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Chinese Medical Journal, 2010, Vol. 123 No. 1, January 5, p 100-104.
Radiological features of lung changes caused by avian influenza subtype A H5N1 virus: report of two severe adult cases with regular follow-up
LU Pu-xuan, Yi-xiang Wang, ZHOU Bo-ping, GE Yang, ZHU Wen-Ke, CHEN Xin-chun, RAN Xian-gui
Several subtypes of avian influenza A have been shown to cross the species barrier and infect humans, leading to human cases of avian influenza.<sup>1,2</sup> Till June 2, 2009, globally there were 433 confirmed human cases of avian influenza caused by H5N1 virus, with a death rate of 60.5%.<sup>3</sup> This is far higher than the reported 11% death rate of severe acute respiratory syndrome (SARS).<sup>4</sup> The epidemiologic features of human case of influenza A subtype H5N1 virus infection consist of high incidence rate in cold weather, high susceptibility in population of younger age associated with rapid onset of the disease and devastating illness in humans.<sup>1,2,5,6</sup> H5N1 virus is mostly transmitted to humans directly through contact with infected birds or their secretions and the patients present with an influenza type illness with fever, cough, sore throat, malaise, and gastrointestinal symptoms; which can result in a rapidly progressive primary viral pneumonia and respiratory failure.<sup>2</sup> Patients above the age of 5 years are likely to have an adverse course of disease.<sup>5</sup>
Recently in our hospitals we successfully treated two adult cases of H5N1 viral human pneumonia, with one moderately severe case and one very severe case. These two cases were regularly followed up for 12 months, with the very severe case an additional follow-up at 24 months. We report the temporal radiological changes of the lung lesions of these two cases.
General clinical information of the patients
These two cases of avian influenza caused by H5N1 virus, include one female aged 26 years (case 1) and one male aged 37 years (case 2). Both cases had history of contacting diseased poultry. High fever (39.0?40.0?C) was the first noted symptom. At the time of hospital admission both cases had a severe influenza syndrome, with symptoms of fever, productive cough, shortness of breath, and diarrhea. The diagnosis of influenza A subtype H5N1 virus infection was confirmed by reverse transcriptase-polymerase chain reaction with primers specific for H5 and N1. The diagnosis was made on day 9 after occurrence of initial symptoms for the case 1 and, on day 7 after occurrence of initial symptoms for case 2.
Treatments included supplementary mechanical ventilation, anti-viral treatment with oseltamivir, short course of steroid, and general supportive treatments. After hematological testing and blood type matching, 300 ml/d of serum taken from case 1 at her convalescent phase was administrated to case 2 at his critical phase on days 12 and 13 (duration of disease refers to time from onset of symptoms). This treatment reduced his blood virus load and improved his general condition promptly (Figure 1). Secondary bacterial infection in the lungs occurred on day 16 in case 1 with Gram-positive cocci, and day 21 in case 2 with Pseudomonas aeruginosa. Together with purulent sputum and a significant rise of white blood cell count, chest X-ray demonstrated added parenchymal infiltrative consolidation. These secondary infections were effectively controlled with further antibiotics treatment, including a combination of vanoomycin and cefuroxime for case 1 and polymyxin B for case 2.
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</td> <td style="background: none repeat scroll 0% 0% rgb(244, 250, 244); padding: 0.75pt;"> Figure 1. Case 2: significant drop of the virus loading after treatment on days 12 and 13 with convalescent serum 300 ml each (total 600 ml) from case 1 at her convalescent phase. The H5N1 virus load was measured by quantitative reverse- transcriptase-polymerase-chain-reaction (RT-PCR) assay.
</td> </tr> </tbody></table> After hospitalization of 34 days for case 1 and 54 days for cases 2, these two patients' general conditions improved. All the physical signs and blood biomarkers returned to normal and they were discharged from hospital. Clinical follow-up has been carried out every 3 months for these two patients for 12 months.
Radiological examinations and image assessment
Following hospitalization, digital chest X-ray was carried out immediately and then every 24 hours during the critical phase and the early recovery phase for both cases. During convalescent phase, chest X-ray was carried out once every 3?7 days. After being discharged from the hospital, chest X-ray was carried out every 3 months for 12 months, chest CT examinations were carried out when indicated. The case 2 had an additional follow-up at 24 months with chest X-ray and CT.
