Category: Commentaries

Corticosteroids for pneumonia

Paolo Balzaretti
S.C. Medicina e Chirurgia d’Accettazione e Urgenza, A.O. “Ordine Mauriziano”, (Torino) Italy

What we already know about this topic

Pneumonia still holds a high prevalence in Western Countries; even mortality rates for admitted patients are relevant, ranging from 5,6% to 10% at 30-days follow up (1,2). For this reason, any therapeutic mean which possibly could lower these figures is worth studying.
In the past years, corticosteroids have been deeply investigated in the field of sepsis and particularly as an adjunctive treatment for pneumonia. Our search revealed 9 metanalyses of randomized controlled trials (RCT) on the matter whose results are synthetized in table 1.
 

Studio

Patients included

N° of studies / N° of patients

30 days-mortality

Chen 2011 (3)

Patients with pneumonia

6 / 437

Odds Ratio 0,26 (95% C.I. 0,05 – 1,37)

Nie 2012 (4)

Hospitalized adults for CAP

9 / 1001

Odds ratio 0,62 (95% C.I. 0,37 – 1,04)

Subgroup analysis: patients with severe CAP

4 / 214

Odds Ratio 0,26 (95% C.I.0,11 – 0,64)

Subgroup analysis: mixed severity CAP patients

4 / 756

Odds Ratio 0,95 (95%

C.I. 0,50 – 1,78)

Shafiq 2013 (5)

Hospitalized adults for CAP

8 / 1119

Relative risk 0,73 (95% C.I. 0,42 – 1,27)

Cheng 2014 (6)

Patients with severe CAP

4 / 268

Relative risk 0,39 (95% C.I. 0,17 – 0,90)

Marti 2015 (7)

Hospitalized adults for CAP

14 / 2077

Risk ratio 0,84 (95% C.I. 0,55 – 1,29)

Subgroup analysis: patients with severe CAP

5 / 334

Risk ratio 0,47 (95% C.I. 0,23 – 0,96)

Subgroup analysis: mixed severity CAP patients

8 / 1712

Risk ratio 1,04 (95% C.I. 0,66 – 1,64)

Horita 2015 (8)

Hospitalized adults for CAP

10 / 1780

Odds ratio 0,80 (95% C.I. 0,53 – 1,21)

Subgroup analysis: patients with severe CAP

5 / 321

Odds Ratio 0,41 (95% C.I.0,19 – 0,90)

Subgroup analysis: mixed severity CAP patients

 6 / 1459

Odds Ratio 1, 02 (95% C.I. 0,63 – 1,65)

Semeniuk 2015 (9)

Hospitalized adults for CAP

12 / 1974 

Risk ratio 0,67 (95% C.I.0,45 – 1,01)

Subgroup analysis: patients with severe CAP

6 / 388

Risk ratio 0,39 (95% C.I.0,20 – 0,77)

Subgroup analysis: less severe pneumonia

6 / 1586

Risk ratio 1,00 (95% C.I. 0,79 – 1,26)

Bi 2016 (10)

Patients with severe CAP

8 / 528

Risk Ratio 0,46 (95% C.I. 0,28 – 0,77)

Wan 2016 (11)

Hospitalized adults for CAP

9 / 1667

Relative risk 0,72 (95% C.I., 0,43 – 1,21)

Subgroup analysis: patients with severe CAP

5 / 347

Relative risk 0,72 (95% C.I., 0,43 – 1,21)

 
Table 1. Summary results of metanalyses on adjunctive steroids therapy in patients with community acquired pneumonia (CAP). Estimates below 1 favor corticosteroids use.
 
Balzaretti_Corticosteroids for pneumonia IMG 1.jpg
 
Altogether, these data show corticosteroids are not useful for the management of unselected patients with pneumonia. Metanalyses of small sized RCTs suggest a possible effect in patients with severe CAP. Accordingly, none of the latest guidelines regarding pneumonia recommend routine use of steroids (12,13,14).
What can a new systematic review add in this context?

The Cochrane review 

Title: Corticosteroids for pneumonia
Authors: Stern A, Skalsky K, Avni T, Carrara E, Leibovici L, Paul M
Bibliographic citation: Cochrane Database Syst Rev. 2017; 12: CD007720.
Objective: to assess the efficacy and safety of corticosteroids in the treatment of pneumonia
Included studies:
Primary outcome: 30-days all-cause mortality 
Secondary outcomes: early clinical failure (death for any cause, radiographic progression or clinical instability as defined in study), time to clinical cure, development of respiratory failure or shock not presented initially, transfer to ICU, duration of ICU or hospital stay, rate of pneumonia complications, secondary infections or adverse events.
Number of included studies: 17 randomized controlled trials, 13 involving adults and 4 children. We will consider only adult patients.
Quality of included studies: over 75% of studies were at high risk for selective reporting bias; in half of the studies there was an unclear risk for selection bias. Low risk for attrition bias was generally reported.
Number of patients: 2264 (1954 adults and 310 children)
Results:
 

Outcome

No. of studies / No. of patients

Risk Ratio (95% C.I.)

