Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure

Chun Hua Wang, Fu Tsai Chung, Shu Min Lin, Shu Yi Huang, Chun Liang Chou, Kang Yun Lee, Tzou Yien Lin, Han Pin Kuo

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

OBJECTIVES:: Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells. DESIGN:: Open-label prospective randomized controlled trial. SETTING:: A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan. PATIENTS:: Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled. MEASUREMENTS AND MAIN RESULTS:: Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO 2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19 and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment. CONCLUSIONS:: In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.

Original languageEnglish
Pages (from-to)313-321
Number of pages9
JournalCritical Care Medicine
Volume42
Issue number2
DOIs
Publication statusPublished - Feb 2014
Externally publishedYes

Fingerprint

Sirolimus
Respiratory Insufficiency
Pneumonia
Steroids
Mechanical Ventilators
Adrenal Cortex Hormones
Organ Dysfunction Scores
Therapeutics
Viruses
Taiwan
B-Lymphocytes
Randomized Controlled Trials
Demography
T-Lymphocytes
Lung
Mortality

Keywords

  • H1N1
  • Outcomes
  • Rapamycin
  • Respiratory Failure
  • Virus Clearance
  • Virus Pneumonia

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Medicine(all)

Cite this

@article{5fc2afd5ed424668a9c45e51444a02ba,
title = "Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure",
abstract = "OBJECTIVES:: Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells. DESIGN:: Open-label prospective randomized controlled trial. SETTING:: A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan. PATIENTS:: Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled. MEASUREMENTS AND MAIN RESULTS:: Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO 2/FIO2 values on day 3 (167.5 [95{\%} CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95{\%} CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95{\%} CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95{\%} CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95{\%} CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95{\%} CI, 4.8-6.9], n = 19 and 6.2 [95{\%} CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment. CONCLUSIONS:: In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.",
keywords = "H1N1, Outcomes, Rapamycin, Respiratory Failure, Virus Clearance, Virus Pneumonia, H1N1, Outcomes, Rapamycin, Respiratory Failure, Virus Clearance, Virus Pneumonia",
author = "Wang, {Chun Hua} and Chung, {Fu Tsai} and Lin, {Shu Min} and Huang, {Shu Yi} and Chou, {Chun Liang} and Lee, {Kang Yun} and Lin, {Tzou Yien} and Kuo, {Han Pin}",
year = "2014",
month = "2",
doi = "10.1097/CCM.0b013e3182a2727d",
language = "English",
volume = "42",
pages = "313--321",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
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}

TY - JOUR

T1 - Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure

AU - Wang, Chun Hua

AU - Chung, Fu Tsai

AU - Lin, Shu Min

AU - Huang, Shu Yi

AU - Chou, Chun Liang

AU - Lee, Kang Yun

AU - Lin, Tzou Yien

AU - Kuo, Han Pin

PY - 2014/2

Y1 - 2014/2

N2 - OBJECTIVES:: Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells. DESIGN:: Open-label prospective randomized controlled trial. SETTING:: A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan. PATIENTS:: Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled. MEASUREMENTS AND MAIN RESULTS:: Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO 2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19 and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment. CONCLUSIONS:: In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.

AB - OBJECTIVES:: Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells. DESIGN:: Open-label prospective randomized controlled trial. SETTING:: A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan. PATIENTS:: Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled. MEASUREMENTS AND MAIN RESULTS:: Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO 2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19 and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment. CONCLUSIONS:: In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.

KW - H1N1

KW - Outcomes

KW - Rapamycin

KW - Respiratory Failure

KW - Virus Clearance

KW - Virus Pneumonia

KW - H1N1

KW - Outcomes

KW - Rapamycin

KW - Respiratory Failure

KW - Virus Clearance

KW - Virus Pneumonia

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