Viral Threat on Respiratory Failure Younsuck Koh, MD, PhD, FCCM Department of Pulmonary and Critical Care Medicine Asan Medical Center University of Ulsan College of Medicine Seoul, Korea
No Conflict of Interest related to this topic
A Major Cause of Unknown RF with MV 512 mechanically ventilated pts in 14 studies. Virus was most common cause of infection (42/84; CMV, Influenza, HSV, Adenovrius) Wong AK & Walkey AJ. Ann Am Thorac Soc 2015;12:1226-30
Respiratory Viruses in ICUs The emergence of different clinical manifestation Requiring ECMO
Virus solely causes LRTI Shieh W-J, et al, Am J Pathol 2010
2009 Pandemic Influenza A (H1N1): Pathology and Pathogenesis of 100 Fatal cases in the United States DAD; most significant & consistent finding - viral antigens : predominantly in the lung parenchyme - a high amount of viral Ag observed in close association with DAD Also showed viral Ag in trachea, bronchi, or bronchioles target both upper and lower respiratory tract tissue Shieh W-J, et al, Am J Pathol 2010
Viral causes seem to be popular in bilateral lung infiltrates. Results in inappropriate Abs use, if not considered
198 (CAP 64, HCAP 134) in AMC Bronchoscopic bronchoalveolar lavage: 58.1% (115/198) 8
Similar detection rate bwt CAP & HCAP In severe pn requiring ICU care (AMC experience) Identified organism Total (n = 198) CAP (n = 64) HCAP (n = 134) P value None 65 (32.8) 16 (25.0) 49 (36.6) 0.11 Bacteria 71 (35.9) 22 (34.4) 49 (36.6) 0.87 Virus 72 (36.4) 26 (40.6) 46 (34.3) 0.43 Rhinovirus 17 (8.6) 4 (6.3) 13 (9.7) 0.59 Parainfluenza virus 15 (7.6) 3 (4.7) 12 (9.0) 0.39 hmpv 13 (6.6) 5 (7.8) 8 (6.0) 0.76 Influenza virus 12 (6.1) 6 (9.4) 6 (4.5) 0.21 RSV 10 (5.1) 7 (10.9) 3 (2.2) 0.01 CMV 8 (4.0) 0 8 (6.0) 0.056 CoV OC43 4 (2.0) 3 (4.7) 1 (0.7) 0.10 Adenovirus 1 (0.5) 1 (1.6) 0 0.32 Enterovirus 1 (0.5) 0 1 (0.7) 1.00 CAP = community-acquired pneumonia; HCAP = healthcare-associated pneumonia Choi SH et al. Am J Respir Crit Care Med. 2012;186:325-32
Similar MR In severe pn requiring ICU care (AMC experience) 35% P = 0.82 30% 25% 20% 15% 10% 5% 25.5% 26.5% 33.3% 0% Bacteria Virus Bacteria + virus Choi SH et al. Am J Respir Crit Care Med. 2012;186:325-32
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Clinical Significance of Rhinovirus in Viral Pn. Rhinovirus - The predominant cause of the common cold - The most frequent virus to exacerbate COP - HRV-C seems to be associated with more severe RF in children
M/73, Farmer 40 PY ex-smoker BAL: rhinovirus PCR+ Expired Rhinovirus 13
F/35 27 weeks pregnant woman NP PCR+ Survived Rhinovirus 14
Rhinovirus infection (+) COPD Rhinovirus with Rhinovirus(+) infection (-) Mallina P, et al. Am J Respir Crit Care Med 2012: 186; 1117-1124
Rhinovirus Severity of Human Rhinovirus Infection in Immunocompromised Adults Is Similar to That of 2009 H1N1 Influenza Kraft CS, et al. JCM. 2012;50:1061-3
Rhinovirus vs. Influenza virus Mar 2010 ~ Feb 2014 in AMC Factor Immunocompromised state Rhinovirus (n=27) Influenza virus (n=51) P value 81.5% 33.3% < 0.001 Viral co-infection 29.6% 11.8% 0.07 Bacterial co-infection 18.5% 37.3% 0.09 Shock at admission 29.6% 54.9% 0.03 28-day mortality 29.6% 35.3% 0.61 In-hospital mortality 55.6% 51.0% 0.70 17
Perennial distribution 18
Parainfluenza virus Factor Non-immunocompromised vs. Immunocompromised Mar 2010 ~ Oct 2013 in AMC Non-IC (n=25) IC (n=32) P value Mean age 71.9 yr 56.5 yr < 0.001 Hematologic malignancy 0 59.4% < 0.001 COPD 20.0% 0 0.01 CAP 44.0% 0 < 0.001 HCAP 36.0% 37.5% 0.91 HAP 20.0% 62.5% < 0.001 Coinfection 40.0% 43.8% 0.78 28-day mortality 8.0% 50.0% 0.001 In-hospital mortality 21.7% 68.8% 0.001 19
M/62 Fever and Cough s/p Kidney Transplanted MSSA with Parainfluenza
F/30 1 st pregnancy with 30 weeks gestation Influenza type A, at ER and 1 & half days later Influenza A
RSV PCR confirmed respiratory syncytial virus infections (n = 123) in Hong Kong - Respiratory insufficiency (52.8%), requirement for assisted ventilation (16.3%), and ICU admission/death at 60 days (12.2%/13.8%). - Nearly all (98.4%) hospitalized RSV patients had received initial antibiotics and 35.8% received systemic corticosteroid treatment. Lee N, et al. JID 2015;21:1237-40 22
