in the same 78 solid organ transplant (18 lung transplant) recipients evaluated PCT’s utility in differentiating rejection from infection and severity of infection.8,13-15 PCT levels were drawn daily, but the time frame of PCT monitoring posttransplant was not reported. PCT values were compared among 5 groups: no rejection or infection, acute rejection, acute rejection and infection, local infection, and systemic infection, with local infections defined as colonization or an “insignificant infection limited to a local area” and systemic infections defined as sepsis or “multiple generalized infections.” There were no significant differences in PCT levels in patients with rejection compared with patients who were rejection and infection free (0.2 ± 0.2 ng/mL vs 0.3 ± 0.3 ng/mL; P = NS).8,13 PCT levels were significantly higher in patients with local and systemic infections when compared with patients experiencing acute rejection (0.6 ± 0.3 ng/mL vs 10.5 ± 18.2 ng/ mL vs 0.2 ± 0.2 ng/mL, P < .01 and P < .0001).8,13-15 Patients with acute rejection and infection had mean PCT values of 0.6 ng/mL ± 0.6; comparisons were not performed between this group and others. Most infectious pathogens were Gram–positive and Gram-negative bacteria; however, some
Downloaded from aop.sagepub.com at UNIV OF ILLINOIS URBANA on March 12, 2015
118
Downloaded from aop.sagepub.com at UNIV OF ILLINOIS URBANA on March 12, 2015
Design
Population
Frequency of PCT Levels
Prospective observational evaluation
Cooper et al Prospective observational (2001)17 evaluation
Qedra et al (2001)16
Assay
Results
AuthorRecommended PCT cutoff
Comments
(continued)
Immunoluminometric Mean (SE) PCT values: Systemic Only lab values on assay noAR, 0.3 (NR) ng/mL; infections: day of diagnosis AR, 0.2 (±0.2) ng/mL; >0.5 ng/mL were included in AR+IF, 0.6 (±0.6) ng/ (sensitivity, evaluation; absolute mL; LIF, 0.6 (±0.3) ng/ 89%; PCT values estimated mL; SIF, 10.5 (±18.2) specificity, from graphical ng/mL. Statistical 89%; representation; no comparisons: AR vs predictive statistical evaluation noAR, NS; AR vs LIF, value, 89%) of AR vs AR+IF; P < .01; AR vs SIF, P < mixed infections .001. Approximate PCT include multiple values by pathogen: bacteria as well as Gram(+) bacteria, bacterial plus fungal 1-2 ng/mL; Gram(−) infections bacteria: 0.8-0.9 ng/ mL; Candida, 2-3 ng/mL; Aspergillus, 10-20 ng/ mL; mixed infections, 2-3 ng/mL N = 72 consecutive Rejection vs nonviral Daily, up to 38 Immunoluminometric Perioperative infection None provided Results available in cardiothoracic infections vs postoperative assay (n = 21) increased vs abstract format only; transplant recipients; no infection days absence of infection (n absolute PCT values n = 19 lung transplant immediately = 51; P < .001); acute were not reported recipients, n = 3 following rejection (n = 15) vs heart-lung transplant transplantation event free (P > .8) recipients N = 110 consecutive Acute rejection and Frequency not Immunoluminometric Peak levels of PCT were Bacterial Absolute PCT values solid organ transplant viral infection reported; total assay higher with bacterial or fungal were not reported; recipients; 34 lung vs bacterial and 910 samples and fungal infections infections: PCT was evaluated transplant recipients; fungal infection (average of than with viral >0.14 ng/ using 15-day blocks 19/34 male; median vs uneventful 8 samples/ infections, rejection, or mL and of time surrounding age, 38 (19-63) years course in the first patient) over uncomplicated courses AUROC = significant events 4 postoperative 4-month study (P < .0001); false-positive 0.79 (95% CI such as rejection and months period rate of recommended = 0.73-0.85; infection diagnosis PCT cutoff for viral sensitivity infection =40% and = 75.6%; rejection =26.7%; specificity false-negative rate of = 73.7%; recommended PCT predictive cutoff for bacterial or efficiency = fungal infection =24% 70.8%)
PCT values in rejection versus infection Hammer et Retrospective N = 78 solid Acute rejection vs Daily observational al (1998, organ transplant infection with 1999, 2000, evaluations recipients; 18 lung 5 comparison 2001)8,13-15 transplants:unilateral groups: 1 (noAR), lung (n = 11), double no rejection lung (n = 7); etiology (grade 0-1A) or of lung disease: infection; 2 (AR), fibrosis (n = 7), acute rejection emphysema (n = 4), (1b-3); 3 (AR+IF), cystic lung disease (n acute rejection and = 5), chronic rejection infection; 4 (LIF), (n = 1) local infection; 5 (SIF), systemic infection
Reference
PCT Comparison Groups
Table 1. Comparison of Studies Utilizing PCT in Lung Transplant Recipients.
