Association of Serum Albumin and Copeptin with Early Clinical Deterioration and Instability in Community-Acquired Pneumonia
Abstract
:Highlights
- Serum albumin lower than 2.85 g/dL is the best predictor of mortality in CAP patients
- The addition of serum albumin and copeptin to the traditional clinical scoring systems increases it’s prognostic power
- Biomarkers serum albumin and copeptin can predict early deterioration and clinical instability in hospitalized CAP patients
- Serum albumin, copeptin and ATS/IDSA criteria should be used to predict mortality in patients for predicting clinical instability after 72 h, ICU admission and mortality at day 7 after hospital admission
Abstract
1. Clinical Rationale for the Study
2. Introduction
3. Methodology
3.1. Study Population
- Chest X-ray with patchy infiltrates, segment/leaf consolidation, interstitial change or ground-glass opacity;
- At least one of the following signs:
- ◦
- Symptoms of cough, phlegm, or dyspnea;
- ◦
- Temperature greater than 38.0 °C;
- ◦
- Abnormal auscultatory findings such as abnormal breath sounds and rales;
- ◦
- Leukocytosis (greater than 10 × 109/L).
- The onset of symptoms should be in a community setting, not a health care setting.
3.2. Laboratory and Clinical Assessments
3.3. Statistical Analysis
4. Results
5. Discussion
6. Conclusions
Clinical Implications/Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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ICU Admission/Death within 7 days | Clinical Instability within 72 h of Admission | ||||||
---|---|---|---|---|---|---|---|
Outcome | Measure | Yes | No | p-Value | Yes | No | p-Value |
(n = 17) | (n = 83) | (n = 38) | (n = 62) | ||||
Age | Mean (SD) | 57.3 (11.5) | 54.7 (18.9) | 0.584 * | 54.7 (17.6) | 55.5 (18.1) | 0.838 * |
Sex | Male | 11 (64.7%) | 53 (63.9%) | 0.947 ^ | 21 (55.3) | 43 (69.4) | 0.226 ^ |
Female | 6 (35.3%) | 30 (36.1%) | 17 (44.7) | 19 (30.6) | |||
Total number of days of admission | Median (IQR) | 6.5 (5.0 to 9.8) | 7.0 (5.0 to 9.0) | 0.917 # | 7.0 (5.0 to 9.5) | 6.0 (5.0 to 8.0) | 0.045 # |
Basal body temperature | Median (IQR) | 97.8 (97.6 to 99.1) | 98.7 (97.5 to 99.5) | 0.381 # | 98.6 (97.6 to 99.5) | 98.6 (97.3 to 99.0) | 0.398 # |
Smokers | N (%) | 7 (41.2%) | 29 (34.9%) | 0.626 # | 16 (42.1) | 20 (32.3) | 0.435 # |
PSI Score | Median (IQR) | 5.0 (4.0 to 5.0) | 4.0 (3.0 to 4.0) | <0.001 # | 4.0 (4.0 to 5.0) | 4.0 (3.0 to 4.0) | <0.01 # |
ATS/IDSA Minor criteria | Median (IQR) | 5.0 (3.0 to 6.0) | 2.0 (1.0 to 4.0) | 0.004 # | 3.0 (2.0 to 4.8) | 2.0 (1.0 to 4.0) | 0.05 # |
CURB-65 score | Median (IQR) | 2.0 (2.0 to 3.0) | 2.0 (1.0 to 2.0) | <0.001 # | 2.0 (2.0 to 2.0) | 2.0 (1.0 to 2.0) | 0.01 # |
Respiratory rate (per min) | Median (IQR) | 29.0 (27.0 to 34.0) | 25.0 (20.0 to 28.0) | <0.001 # | 27.0 (23.0 to 30.0) | 24.0 (20.0 to 28.0) | 0.005 # |
Comorbidities | |||||||
COPD | N (%) | 6 (35.3%) | 23 (27.7%) | 0.53 ^ | 14 (36.8) | 15 (24.2) | 0.26 ^ |
Asthma | N (%) | 1 (5.9%) | 8 (9.6%) | 0.622 ^ | 2 (5.3) | 7 (11.3) | 0.508 ^ |
Diabetes mellitus | N (%) | 5 (29.4%) | 16 (19.3%) | 0.35 ^ | 11 (28.9) | 21 (21.0) | 0.202 ^ |
Obesity | N (%) | 1 (5.9%) | 4 (4.8%) | 0.855 ^ | 1 (2.6) | 4 (6.5) | 0.705 ^ |
Hypertension | N (%) | 4 (23.5%) | 17 (20.5%) | 0.779 ^ | 7 (18.4) | 14 (22.6) | 0.808 ^ |
Haematological Investigations | |||||||
Haemoglobin (g/dL) | Mean (SD) | 13.3 (1.8) | 12.6 (1.9) | 0.172 * | 13.0 (2.2) | 12.6 (1.8) | 0.277 * |
