High CRP: a marker for depression in metastatic lung cancer


Takeaway

  • C-reactive protein (CRP), a measure of inflammation, is a strong predictor of clinically significant depression in patients with lung cancer.
  • Patients with moderate or high inflammation are more likely to have depression.

Why this matters

  • Lung cancer has 1 of the highest rates of comorbid depression among all types of cancer, ranging from 16% to 29%.
  • Inflammation is elevated in both lung cancer and depression.

Study design

  • 109 patients undergoing treatment for stage IV lung cancer.
  • Funding: National Cancer Institute.

Key results

  • 71.8% had NSCLC adenocarcinoma, 6.4% squamous cell carcinoma NSCLC, and 16.5% SCLC; the remaining were unspecified.
  • 23.9% overall had clinically significant depression symptoms.
  • After multiregression analysis, only CRP (log-transformed) was significantly associated with depression (aR2, 0.23; P=.001).
  • After linear regression, CRP was a predictor for approximately 20% of depression variability (aR2, 0.2; P=.001), and patients with clinically significant depression scores had higher median CRP levels (3.4 vs 1.3 mg/mL; P=.003) and were more likely to be receiving advanced lines of treatment (P=.24).
  • Among those with depression, 76.9% had a CRP level ≥1 mg/mL, and 50% had a CRP level ≥3 mg/mL.
  • Only 7 of the patients with clinically significant depression were receiving antidepressants.

Limitations

  • Retrospective study.

How to Calculate Bolus Insulin Dosing for Protein


People with diabetes who use insulin with meals are probably well-aware of the importance of accurately counting carbohydrates in order to calculate their bolus insulin dose. Fewer may be aware that protein can also have a significant impact on their blood glucose level.

In a process called gluconeogenesis, our bodies can actually make glucose from non-carbohydrate sources. Unlike carbohydrates, which are quickly broken down to glucose, protein conversion to glucose takes place over several hours, and thus can have a less pronounced, but a considerable effect, on blood glucose levels.

metabolism summary

For a long time, it was believed that the rate of gluconeogenesis is quite stable. In fact, recent studies have pointed out that shifts in the rate of gluconeogenesis occur based on the individual’s diet.

When it comes to administering insulin for protein, the need for this may be particularly apparent in those who follow a low carbohydrate diet. This is because, while some protein is always converted to glucose, the rate of this process is higher when fewer carbohydrates are taken in.

So how does one determine whether they need to inject insulin for protein? Figuring this out will take some careful observation of blood glucose trends for several hours after a meal as well as some trial and error.

Many people who follow a low carbohydrate diet will always take some bolus insulin to cover protein intake. Websites or apps such as Calorie King can be very useful in learning to calculate the protein content of a meal. Most individuals will start with a trial insulin dose that covers anywhere from 20% – 50% of the protein consumed.

What this means is that the protein content will be estimated and anywhere from 20% – 50% of the protein will be counted as if it were carbohydrate. For example, if one consumes 4 oz (~113 g) of chicken, and chicken is approximately 25% protein by weight, one would estimate that they are likely consuming approximately 30 g of protein. Thus, one may take insulin to account for 6 g (20%) to 15 g (50%).

bolusing for protein

Those individuals who consume more carbohydrates will likely experience a lower rate of gluconeogenesis and the need to administer bolus insulin for protein may be less apparent, or only apparent when a very high-protein meal is consumed. Many people who eat a high-carbohydrate diet chose to only bolus for protein in these circumstances.

Whether using an insulin pump or multiple daily injections, most administer the protein bolus one to two hours after their meal, or when they start to see an upward trend on their CGM. Others have found that regular (R) insulin better matches the protein peak and administer it at the start of their meal. It may be a good idea to try different approaches to see what works best for you, starting conservatively, and increasing the protein bolus if the blood glucose level still increases several hours after the meal.

