Novel influenza A (H1N1) is a new, swine-origin virus first described in 2009 and has become the current dominant strain, as of late 2009 eclipsing seasonal influenza virus in frequency [8
]. Although the most high-risk groups appear to be younger patients [2
] and pregnant women [10
], immunocompromised patients accounted for almost 20% of adult patients hospitalized with novel influenza A (H1N1) [5
]. The mortality rate associated with novel H1N1 influenza is also not clear; however, in one study, 6.5% (58/899) of admitted patients had severe illness, and of those with severe disease, 41.4% died of the infection [11
]. The CT findings of novel influenza A (H1N1) have not been well described. The goal of this paper is to delineate the CT findings of this infection in a series of immunocompromised patients.
In our study, the most common CT findings of novel influenza A (H1N1) included airway thickening/dilatation, peribronchial or diffuse ground glass opacity, peripheral consolidation involving the lower lobes, and centrilobular nodules. In all but one patient, the distribution of findings was closely associated with large and/or small airways.
Two case series have previously described the CT findings of novel influenza A (H1N1). The first of these papers [12
] primarily considered the chest radiographic findings of novel influenza A (H1N1) infection and the presence of pulmonary emboli in patients with severe disease. CTs in these patients revealed diffuse GGO and consolidation and nodular opacities. The demographics of most patients in this study were not reported. The other paper [13
] described the findings of novel influenza A (H1N1) in a series of seven patients, three of which had CT scans. Most patients demonstrated patchy ground glass opacity and consolidation with a peribronchovascular and subpleural distribution, resembling organizing pneumonia. Most of the patients in this study had comorbidities (e.g., diabetes, hypertension, and lung transplant), but in general, the degree of immunocompromise was much less compared to the patients in our study.
There are several important differences that distinguish our paper. First, all of our patients were immunocompromised, and all but one were being treated with immunosuppressive regimes for transplant or chemotherapy. The CT abnormalities in our study seemed much less severe than those in the aforementioned papers. It is likely there is a lower threshold for imaging immunocompromised patients, even those with mild or non-specific symptoms. Thus, CT imaging is likely obtained closer to the onset of clinical symptoms in the typical immunocompromised patient. Second, it is well known that viral infection commonly produces extensive regions of either diffuse or localized diffuse alveolar damage (DAD) in late stage cases. It is likely that DAD accounts for a significant component of the CT findings of patchy or extensive ground glass opacity and consolidation reported in other studies. It is possible that immunocompromised patients, at least initially, do not develop the same inflammatory response to infection as immunocompetent patients, resulting in less extensive DAD. It is interesting that the patient in our study with the most extensive ground glass opacity and consolidation had significantly less immunocompromise than the remainder of patients.
One CT feature that is unique to our study is the small airway involvement as manifested by centrilobular nodules and tree-in-bud opacities. Three of eight patients demonstrated centrilobular nodules on their initial CT scan, and one of these showed tree-in-bud opacities. One additional patient developed centrilobular nodules and another tree-in-bud opacities on an interval follow-up CT. These small airway findings were distinctly absent in the two other series. It is possible that these small airways abnormalities are obscured later in the disease process when more extensive DAD is present.
Last, we detected two patients with novel influenza A (H1N1) who demonstrated findings that could easily be confused with bacterial infection. One patient showed patchy, soft tissue centrilobular nodules with segmental consolidation in the lower lobes resembling a bronchopneumonia. Another patient demonstrated focal right upper lobe consolidation that could be confused with a lobar pneumonia. It is very clinically relevant to understand the spectrum of CT findings of novel influenza A (H1N1) including atypical cases. It is likely that a certain percentage of cases will have an appearance not typical of viral infection.