119
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Design
Population
PCT Comparison Groups
Frequency of PCT Levels Assay
Results
AuthorRecommended PCT cutoff
Comments
Prospective observational evaluation
Abbreviations: PCT, procalcitonin; NR, not reported; AUROC, area under receiver operating curve; PPV, positive-predictive value; NPV, negative predictive value.
Stolz et al (2007)18
PCT as a predictor of infection only N = 107 consecutive Pulmonary bacterial Once, at time of Immunoluminometric Proven pulmonary Pulmonary Nonbacterial causes immunocompromised infection vs bronchoscopy assay bacterial infection bacterial included viral patients who received noninfectious 0.66 ng/mL vs possible infections, infections, fungal bronchoscopy; 20 pulmonary bacterial infection 0.32 0.2 ng/mL infections, and solid organ transplant complications ng/mL vs nonbacterial (sensitivity, noninfectious recipients; 9 lung cause 0.08 ng/mL (P < 68%; complications (eg, transplant recipients .001) specificity, pulmonary edema, 71%); diffuse alveolar AUROC = hemorrhage, 0.746 (95% CI bronchiolitis = 0.602-0.889) obliterans syndrome) N = 25 lung transplant Infection vs no PCT measured Time-resolved Proven infection (n = 6 Bacterial Suberviola et Prospective Absolute PCT observational recipients; mean age infectious before amplified cryptate bacterial infections) infection: al (2012)2 values estimated evaluation = 55.4 ± 11.1 years; complications surgery, on emission technology vs noninfection and 8.18 ng/mL; from graphical male gender, 17; in first 7 admission assay rejection (n = 19). Day AUROC = representation; unilateral lung (n = posttransplant days to ICU, and 0, no difference; day 1, 0.97 (95% CI cutoffs based on 10). Etiology of lung daily on 7 vs
research-article2013
AOPXXX10.1177/1060028013508085Annals of PharmacotherapySammons and Doligalski
Review Article-Drug Information Rounds
Utility of Procalcitonin as a Biomarker for Rejection and Differentiation of Infectious Complications in Lung Transplant Recipients
Annals of Pharmacotherapy 2014, Vol. 48(1) 116–122 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013508085 aop.sagepub.com
Chelsea Sammons, PharmD1 and Christina T. Doligalski, PharmD, BCPS1
Abstract Objective: To evaluate the utility of procalcitonin (PCT) as a biomarker for rejection and differentiation of infectious complications in lung transplant recipients. Data Sources: An English-language literature search was conducted using MEDLINE (1966-September 2013) using the terms procalcitonin, transplantation, and lung transplantation. Additional articles were identified through a manual search of reference lists of the articles obtained. Study Selection and Data Extraction: All articles evaluating PCT use in lung transplant recipients, including those where lung transplant patients were a subgroup of immunocompromised patients, were included. Data Synthesis: Infection and rejection are leading causes of mortality in lung transplant recipients, with similar clinical presentations; PCT could be a valuable biomarker to differentiate between these complications. Five prospective and 2 retrospective single-center observational evaluations were reviewed. Study populations were diverse, with only 3 focused solely on lung transplant recipients. PCT levels were not elevated during episodes of rejection and viral infections, whereas elevations were seen with bacterial infections. The effect of colonization or fungal infection on PCT varied. Conclusions: Current data suggest that PCT can be used to differentiate bacterial infections from rejection in lung transplant recipients, with unclear utility in colonization or fungal infection. It is reasonable to conclude that PCT values more than 8.18 ng/mL and PCT area under receiver operating curve greater than 0.97 indicate bacterial infection in this population, and PCT trends may increase predictive value. Because of the lack of randomized controlled trials, PCT should only be utilized in conjunction with standard tests for infection and rejection diagnosis. Keywords procalcitonin, clinical biomarker, lung transplantation, infection, rejection
Request Is procalcitonin (PCT) a useful biomarker to differentiate between rejection and infectious complications in lung transplant recipients?
