

In the 19th century, pneumonia was regarded by William Osler as “the captain of the men of death”. Pneumonia affects approximately 450 million people worldwide and is responsible for 7% of world’s yearly deaths.
(Ruuskanen, O; Lahti, E, Jennings, LC, Murdoch, DR (2011 Apr 9). “Viral pneumonia”. Lancet 377 (9773): 1264–75.)
(Kabra SK; Lodha R, Pandey RM (2010). Kabra, Sushil K. ed. “Antibiotics for community-acquired pneumonia in children”. Cochrane Database Syst Rev 3 (3): CD004874. )
Pneumonia can be broadly classified into Community Acquired Pneumonia or CAP, Healthcare Associated Pneumonia, Hospital Acquired Pneumonia, ICU Acquired pneumonia, & Ventilator Acquired Pneumonia. Except for CAP all of the rest are called nosocomial pneumonias. Community Acquired pneumonia can be defined as
an acute infection of the pulmonary parenchyma that is associated with some symptoms of acute infection, accompanied by the presence of an acute infiltrate on a chest radiograph, or auscultatory findings consistent with pneumonia, in a patient not hospitalized or residing in a long term care facility for > 14 days before onset of symptoms.
Bartlett. Clin Infect Dis 2000;31:347-82.

Depending on the causative organism there are two types of presentation of pneumonia.
The “classical” presentation of pneumonia is characterised by sudden onset of CAP, High fever, shaking chills, Pleuritic chest pain, SOB, Productive cough, Rusty sputum which may be blood tinged and a poor general condition. The “atypical” presentation of CAP is characterized by gradual & insidious onset, low grade fever, dry cough, No blood tinged sputum and an over all good general condition. The usual causative organism that is responsible for classical presentation of CAP is S. Pneumonia. While many CAP caused by many different organisms like mycoplasma, legionella, chlamydiae etc has atypical picture.
Important risk factors for a complicated course or mortality in community acquired pneumonia include
- Age > 65 years.
- Co-morbid illnesses. like CCF, CRF, Ischemic Heart Disease, Severe COPD, & Concurrent Malignancy.
- Post Splenectomy state
- Altered mental State
- Alcoholism
- Immunosuppressive Therapy
- Resp. Rate > 30 breaths per minutes
- Blood pressure < 90/60 mmHg.
- Hypothermia
- Creatinine >150 mM/l or BUN >7 mm/l
- Leucopenia <3,000/µl or leucocytosis >30,000/µl
- Hemoglobin < 9 g/l
- Albumin <30 g/l
- Pseudomonas Aeruginosa or Staph. Aureus as the cause of pneumonia
- Bacteremic Pneumonia
- Multilobe involvement on CXR
- Rapid radiographic progression of pneumonia defined as increase in the size of pulmonary opacity by 50 % or more within 36 hours.
Prompt idenitfication of the causative organism and immediate therapy can save life in many cases of CAP and the decision to hospitalize or to treat the patient at home is aided by many scoring systems that help determine the prognostic category of a patient suffering from CAP. PSI or PORT scoring and CURB-65 are the most commonly used scoring systems The risk of death within 30 days increases as the score increases in both these systems. I have found CURB-65 scores easier to calculate and determine than PORT score. But, as nothing is perfect in this world, researchers have found that the accuracy of CURB-65 and Pneumonia Severity Index for predicting outcomes is questionable.
(Intensive Care Med. 2007;33(12):2043-4.)
(Thorax. 2006;61(5):419-24.)
That lead to the search of new factors that could help identify the more sikc patients and therefore their timely management. Over the past few years, researchers have identified certain biomarkers that can help physicians as determinants of prognosis in community acquired pneumonia.
Some of these are:
- CORTISOL
- PRO-ADRENOMUDULLIN
- D-DIMERS & COAGULATION PARAMETERS
- PRO CALCITONIN
- ENDOTHELIN-1
CORTISOL
The hypothalamic-pituitary-adrenal axis plays a major role in regulating a patient´s response to infection. A strong association between elevated cortisol levels, illness severity and the risk of death has been demonstrated. In previously healthy subjects, cortisol plasma levels have had a direct correlation with acute disease severity.
A study found a good correlation between the disease severity (as stratified by PSI scoring) and cortisol levels in patients presenting with Non-ICU CAP. (Am J Respir Crit Care Med. 2007;176(9):913-20.)
Another study showed that in patients with severe CAP requiring ICU admission, baseline cortisol levels were better predictors of outcome than scoring systems like APACHE II, SOFA & CURB-65 and other routine lab tests. (Chest. 2008;134(5):947-54.)
