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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 92-98

Serum procalcitonin in predicting bacterial exacerbation of COPD and need for ventilatory support


Department of Respiratory Medicine, Institute of Respiratory Diseases, SMS Medical College, Jaipur, Rajasthan, India

Date of Submission06-Jan-2020
Date of Acceptance29-Jun-2020
Date of Web Publication10-Sep-2020

Correspondence Address:
Dr. Yogendra Rathore
MBBS, MD, Resident Doctor, Department of Respiratory Medicine, Institute of Respiratory Diseases, SMS Medical College, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacp.jacp_1_20

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  Abstract 


Context: Acute exacerbation of COPD is very common disease and 20% of the COPD patients keep getting admitted with exacerbation. Serum procalcitonin (PCT) measurement is important to discriminate bacterial infection from other causes of AECOPD. Quick recognition along with prompt intervention may be the only action that prevents respiratory failure. Aims: To correlate serum PCT level with bacteriological profile and their need for ventilatory support in patients with AECOPD. Settings and Design: Hospital-based comparative type of cross-sectional study was conducted at the department of respiratory medicine in a tertiary care center of Rajasthan. Methods and Material: This comparative type of cross-sectional study was conducted between 45 AECOPD patients and 35 stable COPD patients. Serum PCT levels and sputum pyogenic culture were noted in all subjects. Statistical Analysis Used: Data collected were entered into excel spreadsheet and quantitative data were expressed as number and percentage. Results: There was a highly statistically significant difference of mean PCT value (P value < 0.003) between AECOPD patients (1.34 ± 2.53 ng/ml) and stable COPD patients (0.07 ± 0.05 ng/ml). Also, we found a statistically significant difference of mean PCT value (P value < 0.001) between AECOPD patients infected with Pseudomonas aeruginosa (3.64 ng/dl) and with other bacteria. A statistically significant difference (P value < 0.001) was present among AECOPD patients that needed invasive ventilation (5.41 ± 4.01 ng/ml), non-invasive ventilation (0.65 ± 0.81 ng/ml) and those did not need mechanical ventilation (0.27 ± 0.25 ng/ml) regarding the mean values of PCT. Conclusions: Our study found that higher PCT levels in severe AECOPD patients were associated more with bacterial infection and necessity of ventilatory support. Serum PCT can be used as good biomarker for intensive care unit admission.

Keywords: AECOPD, procalcitonin, ventilatory support


How to cite this article:
Rathore Y, Jindal A, Joshi V, Jain S, Bhati S. Serum procalcitonin in predicting bacterial exacerbation of COPD and need for ventilatory support. J Assoc Chest Physicians 2020;8:92-8

How to cite this URL:
Rathore Y, Jindal A, Joshi V, Jain S, Bhati S. Serum procalcitonin in predicting bacterial exacerbation of COPD and need for ventilatory support. J Assoc Chest Physicians [serial online] 2020 [cited 2020 Oct 27];8:92-8. Available from: https://www.jacpjournal.org/text.asp?2020/8/2/92/294581




  Introduction Top


COPD comes to be important public health challenge and currently the fourth leading cause of death in the world[1] and mortality due to COPD is increasing because of continued exposure to COPD risk factors and aging of the population.[2]

Acute exacerbation of COPD (AECOPD) is common but occasionally overlooked parameter. Risk factors of acute exacerbations of COPD are bacterial, viral infections and by common pollutants such as tobacco and air pollution. But in up 30% of cases, the diagnosis of an exacerbation cannot be achieved. Quick and accurate recognition of these patients are necessary to start with targeted antibiotic therapy and prevent respiratory failure.

The Global Initiative for Chronic Obstructive Lung Disease guidelines have said that if two cardinal symptoms are present out of these three cardinal symptoms: increase in dyspnea, sputum volume, and sputum purulence, or require mechanical ventilation,[3] then antibiotics are recommended. This can lead to overuse of antibiotics because in clinical practice, the signs and symptoms of bacterial and non-bacterial AECOPDs overlap.[4] Several studies studied the various inflammatory markers to find out the etiological factors of exacerbation and prognosis of disease.[5] In this regard, we have evaluated procalcitonin (PCT) as a marker of bacterial exacerbation of COPD.

