• Chun-Hua Wang, Fu-Tsai Chung, Shu-Min Lin, Shu-Yi Huang, Chun-Liang Chou, Kang-Yun Lee, Tzou-Yien Lin, and Han-Pin Kuo.
• 1Pulmonary Disease Research Center, Chang Gung Memorial Hospital, Linkou, Chang Gung University, College of Medicine, Taoyuan, Taiwan. 2Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University, College of Medicine, Taoyuan, Taiwan. 3Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 4Department of Thoracic Medicine, Chang Gung Memorial Hospital, Cha-Yi, Taiwan. 5Chang Gung Children's Hospital, Linkou, Taiwan.
• Crit. Care Med.. 2014 Feb 1;42(2):313-21.

ObjectivesSevere 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.DesignOpen-label prospective randomized controlled trial.SettingA tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan.PatientsBetween 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled.Measurements And Main ResultsThirty-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 PaO2/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.ConclusionsIn 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.

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