Early corticosteroid treatment for severe pneumonia caused by 2009 H1N1 influenza virus

  • Hong-Ryang Kil1,

    Affiliated with

    • Jae-Ho Lee1,

      Affiliated with

      • Kyung-Yil Lee2, 3Email author,

        Affiliated with

        • Jung-Woo Rhim2, 3,

          Affiliated with

          • You-Sook Youn2, 3 and

            Affiliated with

            • Jin-Han Kang3

              Affiliated with

              Critical Care201115:413

              DOI: 10.1186/cc10082

              Published: 22 March 2011

              A pandemic of the 2009 H1N1 influenza A virus infection occurred worldwide in 2009. Some previously healthy patients experienced rapidly progressive pneumonia leading to acute respiratory distress syndrome (ARDS) and even death. The effect of corticosteroids on these severely affected patients is controversial because of a lack of controlled clinical trials [1].

              During the pandemic in South Korea, we observed that early, short-term corticosteroid treatment along with oseltamivir seemed to have a dramatic effect on patients with severe pneumonia, and we proposed a new theory for the pathogenesis of acute lung injury in influenza virus infections [2]. In that study, we wanted to evaluate this beneficial effect of corticosteroid treatment through comparative data based on the use or non-use of corticosteroids at two separate hospitals. The subjects of the study were the pneumonia patients who had severe respiratory distress with hypoxemia at presentation or during admission and who thus required oxygen therapy. The conditions of 17 patients (median of 6 years of age, range of 4 to 9) in our hospital (The Catholic University of Korea, Daejeon St Mary's Hospital, Daejeon, South Korea) (use of corticosteroids) and 15 patients (median of 6 years of age, range of 5 to 18) in a neighboring hospital (Chungnam National University Hospital, Daejeon, South Korea) (non-use of corticosteroids) were diagnosed by reverse transcriptase-polymerase chain reaction. The clinical and laboratory characteristics of patients in the two hospitals are shown in Table 1. Our results suggested that the severe pneumonia patients who were treated with corticosteroids showed shortened durations of fever and oxygen therapy, rapid resolution of pneumonic infiltrations, and possibly no progression to ARDS.
              Table 1

              Clinical and laboratory characteristics of severe pneumonia patients infected with the 2009 H1N1 virus, with and without corticosteroid treatment

              Group

              With steroids (n = 17)

              Without steroids (n = 15)

              P value

              Clinical characteristics

                 

                 Mean age, years

              6.6 ± 1.5

              7.8 ± 3.4

              NS

                 Males/Females, number

              13/4

              12/3

              NS

                 Duration of fever, days

                 

              Before admission

              1.3 ± 0.5

              1.3 ± 0.6

              NS

              Total

              2.1 ± 0.8

              5.8 ± 4.8

              0.009

                 Hospitalization, days

              6.4 ± 1.1

              8.5 ± 7.0

              NS

                 Oxygen treatment, days

              2.5 ± 0.6

              5.1 ± 4.6

              0.04

                 Oseltamivir for less than 48 hours, number (percentage)a

              17 (100)

              13 (93)

              NS

                 Pneumonia, number (percentage)

                 

              Segmental/Lobar

              12 (71)

              13 (87)

              NS

              Progression after admission

              5 (29)

              4 (27)

              NS

                 Intensive care unit care, number (percentage)

              0 (0)

              4 (27)

              0.02

                 ARDS with ventilator, number (percentage)

              0 (0)

              2 (13)

              NS

                 Resolution of pneumonia, number (percentage)b

              15 (88)

              7 (43)

              0.01

              Laboratory findings

                 

                 Hemoglobin, g/dL

              13.1 ± 1.0

              13.2 ± 1.1

              NS

                 Leukocyte, × 109/L

              11.8 ± 3.6

              12.0 ± 5.0

              NS

              Neutrophil, percentage

              83.8 ± 8.0

              86.2 ± 12.9

              NS

              Lymphocyte, percentage

              8.8 ± 6.3

              7.4 ± 7.5

              NS

              Monocyte, percentage

              6.0 ± 2.3

              5.0 ± 3.8

              NS

                 Platelet, × 109/L

              268 ± 74

              246 ± 53

              NS

                 C-reactive protein, mg/dL

              3.0 ± 3.1

              4.6 ± 3.9

              NS

                 Erythrocyte sedimentation rate, mm/hour

              14 ± 8

              15 ± 12

              NS

              Values are presented as mean ± standard deviation unless indicated otherwise. Laboratory findings were obtained at presentation. aNumber (percentage) of patients who received oseltamivir treatment within 48 hours of fever onset. bNumber (percentage) of patients who showed complete resolution of pneumonic infiltrations at discharge. ARDS, acute respiratory distress syndrome; NS, statistically non-specific.

              It is reported that corticosteroid treatment for adult ARDS patients with 2009 H1N1 virus infection was effective in the improvement of lung injury score [3]. Two recent case series suggest a possible life-saving role of corticosteroids in severely ill adult patients with 2009 H1N1 virus infection unresponsive to other treatments [4, 5]. Corticosteroids may not increase the viral load of the patients [4]. To the best of our knowledge, our study may be the first trial addressing an early and preemptive modality before ARDS development in influenza virus infections. Our policy of corticosteroid treatment with a rapid, high-dose (methylprednisolone, 10 mg/kg per day), and short-term (tapered off within a week) schedule did not show any complications in our patients and may avoid the complications that arise from long-term corticosteroid use.

              Although rapid corticosteroid treatment for patients with severe pneumonia halted clinical and radiographic exacerbation and possibly prevented progression to ARDS in our series, further controlled clinical trials are needed to evaluate the role of corticosteroids for severely affected patients with influenza virus infections.

              Abbreviation

              ARDS: 

              acute respiratory distress syndrome.

              Declarations

              Authors’ Affiliations

              (1)
              Department of Pediatrics, School of Medicine, Chungnam National University
              (2)
              Department of Pediatrics, Daejeon St. Mary’s Hospital, The Catholic University of Korea
              (3)
              Department of Pediatrics, College of Medicine, The Catholic University of Korea

              References

              1. World Health Organization: WHO guidelines for pharmacological management of pandemic influenza A (H1N1) 2009 and other influenza viruses. Part II: review of evidence. [http://​www.​who.​int/​csr/​resources/​publications/​swineflu/​h1n1_​guidelines_​pharmaceutical_​mngt_​part2.​pdf]
              2. Lee KY, Rhim JW, Kang JH: Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: a need for early immune-modulators for severe cases. Med Hypotheses 2011, 76:64–69.PubMedView Article
              3. Quispe-Laime AM, Bracco JD, Barberio PA, Campagne CG, Rolfo VE, Umberger R, Meduri GU: H1N1 influenza A virus associated acute lung injury: response to combination oseltamivir and prolonged corticosteroid treatment. Intensive Care Med 2010, 36:33–41.PubMedView Article
              4. Confalonieri M, Cifaldi R, Dreas L, Viviani M, Biolo M, Gabrielli M: Methylprednisolone infusion for life-threatening H1N1-virus infection. Ther Adv Respir Dis 2010, 4:233–237.PubMedView Article
              5. Roberts C, Nirmalan M, O'Shea S: Steroid-sensitive post-viral inflammatory pneumonitis (PVIP). Am J Respir Crit Care Med 2010, 182:1089–1090.PubMed

              Copyright

              © BioMed Central Ltd 2011

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