In a healthy individual, PCT levels are very low (<0.05 ng/mL). The level of procalcitonin raises in a response to a proinflammatory stimulus, especially of bacterial origin. Serum PCT levels are detectable as early as 3–4 h after the invasion, which is much earlier than the increase in the C-reactive protein level or erythrocyte sedimentation rate.[6] PCT levels is not been elevated in other inflammatory conditions, such as inflammatory bowel disease, temporal giant cell arteritis, polyarteritis nodosa, systemic lupus erythematosus, gout, and Still disease[7] and PCT levels are also not influenced by therapy with glucocorticoids or non-steroidal anti-inflammatory agents, viral and fungal infections.[8],[9]


  Subjects and methods Top


This hospital-based comparative type of cross-sectional study was carried out on COPD patients attending OPD or hospitalized at Department of Respiratory Medicine, Institute of respiratory diseases, SMS medical college, Jaipur. We included 35 stable COPD patients (group A) and 46 cases of AECOPD patients (group B) with their written consent. We excluded the patients having history of recent antibiotic therapy (2 weeks), Evidence of pneumonia on chest x-ray, HIV positive and other conditions known to increase serum PCT. (eg. Burns, trauma, renal failure, thyroid tumors). After applying inclusion and exclusion criteria the patients underwent detailed clinical examination, relevant investigations. Then, 0.5 ml blood sample for procalcitonin was sent at cardio Neuro emergency lab in SMS hospital, Jaipur. And, sputum was sent for microscopy by Gram staining. After using Acceptable criteria for suptum specimens, accepted sputum was culture for 48–72 hrs.


  Result Top


Our study shows high WBC count in AECOPD patients. Mean WBC count was 7570.51 ± 1691.35/mm3 in stable COPD group and 15358.04± 5210.20/mm3 in AECOPD group. Hence, significant difference of WBC Count is observed among the study groups (P value < 0.001). There are highly significant difference of PH (P < 0.0006), PCO2 (P < 0.001) and PO2 values (P < 0.017) in between the study groups, but insignificant difference of HCO3 value [Table 1]. In present study, 63% patients of AECOPD required mechanical ventilatory support. Out of which 46% patients required non-invasive ventilation and 17% patients required intubation.
Table 1 Population characteristics and clinical parameters variation in of both groups

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It was observed that among stable COPD patients, sputum pyogenic culture and Gram stain were found to be sterile in maximum patients (around 70%). Whereas 22.85% and 5.71% patients were found to be Gram positive, Gram negative respectively. In 46 AECOPD patients, half of the patient’s (50%) Gram stain and sputum pyogenic culture were found to be Gram negative bacteria. Whereas 41.30% patients were found to be Gram positive bacteria. Only in 8.70% patients, normal commensal flora were grown. Out of 46 patients, most common Streptococcus hemolyticus was isolated in 28.26% patients and followed by Pseudomonas species in 26.09% patients [Table 2].
Table 2 Bacteriological profile in AECOPD patients (N = 46)

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In present study, mean value of serum PCT was 0.07±0.05 ng/ml and 1.34±2.53 ng/ml in stable COPD group and AECOPD group respectively, which shows significant difference of serum PCT level in both groups (P = 0.003) [Figure 1].
Figure 1 Serum PCT value in study groups

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Our study shows that there is positive correlation between WBC count and serum procalcitonin. Patients having WBC count >15000, had significant higher value of procalcitonin (2 ng/ml). Significant correlation between PH, PCO2 value in ABG and procalcitonin value was also observed. As it is seen, patients having PH <7.25 had mean 8.24ng/dl value of procalcitonin whereas patients having PH between 7.25 to 7.45 had procalcitonin values in the range of 0.24 to 1.16ng/dl. Patients having PCO2 value >75mmhg had a reasonably higher procalcitonin value (mean: 4.17 ng/dl). Whereas type1 RF patients and type 2 respiratory failure patients (45-75 pco2) had procalcitonin value in the range of 0.37 to 0.92 ng/dl [Table 3].
Table 3 Correlation between WBC count, PCO2 and PH with serum PCT in AECOPD patients