All chest X-rays and CT were assessed blinded to clinical information and in consensus by two experienced radiologists regarding lesion location, lesion extent, and lesion morphology. Lesion morphology was classified into ground-glass opacities (hazy areas of increased attenuation without obscuration of the underlying vessels), consolidation (homogeneous opacification of the parenchyma with obscuration of the underlying vessels), reticular opacities, linear opacities, interlobular septal thickening, and mixed pattern.
In order to assess the lung lesion extent, a scoring system similar to that reported by Ooi et al<sup>7</sup> was used. The lungs were classified into three zones (upper, middle, and lower); each zone was evaluated separately. Each of the three zones corresponded to approximately one-third of the images from the lung apex to 1 cm below the domes of the diaphragm. Each lung zone was assigned a score that was based on the follows: score 0, 0 involvement; score 1, less than 25% involvement; score 2, 25% to less than 50% involvement; score 3, 50% to less than 75% involvement; and score 4, 75% or greater involvement. Summation of scores provided an evaluation of overall lung involvement (maximal score for both lungs was 24).
Ground-glass opacity was the earliest finding of H5N1 virus pneumonia in the chest radiograph for both cases. Appearing initially in one lung, the lesions expanded quickly and involved both lungs within 48 hours following the initial detection, and had a rapid further progression in a few days (Figures 2?4). Consolidation appeared on day 7 in case 1 and on day 8 in case 2. On CT images, bronchial air sign was shown within the consolidation shadows. At the climax phase on day 11 for case 1 and day 10 for case 2, appearance of ?white lung' was noted on chest X-rays, with the lesion extent score reaching 20 for case 1 and 22 for case 2 (Figure 2). These X-ray findings prompted more intensive clinical treatments such as mechanical ventilation, and in case 2, administration of convalescent phase serum from case 1. Anti-viral serum therapy led to prompt drop of the virus loading of case 2 (Figure 1). The lung lesion score dropped from 17 on day 14 to 13 on day 17, indicating a delay in imaging changes as compared with viral loading changes.
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</td> <td style="background: none repeat scroll 0% 0% rgb(244, 250, 244); padding: 0.75pt;"> Figure 2. Temporal changes of H5N1 virus pneumonia lesions over time (Case 1: A; Case 2: B). Lung lesion reached their climax phase on day 11 for case 1 with a score of 20 and on day 10 for case 2 with a score of 22. In both cases, there was a second phase of increased lesion score due to secondary bacterial infection.
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</td> <td style="background: none repeat scroll 0% 0% rgb(244, 250, 244); padding: 0.75pt;"> Figure 3. Case 1: chest radiographic demonstrations on day 4 (A), day 6 (B), and day 7 (C). Rapid progression of infiltrations is demonstrated.
Figure 4. Case 2: on day 6 post the onset of the disease (A), a large patch of increased density in the middle - lower field of the left lung with ill-defined border is shown. Ground-glass appearance dominates in the lesion. The left hilum is over-shadowed. On day 8 post the onset of the disease (B), infiltration involved all three zones of the left lung, patch shadows are seen in the right lung. Both hilums are over-shadowed.
</td> </tr> </tbody></table> In both cases, pleura were involved with initial minimal fluid accumulation and later pleural thickening. No lymphadenopathy was noted with radiograph and CT at the hilum and mediastinum areas.
During the treatment course, the condition of case 1 temporally improved on day 14, but secondary infection symptoms appeared on day 16 and lung lesion score rose again with parenchymal consolidation (Figure 2A). Following anti-biotic treatment, lung lesion score decreased. For case 2, chest X-ray demonstrated added parenchymal infiltrative consolidation in the lower field of the left lung on day 24 (Figure 2B). With effective antibiotic treatment, lung lesions of secondary infection started to dissolve on day 34.
