European Journal of Cardiovascular Medicine

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, sputum production, exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction.¹ Exacerbation in COPD (associated with worsening of COPD symptoms dyspnea, cough, and sputum production) and co-morbidities have a considerable impact on morbidity, mortality, and quality of life as it affects the health status of patients by accelerating the progression of the disease.^1,2

These are caused either due to bacterial infection, viral infection, or some other trigger factors. It has been estimated that approximately 40%- 50% of acute exacerbation of COPD cases are due to bacterial infections and the cause of approximately one third of severe exacerbation cannot be identified.^3,4 In this context, a rapid, specific test to identify lower respiratory bacterial infections would be a major advancement limiting inappropriate use of antibiotics, which is considered to be a main cause of the spread of antibiotic-resistant bacteria.

Serum procalcitonin levels are suggested to be one of the biomarkers for predicting a bacterial infection.⁵ CRP is a protein that is primarily synthesized by the liver. When there is infection or tissue injury, serum CRP level will elevate.^5,6 Present study was aimed to study procalcitonin combined with c- reactive protein as diagnostic markers in acute exacerbation of chronic obsructive pulmonary disease.

Present study was prospective, observational study, conducted in department of general medicine, Karnataka institute of medical sciences, Hubballi, India. Study duration was of 2 years (July 2020 to June 2022). Study was approved by institutional ethical committee.

Inclusion criteria

• Patients with Age > 40 years, known case of COPD with postbronchodilator FEV1/FVC < 0.7, FEV1 change <12% and having symptoms of acute exacerbation like persistent cough, sputum production, dyspnea, fever and/or a history of exposure to risk factors for the disease, willing to participate in present study

Exclusion criteria

• Patients having history of tuberculosis
• Patients having history of asthma
• Cavitating lung disease
• Patients having radiological evidence of pneumonia
• Patients with congestive heart failure
• Patients with concurrent pulmonary embolism or

Study was explained to participants in local language & written informed consent was taken. Patients with known case of COPD who presented to the hospital with acute exacerbation were considered for the study. Relevant history regarding presenting complaints, past history, family history and smoking history was taken. Following investigations were done in the patients – Complete hemogram, Renal function tests, Serum electrolytes, Liver function tests, Chest X ray PA view, Serum procalcitonin, CRP, Sputum AFB, Gram staining and KOH mount, Sputum culture sensitivity, Spirometry. Clinical severity is determined as per the GOLD criteria.

Data was collected and compiled using Microsoft Excel,  analysed using SPSS 23.0 version. Frequency, percentage, means and standard deviations (SD) was calculated for the continuous variables, while ratios and proportions were calculated for the categorical variables. Difference of proportions between qualitative variables were tested using chi- square test or Fisher exact test as applicable. P value less than 0.5 was considered as statistically significant.

A total 120 patients were enrolled in the present study. Majority were from 61-70 years age group (42.5%), followed by less than 60 years age group (26.7 %) & 71-80 years age group (24.2 %). In present study, 70.8 % (n=85) were men and 29.2%(n=35) were women. Hypertension was the commonest comorbidity (40.8 %) s, followed by diabetes (36.7 %) & IHD (8.3 %). Smoking was reported by 63%(n=76) patients and tobacco chewing was reported by 45%(n=54) patients.

Table 1: General characteristics

Breathlessness was reported by 100 % (n=120) of patients, cough in 83 % (n=100) and fever was reported by 50 % (n=60) of patients. On examination, pallor was seen in 8.3 % (n=10) patients, cyanosis in 15 % (n=18) patients, oedema in 19 % (n=23) and JVP was elevated in 19%(n=23) of patients.

Table 2: Clinical features

Out of 120 patients, 55 % (n=66) of patients were in stage 2 in GOLD criteria, 20% (n=24) in GOLD stage 3, 13.3 % (n=16) in GOLD stage 1 and 11.7 % (n=14) were in GOLD stage 4.

Table 3: Distribution of patients with spirometry

Out of total 120 patients, Procalcitonin level was >0.5ng/ml in 63 patients (52.5%) and CRP level was > 6 mg/L in 85 patients (70.8%). In 66.7%(n=80) of patients, both Procalcitonin and CRP levels were above the cut off.

Table 4: Correlation between Procalcitonin and CRP

CRP level was elevated in 78.9% of patients with Procalcitonin levels ≤0.5 compared to 63.5% of patients with elevated procalcitonin level (>0.5). This difference was not statistically significant (P=0.063). There was a good positive correlation between Procalcitonin and CRP (Pearson Correlation coefficient of 0.7) and this correlation was statistically significant with p value of <0.001.