Response Background Infection and rejection remain the two most common complications following solid organ transplantation and are associated with significant morbidity and mortality.1 Lung transplant recipients are at an increased risk for these complications because of the unique situation of contact of the graft with the outside environment and subsequent need for higher immunosuppression as compared with other allografts.1 Additionally, the newly transplanted lungs have an impaired cough reflex and decreased mucociliary
clearance that further increases infectious risk.2 Bacterial infections are the second most common cause of death in the first 30 days after lung transplantation and the leading cause of death in the first year. Furthermore, 35% of lung transplant recipients will be diagnosed with acute rejection in the first year following transplant.1 Unfortunately, clinical manifestations of infection and rejection are similar, including decreased lung function, increased sputum production, and cough. Due to these similarities, clinicians often struggle to arrive at a prompt and accurate diagnosis. The search for an accurate and specific biomarker of infection has yielded many candidates, including leukocyte 1
Tampa General Hospital, Tampa, FL, USA
Corresponding Author: Christina Doligalski, Pharmacy Department, Tampa General Hospital, 1 Tampa General Circle, Tampa, FL 33611, USA. Email: [email protected]
Downloaded from aop.sagepub.com at UNIV OF ILLINOIS URBANA on March 12, 2015
117
Sammons and Doligalski counts (white blood cell [WBCs]), C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor, each with advantages and limitations. The most common limitation of these biomarkers is lack of sensitivity and specificity for infection. Serum PCT has shown promise as a more specific and sensitive biomarker of bacterial infections in intensive care as well as emergency room settings.3,4 PCT, along with immature calcitonin and katacalcin, are initial by-products of preprocalcitnonin.5-7 Under normal physiological conditions, PCT is converted to calcitonin in the neuroendocrine parafollicular cells of the thyroid (C-cells),5-7 and serum levels of PCT are less than 0.5 ng/ mL.8 The half-life of PCT is approximately 24 hours; although some evidence suggests renal elimination of PCT, studies of PCT trends in renal failure patients fail to demonstrate “false positives” or a prolonged half-life when compared with those in patients with normal renal function.9 The exact physiological function of PCT remains unclear as it does not appear to play a role in calcium homeostasis or regulation of the parathyroid hormone. However, in response to stress events causing cytokine release such as sepsis, shock, trauma, major surgery, and most importantly, bacterial infection, other organs, including the liver, lung, pancreas, and colon will produce PCT leading to its serum elevation.5,7 Under stress conditions, PCT rises quickly, typically peaking within 6 hours of insult.10 To measure serum PCT, several assays are available, none of which directly measure PCT but rather the other by-products ofpreprocalcitonin: katacalcin, or immature calcitonin. A more detailed review of available assays has previously been reported.5 A commonly used assay is the immunoluminometric quantitative assay, which uses antikatacalcin antibodies linked to fluorescent tracers to indirectly quantify the elevation of PCT, with a relatively quick test result time (less than 1 hour). Newer assays utilizing time-resolved amplified cryptate emission technology appear to be more sensitive and quick (less than 30 minutes) but are more expensive. Although most assays report the same standard reference ranges, test sensitivity may impair direct comparison between assays.5 The major advantages of PCT over other clinical biomarkers such as CRP, ILs, and WBCs include its rapid rise following an inciting physiological insult (6-hour peak), relatively short half-life (24 hours), and ability to predict etiology of the infection. Additionally, serial PCT tends to mirror clinical course; severe systemic infections will cause a larger release of cytokines and, therefore, a higher PCT concentration compared with less-severe localized infections, and untreated infections will result in persistently elevated PCT values. However, as appropriate antibiotic therapy begins to attenuate the cytokine release, PCT levels will decrease in response.5,6 Recently, the utility of PCT has been evaluated in more diverse patient populations, including lung transplant
recipients; however, its role in this unique subset of patients is not well established. Specific to the transplant population, PCT concentrations peak between postoperative day (POD) 0 and 1 because of the stress of surgery, and if no complications arise, these levels steadily decline to normal in the first week.5 PCT levels will increase up to 10-fold in response to muromonab and antithymocyte globulin induction therapy but is unaffected by routine maintenance immunosuppression.11,12 If PCT can demonstrate utility in differentiating between posttransplant complications, such as rejection and infection, it could be a key tool in increasing the accuracy and timeliness of diagnosis and treatment.