The lesion resolving process was slow (Figures 2, 5). During the convalescent phase, consolidation opacities in the lungs became smaller and then disappeared, but reticular pattern, irregular linear opacities were observed. At the time of discharge, though all the physical signs and blood biomarkers returned back to normal, reticular pattern and irregular linear opacities were still seen in both cases. During the follow-up period, these two patients had no physical discomfort, with normal respiratory function and blood biomarkers. However, with case 1, chest CT demonstrated mixed pattern changes in both lungs, amounting to lesion extent score of 5 at week 10. The 7th month follow-up CT showed fibrotic reticular opacities, fibrotic linear opacities, and small patchy opacities, but 12th month follow-up CT demonstrated only minimal residual fibrous lines in the lungs (Figure 6). With case 2 who had severer disease course and longer hospitalization, 10 weeks after being discharged from hospital there was no discomfort and he was able to take part in regular physical labors, however, chest CT still showed patchy consolidations, reticular opacities and linear fibrotic opacities, with a lesion extent score of 7 (Figure 7), indicating radiological abnormalities not coincident with clinical symptoms and physical signs, i.e. lung lesions could exist after the clearance of clinical symptoms and physical signs. The 12th and 24th month follow-up CT of case 2 demonstrated ground-grass shadows, apparent reticular pattern, irregular linear opacities, and interlobular septal thickening and intra-lobular lines, with a CT lesion score of 3 (Figures 7, 8). Additionally, multiple emphysematous pathologies were seen adjacent to the interlobular septum on CT and also ground-grass shadows (Figure 7D, Figure 8B). Interestingly, for both cases, lesion appeared the earliest resolved the latest, and lesions appeared latest absorbed the earliest (Figures 4, 7, 8). The lung lesions at 24th month follow-up CT was similar to those at 12th month follow-up CT.
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</td> <td style="background: none repeat scroll 0% 0% rgb(244, 250, 244); padding: 0.75pt;"> Figure 5. Case 2: changes of H5N1 virus pneumonia lung lesion extent over time as shown with chest CT. Absorption of the lesions is slow.
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</td> <td style="background: none repeat scroll 0% 0% rgb(244, 250, 244); padding: 0.75pt;"> Figure 6. Case 1: On CT of 10 weeks post the onset of the disease (A), mixed shadows of consolidation patches and reticular pattern are seen in the lungs. Twelve months post the onset of the disease (B), no apparent pathology is seen in the lungs.
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</td> <td style="background: none repeat scroll 0% 0% rgb(244, 250, 244); padding: 0.75pt;"> Figure 7. Case 2: On CT of day 40 post the onset of the disease (A), mixed shadows of consolidation, reticular pattern and irregular linear opacities are seen in the lungs. On day 95 (B), same level as A, mixed shadows are still seen in both lungs, with decreased severity. At 12 months post the onset of the disease (C), same level as A and B, irregular fibrous linear opacities are seen in the lungs. Lesion severity much decreased compared to A & B. Same CT scan as C, ground-grass shadows, apparent reticular pattern, irregular linear opacities, and interlobular septal thickening and intra-lobular line are seen (D). Multiple emphysematous pathologies are noted adjacent to the interlobular septum.
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</td> <td style="background: none repeat scroll 0% 0% rgb(244, 250, 244); padding: 0.75pt;"> Figure 8. Case 2: 24 months post the onset of the disease, X-ray (A) and CT (B) of the chest. Residual lesions similar to 12 months CT are seen.
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DISCUSSION The diagnosis of influenza A subtype highly pathogenic H5N1 induced viral pneumonia primarily depends on the detection of this virus. Imaging examinations have an important role in assessing the status of the disease, evaluation of response to the treatment and detecting complications. If possible, chest X-ray should be obtained every day in acute phase because of rapid change of the lung pathology that may necessitate prompt action. The occurrence of complications can be the direct cause of death of patient. Because of the involvement of immunological system in the H5N1 infected patients, together with the mechanical ventilation, patient is very susceptible to secondary infection. In our cases, chest X-ray demonstrated important complications including adult respiratory distress syndrome (ARDS) and secondary bacterial infection for both cases. The initial predominance of ground-glass opacities over consolidation may allow differentiation of avian influenza pneumonia from bacterial pneumonia, which characteristically manifests as consolidation in a segmental or lobular distribution. Radiological investigation can also detect the mechanical ventilation related complications such as pneumo-thorax, pneumo-mediastinum, though none of which was shown in our cases.