MRI Findings Match Patients’ Experience With RA


Patient-reported outcomes in rheumatoid arthritis (RA) correlate independently with measures of inflammation and structural damage on MRI scans, according to data from a longitudinal study.

For example, at 1 year, the change in MRI-detected synovitis was significantly associated with changes in physical function on the Health Assessment Questionnaire (HAQ) (beta = 0.53, 95% CI 0.029-0.077, P<0.001), according to Joshua F. Baker, MD, of the University of Pennsylvania in Philadelphia, and colleagues.

In addition, change in synovitis at 1 year was associated with pain scores (beta = 0.16, 95% CI 0.058-0.25, P=0.002) and patient global assessment (beta = 0.16, 95% CI 0.066-0.25, P=0.001), the researchers reported in Annals of the Rheumatic Diseases.
The association between longitudinal MRI measures and changes in patient-reported outcomes had not been assessed previously. For this analysis, the researchers used a cohort of 291 patients with MRI scores for synovitis, osteitis, and/or bone erosion from a larger group enrolled in the Go-BEFORE placebo-controlled clinical trial, which randomized methotrexate-naïve patients to golimumab (Simponi), methotrexate, or the combination.
MRIs were obtained at the patient’s dominant wrist and second to fifth metacarpophalangeal joints, and the images were scored by two independent readers.
Correlations between the RA-MRI scoring system (synovitis, osteitis, and bone erosion) and physical function, pain, and global patient scores, were determined at weeks 0, 12, 24, and 52. Patients then were followed for an additional year.
MRI measures were associated with scores on the HAQ at all assessments, while MRI measures were increasingly associated with pain and patient global scores at later follow-up time points.

“Improvements in synovitis at 12, 24, and 52 weeks were generally associated with greater improvements in HAQ, pain and patient global scores,” wrote Baker and colleagues. Changes in bone erosion were associated positively with changes in pain and patient global at later follow-up times.
In longitudinal regression models, synovitis was significantly associated with HAQ independent of the disease activity score in 28 joints (DAS28) using C-reactive protein (CRP). Synovitis was also associated with pain and patient global scores independent of CRP and swollen and tender joint counts.
Further, longitudinal models demonstrated that progression in bone erosion was associated with worse physical functioning, independent of synovitis and DAS28-CRP. These findings suggest that MRI measures are valid as RA biomarkers, and that the associations are independent of clinical disease activity.
“Thus, for two individuals with similar clinical assessments, the individual with greater synovitis on MRI is likely to have worse pain and function. These data indicate that synovitis and bone erosion are complementary to other clinical parameters in terms of relevance to the patient experience.”
“The current study suggests that progression in the MRI erosion score (>0.5) is associated with a change in HAQ of 0.35 at 1 year,” the investigators wrote. “In addition, a 4.4-unit change in MRI erosion score would translate into a change in HAQ of 0.2.”
There was no relationship found between x-ray progression of disease and functional decline over 1 year, which suggests that MRI may be a better discriminator of functional decline, the authors suggested.
“Of note, we found that changes in synovitis were more strongly correlated with HAQ during the treatment of active inflammation in year 1, while changes in bone erosion were correlated similarly throughout the 2-year period,” the authors added.
The correlations between patient-reported outcomes and MRI measures were similar regardless of the treatment received.
They concluded that, “improvements over time in MRI inflammation and deterioration in MRI damage correlate with changes in function, pain and patient global scores, suggesting that these objective measures reflect how patients experience their disease.”
Because of the correlation found between patient-reported outcomes and MRI measures, these measures may serve as a reasonable surrogate endpoint in observational and early interventional studies, they noted.
The findings of this analysis may not be entirely generalizable beyond the study population, according to the authors. The study also was limited in the patient-reported outcomes that were available as part of the randomized trial. Furthermore, there have been advances in MRI since the study was undertaken some 10 years ago, which may improve visualization of inflammation and structural changes.

