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DOI:10.2214/AJR.09.3758
AJR 2009; 193:1486-1487
[FONT=arial, helvetica] Conventional Wisdom: Unconventional Virus[/FONT]
[FONT=arial, helvetica] <nobr>Loren H. Ketai<sup>1</sup></nobr> [/FONT] [FONT=arial, helvetica][SIZE=-1] <sup>1</sup> Department of Radiology, University of New Mexico, 1 University of New Mexico, MSC10 5530, Albuquerque, NM 87131-0001. [/SIZE][/FONT]
[FONT=arial, helvetica][SIZE=-1]Received October 6, 2009;[/SIZE][/FONT] [FONT=arial, helvetica][SIZE=-1]accepted after revision October 7, 2009.[/SIZE][/FONT]
<!-- null --> [FONT=arial, helvetica][SIZE=-1]Address correspondence to L. H. Ketai (lketai@unm.edu<script type="text/javascript"><!-- var u = "lketai", d = "unm.edu"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></script>).<sup> </sup>[/SIZE][/FONT]
Keywords: CT imaging ? H1N1 ? S-OIV ? swine-origin influenza A
It is unsettling when clinical observations contradict conventional<sup> </sup>wisdom; three articles in this issue of AJR are unsettling.<sup> </sup>These articles detail imaging findings of patients infected<sup> </sup>with swine-origin influenza A (H1N1), S-OIV [1?3]. The<sup> </sup>patients described in these articles vary widely with respect<sup> </sup>to underlying illnesses, severity of infection, and the point<sup> </sup>in the course of the disease when imaging was performed. Nevertheless,<sup> </sup>the articles are more than sufficient to disrupt assumptions<sup> </sup>about the imaging appearance of novel influenza.<sup> </sup>
While most patients with S-OIV infection were not ill enough<sup> </sup>to require diagnostic imaging of any kind, CT of more severely<sup> </sup>affected patients showed localized groundglass opacities and<sup> </sup>consolidation. In some cases these opacities were subpleural,<sup> </sup>similar to the appearance of opacities seen on CTs performed<sup> </sup>early in the course of severe acute respiratory syndrome (SARS) infections<sup> </sup>[4]. In other patients opacities were observed in a central<sup> </sup>or peribronchovascular distribution. None of the series published<sup> </sup>here describes the findings of small airways disease that are<sup> </sup>commonly associated with viral pulmonary infection. Centrilobular<sup> </sup>nodules, tree-in-bud opacities, and mosaic perfusion were conspicuously<sup> </sup>absent. Nodular consolidation was observed in a few patients,<sup> </sup>but neither size nor distribution of the opacities suggested<sup> </sup>small airways disease.<sup> </sup>
Other emerging diseases have challenged previously held concepts<sup> </sup>about the imaging findings of viral respiratory infections.<sup> </sup>In several of these infections the lack of apparent small airways<sup> </sup>disease is easy to explain. North American Hantaviruses attack<sup> </sup>the lung endothelium rather than the airway epithelium and H5N1<sup> </sup>influenza may preferentially damage alveoli because it binds<sup> </sup>to the epithelium there more tightly than it does in the small<sup> </sup>airways [5]. The lack of small airways disease in SARS is more<sup> </sup>difficult to explain. The SARS organism infects airway epithelium<sup> </sup>but most of its radiologic findings can be attributed to alveolar damage<sup> </sup>caused through cytokine release or, perhaps, by novel mechanisms involving<sup> </sup>angiotensin-converting enzyme.<sup> </sup>
