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Clinical Perspective |
1 All authors: Department of Radiology, Vancouver General Hospital, University of British Columbia, 855 W 12th Ave., Vancouver, BC, Canada V5Z 1M9.
Received September 13, 2009; accepted after revision October 3, 2009.
Address correspondence to A. M. Ajlan
(amrajlan{at}yahoo.com).
OBJECTIVE. The objective of our study was to review the chest radiographic and CT findings in patients with swine-origin influenza A (H1N1) virus (S-OIV) infection.
CONCLUSION. The most common radiographic and CT findings in seven patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On MDCT, the ground-glass opacities and areas of consolidation had a predominant peribronchovascular and subpleural distribution, resembling organizing pneumonia.
Keywords: CT • emergency medicine • ground-glass opacity • H1N1 • infectious diseases • organizing pneumonia • radiography • swine-origin influenza A • viral infections
Swine influenza is a highly contagious acute respiratory disease of pigs caused by a subtype of influenza A virus [1]. In the spring of 2009, multiple cases of human-to-human transmission caused by a subtype known as H1N1 were documented. The disease has spread rapidly since then, with 254,206 cases having been documented worldwide as of September 7, 2009, and an estimated 2,837 deaths [2]. A level 6 pandemic was raised by the World Health Organization [3].
Patients with swine-origin influenza A virus (S-OIV) infection typically present with fever, cough, sore throat, chills, headache, rhinorrhea, shortness of breath, myalgias, arthralgias, fatigue, vomiting, or diarrhea [4]. Most patients have mild illness, but a small percentage of patients have a severe course that may result in respiratory failure and death [2, 4]. Laboratory findings in patients with S-OIV include lymphopenia, elevated serum lactate dehydrogenase level, and increased serum creatine kinase level [5]. Thrombocytopenia has been observed in a small number of cases [5].
The description of the radiologic manifestations of S-OIV has been limited to a few case reports [5–7]. The reported findings were those of unilateral or bilateral; focal, multifocal, or diffuse; ground-glass opacities, consolidation, or interstitial markings [5–7]. Some cases had a predominant basal or axial distribution [5, 7]. The resemblance of the radiographic appearance of S-OIV with that of severe acute respiratory syndrome (SARS) has been raised [7]. In one report, the radiographs suggested the presence of mediastinal lymphadenopathy [6]. The aim of this study was to review the chest radiographic and CT findings in seven patients with confirmed S-OIV.
Materials and Methods
Subjects
Approval for this study was obtained from the institutional clinical
research ethics board. Because the study was retrospective, informed consent
was waived. We retrospectively reviewed the electronic archive of the
infection control department at our hospital for cases in which the results of
real-time reverse transcriptase polymerase chain reaction (RT-PCR) of nasal
swabs or aspirates were positive for S-OIV. The respiratory samples were
initially collected, processed, and tested using real-time RT-PCR according to
the guidelines of the Centers for Disease Control and Prevention (CDC)
[8,
9]. Our search yielded eight
cases of S-OIV, but only seven patients had undergone chest imaging. All seven
patients had initially presented with an influenzalike illness, thereby
fulfilling the clinical criteria for diagnosing S-OIV infection as established
by the CDC [10].
Our study group of patients consisted of six males and one female ranging in age from 16 to 73 years (median age, 43 years). One of the seven patients had no significant medical history. The remaining six patients had one or more underlying comorbidities, which included asthma (n = 1), multiple myeloma with previous stem cell transplantation (n = 1), sickle cell anemia and glucose-6-phosphate dehydrogenase deficiency (n = 1), hypertension (n = 2), diabetes (n = 2), coronary artery disease (n = 2), renal transplantation after renal failure due to Alport syndrome (n = 1), single lung transplantation for idiopathic pulmonary fibrosis (IPF) (n = 1), inflammatory bowel disease (n = 1), and long-term steroid treatment (n = 2). Five of the seven patients had lymphopenia (absolute lymphocyte count < 1.0 x 103/L) on presentation or during hospitalization. Neutrophil and platelet counts were normal in all seven patients. In four of the seven patients, serum lactate dehydrogenase levels were elevated (> 210 U/L) on presentation or during hospitalization. Creatine kinase levels were not obtained on any of the seven patients. Blood and sputum cultures were negative for organisms in all seven patients.