Monocytes ×109 cells/L | Mean (SD) | 5.8 (2.7) | 5.3 (2.3) | 0.507 * | 5.4 (2.6) | 5.4 (2.3) | 0.898 * |
TLC ×109 cells/L | Mean (SD) | 16638.3 (6651.8) | 11315.9 (5137.7) | <0.001 * | 13452.1 (6400.9) | 11551.8 (5290.5) | 0.111 * |
ANC ×109 cells/L | Median (IQR) | 87.2 (82.0 to 91.8) | 83.7 (77.0 to 89.0) | 0.111 # | 82.3 (75.2 to 88.0) | 86.8 (77.8 to 91.5) | 0.03 # |
ALC ×109 cells/L | Median (IQR) | 8.6 (6.0 to 13.0) | 9.9 (6.7 to 16.8) | 0.476 # | 11.0 (7.6 to 17.6) | 9.0 (6.0 to 15.2) | 0.092 # |
Platelets (lakh cells/cu.mm) | Median (IQR) | 2.7 (1.9 to 3.1) | 2.7 (2.3 to 3.3) | 0.481 # | 2.7 (2.2 to 3.3) | 2.7 (2.1 to 3.5) | 0.699 # |
NLR | Median (IQR) | 10.1 (6.4 to 15.3) | 8.5 (4.6 to 13.4) | 0.419 # | 7.5 (4.6 to 11.7) | 9.8 (5.1 to 15.2) | 0.079 # |
PLR | Median (IQR) | 0.2 (0.2 to 0.3) | 0.3 (0.2 to 0.4) | 0.6 # | 0.2 (0.2 to 0.4) | 0.3 (0.2 to 0.5) | 0.076 # |
CRP (mg/L) | Mean (SD) | 29.2 (13.6) | 23.1 (13.0) | 0.079 * | 24.8 (12.5) | 23.9 (13.7) | 0.75 * |
Serum Albumin (g/dL) | Mean (SD) | 2.6 (0.4) | 3.4 (0.4) | <0.001 * | 3.1 (0.6) | 3.4 (0.4) | 0.002 * |
Serum Copeptin (ng/mL) | Mean (SD) | 33.1 (7.1) | 18.1 (6.7) | <0.001 * | 24.0 (9.9) | 18.9 (7.6) | 0.004 * |
Complications ** | Yes | 8 (44.4) | 4 (4.9) | <0.001 ^ | 10 (26.3) | 4 (6.5) | 0.013 ^ |
No | 10 (55.6) | 78 (95.1) | 28 (73.7) | 58 (93.5) |
Albumin | Copeptin | PSI | ATS | CURB-65 | ||
---|---|---|---|---|---|---|
Albumin | Pearson’s r | - | ||||
p-value | - | |||||
95% CI Upper | - | |||||
95% CI Lower | - | |||||
Spearman’s rho | - | |||||
p-value | - | |||||
Copeptin | Pearson’s r | −0.554 *** | - | |||
p-value | <0.001 | - | ||||
95% CI Upper | −0.401 | - | ||||
95% CI Lower | −0.677 | - | ||||
PSI | Spearman’s rho | −0.333 *** | 0.865 *** | - | ||
p-value | <0.001 | <0.001 | - | |||
95% CI Upper | −0.137 | 0.88 | - | |||
95% CI Lower | −0.49 | 0.751 | - | |||
ATS/IDSA | Spearman’s rho | −0.326 *** | 0.295 ** | 0.22 * | - | |
p-value | < .001 | 0.003 | 0.028 | - | ||
95% CI Upper | −0.195 | 0.457 | 0.39 | - | ||
95% CI Lower | −0.534 | 0.095 | 0.013 | - | ||
CURB-65 | Spearman’s rho | −0.207 * | 0.274 ** | 0.209 * | 0.822 *** | 0.539 *** |
p-value | 0.038 | 0.006 | 0.037 | <0.001 | <0.001 | |
95% CI Upper | −0.051 | 0.432 | 0.366 | 0.861 | 0.552 | |
95% CI Lower | −0.421 | 0.065 | −0.014 | 0.716 | 0.22 |
Dependent | HR (Univariable) | HR (Multivariable) |
---|---|---|
PSI | 2.06 (1.06–4.03, p = 0.034) | 1.31 (0.61–2.78, p = 0.487) |
CURB-65 | 11.31 (1.25–102.27, p = 0.031) | 8.92 (0.74–107.35, p = 0.085) |
ATS/IDSA | 7.16 (1.01–56.10, p = 0.041) | 1.35 (0.06–30.93, p = 0.849) |
Respiratory rate | 1.12 (1.05–1.20, p < 0.001) | 1.42 (1.08-1.88, p = 0.013) |
TLC | 1.00 (1.00–1.00, p = 0.113) | 1.00 (1.00–1.00, p = 0.873) |
Complications * | 5.35 (2.26–12.68, p < 0.001) | 3.02 (1.02–9.25, p = 0.048) |
Albumin | 0.28 (0.15–0.54, p < 0.001) | 0.41 (0.18–0.94, p = 0.034) |
Copeptin | 1.09 (1.04–1.15, p ≤0.001) | 1.94 (1.03–3.67, p = 0.042) |
Clinical Instability | ||||
---|---|---|---|---|
Predictor | SENS | SPE | AUC | p-Value |
Serum Albumin + PSI | 0.857 | 0.706 | 0.885 | 0.021 * |
Serum Albumin + ATS/IDSA | 0.857 | 0.765 | 0.894 | 0.012 * |
Serum Albumin + CURB-65 | 0.81 | 0.765 | 0.838 | 0.15 |
Serum Copeptin + PSI | 0.81 | 0.706 | 0.84 | 0.026 * |
Serum Copeptin + ATS/IDSA | 0.857 | 0.706 | 0.863 | 0.007 * |
Serum Copeptin + CURB-65 | 0.81 | 0.647 | 0.849 | 0.026 * |