The lack of small airways disease in S-OIV infection is still<sup> </sup>more difficult to explain than the imaging appearance of SARS.<sup> </sup>One explanation would be that our imaging concepts of viral<sup> </sup>lower respiratory tract infections have been overly influenced<sup> </sup>by their appearance in abnormal hosts. In that setting, infections<sup> </sup>with adenovirus, respiratory syncytial virus, metapneumovirus,<sup> </sup>and other pathogens have been associated the presence of centrilobular<sup> </sup>nodules on CT images [6]. A second possibility is that patients<sup> </sup>with S-OIV infections develop small airways disease early in<sup> </sup>the course of the disease and then either improve clinically<sup> </sup>or progress to a different pattern of lung involvement by the<sup> </sup>time they become sufficiently ill to seek medical attention<sup> </sup>(in the Mexico City series, symptoms began approximately 6 days<sup> </sup>before hospital admission) [7]. The peribronchovascular pattern<sup> </sup>in many of these more severely ill patients favors involvement<sup> </sup>of large rather than small airways.<sup> </sup>
The apparent absence of small airways disease is not the only<sup> </sup>unexpected finding related to S-OIV pneumonia. The University<sup> </sup>of Michigan series reports both a high prevalence of obesity<sup> </sup>and a high incidence of pulmonary emboli among its most severely<sup> </sup>affected patients. An association of viral infection and thromboembolic<sup> </sup>disease has been questioned on occasion, including with SARS,<sup> </sup>but is not common [8]. It is possible that the causal association<sup> </sup>is between obesity and severe S-OIV infection, and the increased<sup> </sup>rate of thromboembolic disease a secondary phenomenon related<sup> </sup>to obesity [9]. Similar uncertainty remains about the role of<sup> </sup>bacterial superinfection on the clinical and imaging presentation<sup> </sup>of S-OIV. On the basis of clinical findings (e.g., bronchoalveolar<sup> </sup>lavage), none of these three articles suggests a major role for<sup> </sup>bacterial infection in contributing to imaging abnormalities.<sup> </sup>Recent analysis of postmortem material by the Centers for Disease<sup> </sup>Control, however, identified bacterial infection in approximately<sup> </sup>30% of patients, half due to pneumococcus [10]. The latter findings<sup> </sup>are more congruent with recent evaluation of pathologic specimens from<sup> </sup>the 1918 influenza pandemic that show bacterial superinfection<sup> </sup>to have been the principal cause of mortality.<sup> </sup>
The questions about the role of small airways disease, predilection<sup> </sup>for thromboembolic disease, and bacterial superinfection in<sup> </sup>the setting of S-OIV are important ones. Unfortunately, with<sup> </sup>the approach of the influenza season much more clinical and<sup> </sup>radiologic data are likely to be accrued in the months ahead.<sup> </sup>As those data accumulate we will need to keep an open mind to<sup> </sup>possible imaging presentations and causal associations and not<sup> </sup>be confined by conventional wisdom. Three millennia ago physicians<sup> </sup>realized that experience is treacherous. It remains so today.<sup> </sup>
[SIZE=+1]References[/SIZE]
DOI:10.2214/AJR.09.3758
AJR 2009; 193:1486-1487
[FONT=arial, helvetica] Conventional Wisdom: Unconventional Virus[/FONT]
[FONT=arial, helvetica] <nobr>Loren H. Ketai<sup>1</sup></nobr> [/FONT] [FONT=arial, helvetica][SIZE=-1] <sup>1</sup> Department of Radiology, University of New Mexico, 1 University of New Mexico, MSC10 5530, Albuquerque, NM 87131-0001. [/SIZE][/FONT]
[FONT=arial, helvetica][SIZE=-1]Received October 6, 2009;[/SIZE][/FONT] [FONT=arial, helvetica][SIZE=-1]accepted after revision October 7, 2009.[/SIZE][/FONT]
<!-- null --> [FONT=arial, helvetica][SIZE=-1]Address correspondence to L. H. Ketai (lketai@unm.edu<script type="text/javascript"><!-- var u = "lketai", d = "unm.edu"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></script>).<sup> </sup>[/SIZE][/FONT]
Keywords: CT imaging ? H1N1 ? S-OIV ? swine-origin influenza A
It is unsettling when clinical observations contradict conventional<sup> </sup>wisdom; three articles in this issue of AJR are unsettling.<sup> </sup>These articles detail imaging findings of patients infected<sup> </sup>with swine-origin influenza A (H1N1), S-OIV [1?3]. The<sup> </sup>patients described in these articles vary widely with respect<sup> </sup>to underlying illnesses, severity of infection, and the point<sup> </sup>in the course of the disease when imaging was performed. Nevertheless,<sup> </sup>the articles are more than sufficient to disrupt assumptions<sup> </sup>about the imaging appearance of novel influenza.<sup> </sup>