The pleura involvement without substantial fluid accumulation was seen with CT in both our cases. In the two series reported by Bay et al<sup>5</sup> and Grose and Chokephaibulkit,<sup>8</sup> no pleural effusion was demonstrated by chest X-ray. It remains unknown whether there was no pleural effusion in those patients, or minimal pleural effusion was missed on chest X-ray. In agreement with the report by Bay et al,<sup>5</sup> no mediastinal and hilar lymphadenopathy was noted in our two cases. Our study findings reinforced the absence of mediastinal lymph nodes or substantial effusions in human avian influenza pneumonia, which may be used as additional helpful diagnostic signs.
Though the initial progress can be very fast, absorption of H5N1 viral pneumonia lesion was a slow process. In both our cases, at the time when general condition and blood biomarkers returned to normal, chest CT still showed the existence of parenchyma lesions of both lungs in forms of patchy consolidations, reticular opacities and linear opacities. With our case 1, the 7th month follow-up CT showed fibrotic reticular opacities, fibrotic linear opacities, and small patchy opacities. However, the 12th month follow-up CT showed only minimal residual fibrous lines. This indicates that though it is prolonged, lesion absorption is still possible. In the case 2, together with other lung changes, ground-grass shadow was still seen with CT at 12 months follow up (Figure 7). Wong et al<sup>9</sup> reported that in their SARS patients the areas with persistent ground-glass opacification after 6 months represented fibrosis. The multiple emphysematous pathologies seen adjacent to the interlobular septum on CT was possibly due to the blockage of bronchiole. From 41 weeks onwards, the further radiological changes were only marginal with same lesion score (Figure 5), and these residual changes may not represent active inflammation, instead, they might be mainly fibrosis and blockage of bronchiole. These changes may not be absorbable, and in cases where these lesions are substantial, they may negatively affect lung function.
It has been reported that human avian influenza pneumonias with consolidation that involves equal or more than 4 zones on presentation or at day 7 after the onset of symptoms and subsequent development of acute respiratory distress syndrome are generally associated with an adverse outcome.<sup>10</sup> As an adult case with severe initial disease course, based on experience reported in literature it would be difficult to treat our case 2. We believe that the administration of convalescent phase serum from case 1 played an important role in the successful treatment, as the administration of the serum led to significant drop of viral load as shown in Figure 1. The serum from the recovery phase of an infected patient has been considered to have high level of specific anti-body against the virus. However, till this case 2 reported in this paper, the efficacy of convalescent immune serum in human beings remains speculative.
In conclusion, to our knowledge this is the first report on the imaging findings of two adult cases of H5N1 virus pneumonia with regular follow-up. Similar to those in the previous outbreak of influenza A H5N1 virus infection in Hong Kong, China and Vietnam,<sup>1,2</sup> at presentation, our two cases were characterized by a severe influenza syndrome with symptoms of high fever and cough, and radiological evidence of pneumonia. Radiologically, at the early acute phase these two cases of H5N1 viral pneumonia demonstrated regional ground glass opacities; then the virus affected the lungs further and lesions expanded rapidly in a few days, leading to disseminated exudation changes in both lungs. During the climax phase, majority of the pulmonary zones in both sides were involved. There was a secondary bacterial lung infection in both our cases, stressing the importance of radiological surveillance and also the preventive use of antibiotics. Following clinical recovery, H5N1 viral pneumonia demonstrated a slow absorption.
1. Chan P. Outbreak of avian influenza A (H5N1) virus infection in Hong Kong in 1997. Clin Infect Dis 2002; 1: 58-64.
2. Tran TH, Nguyen TL, Nguyen TD, Luong TS, Pham PM, Nguyen VC, et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 2004; 350: 1179-1188.
3. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. (Accessed June 12, 2009 at http://www.who.int/csr/disease/avian_influenza/ country/cases_table_2009_06_02/en/index.html)
4. Chan KS, Zheng JP, Mok YW, Li YM, Liu YN, Chu CM, et al. SARS: prognosis, outcome and sequelae. Respirology 2003; 8 Suppl: S36-S40.