Literature Review An English-language literature search was conducted using MEDLINE (1966-September 2013) using the terms procalcitonin, transplantation, and lung transplantation. Additional articles were identified through a manual search of the reference lists of the articles obtained. In all, 9 publications and one abstract representing 7 distinct patient populations were reviewed and are included below; all evaluations were observational and single center in nature, with 2 retrospective and 5 prospective evaluations (Table 1). Only 3 evaluated lung transplant recipients alone; 3 included a variety of solid organ transplant recipients, and one assessed an immunocompromised population. Of note, all studies utilized immunoluminometric assays for PCT quantification except one, which used a time-resolved amplified cryptate emission assay. PCT Values in Rejection Versus Infection. Four retrospective, observational publications in the same 78 solid organ transplant (18 lung transplant) recipients evaluated PCT’s utility in differentiating rejection from infection and severity of infection.8,13-15 PCT levels were drawn daily, but the time frame of PCT monitoring posttransplant was not reported. PCT values were compared among 5 groups: no rejection or infection, acute rejection, acute rejection and infection, local infection, and systemic infection, with local infections defined as colonization or an “insignificant infection limited to a local area” and systemic infections defined as sepsis or “multiple generalized infections.” There were no significant differences in PCT levels in patients with rejection compared with patients who were rejection and infection free (0.2 ± 0.2 ng/mL vs 0.3 ± 0.3 ng/mL; P = NS).8,13 PCT levels were significantly higher in patients with local and systemic infections when compared with patients experiencing acute rejection (0.6 ± 0.3 ng/mL vs 10.5 ± 18.2 ng/ mL vs 0.2 ± 0.2 ng/mL, P < .01 and P < .0001).8,13-15 Patients with acute rejection and infection had mean PCT values of 0.6 ng/mL ± 0.6; comparisons were not performed between this group and others. Most infectious pathogens were Gram–positive and Gram-negative bacteria; however, some
Downloaded from aop.sagepub.com at UNIV OF ILLINOIS URBANA on March 12, 2015
118
Downloaded from aop.sagepub.com at UNIV OF ILLINOIS URBANA on March 12, 2015
Design
Population
Frequency of PCT Levels
Prospective observational evaluation
Cooper et al Prospective observational (2001)17 evaluation
Qedra et al (2001)16
Assay
Results
AuthorRecommended PCT cutoff
Comments
(continued)
Immunoluminometric Mean (SE) PCT values: Systemic Only lab values on assay noAR, 0.3 (NR) ng/mL; infections: day of diagnosis AR, 0.2 (±0.2) ng/mL; >0.5 ng/mL were included in AR+IF, 0.6 (±0.6) ng/ (sensitivity, evaluation; absolute mL; LIF, 0.6 (±0.3) ng/ 89%; PCT values estimated mL; SIF, 10.5 (±18.2) specificity, from graphical ng/mL. Statistical 89%; representation; no comparisons: AR vs predictive statistical evaluation noAR, NS; AR vs LIF, value, 89%) of AR vs AR+IF; P < .01; AR vs SIF, P < mixed infections .001. Approximate PCT include multiple values by pathogen: bacteria as well as Gram(+) bacteria, bacterial plus fungal 1-2 ng/mL; Gram(−) infections bacteria: 0.8-0.9 ng/ mL; Candida, 2-3 ng/mL; Aspergillus, 10-20 ng/ mL; mixed infections, 2-3 ng/mL N = 72 consecutive Rejection vs nonviral Daily, up to 38 Immunoluminometric Perioperative infection None provided Results available in cardiothoracic infections vs postoperative assay (n = 21) increased vs abstract format only; transplant recipients; no infection days absence of infection (n absolute PCT values n = 19 lung