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It was observed that in AECOPD patients requiring invasive ventilation had highest mean value of procalcitonin that is 5.41ng/ml and those requiring NIV had mean procalcitonin value of 0.65 ng/ml which shows significant difference in PCT values with NIV and IV (P <0.001). Whereas, patients who didn’t require ventilatory support had mean procalcitonin value of 0.27ng/ml which is lower compared to those requiring ventilator support. Hence, significant difference was found in PCT values with ventilator and non-ventilator support [Table 4] and [Table 5].
Table 4 PCT level in relation to ventilator support requirement among AECOPD patients

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Table 5 Comparison of mean PCT values with bacteriological profile in AECOPD patients

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In AECOPD patients it was observed that highest procalcitonin value was found with pseudomonas species (3.64 ng/ml), followed by coagulase positive staphylococci (1.52 ng/ml) and streptococcus pneumonia (1.21 ng/ml) [Table 4]. It was observed that procalcitonin value is much higher in gram negative compared to gram positive bacteria in AECOPD patients (P = 0.048). Serum PCT mean is much higher in patients having pseudomonas (3.64 ng/ml) than other bacteria (0.59ng/ml). Hence, there is a significant difference in procalcitonin values between pseudomonas and other species (P < 0.001) [Figure 2].
Figure 2 Correlation of PCT level in pseudomonas species with other cultured bacteria among AECOPD patients

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  Discussion Top


Our study population were male dominant and greater in older age groups. This observation corresponds to Curkendall et al.[10] study showed that COPD risk increases steeply with age, with the highest prevalence among those over 60 years. This supported by the fact that there is decline in natural defense mechanism of lung with aging. It was found in our study that maximum number of patients diagnosed with stable COPD were smokers and AECOPD were exsmokers. This observation was similar to Erkan et al.[11] study.

Our study shows significant difference of WBC count among the study groups (P value < 0.001). It is fairly possible that COPD patients having exacerbation had higher WBC count and bacterial infection was likely to be the cause of exacerbation in them. Hyeon-Kyoung-Koo et al. study showed that in COPD patients, the WBC count increased according to severity of airflow limitation (6,345±1,769 in GOLD 1, 6,584±1,844 in GOLD 2, 6,833±1,875 in GOLD 3–4; P = 0.03) and was higher in current smokers than in non-current smokers.

In our study most of the patients were having very severe obstruction in both the study groups. In stable COPD, 48% patients were very severe and in AECOPD, 50% patients were very severe. Hence, there was no significant difference found in severity of obstruction among both the groups. There are only limited data available on the reproducibility of spirometry when comparing tests between AECOPD and stable COPD[12] because there is a hypothesis that spirometry performed in the inpatients setting lacks sensitivity to judge severity of air flow obstruction.

In AECOPD patients, most common Streptococcus hemolyticus was isolated (28.26%) followed by Pseudomonas species in (26.09%). Whereas Coagulase positive staphylococci, Enterobacter Aerogenes and Klebsiella species were isolated in same percentage of patients i.e. 8.70%.

In a study by Nakou et al.[15] conducted on the exacerbated COPD patients, the most common bacteria isolated were H.influenzae and P.aeruginosa. All other similar studies[13],[14],[15],[16] showed that gram negative bacteria were most common cause of bacterial exacerbation which is similar to our study. In our study most common bacteria grown in AECOPD was Streptococcus Haemolyticus and second common was Pseudomonas aeruginosa which is different from other studies where most common was Haemophillus Influenza and second common was pseudomonas aueroginosa. This could be the limitation of our study as medium for atypical organism like Haemophillus Influenza is different.

In our study, mean value of serum PCT was 0.07±0.05 ng/ml and 1.34±2.53 ng/ml in stable COPD and AECOPD respectively which shows significant difference of serum PCT level in both groups (P = 0.003). Ashraf Abd El Halim et al.[16] also found highly statistically significant difference (P value<0.001) between AECOPD patients and stable COPD patients regarding the mean values of PCT (1.44±0.542ng/ml among AECOPD patients, 0.05±0.012ng/ml among stable COPD patients).