Beyond Coronary Calcification, Family History, and C-Reactive Protein: Cholesterol Efflux Capacity and Cardiovascular Risk Prediction


TAKE-HOME MESSAGE

Meta-analysis shows some benefits of steroids in CAP


The use of steroids in people with community acquired pneumonia (CAP) led to shorter recovery time and fewer hospital days, with the added benefits of reduced mortality and acute respiratory distress syndrome (ARDS), in a systematic review and meta-analysis.

Corticosteroid therapy reduced the length of hospital day by an average of 1 day in six trials with 1,500 patients and the time to clinical stability by an average of 1.22 days in five trials with over 1,100 patients. It was also associated with 3 percent lower mortality in a subgroup of patients with severe CAP and 5 percent reduction in need for mechanical ventilation. [Ann Intern Med 2015;163:519-528]

“The analysis offers high-quality evidence for the benefits of adjunctive corticosteroids in hospitalized patients with CAP,” said researchers led by Dr. Reed Siemieniuk of Mc Master University in Hamilton, Ontario, Canada.  There was an increased risk of hyperglycaemia that required treatment, but not gastrointestinal haemorrhage, rehospitalisation or neuropsychiatric symptoms.

Current guidelines for CAP do not recommend corticosteroids. Several randomized controlled trials (RCTS) of corticosteroids have demonstrated benefits, but others have come up empty. Siemieniuk and colleagues sought to investigate if the anti-inflammatory action of corticosteroids can improve outcomes in patients with CAP. The analysis mainly focused on 13 RCTs comparing corticosteroids with placebo or no treatment and looked into one of several outcomes that included clinical stability, length of hospital stay, all-cause mortality, use of mechanical ventilation, ARDS or ICU admission. Sixty percent of patients were men (median age, 60 years).

In 12 trials looking at all-cause mortality, the relative risk (RR) was 0.67 in favour of corticosteroids (risk difference [RD], 2.8 percent) whereas in three studies with 950 patients, the RR for ICU admission was 0.69.

The benefit may be greater in severely ill patients, said the researchers.

In an accompanying editorial, Drs. Marcos Restrepo, Antonio Anzueto and Antoni Torres of the University of Texas Health Science Center at San Antonio in San Antonio, Texas, US praised the rigorousness of the analysis but cautioned that clinicians need to balance the benefits and harms of corticosteroid therapy to provide optimal care for patients with CAP. They also suggested the use of C-reactive protein (CRP) biomarker to measure the systemic inflammation characteristic of pneumonia and identify hospitalized patients who would best respond to corticosteroid treatment.

High traffic pollution may increase inflammation for insulin users


Exposure to heavy traffic pollution may lead to an increase in C-reactive protein for those living with type 2 diabetes and using insulin, according to research in Environmental Pollution.

In contrast, adults assigned oral diabetes medications did not experience increases in C-reactive protein (CRP), a marker for inflammation, while exposed to the same amount of heavy traffic, according to researchers.

“According to our findings, [oral diabetes medication] users may be protected over time compared to insulin users,” the researchers wrote. “CRP concentration progressed in those on insulin but remained steady in those on [oral diabetes medications], in relation to proximity or number of major roadways.”

Christine Rioux, PhD, MS, assistant professor in the department of public health and community medicine at Tufts University School of Medicine in Boston, and colleagues analyzed data from 356 Puerto Rican adults (aged 44 to 75 years) with type 2 diabetes living in the Boston area. Within that group, 26% used insulin, 55% used oral diabetes medications and 19% reported using no diabetes medications.

Christine Rioux

Christine Rioux

Researchers assessed major road proximity and traffic density for each participant’s residential address. Approximately 20% of the group lived within 100 meters of one or more roads with more than 20,000 vehicles per day, and another 20% lived within 100 to 200 meters of roads with the same amount of traffic. Approximately 70% of the participants resided in the greater Boston area. Traffic considerations did not affect the selection criteria for the study.

Researchers measured CRP at the beginning of the study and again 2 years later.