While most patients with S-OIV infection were not ill enough<sup> </sup>to require diagnostic imaging of any kind, CT of more severely<sup> </sup>affected patients showed localized groundglass opacities and<sup> </sup>consolidation. In some cases these opacities were subpleural,<sup> </sup>similar to the appearance of opacities seen on CTs performed<sup> </sup>early in the course of severe acute respiratory syndrome (SARS) infections<sup> </sup>[4]. In other patients opacities were observed in a central<sup> </sup>or peribronchovascular distribution. None of the series published<sup> </sup>here describes the findings of small airways disease that are<sup> </sup>commonly associated with viral pulmonary infection. Centrilobular<sup> </sup>nodules, tree-in-bud opacities, and mosaic perfusion were conspicuously<sup> </sup>absent. Nodular consolidation was observed in a few patients,<sup> </sup>but neither size nor distribution of the opacities suggested<sup> </sup>small airways disease.<sup> </sup>
Other emerging diseases have challenged previously held concepts<sup> </sup>about the imaging findings of viral respiratory infections.<sup> </sup>In several of these infections the lack of apparent small airways<sup> </sup>disease is easy to explain. North American Hantaviruses attack<sup> </sup>the lung endothelium rather than the airway epithelium and H5N1<sup> </sup>influenza may preferentially damage alveoli because it binds<sup> </sup>to the epithelium there more tightly than it does in the small<sup> </sup>airways [5]. The lack of small airways disease in SARS is more<sup> </sup>difficult to explain. The SARS organism infects airway epithelium<sup> </sup>but most of its radiologic findings can be attributed to alveolar damage<sup> </sup>caused through cytokine release or, perhaps, by novel mechanisms involving<sup> </sup>angiotensin-converting enzyme.<sup> </sup>
The lack of small airways disease in S-OIV infection is still<sup> </sup>more difficult to explain than the imaging appearance of SARS.<sup> </sup>One explanation would be that our imaging concepts of viral<sup> </sup>lower respiratory tract infections have been overly influenced<sup> </sup>by their appearance in abnormal hosts. In that setting, infections<sup> </sup>with adenovirus, respiratory syncytial virus, metapneumovirus,<sup> </sup>and other pathogens have been associated the presence of centrilobular<sup> </sup>nodules on CT images [6]. A second possibility is that patients<sup> </sup>with S-OIV infections develop small airways disease early in<sup> </sup>the course of the disease and then either improve clinically<sup> </sup>or progress to a different pattern of lung involvement by the<sup> </sup>time they become sufficiently ill to seek medical attention<sup> </sup>(in the Mexico City series, symptoms began approximately 6 days<sup> </sup>before hospital admission) [7]. The peribronchovascular pattern<sup> </sup>in many of these more severely ill patients favors involvement<sup> </sup>of large rather than small airways.<sup> </sup>
The apparent absence of small airways disease is not the only<sup> </sup>unexpected finding related to S-OIV pneumonia. The University<sup> </sup>of Michigan series reports both a high prevalence of obesity<sup> </sup>and a high incidence of pulmonary emboli among its most severely<sup> </sup>affected patients. An association of viral infection and thromboembolic<sup> </sup>disease has been questioned on occasion, including with SARS,<sup> </sup>but is not common [8]. It is possible that the causal association<sup> </sup>is between obesity and severe S-OIV infection, and the increased<sup> </sup>rate of thromboembolic disease a secondary phenomenon related<sup> </sup>to obesity [9]. Similar uncertainty remains about the role of<sup> </sup>bacterial superinfection on the clinical and imaging presentation<sup> </sup>of S-OIV. On the basis of clinical findings (e.g., bronchoalveolar<sup> </sup>lavage), none of these three articles suggests a major role for<sup> </sup>bacterial infection in contributing to imaging abnormalities.