5. Bay A, Etlik O, Oner AF, Unal O, Arslan H, Bora A, et al. Radiological and clinical course of pneumonia in patients with avian influenza H5N1. Eur J Radiol 2007; 61: 245-250.
6. Oner AF, Bay A, Arslan S, Akdeniz H, Sahin HA, Cesur Y, et al. Avian influenza A (H5N1) infection in eastern Turkey in 2006. N Engl J Med 2006; 355: 2179-2185.
7. Ooi GC, Khong PL, Muller NL, Yiu WC, Zhou LJ, Ho JC, et al. Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients. Radiology 2004; 230: 836-844.
8. Grose C, Chokephaibulkit K. Avian influenza virus infection of children in Vietnam and Thailand. Pediatr Infect Dis J 2004; 23: 793-794.
9. Wong KT, Antonio GE, Hui DS, Ho C, Chan PN, Ng WH, et al. Severe acute respiratory syndrome: thin-section computed tomography features, temporal changes, and clinicoradiologic correlation during the convalescent period. J Comput Assist Tomogr 2004; 28: 790-795.
10. Qureshi NR, Hien TT, Farrar J, Gleeson FV. The radiologic manifestations of H5N1 avian influenza. J Thorac Imaging 2006; 21: 259-264.
For figures see original article at:
http://www.cmj.org/Periodical/PaperList.asp?id=LW201015566311809932
Radiological features of lung changes caused by avian influenza subtype A H5N1 virus: report of two severe adult cases with regular follow-up
LU Pu-xuan, Yi-xiang Wang, ZHOU Bo-ping, GE Yang, ZHU Wen-Ke, CHEN Xin-chun, RAN Xian-gui
Several subtypes of avian influenza A have been shown to cross the species barrier and infect humans, leading to human cases of avian influenza.<sup>1,2</sup> Till June 2, 2009, globally there were 433 confirmed human cases of avian influenza caused by H5N1 virus, with a death rate of 60.5%.<sup>3</sup> This is far higher than the reported 11% death rate of severe acute respiratory syndrome (SARS).<sup>4</sup> The epidemiologic features of human case of influenza A subtype H5N1 virus infection consist of high incidence rate in cold weather, high susceptibility in population of younger age associated with rapid onset of the disease and devastating illness in humans.<sup>1,2,5,6</sup> H5N1 virus is mostly transmitted to humans directly through contact with infected birds or their secretions and the patients present with an influenza type illness with fever, cough, sore throat, malaise, and gastrointestinal symptoms; which can result in a rapidly progressive primary viral pneumonia and respiratory failure.<sup>2</sup> Patients above the age of 5 years are likely to have an adverse course of disease.<sup>5</sup>
Recently in our hospitals we successfully treated two adult cases of H5N1 viral human pneumonia, with one moderately severe case and one very severe case. These two cases were regularly followed up for 12 months, with the very severe case an additional follow-up at 24 months. We report the temporal radiological changes of the lung lesions of these two cases.
METHODS
These two cases of avian influenza caused by H5N1 virus, include one female aged 26 years (case 1) and one male aged 37 years (case 2). Both cases had history of contacting diseased poultry. High fever (39.0?40.0?C) was the first noted symptom. At the time of hospital admission both cases had a severe influenza syndrome, with symptoms of fever, productive cough, shortness of breath, and diarrhea. The diagnosis of influenza A subtype H5N1 virus infection was confirmed by reverse transcriptase-polymerase chain reaction with primers specific for H5 and N1. The diagnosis was made on day 9 after occurrence of initial symptoms for the case 1 and, on day 7 after occurrence of initial symptoms for case 2.
Treatments included supplementary mechanical ventilation, anti-viral treatment with oseltamivir, short course of steroid, and general supportive treatments. After hematological testing and blood type matching, 300 ml/d of serum taken from case 1 at her convalescent phase was administrated to case 2 at his critical phase on days 12 and 13 (duration of disease refers to time from onset of symptoms). This treatment reduced his blood virus load and improved his general condition promptly (Figure 1). Secondary bacterial infection in the lungs occurred on day 16 in case 1 with Gram-positive cocci, and day 21 in case 2 with Pseudomonas aeruginosa. Together with purulent sputum and a significant rise of white blood cell count, chest X-ray demonstrated added parenchymal infiltrative consolidation. These secondary infections were effectively controlled with further antibiotics treatment, including a combination of vanoomycin and cefuroxime for case 1 and polymyxin B for case 2.