Participants living within 100 meters of a busy roadway showed a 58.2% greater increase in CRP concentration (P =.054) compared with those living more than 200 meters away. Participants living between 100 and 200 meters of a busy roadway showed an 81% greater increase in CRP concentration (P = .03) compared with those living farther from busy roadways. Living near two or more busy roadways was associated with a 190% greater increase in CRP concentration (P = .001) compared with zero roadways.

Participants using oral diabetes medications and living near the highest traffic density showed a 49.3% relative decline in CRP concentration (P = .04).

The study is the first to examine the role that various type 2 diabetes medications may play when combined with a patient’s exposure to traffic pollution, according to researchers. The study builds on the research team’s previous work that suggested oral diabetes medications may provide a protective effect against inflammation for adults with type 2 diabetes.

“People on insulin appear to be even more susceptible to increases in inflammation when living in high traffic area,” Rioux said in a press release. “People can reduce their exposure to traffic pollution by keeping windows closed during the heaviest traffic periods of the day, using air conditioners in the summer months, and avoiding heavy exercise near busy roads, especially during peak traffic times.”

“We would like to examine the relationship between traffic pollution exposure, inflammation and type of diabetes medication in larger cohorts in other parts of the U.S. and world,” Rioux told Endocrine Today.  – by Regina Schaffer

High-Sensitivity C-Reactive Protein and Cardiovascular Disease.


Abstract

The role of inflammation in the propagation of atherosclerosis and susceptibility to cardiovascular (CV) events is well established. Of the wide array of inflammatory biomarkers that have been studied, high-sensitivity C-reactive protein (hsCRP) has received the most attention for its use in screening and risk reclassification and as a predictor of clinical response to statin therapy. Although CRP is involved in the immunologic process that triggers vascular remodeling and plaque deposition and is associated with increased CV disease (CVD) risk, definitive randomized evidence for its role as a causative factor in atherothrombosis is lacking. Whether measurement of hsCRP levels provides consistent, clinically meaningful incremental predictive value in risk prediction and reclassification beyond conventional factors remains debated. Despite publication of guidelines on the use of hsCRP in CVD risk prediction by several leading professional organizations, there is a lack of clear consensus regarding the optimal clinical use of hsCRP. This article reviews 4 distinct points from the literature to better understand the current state and application of hsCRP in clinical practice: 1) the biology of hsCRP and its role in atherosclerosis; 2) the epidemiological association of hsCRP with CVD; 3) the quality of hsCRP as a biomarker of risk; and 4) the use of hsCRP as a tool to initiate or tailor statin therapy. Furthermore, we highlight recommendations from societies and important considerations when using hsCRP to guide treatment decisions in the primary prevention setting.

Source: Journal of the American College of Cardiology

 

Low C-reactive protein levels helped rule out pneumonia.


  Acute bronchitis is managed expectantly, and pneumonia is managed with antibiotics. However, accurately distinguishing these conditions, based on history and physical examination alone, is difficult. Although chest x-ray can distinguish acute bronchitis from pneumonia, it is expensive, exposes patients to radiation (often unnecessarily), and is unavailable in some settings. In this European study, investigators determined whether measuring blood C-reactive protein (CRP) and procalcitonin concentrations, in addition to history and physical examination, improved diagnostic accuracy. Among 2820 adults (mean age, 50) who presented with cough to primary care practices, chest x-ray confirmed pneumonia in 140 patients (5%). The optimum combination of history and examination findings for pneumonia was absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever. Adding CRP level as a continuous variable resulted in significantly improved ability to predict pneumonia (multivariate odds ratio, 1.2 per 10 mg/L rise in CRP concentration). Adding CRP as a dichotomized variable (>30 mg/L as high-risk for pneumonia) yielded similar results. Of 665 patients with low probability (<2.5%) for pneumonia based on history and examination findings only, 11 (2%) actually had pneumonia. Adding CRP level reclassified 891 additional patients into the low-risk group (total, 1556); of these, 31 (2%) actually had pneumonia. Procalcitonin added no diagnostic information. Comment: In this study, adding blood CRP concentration to history and examination findings improved diagnostic accuracy for pneumonia — mainly by ruling out the infection. Of course, this approach depends on the availability of timely point-of-care CRP testing.   Source:  Journal Watch General Medicine  

patients presenting to primary care with acute cough: diagnostic study.