The CT findings of viral infection in general are numerous with previously reported studies demonstrating a myriad of different findings including: consolidation, ground glass opacity, interlobular septal thickening, centrilobular nodules, airway thickening, and air trapping/mosaic perfusion [14
]. These findings often overlap with those of other infections such as bacterial, fungal, and mycobacterial disease [16
]. Thus, the imaging findings are often non-specific with regards to the offending organism, although CT may be helpful in distinguishing bacterial from atypical organisms [17
The CT findings of influenza described prior to the emergence of the novel H1N1 strain have not been well documented as most studies have included only a small number of patients or have focused on chest X-rays. The larger studies performed using CT have primarily shown a pattern of extensive or diffuse bilateral GGO and consolidation [18
Our findings are consistent with prior studies of viral infection that have specifically analyzed immunosuppressed patient populations. For instance, Kanne et al. demonstrated that the most common CT findings in patients with viral pneumonias in the setting of hematopoetic stem cell transplant were poorly defined centrilobular nodules, and bilateral peribronchial GGO and consolidation [21
]. Another study evaluating viral infection in hematopoetic transplant patients, which included five patients with influenza pneumonia, showed that the most common findings were patchy bilateral ground glass opacities, nodules, and thickening of the bronchovascular bundles [22
]. In a study looking specifically at influenza infection in the setting of immunosuppression, all three patients who underwent chest CT imaging had GGO, consolidation, and centrilobular nodules with tree-in-bud opacities [23
Also of interest in our study was the diffuse nature of findings in the majority of patients. A diffuse distribution on imaging is very commonly seen in viral and atypical infections [16
]. It is important to note, however, that a subset of patients with novel influenza A (H1N1) will have non-diffuse findings that may simulate infection with other types of organisms. The one patient that did not have diffuse abnormalities was initially thought to have bacterial infection. Infection with influenza is a well-known risk factor for the development of bacterial superinfection. Although the majority of patients were also empirically treated with antibiotic therapy and one cannot completely exclude the possibility of concomitant bacterial infection, no clinically significant bacterial pathogens were isolated from respiratory culture, suggesting that novel influenza A (H1N1) very likely accounted for the radiographic findings in all of these cases.
Progression of disease on serial CTs was most commonly manifested by interval worsening of the airways disease (peribronchial consolidation, airway thickening, and centrilobular nodules) and development of symmetric or diffuse GGO. This later finding is typical of diffuse alveolar damage as a reaction to the viral infection. Of the patients who survived, all but one showed near complete resolution of the findings on interval follow-up CT within 35 days of the onset of clinical symptoms. One patient showed interval improvement at 50 days after the initial CT.
There are several limitations to this study. Firstly, this is small retrospective case series of eight immunocompromised patients, and thus, it is difficult to make definitive statements about the most common manifestations of novel influenza A (H1N1) in general. The goal of this series is simply to describe some of the CT findings that may be seen with this infection and to suggest patterns that may be suggestive of novel influenza A (H1N1) in the appropriate clinical setting. Second, many of the CT scans were done without a high-resolution technique, and thus, precise characterization of abnormalities such as centrilobular nodules is not ideal. With that in mind, standard CT scans, particularly with the routine 2.5-mm reconstructions used at our institution, can assess many of the same findings optimally evaluated with the high-resolution technique. In all cases of nodular disease, we were able to confidently determine that the distribution of nodules was centrilobular despite many of the CTs not being performed with the high-resolution technique. Another limitation is that influenza A infections are not uncommonly complicated by superinfection with other organisms, particularly bacterial. It is possible that some of the findings seen on serial scans performed after the initial diagnosis are due to an infection other than influenza. This is complicated by the fact that many of these patients, because of their immunocompomised state, were also treated empirically with anti-bacterial agents.
In summary, the CT findings of novel influenza A (H1N1) infection in this series of immunocompromised patients tended to be highly airway predominant and most commonly presented with airway thickening/dilatation, peribronchial ground glass, centrilobular nodules, and tree-in-bud opacities. Peripheral consolidation involving the lower lobes was also a common pattern. While these findings can be associated with other infections, they may be suggestive of novel influenza A (H1N1) in the appropriate clinical setting. A high level of suspicion for influenza should be maintained as occasionally it may have an appearance identical to bacterial pneumonia. Most immunocompromised patients with uncomplicated novel influenza A (H1N1) infection show significant radiographic improvement in 35 days or less after the onset of symptoms.