Lung ultrasound imaging in avian influenza A (H7N9) respiratory failure
© Tsai et al.; licensee Springer. 2014
Received: 10 March 2014
Accepted: 24 April 2014
Published: 20 May 2014
Lung ultrasound has been shown to identify in real-time, various pathologies of the lung such as pneumonia, viral pneumonia, and acute respiratory distress syndrome (ARDS). Lung ultrasound maybe a first-line alternative to chest X-ray and CT scan in critically ill patients with respiratory failure. We describe the use of lung ultrasound imaging and findings in two cases of severe respiratory failure from avian influenza A (H7N9) infection.
Serial lung ultrasound images and video from two cases of H7N9 respiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation in a tertiary care intensive care unit were analyzed for characteristic lung ultrasound findings described previously for respiratory failure and infection. These findings were followed serially, correlated with clinical course and chest X-ray.
In both patients, characteristic lung ultrasound findings have been observed as previously described in viral pulmonary infections: subpleural consolidations associated or not with local pleural effusion. In addition, numerous, confluent, or coalescing B-lines leading to ‘white lung’ with corresponding pleural line thickening are associated with ARDS. Extension or reduction of lesions observed with ultrasound was also correlated respectively with clinical worsening or improvement. Coexisting consolidated pneumonia with sonographic air bronchograms was noted in one patient who did not survive.
Clinicians with access to point-of-care ultrasonography may use these findings as an alternative to chest X-ray or CT scan. Lung ultrasound imaging may assist in the efficient allocation of intensive care for patients with respiratory failure from viral pulmonary infections, especially in resource scarce settings or situations such as future respiratory virus outbreaks or pandemics.
KeywordsUltrasonography Lung ultrasound Influenza A virus H7N9 Viral pneumonia Point-of-care Pandemics Respiratory failure Emergency medicine Critical care medicine
The first human infections with avian influenza A (H7N9) associated with poultry exposure were reported in China in March of 2013. Although mild illnesses have been observed, more concerning are the presentations of severe respiratory failure that have occurred in most cases, of which approximately one-third have resulted in death. No evidence of human-to-human transmission has been found so far. However, a pandemic outbreak of this virus or other similarly lethal viruses such as MERS coronavirus or influenza A (H5N1) with rapid human-to-human spread would constitute a dire public health emergency.
Experiences with prior respiratory virus outbreaks[3–5] have demonstrated that point-of-care lung ultrasound can assist in distinguishing between various acute respiratory pathologies such as pneumonia, viral pneumonia[3–5, 7], and acute respiratory distress syndrome[8–10]. Point-of-care lung ultrasound may be a first-line diagnostic imaging alternative to chest X-ray early in the course of disease or CT scan in critically ill patients that cannot be moved and may be used repeatedly to monitor disease progression or resolution especially in pandemic conditions when time and resources are scarce or overwhelmed.
Our objectives are to describe lung ultrasound findings in two patients with severe respiratory failure from avian influenza A (H7N9) infection, provide clinical pathologic correlation, and to discuss the implications for viral pandemic preparedness.
Avian-origin influenza A (H7N9) virus was confirmed from nasopharyngeal aspirate, throat swab, and pleural fluid by real time reverse transcriptase-polymerase chain reaction. Treatment with intravenous zanamivir 600 mg twice daily was started. Empiric tazobactam/piperacillin and levofloxacin was also given. Her condition improved and she was extubated, and ECMO catheter was removed on day 10. H7N9 virus was found negative from day 9 onwards. A total 7-day course of intravenous zanamivir was completed, followed by prolonged course of oral oseltamivir. Patient was discharged from the intensive care unit on day 18 and was transferred to convalescent hospital for a course of pulmonary rehabilitation 2 weeks later. She was discharged home on day 45.
Ultrasound technique, image analysis, and findings
Serial lung ultrasound (Esaote MyLabFive) with an 11- to 3-MHz linear array transducer was performed on day 16, day 21, and day 24 of case 1's hospital stay. They were performed on hospital days 3 and 4 for case 2. A six-zone scanning protocol was used to image the lungs in perpendicular planes (transverse and coronal or parasagittal) for the anterior, lateral, and posterior lung area "AT the" midclavicular line, midaxillary line and parasaggital line medial to the scapulae. A modified protocol scanning along the midclavicular line, anterior-axillary, and posterior-axillary lines described by Lichtenstein and Meziere was used in case 2 due to critical illness. Lung ultrasound examinations were compared and correlated to the chest radiograph done that day for both patients (Figures 1 and2).