Abstract

Objectives To quantify the diagnostic accuracy of selected inflammatory markers in addition to symptoms and signs for predicting pneumonia and to derive a diagnostic tool.

Design Diagnostic study performed between 2007 and 2010. Participants had their history taken, underwent physical examination and measurement of C reactive protein (CRP) and procalcitonin in venous blood on the day they first consulted, and underwent chest radiography within seven days.

Setting Primary care centres in 12 European countries.

Participants Adults presenting with acute cough.

Main outcome measures Pneumonia as determined by radiologists, who were blind to all other information when they judged chest radiographs.

Results Of 3106 eligible patients, 286 were excluded because of missing or inadequate chest radiographs, leaving 2820 patients (mean age 50, 40% men) of whom 140 (5%) had pneumonia. Re-assessment of a subset of 1675 chest radiographs showed agreement in 94% (κ 0.45, 95% confidence interval 0.36 to 0.54). Six published “symptoms and signs models” varied in their discrimination (area under receiver operating characteristics curve (ROC) ranged from 0.55 (95% confidence interval 0.50 to 0.61) to 0.71 (0.66 to 0.76)). The optimal combination of clinical prediction items derived from our patients included absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever, with an ROC area of 0.70 (0.65 to 0.75). Addition of CRP at the optimal cut off of >30 mg/L increased the ROC area to 0.77 (0.73 to 0.81) and improved the diagnostic classification (net reclassification improvement 28%). In the 1556 patients classified according to symptoms, signs, and CRP >30 mg/L as “low risk” (<2.5%) for pneumonia, the prevalence of pneumonia was 2%. In the 132 patients classified as “high risk” (>20%), the prevalence of pneumonia was 31%. The positive likelihood ratio of low, intermediate, and high risk for pneumonia was 0.4, 1.2, and 8.6 respectively. Measurement of procalcitonin added no relevant additional diagnostic information. A simplified diagnostic score based on symptoms, signs, and CRP >30 mg/L resulted in proportions of pneumonia of 0.7%, 3.8%, and 18.2% in the low, intermediate, and high risk group respectively.

Conclusions A clinical rule based on symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough performed best in patients with mild or severe clinical presentation. Addition of CRP concentration at the optimal cut off of >30 mg/L improved diagnostic information, but measurement of procalcitonin concentration did not add clinically relevant information in this group.

 

What is already known on this topic

  • Studies have evaluated the diagnostic accuracy of signs and symptoms for pneumonia, but there is limited evidence applicable to primary care
  • The added diagnostic value of C reactive protein (CRP) and procalcitonin concentrations to clinical signs and symptoms is unknown
  • Symptoms and signs (absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever) have moderate diagnostic accuracy for pneumonia in patients who present in primary care with acute cough
  • CRP concentration at the optimal threshold of >30 mg/L adds some diagnostic information by increasing diagnostic certainty in the patients when doubt remains after history and physical examination
  • Procalcitonin concentration adds no clinically relevant information in primary care

What this study adds

 

Source: BMJ

Use of serum C reactive protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: diagnostic study.


Abstract

Objectives To quantify the diagnostic accuracy of selected inflammatory markers in addition to symptoms and signs for predicting pneumonia and to derive a diagnostic tool.

Design Diagnostic study performed between 2007 and 2010. Participants had their history taken, underwent physical examination and measurement of C reactive protein (CRP) and procalcitonin in venous blood on the day they first consulted, and underwent chest radiography within seven days.