Two of the seven patients were observed for a few hours in the emergency department and were then discharged with instructions to continue supportive treatment. The remaining five patients were hospitalized, with the duration of hospital stay ranging from 3 to 29 days (median duration, 12 days). Two patients required intubation and mechanical ventilation. One of these two patients improved after receiving antiviral therapy with oseltamivir, whereas the second patient, who had a previous unilateral lung transplant, died in the hospital after a 17-day-long complicated course. The remaining three of five hospitalized patients improved with no need for intubation and mechanical ventilation. Of this latter group, only two of three were treated with oseltamivir during their hospital stay.
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Posteroanterior- and lateral-projection radiographs were obtained using a Multix unit (Siemens Healthcare). A technique of 90 kV, 4 mAs, and 180-cm film–focus distance was used for the posteroanterior-projection radiographs. The same technique was used for the lateral-projection radiographs except that the tube current setting was 12 mAs instead of 4 mAs. Bedside anteroposterior-projection radiographs were obtained with a mobile unit (AMX 4, GE Healthcare) using 90 kV, 4 mAs, and a 100-cm film–focus distance.
Thin-section MDCT was performed in three of the seven patients, all of whom were hospitalized. Two patients underwent MDCT on admission, whereas the remaining patient underwent scanning within 24 hours after admission. One of the three patients had a repeat MDCT scan 12 days after the initial study. The studies were performed on a 64-MDCT scanner (Definition, Siemens Healthcare). The protocol used was as follows: end-inspiratory acquisition, 120 kV, 150–200 mAs, and 1-mm reformation. The images were viewed on both lung (window width, 1,500 HU; level, –700 HU) and mediastinal (window width, 350 HU; level, 40 HU) settings. One patient received IV contrast medium for the initial CT examination because of clinical suspicion of pulmonary embolism. All the other CT studies were unenhanced.
Image Analysis
Two experienced radiologists reviewed the radiographs and MDCT scans
independently and reached a decision on the final interpretations by
consensus. All images were reviewed on a PACS workstation. The radiographs and
CT scans were assessed for the presence of ground-glass opacities,
consolidation, nodular opacities, tree-in-bud pattern, septal lines, and
reticular opacities. The presence of associated hilar, mediastinal, or pleural
abnormalities was also assessed. Ground-glass opacities were defined as hazy
areas of increased opacity or attenuation without obscuration of the
underlying vessels. Consolidation was defined as homogeneous opacification of
the parenchyma with obscuration of the underlying vessels. Nodular opacities
were defined as focal round opacities. Reticular opacities were defined as
linear opacities forming a meshlike pattern.
The involvement was categorized as unilateral or bilateral. If the involvement was deemed bilateral, the process was categorized as symmetric or asymmetric in nature. The distribution was categorized as focal, multifocal, and diffuse. Focal was defined as a single focus of abnormality, multifocal as more than one focus, and diffuse as involving the volume of one lung. Predominant distribution was also assessed as being in the upper, middle, or lower lung zone and as being in a random, predominantly central or peribronchovascular, or subpleural location.
Results
The initial chest radiograph was normal in four of the seven patients (Table 1). In one of those four patients, the follow-up radiograph 2 days later showed the development of bilateral symmetric lower lobar ground-glass opacities and consolidations. Another patient, known to have a remote left lung transplant for IPF, showed the development of extensive diffuse ground-glass opacities and poorly defined multifocal areas of consolidation in the transplanted lung 10 days after the initial radiograph (Fig. 1A). In the remaining two of four patients, one had no follow-up imaging, and the other had a normal radiograph 1 day later.