<sup> </sup>Recent analysis of postmortem material by the Centers for Disease<sup> </sup>Control, however, identified bacterial infection in approximately<sup> </sup>30% of patients, half due to pneumococcus [10]. The latter findings<sup> </sup>are more congruent with recent evaluation of pathologic specimens from<sup> </sup>the 1918 influenza pandemic that show bacterial superinfection<sup> </sup>to have been the principal cause of mortality.<sup> </sup>
The questions about the role of small airways disease, predilection<sup> </sup>for thromboembolic disease, and bacterial superinfection in<sup> </sup>the setting of S-OIV are important ones. Unfortunately, with<sup> </sup>the approach of the influenza season much more clinical and<sup> </sup>radiologic data are likely to be accrued in the months ahead.<sup> </sup>As those data accumulate we will need to keep an open mind to<sup> </sup>possible imaging presentations and causal associations and not<sup> </sup>be confined by conventional wisdom. Three millennia ago physicians<sup> </sup>realized that experience is treacherous. It remains so today.<sup> </sup>
[SIZE=+1]References[/SIZE]
- <!-- null -->
- Agarwal PP, Cinti S, Kazerooni EA. Chest radiographic and CT findings in novel swine-origin influenza A (H1N1) virus (S-OIV) infection. AJR 2009; 193:1488 ?1493<!-- HIGHWIRE ID="193:6:1486:1" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
- Ajlan AM, Quiney B, Nicolaou S, M?ller NL. Swine-origin influenza A (H1N1) viral infection: radiographic and CT findings. AJR 2009; 193:1494 ?1499<!-- HIGHWIRE ID="193:6:1486:2" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
- Mollura DJ, Asnis DS, Conetta R, et al. Imaging findings in a fatal case of pandemic swine-origin influenza A (H1N1). AJR2009; 193:1500 ?1503<!-- HIGHWIRE ID="193:6:1486:3" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
- Ketai L, Paul N, Wong K. Radiology of severe acute respiratory syndrome (SARS): the emerging pathologic?radiologic correlates of an emerging disease. J Thorac Imaging 2006;21 : 276?283<!-- HIGHWIRE ID="193:6:1486:4" -->[CrossRef][Medline]<!-- /HIGHWIRE --><!-- null -->
- van Riel D, Munster V, de Wit E, et al. Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals. Am J Pathol 2007;171 :1215 ?1223<!-- HIGHWIRE ID="193:6:1486:5" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
- Franquet T, Rodriguez S, Martino R, Gim?nez A, Salinas T, Hidalgo A. Thin-section CT findings in hematopoietic stem cell transplantation recipients with respiratory virus pneumonia. AJR2006; 187:1085 ?1090<!-- HIGHWIRE ID="193:6:1486:6" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
- Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009;361 : 680?689<!-- HIGHWIRE ID="193:6:1486:7" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
- Ng KH, Wu A, Cheng C, et al. Pulmonary artery thrombosis in a patient with severe acute respiratory syndrome. Postgrad Med J 2005; 81:e3<!-- HIGHWIRE ID="193:6:1486:8" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
- Kabrhel C, Varraso R, Goldhaber S, Rimm EB, Camargo C. Prospective study of BMI and the risk of pulmonary embolism in women. Obesity (16 April 2009). www.nature.com/oby/journal/vaop/ncurrent/full/oby200992a.html. Accessed October 8, 2009<!-- HIGHWIRE ID="193:6:1486:9" --><!-- /HIGHWIRE --><!-- null -->
- Centers for Disease Control and Prevention. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1)?United States, May?August 2009. MMWR Morb Mortal Wkly Rep 2009; 58:1071 ?1074<!-- HIGHWIRE ID="193:6:1486:10" -->[Medline]