Setting Primary care centres in 12 European countries.

Participants Adults presenting with acute cough.

Main outcome measures Pneumonia as determined by radiologists, who were blind to all other information when they judged chest radiographs.

Results Of 3106 eligible patients, 286 were excluded because of missing or inadequate chest radiographs, leaving 2820 patients (mean age 50, 40% men) of whom 140 (5%) had pneumonia. Re-assessment of a subset of 1675 chest radiographs showed agreement in 94% (κ 0.45, 95% confidence interval 0.36 to 0.54). Six published “symptoms and signs models” varied in their discrimination (area under receiver operating characteristics curve (ROC) ranged from 0.55 (95% confidence interval 0.50 to 0.61) to 0.71 (0.66 to 0.76)). The optimal combination of clinical prediction items derived from our patients included absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever, with an ROC area of 0.70 (0.65 to 0.75). Addition of CRP at the optimal cut off of >30 mg/L increased the ROC area to 0.77 (0.73 to 0.81) and improved the diagnostic classification (net reclassification improvement 28%). In the 1556 patients classified according to symptoms, signs, and CRP >30 mg/L as “low risk” (<2.5%) for pneumonia, the prevalence of pneumonia was 2%. In the 132 patients classified as “high risk” (>20%), the prevalence of pneumonia was 31%. The positive likelihood ratio of low, intermediate, and high risk for pneumonia was 0.4, 1.2, and 8.6 respectively. Measurement of procalcitonin added no relevant additional diagnostic information. A simplified diagnostic score based on symptoms, signs, and CRP >30 mg/L resulted in proportions of pneumonia of 0.7%, 3.8%, and 18.2% in the low, intermediate, and high risk group respectively.

Conclusions A clinical rule based on symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough performed best in patients with mild or severe clinical presentation. Addition of CRP concentration at the optimal cut off of >30 mg/L improved diagnostic information, but measurement of procalcitonin concentration did not add clinically relevant information in this group.

Discussion

Main findings

Pneumonia was diagnosed by chest x radiography in 140 (5%) of the 2820 patients presenting to primary care with acute cough. The optimal combination of symptoms and signs for predicting pneumonia was absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever. Signs and symptoms were useful in correctly identifying patients with a “low” (<2.5%) or “high” (>20%) diagnostic risk in 26% of patients. In the 74% of patients in whom diagnostic doubt remained (estimated risk 2.5%-20%), measurement of C reactive protein (CRP) concentration helped to correctly exclude pneumonia. A simplified diagnostic score based on symptoms, signs, and CRP concentration resulted in proportions of pneumonia of 0.7%, 4%, and 18% in the low, intermediate, and high risk group, respectively. Measurement of procalcitonin concentration had no clinically relevant added value in this setting.

Strengths and limitations

This is the first study to quantify the independent diagnostic value of symptoms, signs, and additional diagnostic value of inflammatory markers for pneumonia in patients presenting with acute cough in primary care that included an adequate number of cases of pneumonia. All blood samples were analysed in the same laboratory with standardised procedures. Serum CRP and procalcitonin concentrations were measured by conventional venous blood tests in a diagnostic laboratory and not with a point of care test. The added value of CRP might be different and could be lower when measured with a point of care test in general practice. Nonetheless, agreement between point of care test results and a conventional reference test has been shown to be good.44

Given how common lower respiratory tract infections are, many more eligible patients presented during the recruitment period than were approached about participation in this study, and therefore we probably did not achieve the goals of recruiting all consecutive, eligible patients. Nevertheless, we do not believe that there was important clinical selection bias because feedback from recruiting clinicians during and after the study was that the time required to recruit and assess each patient made sequential recruitment of every eligible patient impossible.