Serum Albumin + Serum Copeptin + PSI | 0.857 | 0.765 | 0.894 | 0.043 * |
Serum Albumin + Serum Copeptin + ATS/IDSA | 0.857 | 0.785 | 0.905 | 0.019 * |
Serum Albumin + Serum Copeptin + CURB-65 | 0.857 | 0.706 | 0.885 | 0.096 * |
Mortality/ICU admission in 7 days | ||||
Predictor | SENS | SPE | AUC | p-value |
Serum Albumin + PSI | 0.947 | 0.625 | 0.89 | 0.010 * |
Serum Albumin + ATS/IDSA | 0.934 | 0.583 | 0.885 | 0.004 * |
Serum Albumin + CURB-65 | 0.947 | 0.542 | 0.897 | 0.061 * |
Serum Copeptin + PSI | 0.974 | 0.542 | 0.852 | 0.351 |
Serum Copeptin + ATS/IDSA | 0.961 | 0.708 | 0.898 | 0.001 * |
Serum Copeptin + CURB-65 | 0.974 | 0.583 | 0.864 | 0.075 * |
Serum Albumin + Serum Copeptin + PSI | 0.947 | 0.667 | 0.888 | 0.942 |
Serum Albumin + Serum Copeptin + ATS/IDSA | 0.947 | 0.75 | 0.911 | 0.007 * |
Serum Albumin + Serum Copeptin + CURB-65 | 0.947 | 0.667 | 0.895 | 0.013 * |
Author | Sample Size | Marker | Outcome | Result |
---|---|---|---|---|
Present study, 2021, India | 100 | Albumin, copeptin | Combined ICU admission or mortality at day 7 and clinical instability after 72 h. | Albumin was the best predictor of mortality (AUC = 0.854), followed by copeptin (AUC = 0.848). The combination of serum albumin + serum copeptin + ATS/IDSA had the highest AUC for prediction of ICU admission or death within 7 days (AUC = 0.911) and for prediction of clinical instability after 72 h of admission (AUC = 0.905). |
Zhao L et al. [37], 2021, China | 366 | Albumin | 30-day mortality | PSI and CURB-65 were found to be better independent predictors compared to albumin (AUC: 0.79 and 0.78 vs. 0.76) |
Avci S et al. [39], 2020, Turkey | 206 | Albumin, c-reactive protein/albumin ratio (CAR), CRP, NLR, PLR, procalcitonin, A-a o2 gradient, A-a o2 difference | Prediction of 30-day mortality | Albumin (AUC: 0.80) was found to be a better predictor of 30-day mortality than all blood parameters and CURB-65 scores. PSI score was found to be better than albumin (AUC: 0.86) |
Celikhisar H et al. [34], 2020, Turkey | 86 | Lactate, procalcitonin, blood glucose, serum albumin | Risk factors for ICU mortality | Lactate, procalcitonin, albumin (OR: 3.34) and blood glucose were found to be significant independent risk factors |
Shi T et al. [35], 2020, China | 113 | Albumin, ALT, AST, hemoglobin | Risk factors for mortality | <90% oxygen saturation and albumin < 35 g/L were found to be significant risk factors for mortality (OR: 8.77 and 4.73, respectively) |
He Y et al. [40], 2019, China | 175 | WBC count, CRP, procalcitonin, hemoglobin, platelet count, albumin, BUN, creatinine, uric acid, AST and ALT | Risk factors for severe pneumonia | On admission, albumin was significantly lower in SCAP patients compared to non-severe patients |
Adnan M et al. [41], 2018, Pakistan | 134 | Albumin, B/A ratio, BUN | Prediction of ICU admission | Albumin was found to be the better predictor for ICU admission (AUC: 0.718) compared to B/A ratio, BUN or CURB-65 |
Miyazaki H et al. [42], 2018, Japan | 534 | Albumin, PCT | 30-day mortality | Lowest albumin within 1 week of admission was found to be the best predictor (AUC:0.85), followed by albumin at admission (0.81) |
Curbelo J et al. [43], 2017, Spain | 154 | Copeptin, proadrenomedullin, lymphocyte%, neutrophil%, NLR, procalcitonin | Prediction of 30-day and 90-day mortality | On admission, pro-ADM followed by copeptin were found to be the best predictors of both 30-day (AUC: 0.89 and 0.84, respectively) and 90-day (AUC: 0.84 and 0.79, respectively) mortality |