Additional file 1: Video S1. Series of video clips depicting progression of A-lines to B-lines, to confluent B-lines, to white lung (ARDS). (MPEG )
Additional file 2: Video S2. Series of video clips demonstrating sub-pleural consolidations observed in viral pulmonary infections. (MPEG )
Additional file 3: Video S3. Video clip of lung consolidation with sonographic air bronchograms consistent with pneumonia from patient 2. (MPEG )
The development and description of point-of-care lung ultrasonography has been reviewed, and evidence-based recommendations for its use published[11, 14]. Discrete ultrasonographic findings seen in our patients (B lines, confluent B lines, pleural effusion, and most specifically, small subpleural consolidations) have similarly been observed in other viral pulmonary infections such as measles, other influenza A subtypes (H1N1), and respiratory syncytial virus by multiple investigators around the world in pandemic and non-pandemic situations[3–5, 7]. Our second patient had co-existing consolidated pneumonia based on the finding of lung consolidation and air bronchograms visualized by ultrasound[6, 13].
These ultrasonographic findings can be investigated using a high frequency linear transducer as small subpleural consolidations as well as small pleural effusions can be missed with lower frequency curvilinear probes and cannot be visualized by chest X-ray[4, 15, 16]. Larger footprint lower frequency curvilinear (up to 60 mm in length) or microconvex probes can be used to rapidly assess the extent of lung pathology, especially in patients with impending respiratory failure[5, 15]. Interstitial syndrome on ultrasound is visualized as numerous B-lines (at least 3 per field of view)[8, 11, 12]. Acute respiratory distress syndrome (ARDS) is seen as the predominant presence of confluent B lines ( at least >3 B lines per field) or white lung associated with pleural line abnormalities described as thickening (>2 mm) or coarsening, with few spared areas (observation of A lines). Bacterial (consolidated) pneumonia is distinguished from viral (interstitial) pneumonia by ultrasonography visualized as lung consolidations with sonographic air bronchograms, typically larger than 0.5 cm in depth[4, 5, 7, 16, 17].
Our cases were confirmed to have influenza A H7N9 by RT-PCR, where prior research efforts to characterize the diagnostic accuracy of these findings have been hampered by the lack of access to an appropriate or logistically feasible reference gold standard for viral pneumonia[4, 5, 7]. However, it has been noted that these findings have very high interobserver reliability (Cohen's K = 0.82) and can be detected early in the course of disease when chest X-ray may often be normal. Additionally, numbers of viral ultrasound findings have been shown to correlate with disease severity in admitted infants with viral bronchiolitis, with resolution of ultrasound findings as symptoms resolve.
This high interobserver agreement in ultrasonographic findings may promote reduced practice variation in antibiotic or antiviral medication prescribing relative to chest X-ray for improved antibiotic or antiviral medication stewardship. In severe cases, point-of-care lung ultrasound may lead to efficient allocation of resources such as respiratory isolation rooms, ventilatory support, and ECMO. It is unclear if different virus types (e.g., H7N9 vs. H5N1 vs. H1N1 vs. RSV) manifest different patterns in viral lung ultrasonographic findings (relative numbers of B lines, confluent B lines, and small subpleural consolidations). Further investigation into these ultrasound patterns may allow distinguishing between different virus types on the basis of ultrasonographic findings. Autopsies of patients with influenza A (H5N1) virus infection have ‘shown diffuse alveolar damage with hyaline membrane formation, patchy interstitial lymphoplasmacytic infiltrates, bronchiolitis with squamous metaplasia and pulmonary congestion with varying degrees of hemorrhage’. Our second patient had similar findings on postmortem examination (Figure 3). We speculate that these interstitial infiltrates and pulmonary congestion would appear on ultrasound as B lines or confluent B lines (or white lung), with hemorrhage appearing as small subpleural consolidations similar to that observed in our cases and in other viruses.
From a practical and logistical viewpoint of managing large numbers of patients during a pandemic outbreak, point-of-care lung ultrasonographic evaluation can be performed more rapidly, efficiently, and cheaply than chest X-ray. During pandemic overcrowding from 2009 influenza A (H1N1), emergency department volumes quadrupled and waiting times for chest X-ray tripled from a median of 29 to 98 min, contributing to delays for all patients requiring imaging. With reported median lung ultrasound exam times of 6 min, point-of-care ultrasound can be used to reduce ED congestion and is scalable by increasing numbers of portable ultrasound units with clinicians capable of performing lung ultrasound. For patients too critically ill to be transported for CT scan, point-of-care ultrasound is a feasible imaging alternative. A greater concern when evaluating children who are at risk for higher mortality from avian influenza A (H5N1) infection is that ultrasonography avoids radiation exposure that elevates future cancer risk when using chest X-ray or CT scan[20, 21].