Chest radiographs were examined by local radiologists. We attempted to increase uniformity in assessment by implementing a protocol for reporting. While there was some variability between observers, the moderate unweighted κ of 0.45 was similar to that reported in other studies.18 20

We did not attempt to distinguish between bacterial and viral pneumonia as this is not feasible in routine primary care.14 45 All available relevant guidelines advocate identification of patients with pneumonia and treatment with antibiotics without further aetiological testing.14

Comparison with other studies

Absence of a runny nose and presence of dry cough, breathlessness, chest pain, diarrhoea, fever, and crackles have previously been found to have diagnostic value for pneumonia in primary care populations.7 9 “Tachycardia” and “diminished vesicular breathing” have diagnostic value in secondary care populations.3 6 8 11 We were able to confirm the predictive value of most of these items, apart from chest pain and diarrhoea. Differences between our findings and those from previous studies could relate to the difference in prevalence of pneumonia, inclusion criteria, and outcome definition.

Our finding that CRP concentration can be low in people with pneumonia is not new. Flanders and colleagues reported on a small subgroup of patients with pneumonia who had a CRP of less than 11 mg/L.3 In the 54 patients with pneumonia with low CRP in our study, the estimated diagnostic risk of pneumonia was high (n=3) or intermediate (n=51) based on history and physical examination results as defined in our model. These findings emphasise that CRP test results should be interpreted together with clinical findings.

Of the factors known to lower CRP—such as steroid use46 and duration of disease47—only steroid use (including both oral and inhaled steroids) was significantly more prevalent in the group of patients with pneumonia with low CRP concentration. Exclusion of all steroid users from our analyses resulted in a similar association between CRP concentration and pneumonia.

Procalcitonin concentrations in our study were higher in patients with pneumonia and comparable with previous findings in patients with lower respiratory tract infection in primary care.17 48 They did not, however, add meaningful diagnostic information. Holm and colleagues showed a clear association between procalcitonin concentration and radiographic pneumonia as well as bacterial infection,17 but the positive predictive value was too low to be useful in clinical practice. Our findings support this conclusion. Moreover, Holm and colleagues studied a population with a higher prevalence of pneumonia (13%) and did not combine history and physical examination with procalcitonin test results.17

Implications for practice and conclusions

Although the diagnostic “symptoms and signs” model presented in this study assigned an intermediate diagnostic risk of pneumonia to most patients, history taking and physical examination alone enabled general practitioners to correctly identify a small group of patients at high risk. Chest radiography and/or (empirical) antibiotic treatment should therefore be considered in these patients. In these more severely ill patients, point of care tests, including CRP, do not seem to be useful. In patients with a low risk of pneumonia based on symptoms and signs, it seems justified to withhold further diagnostic investigation and not to treat with antibiotics.

CRP has additional diagnostic value in patients with an intermediate diagnostic risk of pneumonia as determined by symptoms and signs alone, especially in appropriately excluding pneumonia. Procalcitonin has no additional diagnostic value in primary care.

The simplified score derived from the regression models is more suitable for uptake in daily care than the regression models. The downside of the simplified score is that it is less precise and contains less diagnostic information. To determine whether our diagnostic model improves clinical outcomes in everyday practice would require an implementation study in which general practitioners use point of care CRP testing with outcomes such as patient recovery and the unnecessary prescription of antibiotics. Further research should also determine the performance of CRP in other settings where pneumonia is more prevalent or where patients are more severely ill.

What is already known on this topic

  • Studies have evaluated the diagnostic accuracy of signs and symptoms for pneumonia, but there is limited evidence applicable to primary care
  • The added diagnostic value of C reactive protein (CRP) and procalcitonin concentrations to clinical signs and symptoms is unknown
  • Symptoms and signs (absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever) have moderate diagnostic accuracy for pneumonia in patients who present in primary care with acute cough
  • CRP concentration at the optimal threshold of >30 mg/L adds some diagnostic information by increasing diagnostic certainty in the patients when doubt remains after history and physical examination
  • Procalcitonin concentration adds no clinically relevant information in primary care

What this study adds

Source: BMj