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Three patients had abnormal findings on the initial radiograph (Table 1). One patient had faint ground-glass opacities in the lower zone of the right lung (Fig. 2A). This case progressed to involve the middle zone of the right lung and showed superimposition of poorly defined multifocal areas of consolidation in the lower zone of the same lung on the follow-up radiograph 2 days later (Fig. 2B). Another patient showed initial extensive bilateral ground-glass opacities and poorly defined areas of consolidation. The ground-glass opacities were diffuse on the right side and involved the middle and lower zones on the left side. This patient had minimal increase in the consolidation at the right base on the 1-day follow-up radiograph. The third patient showed initial bilateral poorly defined hazy increase in density (ground-glass opacities), which had increased in severity on the 2-day follow-up radiograph and become associated with new extensive consolidation and volume loss of the left lower lobe (Fig. 3A, 3B).
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Discussion
S-OIV is transmitted in a manner similar to that of seasonal human influenza viruses, which includes person-to-person large-particle respiratory droplet transmission produced by coughing or sneezing or touching contaminated surfaces [4]. The incubation period is estimated to range from 1 to 7 days [4]. The patient is considered infectious 1 day before and 7 days after the onset of symptoms [4, 11]. The most common clinical findings at presentation are fever, cough, dyspnea, and respiratory distress [4, 5]. Most cases are mild and self-limited; however, S-OIV infection in high-risk patients is more likely to have severe and complicated courses [4, 11]. The high-risk group includes children younger than 5 years old, adults 65 years old or older, patients with chronic underlying conditions (e.g., asthma, diabetes, cardiac disease, renal disease, neurocognitive disease, and neuromuscular disorders), and immunosuppressed patients [4, 5, 11]. The time from hospitalization to the need for mechanical ventilation might be as short as 24 hours or less [5]. Up to the time of writing this article, no vaccine has become available to protect against S-OIV. However, the preparation of such a vaccine is currently under production [11]. Oseltamivir phosphate (Tamiflu, Roche Laboratories) and zanamivir (Relenza, GlaxoSmithKline) are considered effective medications against the S-OIV infection [10, 11].
Our radiographic findings—that is, ground-glass opacities and consolidations in most patients—corroborate those in previous preliminary reports [5–7]. However, hazy areas of increased opacity without obscuration of the underlying vessels (ground-glass opacities) were by far the most common finding in our group of patients, being more commonly bilateral (n = 3) than unilateral (n = 2). In our group, four patients also had a normal initial radiographic appearance, one of which remained normal on the 24 hours follow-up. Normal-appearing radiographs in the setting of mild or even severe S-OIV illness have been previously reported [12, 13]. We also noted that none of our patients showed a reticular or nodular pattern on the initial or follow-up radiographs. Another observation in our patients was that the progression of radiographic abnormalities was mostly in the form of developing multifocal areas of consolidation on follow-up.
In all the patients with abnormal radiographic findings, the MDCT study showed more extensive involvement. In addition, MDCT was superior to radiography in showing the distribution of the disease. Again, ground-glass opacities with multifocal consolidation were the predominant findings in our group of patients. An interesting observation on the MDCT scans was the distinctive peribronchovascular (n = 3) and peripheral (n = 2) distribution of the disease. This appearance is similar to that seen in cases of organizing pneumonia [14].
The similarity of radiographic findings in cases of S-OIV and in cases of SARS has been previously raised [7]. We also noted that similarity in our group of patients. In particular, both diseases had ground-glass opacities as the predominant radiographic finding [15]. We found that this was also true on the MDCT studies. In addition, both diseases showed no centrilobular nodules, tree-in-bud pattern, or enlarged mediastinal or hilar lymph nodes [15, 16].
Our study has several limitations. First, it is a retrospective study that includes only a small number of cases. Second, only three of the seven patients had MDCT correlation. Finally, none of the patients underwent lung biopsy or autopsy that would have allowed radiographic–histopathologic correlation.
In conclusion, the most common radiographic and MDCT findings in patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On MDCT, the ground-glass opacities and areas of consolidation had a predominant peribronchovascular and subpleural distribution that resembled the appearance of organizing pneumonia.
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