Table 5: Comparison of Procalcitonin and CRP

Growth was seen in sputum culture in 82.5% of patients with raised Procalcitonin compared to 50.9% in those with Procalcitonin<0.5ng/ml. This difference in sputum culture-growth was statistically significant with a p value<0.001.

Growth was seen in sputum culture in 66% of patients with raised CRP levels compared to 71.4% in those with normal CRP levels. This difference in sputum culture-growth was not statistically significant.

Growth was seen in sputum culture in 87.5% of patients with raised Procalcitonin and raised CRP compared to 57.5% in those with either Procalcitonin<0.5ng/dl or CRP<6mg/L. This difference in sputum culture-growth was statistically significant with a p value of <0.001.

Table 6: Comparison of Sputum culture with procalcitonin & CRP

Growth was seen in blood culture in 12.7% of patients with raised Procalcitonin compared to 12.3% in those with Procalcitonin<0.5ng/ml. This difference in blood culture-growth was less and it was not statistically significant with a p value of 0.945.

Growth was seen in blood culture in 14% of patients with raised CRP levels compared to 8.6% in those with normal CRP levels. This difference in blood culture-growth was not statistically significant.

Growth was seen in blood culture in 20% of patients with raised Procalcitonin and raised CRP compared to only 8.8% in those with either Procalcitonin<0.5ng/dl or CRP<6mg/L. This difference in blood culture-growth was not statistically significant (p value=0.079).

Table 7: Comparison of Procalcitonin and blood culture

Mean total count in patients with Procalcitonin <0.5ng/dl was 7660 compared to 10835 in those with Procalcitonin >0.5ng/dl and this difference was statistically significant (P<0.001). Mean total count in patients with CRP<6mg/L was 11222 compared to 8546 in those with CRP>6mg/L and this difference was statistically significant (P<0.001). Mean total count in patients with raised Procalcitonin and raised CRP was 9782 compared to 9099 in those with normal Procalcitonin or normal CRP levels and this difference was less and not statistically significant (P=0.159).

Table 8: Comparison of serum Procalcitonin levels and total counts

Mean days of length of hospital stay in patients with Procalcitonin <0.5ng/dl was 5.8 days compared to 7.8 days in those with Procalcitonin >0.5ng/dl and this difference was statistically significant (P<0.001).

Table 9: Comparison of Procalcitonin levels and length of hospital stay

Of 120 patients, 19 patients (15.8%) required mechanical ventilation. Mechanical ventilation was needed in 20% of patients with raised Procalcitonin and raised CRP compared to 13.8% in those with either Procalcitonin<0.5ng/dl or CRP<6mg/L. This difference in requirement of mechanical ventilation was not statistically significant (p value=0.377)

Table 10: Comparison of Procalcitonin plus CRP and Mechanical ventilation

Out of total 120 patients, two patients (1.7%) died and rest 118 (98.3%) were discharged. Two of 40 patients (5%) died in the group with raised Procalcitonin and raised CRP compared to none in those with either Procalcitonin<0.5ng/dl or CRP<6mg/L. This difference in mortality was statistically significant (p value=0.044).

Table 11: Comparison of Procalcitonin plus CRP and mortality

The present study is a prospective observational study with a sample of 120 patients, conducted to study levels of serum procalcitonin combined with CRP as a diagnostic marker in acute exacerbation of COPD to differentiate cause for exacerbation from bacterial infections and other causes.

The study population includes 120 patients with mean age 66.8 years which is comparable to other studies like Alicia et al.,⁶ which has population with mean age 71.4 years, Ying Zou et al.,⁷ which has population with mean age 67.36 years and Wen Song et al.,⁸ which has population with mean age 72.62 years.

The present study population includes 85(70.83%) males and 35(29.16%) females which is comparable to other studies. Ying Zou et al.,⁷ study had 40(66.66%) males and 20(33.33%) females, Alicia et al.,⁶ study had 204(94%) males and 13(6%) females, and Wen Song et al.,⁸ study had 200(61.53%) males and 125(38.46) females.