Another study found that cortisol may be a useful biomarker for assessing the risk in patients with severe CAP in ER. Elevated cortisol levels (esp. more than 26 mcg/dl) are associated with disease severity and higher risk of death. (J Crit Care. 2010;25(3):541.e1-8.)
PRO ADRENOMEDULLIN
Pro-adrenomedullin is a peptide produced by multiple types of tissue during physiologic stress. Its many functions include Vasoregulatory, Antimicrobial & Anti inflammatory activity. Increased levels of pro adrenomedullin have been found in body during infections. Increased production of ADM as well as decreased clearance by kidneys have been postulated as the mechanisms responsible for Increased pro-ADM. A recent study showed that pro-ADM levels increased with the increasing severity of CAP, classified according to PSI scoring. (Crit Care. 2006;10(3):96). Subsequently another multicenter prospective cohort study confirmed the prognostic value of pro-ADM.( Chest. 2009;136(3):823-31.)
Recently a practical algorithm combining the CURB-65 scoring with pro-ADM levels in patients with CAP and non-CAP-LRTI has been proposed. (BMC Infect Dis. 2011;11:112). It (CURB-65-A) has been effective in accurately predicting adverse events and mortality in patients with CAP and non-CAP-LRTI. Patients in the lowest CURB-65 groups and with pro-ADM levels less than 0.75 nmol/l were at a very low risk of adverse events and mortality. Patients in the highest CURB-65 groups and pro-ADM groups (CURB-65-A risk Class III) had the highest risk of adverse events and mortality. Finally, patients with CURB-65 class 2 and pro ADM levels less than 1.5 nmol/l or CURB Classes 0-1 and pro-ADM levels between 0.75-1.5 nmol/l had intermediate risks. It looks promising, yet more studies are required before it can be added to CURB-65 algrithm.
D-DIMERS
D-Dimers are the most studied coagulation parameters that have been evaulated in severe CAP. Elevated D-dimer levels can be seen in
- DIC
- Severe Sepsis
- Thromboembolic events
- Pregnancy
- Liver diseases
- Surgery & Trauma
In patients without clinical or overt evidence of coagulopathy, high d-dimer levels may indicate microvascular thrombosis and therefore disease severity. (Thromb Haemost.1987;57(1): 59-61.)
In a prospective observational study that evaluated 68 CAP patients that presented to the A&E, D-dimer levels were positively correlated with APACHE II, Pneumonia PORT scores and the length of hospital stay. Mean d-dimer levels of hospitalized patients were higher than the non-hospitalized patients. It demonstrated that d-dimer is associated with disease severity and clinically relevant outcome.
(Blood Coagul Fibrinolysis. 2003;14(8):745-8.)
Another prospective observational study showed a direct relationship between d-dimer levels and outcome in CAP patients.
The mean d-dimer level in nonsurvivors was 3.786 ng/ml while in survivors the mean level was 1.609 ng/ml. There was a significant association between the presence of elevated d-dimer levels and PSI and APACHE II scores.( Am J Respir Crit Care Med. 2011;184(2):186-90.) Addition of d-dimers increased the predictive ability of scoring systems like SOFA & APACHE II.
(J Crit Care. 2011;26(5):496-501.)
PRO CALCITONIN
New promising information suggests that pro-calcitonin (PCT), a precursor of calcitonin is released into the blood of persons with bacterial infections. This biomarker, released in blood, has been used to evaluate the severity & prognosis of CAP in patients and to de-escalate the antibiotic therapy. At levels of less than or equal to 0.25 µg/l, antibiotic therapy has been successfully discontinued in patients with pneumonia.
ENDOTHELIN 1
Endo thelin-1 is a potent vasoconstrictor agent primarily synthesized by endothelial cells. Endothelin-1 itself is unstable and rapidly cleared from circulation, however its precursor peptides can be detected in circulation. Recently a study assessed the diagnostic & prognostic value of pro-Endothelin-1 in patients with septic CAP.
In these patients, circulating ET-1 precursor peptide levels had a good correlation with the severity of CAP, as assessed by PSI and CURB-65 scores. (BMC Infect Dis. 2008;8:22). The pro-ET-1 levels can improve the prognostic accuracy CURB-65 scores in predicting adverse outcomes. Over all the discriminatory ability of pro-ET1 to predict death and ICU admission was significantly better that CRP & TLC.
I have briefly prsented the research that is done in this regard. The future looks promising however I am not much sure that thesenew factors will be able to help physicians all across the globe. It is because measurement of many of these factors is not universally available. and even if future research proves one or more of the above mentioned factors as helpful in predicting the prognosis of CAP in patients, the application of such criteria will be dependent on the availability of laboratory facilities for measurement of these substances and the patient affordability. At present, except for D-dimers, none of the above can be measured easily across the world in an OPD setting.
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