Zoonotic Viral Threat on Resp. Failure - Hantaviruses by rodents - Dengue (the Flavirididae family) by Mosquitoes - Ebolar virus (Filoviridae family) by a monkey - Coronavirues: SARS by a bat (?), MERS by camel
MERS Epidemic in Korea 7 days June 7 th, 2015 40 yr N=14 35 yr 7 days N=34
Clinical Manifestations of Viral Pneumonia Prodromal sx: Rhinorrhea Absence of purulent sputum Diffuse infiltration Bilaterality Ground-glass opacity Centrilobular nodules Interstitial pneumonitis 26
Co-infection is not rare 2ndary bacterial infection followed by viral infection - 2009 H1N1: 4-24% Concomitant virus-bacterial infection - 14-15 % in reported 2 CAP studies - rhino/s. pn, influenza A/S. pn, influenza/s. aureus Concomitant viruses infection - two viruses identified; 9 among 63 pts (14%) in our study* *Choi SH et al. Am J Respir Crit Care Med. 2012;186:325-32
How to diagnose viral pn? Pneumonia Bacterial/Fungal Viral Mixed Age Epidemics, seasonality Sx & signs Labs Culture CRP/WBC/CXR pattern Procalcitonin
Seasonality Choi SH et al. Am J Respir Crit Care Med. 2012;186:325-32
Usual Approach with CXR infiltrates with RF in ICU Lung infiltrate with RF Pneumonia Unilateral Bilateral
Usual Approach with Bilateral Infiltrate Bilateral lung infiltrate with Pn. Noninfectious Edema, Hemorrhage Toxic Immunologic Others
Usual Approach with Bilateral Infiltrate Bilateral lung infiltrate with Pn. Noninfectious CAP/HCAP Opportunistic Severity Influenza CMV
Recent Advance in Molecular Diagnostic Technology Pneumonia Bacterial/Fungal Viral Mixed Age Epidemics, seasonal Sx & signs Labs Culture CRP/WBC/CXR pattern Procalcitonin RT-PCR (BAL, nasopharyngel specimen)
Needs BAL? concordance *N: nasopharyngeal specimen, B: BAL specimen Only + in BAL specimen: about 15% among 94 + cases in AMC data. 34
PREDICTORS FOR THE DIAGNOSIS OF BACTERIAL PNEUMONIA compared with viral pn in matched cases Choi SH et al. J Clin Microbiol 2015; 53:1310-6
Prevention Obligate airborne - TB Preferential or obligate airborne - measles, smallpox Opportunistic airborne -SARS-CoV, MERS-CoV? the aerosol becomes so dilute as it travels away from the source that most secondary infections occur in the immediate vicinity of the index patient a dilute aerosol mimics that expected with large-droplet or surface contact it should be also not be dismissed out of hand. Roy CJ, et al. NEJM 2004;350:1710-2
Lessons, you may already know: Appropriate use of personal protective equipment (Gown-Mask- Goggles-Gloves) From CDC KCDC
Treatments Neuraminidase inhibitors: oseltamivir, zanamivir M2 ion channel blockers: amantadine or rimantadine Antivirals for Treatment of Influenza A Systematic Review and Meta-analysis of Observational Studies J Hsu, et al. Ann Intern Med. 2012;156:512-524.
Role of Steroid in Viral Pn.
Steroid therapy seems to be harmful in H1N1 virus pneumonia without steroid with steroid Kim SH, et al. Am J Respir Crit Care Med 2011 ;183:1207-14
Empirical Antibiotics Use 36 fatal children analysis 10 of 23 pts with culture results (43%) detected bacterial infection 5 S. aureus 3 pneumococcus 1 S. pyogenes, 1 S. constellatus Empiric antibacterial therapy, when indicated, should be directed at likely
DK Oh, et al. J Crit Care 2013
PRONE POSITIONING
Referral to an Extracorporeal Membrane Oxygenation Center and Mortality Among Patients With Severe 2009 Influenza A (H1N1). Noah et al. JAMA 2011 36(15):1659 Non-ECMO-referred Pts (85 hospitals) VS. ECMO-referred Pts (UK ECMO centers) H1N1-related ARDS by matching patients
Conclusion Significant? Truly, significant problem.
Conclusion The emergence of new subtype viruses enhanced intensivists awareness about viral pn. Viral cause is not rare in severe RF with pn even in HCAP. Molecular diagnostic methods improved our understanding about viral pn. Needs of a Global Collaboration in case of global viral epidemics Further studies are needed to address questions.