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</td> </tr> </tbody></table> After hospitalization of 34 days for case 1 and 54 days for cases 2, these two patients' general conditions improved. All the physical signs and blood biomarkers returned to normal and they were discharged from hospital. Clinical follow-up has been carried out every 3 months for these two patients for 12 months.
Radiological examinations and image assessment
Following hospitalization, digital chest X-ray was carried out immediately and then every 24 hours during the critical phase and the early recovery phase for both cases. During convalescent phase, chest X-ray was carried out once every 3?7 days. After being discharged from the hospital, chest X-ray was carried out every 3 months for 12 months, chest CT examinations were carried out when indicated. The case 2 had an additional follow-up at 24 months with chest X-ray and CT.
All chest X-rays and CT were assessed blinded to clinical information and in consensus by two experienced radiologists regarding lesion location, lesion extent, and lesion morphology. Lesion morphology was classified into ground-glass opacities (hazy areas of increased attenuation without obscuration of the underlying vessels), consolidation (homogeneous opacification of the parenchyma with obscuration of the underlying vessels), reticular opacities, linear opacities, interlobular septal thickening, and mixed pattern.
In order to assess the lung lesion extent, a scoring system similar to that reported by Ooi et al<sup>7</sup> was used. The lungs were classified into three zones (upper, middle, and lower); each zone was evaluated separately. Each of the three zones corresponded to approximately one-third of the images from the lung apex to 1 cm below the domes of the diaphragm. Each lung zone was assigned a score that was based on the follows: score 0, 0 involvement; score 1, less than 25% involvement; score 2, 25% to less than 50% involvement; score 3, 50% to less than 75% involvement; and score 4, 75% or greater involvement. Summation of scores provided an evaluation of overall lung involvement (maximal score for both lungs was 24).
RESULTS
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</td> <td style="background: none repeat scroll 0% 0% rgb(244, 250, 244); padding: 0.75pt;"> Figure 2. Temporal changes of H5N1 virus pneumonia lesions over time (Case 1: A; Case 2: B). Lung lesion reached their climax phase on day 11 for case 1 with a score of 20 and on day 10 for case 2 with a score of 22. In both cases, there was a second phase of increased lesion score due to secondary bacterial infection.
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Figure 4. Case 2: on day 6 post the onset of the disease (A), a large patch of increased density in the middle - lower field of the left lung with ill-defined border is shown. Ground-glass appearance dominates in the lesion. The left hilum is over-shadowed. On day 8 post the onset of the disease (B), infiltration involved all three zones of the left lung, patch shadows are seen in the right lung. Both hilums are over-shadowed.
</td> </tr> </tbody></table> In both cases, pleura were involved with initial minimal fluid accumulation and later pleural thickening. No lymphadenopathy was noted with radiograph and CT at the hilum and mediastinum areas.
During the treatment course, the condition of case 1 temporally improved on day 14, but secondary infection symptoms appeared on day 16 and lung lesion score rose again with parenchymal consolidation (Figure 2A). Following anti-biotic treatment, lung lesion score decreased. For case 2, chest X-ray demonstrated added parenchymal infiltrative consolidation in the lower field of the left lung on day 24 (Figure 2B). With effective antibiotic treatment, lung lesions of secondary infection started to dissolve on day 34.