Quality of evidence

Mortality

11 / 1863

0,66 (0,47 – 0,92)

Moderate

Mortality – severe CAP

9 / 995

0,58 (0,40 – 0,84)

Moderate

Mortality – non-severe CAP

4 / 868

0,95 (0,45 – 2,00)

Moderate

Early clinical failure

6 / 1324

0,40 (0,23 – 0,70)

Moderate

Early clinical failure – severe CAP

5 / 419

0,32 (0,15 – 0,70)

High

Early clinical failure – non severe CAP

2 / 905

0,68 (0,56 – 0,68)

High

Adverse events

3 / 1028

1,21 (0,99 – 1,47)

 

Hyperglycemia

7 / 1578

1,72 (1,38 – 2,14)

 
 
Table 2. Results of the systematic review. Only results for adult patients were considered. Estimates below 1 favor corticosteroids use. CAP: Community Acquired Pneumonia. C.I.: confidence interval.

Comment and conclusions

Results from this systematic review demonstrate a beneficial impact of adjuvant corticosteroids therapy in adult patients hospitalized for pneumonia, with a 34% relative reduction in mortality and a 60% decrease of early clinical failure risk. Efficacy in preventing mortality appears stronger in subject affected by severe pneumonia (Pneumonia Severity Index class IV or higher), disappearing in those presenting with less severe disease (Risk Ratio 0,95 [95% C.I. 0,45 – 2,00]). The beneficial effect on early clinical failure was registered in both the disease severity classes.

Number of patients in the subgroup analysis relative to severe CAP was higher than in previous systematic reviews because additional data from two large RCTs (which originally presented their data only in an aggregate form) were used. Even though using mortality estimates for treatment and control groups in the metanalysis the sample size of the subgroup analysis appears large enough for reaching a study power > 80%, some perplexities remain, related to the heterogeneity of definitions of severity of the patients in the studies, the differences in therapeutic regimens adopted (on average a dose equivalent to 40 – 50 mg of prednisone a day for 5 to 10 days, mainly iv) and the small size of the majority of studies focusing on severe CAP patients.

In conclusion, moderate quality evidence shows that corticosteroid may be useful in the treatment of patients hospitalized with severe CAP. We will see whether future guidelines on pneumonia patients will incorporate these results to modify current recommendations.

Bibliography
  1. Yu H, Rubin J, Dunning S, Li S, Sato R. Clinical and economic burden of community-acquired pneumonia in the Medicare fee-for-service population. J Am Geriatr Soc. 2012; 60:2137-43.
  2. Ross JS, Normand SL, Wang Y, Ko DT, Chen J, Drye EE, Keenan PS, Lichtman JH, Bueno H, Schreiner GC, Krumholz HM. Hospital volume and 30-day mortality for three common medical conditions. N Engl J Med2010; 362:1110-8.
  3. Chen Y, Li K, Pu H, Wu T. Corticosteroids for pneumonia. Cochrane Database Syst Rev 2011; 3: CD007720.
  4. Nie W, Zhang Y, Cheng J, Xiu Q (2012) Corticosteroids in the Treatment of Community-Acquired Pneumonia in Adults: A Meta-Analysis. PLoS ONE 7(10): e47926. 
  5. Shafiq M, Mansoor MS, Khan AA, Sohail MR, Murad MH. Adjuvant Steroid Therapy in Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. J Hosp Med 2013; 8: 68–75.
  6. Cheng M, Pan Z-Y, Yang J, Gao Y-D. Corticosteroid Therapy for Severe Community-Acquired Pneumonia: A Meta-Analysis. Respir Care 2014; 59: 557–563.
  7. Marti C, Grosgurin O, Harbarth S, Combescure C, Abbas M, Rutschmann O, Arnaud Perrier A, Garin N.Adjunctive Corticotherapy for Community Acquired Pneumonia: A Systematic Review and Meta-Analysis. PLoS ONE 2015; 10: e0144032.
  8. Horita N, Otsuka T, Haranaga S, Namkoong H, Miki M, Miyashita N, Higa F, Takahashi H, Yoshida M, Kohno S, Kaneko T. Adjunctive Systemic Corticosteroids for Hospitalized Community-Acquired Pneumonia: Systematic Review and Meta-Analysis 2015 Update. Sci Rep 2015;5: 14061.
  9. Siemieniuk RAC, Meade MO, Alonso-Coello P, Briel M, Evaniew N, Prasad M, Alexander PE, Fei Y, Vandvik PO, Loeb M, Guyatt GH. Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia. A Systematic Review and Meta-analysis. Ann Intern Med 2015; 163: 519-528.
  10. Bi J, Yang J, Wang Y, Yao C, Mei J, Liu Y, Cao J, Lu Y. Efficacy and Safety of Adjunctive Corticosteroids Therapy for Severe Community-Acquired Pneumonia in Adults: An Updated Systematic Review and Meta-Analysis. PLoS ONE 2016; 11: e0165942.
  11. Wan YD, Sun TW, Liu ZQ, Zhang SG, Wang LX, Kan QC. Efficacy and Safety of Corticosteroids for Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis. Chest 2016; 149: 209-19. 
  12. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM, Jr., Musher DM, Niederman MS, Torres A, Whitney CG. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis 2007; 44: S27–72.
  13. Lim WS, Baudouin SV, George RC, Hill AT, Jamieson C, Le Jeune I, Macfarlane JT, Read RC, Roberts HJ, Levy ML, Wani M, Woodhead MA. Pneumonia Guidelines Committee of the BTS Standards of Care Committee. British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009; 64(Suppl III): iii1–iii55. 
  14. National Institute for Health and Care Excellence (2014). Pneumonia in adults: diagnosis and management(NICE Guideline 191). Available at: https://www.nice.org.uk/guidance/cg191[Accessed 09 September 2018].

 

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