transplant immediately = 51; P < .001); acute were not reported recipients, n = 3 following rejection (n = 15) vs heart-lung transplant transplantation event free (P > .8) recipients N = 110 consecutive Acute rejection and Frequency not Immunoluminometric Peak levels of PCT were Bacterial Absolute PCT values solid organ transplant viral infection reported; total assay higher with bacterial or fungal were not reported; recipients; 34 lung vs bacterial and 910 samples and fungal infections infections: PCT was evaluated transplant recipients; fungal infection (average of than with viral >0.14 ng/ using 15-day blocks 19/34 male; median vs uneventful 8 samples/ infections, rejection, or mL and of time surrounding age, 38 (19-63) years course in the first patient) over uncomplicated courses AUROC = significant events 4 postoperative 4-month study (P < .0001); false-positive 0.79 (95% CI such as rejection and months period rate of recommended = 0.73-0.85; infection diagnosis PCT cutoff for viral sensitivity infection =40% and = 75.6%; rejection =26.7%; specificity false-negative rate of = 73.7%; recommended PCT predictive cutoff for bacterial or efficiency = fungal infection =24% 70.8%)
PCT values in rejection versus infection Hammer et Retrospective N = 78 solid Acute rejection vs Daily observational al (1998, organ transplant infection with 1999, 2000, evaluations recipients; 18 lung 5 comparison 2001)8,13-15 transplants:unilateral groups: 1 (noAR), lung (n = 11), double no rejection lung (n = 7); etiology (grade 0-1A) or of lung disease: infection; 2 (AR), fibrosis (n = 7), acute rejection emphysema (n = 4), (1b-3); 3 (AR+IF), cystic lung disease (n acute rejection and = 5), chronic rejection infection; 4 (LIF), (n = 1) local infection; 5 (SIF), systemic infection
Reference
PCT Comparison Groups
Table 1. Comparison of Studies Utilizing PCT in Lung Transplant Recipients.
119
Downloaded from aop.sagepub.com at UNIV OF ILLINOIS URBANA on March 12, 2015
Design
Population
PCT Comparison Groups
Frequency of PCT Levels Assay
Results
AuthorRecommended PCT cutoff
Comments
Prospective observational evaluation
Abbreviations: PCT, procalcitonin; NR, not reported; AUROC, area under receiver operating curve; PPV, positive-predictive value; NPV, negative predictive value.
Stolz et al (2007)18
PCT as a predictor of infection only N = 107 consecutive Pulmonary bacterial Once, at time of Immunoluminometric Proven pulmonary Pulmonary Nonbacterial causes immunocompromised infection vs bronchoscopy assay bacterial infection bacterial included viral patients who received noninfectious 0.66 ng/mL vs possible infections, infections, fungal bronchoscopy; 20 pulmonary bacterial infection 0.32 0.2 ng/mL infections, and solid organ transplant complications ng/mL vs nonbacterial (sensitivity, noninfectious recipients; 9 lung cause 0.08 ng/mL (P < 68%; complications (eg, transplant recipients .001) specificity, pulmonary edema, 71%); diffuse alveolar AUROC = hemorrhage, 0.746 (95% CI bronchiolitis = 0.602-0.889) obliterans syndrome) N = 25 lung transplant Infection vs no PCT measured Time-resolved Proven infection (n = 6 Bacterial Suberviola et Prospective Absolute PCT observational recipients; mean age infectious before amplified cryptate bacterial infections) infection: al (2012)2 values estimated evaluation = 55.4 ± 11.1 years; complications surgery, on emission technology vs noninfection and 8.18 ng/mL; from graphical male gender, 17; in first 7 admission assay rejection (n = 19). Day AUROC = representation; unilateral lung (n = posttransplant days to ICU, and 0, no difference; day 1, 0.97 (95% CI cutoffs based on 10). Etiology of lung daily on 7 vs