In this present study, 50%(n=60) patients had fever, 83.3%(n=100) patients had cough and 100%(n=120) patients had breathlessness. In Daiana et al. study 32.69%(n=68) patients had fever, 68.26%(n=142) patients had cough and 74.51%(n=155) had breathlessness. In Wen Song et al.,⁸ study 37.23%(n=121) patients had fever, 98.76%(n=321) patients had cough and 34.76% (n=113) patients had breathlessness. In Falsey et al.,⁵ study 22.28%(n=41) patients had fever, 94.02%(n=173) patients had cough and 96.73%(n=178) had breathlessness. Distribution of symptoms in present study is most comparable to Falsey et al.,⁹ study in which 22.28% patients had fever, 94.02% patients had cough and 96.73% had breathlessness. Thus most of the patients with AECOPD will have breathlessness followed by cough as major symptom.

In the present study, 36.7%(n=44) patients had diabetes mellitus, 40.8%(n=49) patients had hypertension and 8.3%(n=10) patients had ischemic heart disease which is most comparable to Alicia et al. study. In Alicia et al.,⁶ study 23.96%(n=52) patients had diabetes mellitus, 37.78%(n=82) patients had hypertension and 28.11%(n=61) patients had ischemic heart disease. In Ying Zou et al.,⁷ study, 26.66%(n=16) patients had diabetes mellitus, 41.66%(n=25) patients had hypertension and 30% (n=18) patients had ischemic heart disease. In Wen Song et al.,⁸ study 20%(n=65) patients had diabetes mellitus, 57.53%(n=187) patients had hypertension and 31.07%(n=101) patients had ischemic heart disease. Distribution of comorbidities in COPD patients can vary depending on prevalence pattern and exposure to risk factors.

The present study population has 63.3%(n=76) patients who are smokers where as Alicia et al.,⁶ study had 86.63%(n=188) patients who are smokers, Ying Zou et al.,⁷ study had 85%(n=51) patients who are smokers and Sarika et al. study had 77.5%(n=62) patients who are smokers thus present study is more comparable to Sarika et al.,¹⁰ study in terms of patients who are smokers. In all the above studies including present study COPD is more prevalent in smokers thus smoking is major risk factor for COPD.

The present study has 52.5%(n=63) patients with positive serum procalcitonin levels. In Falsey et al. study 47.82%(n=88) patients had positive serum procalcitonin levels, in Ying Zou et al.,⁷ study 70%(n=42) patients had positive procalcitonin levels and in Daiana et al.,⁹ study 18.56%(n=31) patients had positive procalcitonin levels. Thus positive serum procalcitonin levels in present study is comparable to Falsey et al.,⁵ study in which 47.82% patients with AECOPD had positive serum procalcitonin levels.

The present study has 70.8%(n=85) patients with positive CRP levels. In Prins et al.,¹¹ study 36.81%(n=81) patients had positive CRP levels, in Ying Zou et al.,⁷ study 46.66%(n=28) patients had positive CRP levels and in Daiana et al.,⁹ study 31.13%(n=52) patients had positive procalcitonin levels. In present study more patients have positive CRP levels which is not comparable to other studies as in present study has more number of patients with positive CRP levels compared other studies.

In the present study majority of study population 55%(n=66) are in GOLD 2 stage. In Johanenes et al.,¹² study majority of study population 43.41%(n=89) are in GOLD 3 stage. In Daubin et al.,¹³ study majority of study population 66.66%(n=26) are in GOLD 4 stage. In Daiana et al.,⁹ study majority of study population 46.07%(n=47) are in GOLD 2 stage. Distribution of patients according to spirometry criteria can vary in different study based on severity of COPD thus distribution in spirometry criteria is different in other studies.

Acute exacerbations of COPD are important events in treatment of COPD they negatively affect health status, rate of hospitalisation and disease progression. Thus management of these exacerbations is important. Main treatment includes pharmacological therapy with bronchodilators, glucocorticoids and antibiotics along with respiratory support. Among these roles of antibiotics remain controversial although most common cause of exacerbations are infections which can be viral or bacterial.

Limitations of the study were small sample size, single centre study & serial serum procalcitonin levels are not monitored in the follow up.

The present study suggests that procalcitonin and CRP levels are specific for infection related exacerbations, especially serum procalcitonin levels are specific for bacterial cause of acute exacerbations when appropriate cut off values are defined (in this study >0.5ng/dl), these patients can be benefitted with antibiotics. As there is positive correlation between growth in sputum culture and raised levels of serum procalcitonin and CRP. Whereas patients with both CRP and serum procalcitonin less than defined cut off value can be treated without antibiotics thus reducing antibiotic associated adverse effects and antibiotic resistance.

Conflict of Interest: None to declare

Source of funding: Nil

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