Holter JC et al. [44], 2016, Norway | 259 | CRP, creatinine, albumin | Prediction of risk of long-term mortality | It was found that every 5 g/L decrease in albumin levels increased the risk of death by 25%. |
Alcoba G et. [45], 2015, Switzerland | 88 | Copeptin, proadrenomedullin, CRP | Prediction of complicated pneumonia | Proadrenomedullin and CRP performed much better than copeptin in predicting complicated pneumonia (AUC: 0.85 each vs. 0.59) |
Kruger S et al. [28], 2013, Germany | 1740 | CRP, procalcitonin, MR-proadrenomedullin, WBC count and copeptin | 28-day mortality and 180-day mortality | Copeptin was found to have superior diagnostic accuracy to MR-proANP, CRP, CRB-65 and WBC count (AUC: 0.84) in prediction of 28-day mortality. Similar results were found for 180-day mortality (AUC: 0.78), except for MR-proANP (AUC: 0.81) |
Kolditz M et al. [27], 2012, Germany | 51 | Copeptin, C-reactive protein, MR-proadrenomedullin and pro-calcitonin | Combined ICU admission or mortality at day 7 and clinical instability after 72 h. | The diagnostic accuracy of copeptin for both ICU admission and mortality, as well as clinical instability (AUC: 0.81 and 0.74, respectively). Addition of copeptin to ATS/IDSA minor criteria resulted in significant improvement in prediction of 7-day mortality (AUC: 0.85) and prediction of clinical instability (combined AUC: 0.81). |
Suter-Widmer I et al. [46], 2012, Switzerland | 875 | Albumin, CRP, procalcitonin | Prediction of length of hospital stay | Albumin was associated with increased duration of hospital stay (HR: 0.77) |
Lee JH et al. [47], 2011, South Korea | 424 | Albumin, CRP | 28-day mortality, ICU admission or vasopressor use or mechanical ventilation | Albumin was found to be the best predictor of 28-day mortality (AUC: 0.66). When added with PSI and CRP, the predictive capability significantly increased (AUC: 0.76) |
Schuetz P et al. [48], 2010, Switzerland | 925 | Procalcitonin, pro-ADM, pro-ANP, pro-ET1, copeptin | Prediction of severe outcome | Copeptin (AUC: 0.70) was superior to PSI and curb-65 alone but inferior to pro-ET1 and pro-ADM (AUC: 0.72, respectively) |
Muller B et al. [26], 2007, Germany | 545 | Copeptin, CRP, leucocyte count, procalcitonin | 6-week mortality | Copeptin was found to be the better predictor (AUC: 0.75) |
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Parthasarathi, A.; Padashetti, V.C.; Padukudru, S.; Chaya, S.K.; Siddaiah, J.B.; Anand, M.P. Association of Serum Albumin and Copeptin with Early Clinical Deterioration and Instability in Community-Acquired Pneumonia. Adv. Respir. Med. 2022, 90, 323-337. https://doi.org/10.3390/arm90040042
Parthasarathi A, Padashetti VC, Padukudru S, Chaya SK, Siddaiah JB, Anand MP. Association of Serum Albumin and Copeptin with Early Clinical Deterioration and Instability in Community-Acquired Pneumonia. Advances in Respiratory Medicine. 2022; 90(4):323-337. https://doi.org/10.3390/arm90040042
Chicago/Turabian StyleParthasarathi, Ashwaghosha, Vaibhav C. Padashetti, Sunag Padukudru, Sindaghatta Krishnarao Chaya, Jayaraj Biligere Siddaiah, and Mahesh Padukudru Anand. 2022. "Association of Serum Albumin and Copeptin with Early Clinical Deterioration and Instability in Community-Acquired Pneumonia" Advances in Respiratory Medicine 90, no. 4: 323-337. https://doi.org/10.3390/arm90040042