Hence, from our study we found that cut off value of PCT for predicting the exacerbation of COPD was 0.1435ng/ml, which had 84.8 % sensitivity and 91.4% specificity . The area under the curve was 0.930 (P value < 0.001) [Figure 3].
Figure 3 ROC curve for PCT as a predictor of acute exacerbation of COPD

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Our study found that at cut off 0.51ng/ml, PCT had 83.3 % sensitivity and 72.5 % specificity for predicting of WBC >15000 among AECOPD patients. The area under the curve was 0.790 (P value =0.023). Hence, with WBC count in AECOPD patients, we can analyze serum PCT level and further the type of bacteria and need for ventilator support.

In our study, there was significant correlation between PH and procalcitonin value. At cut off value of 0.92 ng/ml, PCT had 100% sensitivity and 95.2 % specificity for predicting of pH < 7.25 among AECOPD patient. The area under the curve was 0.988. (P value < 0.001). As the literature suggests that PH less than 7.2 is indication for intubation, we can very well correlate in our study that cut off value of PCT for predicting pH <7 .25 is much similar to cut off value for predicting intubation (0.94 ng/ml). We observed that in our study AECOPD patients had higher PCO2, more of respiratory acidosis and higher percentage of patients were in type 2 respiratory failure leading to requirement of mechanical ventilator support, out of that one third underwent intubation and rest required NIV.

In our study, it was observed that those AECOPD patients requiring invasive ventilation had highest mean value of procalcitonin (5.41ng/ml) followed by those requiring NIV (0.65 ng/ml) followed by who didn’t require ventilatory support (0.27ng/ml). At cut off value of 0.40ng/ml, PCT had 62% sensitivity and 94% specificity for predicting ventilatory requirement among AECOPD patients. The area under the curve was 0.78. (P value = 0.001). At cut off value of 0.94ng/ml, PCT had 100% sensitivity and 87% specificity for predicting of invasive Ventilatory requirement among AECOPD patient. The area under the curve was 0.970([Figure 4]). Ashraf Abd El Halim et al.[16] also reported that at cutoff value of 1.495 ng/ml, PCT had 85.7% sensitivity and 78.3% specificity for predicting AECOPD patients that needed ventilator support. This observation also supported by studies such as Rammaert et al.[17] and Pazarli et al.[18]In AECOPD patients it was observed that highest procalcitonin value was found with pseudomonas species(3.64 ng/ml), followed by coagulase positive staphylococci(1.52 ng/ml) and streptococcus pneumonia (1.21 ng/ml). It was observed that procalcitonin value was much higher in gram negative compared to gram positive bacteria in AECOPD patients and it was much higher in patients having pseudomonas (3.64ng/ml) than other bacteria (0.59ng/ml). At cut off value of 0.91ng/ml, PCT had 67% sensitivity and 85% specificity for predicting of pseudomonas infection among AECOPD patients. The area under the curve was 0.797 (P value = 0.002). Hence, we observed that PCT cut off value are almost similar for predicting pseudomonas infection, intubation and pH < 7.2 which is around 0.9 ng/ml. Ashraf Abd El Halim et al.[16] also found a cut off value of 1.215ng/ml PCT serum level has 66.7% sensitivity and 100% specificity for P. aeruginosa. Daubin and his group[19] also detected high PCT serum levels among COPD patients with P. aeruginosa. These results are expected due to the virulence of P. aeruginosa.
Figure 4 ROC curve for PCT as a predictor of invasive ventilation among AECOPD patients

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  Conclusion Top


Our study found that higher PCT levels in severe AECOPD patients were associated more with bacterial infection and necessity of ventilatory support. serum PCT is good biomarker among AECOPD patients suggests a role in the predicting of bacterial infections and their need for ventilatory support. Serum PCT can also be used as good biomarker for intensive care unit admission and antibiotic use. More number of studies are needed to augment our finding.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Daubin C, Parienti J, Vabret A, Ramakers M, Fradin S, Terzi N et al. Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study. BMC Infect Dis 2008:145.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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