Our first patient had all of the sonographic findings (B lines, confluent B lines, small subpleural consolidations, spared areas, and pleural effusion) described for ARDS that were noted to be resolving on serial ultrasonographic examinations with clinical improvement. Our second patient had similar findings with ominous changes in the left upper lobe with normal aeration (A lines) initially, progressing to interstitial syndrome (B lines) or pulmonary congestion (Figure 2C,G) noted on serial lung ultrasounds prior to succumbing. These findings are similar to ultrasound findings described with other influenza A subtypes (H1N1 and seasonal), as well as other viral pulmonary infections[3–5].
Clinicians with access to point-of-care ultrasonography may use these findings as an alternative to chest X-ray or CT scan. Lung ultrasound imaging may help guide triage of resources (e.g., respiratory isolation rooms, ventilators), medical decision-making (e.g. antivirals, antibiotics, fluid administration, or ECMO) and monitor disease progression or resolution with therapy, especially in resource scarce settings or situations such as future respiratory virus outbreaks or pandemics[19, 22].
Written informed consent was obtained from the patient (for case 1) and the patient's next of kin (for case 2) for publication of this report and any accompanying images.
The authors would like to thank the World Interactive Network on Critical UltraSound and Wai Ming Chan, FRCP for fostering this collaboration.
- Gao HN, Lu HZ, Cao B, Du B, Shang H, Gan JH, Lu SH, Yang YD, Fang Q, Shen YZ, Xi XM, Gu Q, Zhou XM, Qu HP, Yan Z, Li FM, Zhao W, Gao ZC, Wang GF, Ruan LX, Wang WH, Ye J, Cao HF, Li XW, Zhang WH, Fang XC, He J, Liang WF, Xie J, Zeng M, et al.: Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med 2013,368(24):2277–2285. 10.1056/NEJMoa1305584View ArticlePubMedGoogle Scholar
- Li Q, Zhou L, Zhou M, Chen Z, Li F, Wu H, Xiang N, Chen E, Tang F, Wang D, Meng L, Hong Z, Tu W, Cao Y, Li L, Ding F, Liu B, Wang M, Xie R, Gao R, Li X, Bai T, Zou S, He J, Hu J, Xu Y, Chai C, Wang S, Gao Y, Jin L, et al.: Epidemiology of human infections with avian influenza A (H7N9) virus in China. N Engl J Med 2014,370(6):520–532. doi:10.1056/NEJMoa1304617. Epub 2013 Apr 24 10.1056/NEJMoa1304617View ArticlePubMedGoogle Scholar
- Volpicelli G, Frascisco M: Sonographic detection of radio-occult interstitial lung involvement in measles pneumonia. Am J Emerg Med 2009,27(1):128.e1–128.e3.View ArticleGoogle Scholar
- Tsung JW, Kessler DO, Shah VP: Prospective application of clinician-performed lung ultrasonography during the 2009 H1N1 influenza A pandemic: distinguishing viral from bacterial pneumonia. Crit Ultrasound J 2012,4(1):16. 10.1186/2036-7902-4-16PubMed CentralView ArticlePubMedGoogle Scholar
- Testa A, Soldati G, Copetti R, Giannuzzi R, Portale G, Gentiloni-Silveri N: Early recognition of the 2009 pandemic influenza A (H1N1) pneumonia by chest ultrasound. Crit Care 2012,16(1):R30. 10.1186/cc11201PubMed CentralView ArticlePubMedGoogle Scholar
- Lichtenstein DA, Lascols N, Mezière G, Gepner A: Ultrasound diagnosis of alveolar consolidation in the critically ill. Intensive Care Med 2004,30(2):276–281. 10.1007/s00134-003-2075-6View ArticlePubMedGoogle Scholar
- Caiulo VA, Gargani L, Caiulo S, Fisicaro A, Moramarco F, Latini G, Picano E: Lung ultrasound in bronchiolitis: comparison with chest X-ray. Eur J Pediatr 2011,170(11):1427–1433. 10.1007/s00431-011-1461-2View ArticlePubMedGoogle Scholar
- Lichtenstein DA, Meziere GA: Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol. Chest 2008,134(1):117–125. 10.1378/chest.07-2800PubMed CentralView ArticlePubMedGoogle Scholar
- Lichtenstein D, Goldstein I, Mourgeon E, Cluzel P, Greier P, Rouby JJ: Comparative diagnostic performances of auscultation, chest radiography, and lung ultrasonography in acute respiratory distress syndrome. Anesthesiology 2004,100(1):9–15. 10.1097/00000542-200401000-00006View ArticlePubMedGoogle Scholar
- Copetti R, Soldati G, Copetti P: Chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome. Cardiovasc Ultrasound 2008, 6: 16. doi:10.1186/1476–7120–6-16 10.1186/1476-7120-6-16PubMed CentralView ArticlePubMedGoogle Scholar
- Volpicelli G, Elbarbary M, Blaivas M, Lichtenstein DA, Mathis G, Kirkpatrick AW, Melniker L, Gargani L, Noble VE, Via G, Dean A, Tsung JW, Soldati G, Copetti R, Bouhemad B, Reissig A, Agricola E, Rouby JJ, Arbelot C, Liteplo A, Sargsyan A, Silva F, Hoppmann R, Breitkreutz R, Seibel A, Neri L, Storti E, Petrovic T: International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med 2012,38(4):577–591. 10.1007/s00134-012-2513-4View ArticlePubMedGoogle Scholar
- Agricola E, Bove T, Oppizi M, Marino G, Zangrillo A, Margonato A, Picano E: Ultrasound comet-tail images: a marker of pulmonary edema. A comparative study with wedge pressure and extravascular lung water. Chest 2005, 127: 1690–1695. 10.1378/chest.127.5.1690View ArticlePubMedGoogle Scholar
- Weinberg B, Diakoumakis EE, Kass EG, Seife B, Zvi ZB: The air bronchogram: sonographic demonstration. AJR Am J Roentgenol 1986,147(3):593–595. 10.2214/ajr.147.3.593View ArticlePubMedGoogle Scholar
- Moore CL, Copel JA: Point-of-care ultrasonography. N Engl J Med 2011,364(8):749–757. 10.1056/NEJMra0909487View ArticlePubMedGoogle Scholar
- Shen P, Zong YM, Shu J, Shi YC, Zhu WJ, Qian HJ, Yang MX, Zhang M: Dynamic assessment of lung injury by ultrasound in a case with H7N9 influenza. Crit Care 2013, 17: 438. 10.1186/cc12751PubMed CentralView ArticlePubMedGoogle Scholar
- Shah VP, Tunik MG, Tsung JW: Prospective evaluation of point-of-care ultrasonography for the diagnosis of pneumonia in children and young adults. JAMA Pediatr 2013,167(2):119–125. 10.1001/2013.jamapediatrics.107View ArticlePubMedGoogle Scholar
- Reissig A, Copetti R, Mathis G, Mempel C, Schuler A, Zechner P, Aliberti S, Neumann R, Kroegel C, Hoyer H: Lung ultrasound in the diagnosis and follow-up of community acquired pneumonia: a prospective, multicenter diagnostic accuracy study. Chest 2012,142(4):965–972. 10.1378/chest.12-0364View ArticlePubMedGoogle Scholar
- Brattain LJ, Telfer BA, Liteplo AS, Noble VE: Automated B-line scoring on thoracic sonography. J Ultrasound Med 2013,32(12):2185–2190. 10.7863/ultra.32.12.2185View ArticlePubMedGoogle Scholar
- Writing committee of the second World Health Organization consultation on clinical aspects of human infection with avian influenza A (H5N1) virus: Current concepts: Update on Avian Influenza A (H5N1) Virus Infection in Humans. N Engl J Med 2008,358(3):261–273.View ArticleGoogle Scholar
- Shu X, Jin F, Linet MS, Zheng W, Clemens J, Mills J, Gao YT: Diagnostic X-ray and ultrasound exposure and risk of childhood cancer. Br J Cancer 1994,70(3):531–536. 10.1038/bjc.1994.340PubMed CentralView ArticlePubMedGoogle Scholar
- Andrieu N, Easton DF, Chang-Claude J, Rookus MA, Brohet R, Cardis E, Antoniou AC, Wagner T, Simard J, Evans G, Peock S, Fricker JP, Nogues C, Van’t Veer L, Van Leeuwen FE, Goldgar DE: Effect of chest X-ray on the risk of breast cancer among BRCA1/2 mutation carriers in the International BRCA1/2 Carrier Cohort Study: a report on the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators’ Group. J Clin Oncol 2006,24(21):3361–3366. 10.1200/JCO.2005.03.3126View ArticlePubMedGoogle Scholar
- Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA: Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012,367(19):1814–1820. 10.1056/NEJMoa1211721View ArticlePubMedGoogle Scholar
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