The lesion resolving process was slow (Figures 2, 5). During the convalescent phase, consolidation opacities in the lungs became smaller and then disappeared, but reticular pattern, irregular linear opacities were observed. At the time of discharge, though all the physical signs and blood biomarkers returned back to normal, reticular pattern and irregular linear opacities were still seen in both cases. During the follow-up period, these two patients had no physical discomfort, with normal respiratory function and blood biomarkers. However, with case 1, chest CT demonstrated mixed pattern changes in both lungs, amounting to lesion extent score of 5 at week 10. The 7th month follow-up CT showed fibrotic reticular opacities, fibrotic linear opacities, and small patchy opacities, but 12th month follow-up CT demonstrated only minimal residual fibrous lines in the lungs (Figure 6). With case 2 who had severer disease course and longer hospitalization, 10 weeks after being discharged from hospital there was no discomfort and he was able to take part in regular physical labors, however, chest CT still showed patchy consolidations, reticular opacities and linear fibrotic opacities, with a lesion extent score of 7 (Figure 7), indicating radiological abnormalities not coincident with clinical symptoms and physical signs, i.e. lung lesions could exist after the clearance of clinical symptoms and physical signs. The 12th and 24th month follow-up CT of case 2 demonstrated ground-grass shadows, apparent reticular pattern, irregular linear opacities, and interlobular septal thickening and intra-lobular lines, with a CT lesion score of 3 (Figures 7, 8). Additionally, multiple emphysematous pathologies were seen adjacent to the interlobular septum on CT and also ground-grass shadows (Figure 7D, Figure 8B). Interestingly, for both cases, lesion appeared the earliest resolved the latest, and lesions appeared latest absorbed the earliest (Figures 4, 7, 8). The lung lesions at 24th month follow-up CT was similar to those at 12th month follow-up CT.
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DISCUSSION
The pleura involvement without substantial fluid accumulation was seen with CT in both our cases. In the two series reported by Bay et al<sup>5</sup> and Grose and Chokephaibulkit,<sup>8</sup> no pleural effusion was demonstrated by chest X-ray. It remains unknown whether there was no pleural effusion in those patients, or minimal pleural effusion was missed on chest X-ray. In agreement with the report by Bay et al,<sup>5</sup> no mediastinal and hilar lymphadenopathy was noted in our two cases. Our study findings reinforced the absence of mediastinal lymph nodes or substantial effusions in human avian influenza pneumonia, which may be used as additional helpful diagnostic signs.
Though the initial progress can be very fast, absorption of H5N1 viral pneumonia lesion was a slow process. In both our cases, at the time when general condition and blood biomarkers returned to normal, chest CT still showed the existence of parenchyma lesions of both lungs in forms of patchy consolidations, reticular opacities and linear opacities. With our case 1, the 7th month follow-up CT showed fibrotic reticular opacities, fibrotic linear opacities, and small patchy opacities. However, the 12th month follow-up CT showed only minimal residual fibrous lines. This indicates that though it is prolonged, lesion absorption is still possible. In the case 2, together with other lung changes, ground-grass shadow was still seen with CT at 12 months follow up (Figure 7). Wong et al<sup>9</sup> reported that in their SARS patients the areas with persistent ground-glass opacification after 6 months represented fibrosis. The multiple emphysematous pathologies seen adjacent to the interlobular septum on CT was possibly due to the blockage of bronchiole. From 41 weeks onwards, the further radiological changes were only marginal with same lesion score (Figure 5), and these residual changes may not represent active inflammation, instead, they might be mainly fibrosis and blockage of bronchiole. These changes may not be absorbable, and in cases where these lesions are substantial, they may negatively affect lung function.
It has been reported that human avian influenza pneumonias with consolidation that involves equal or more than 4 zones on presentation or at day 7 after the onset of symptoms and subsequent development of acute respiratory distress syndrome are generally associated with an adverse outcome.<sup>10</sup> As an adult case with severe initial disease course, based on experience reported in literature it would be difficult to treat our case 2. We believe that the administration of convalescent phase serum from case 1 played an important role in the successful treatment, as the administration of the serum led to significant drop of viral load as shown in Figure 1. The serum from the recovery phase of an infected patient has been considered to have high level of specific anti-body against the virus. However, till this case 2 reported in this paper, the efficacy of convalescent immune serum in human beings remains speculative.
In conclusion, to our knowledge this is the first report on the imaging findings of two adult cases of H5N1 virus pneumonia with regular follow-up. Similar to those in the previous outbreak of influenza A H5N1 virus infection in Hong Kong, China and Vietnam,<sup>1,2</sup> at presentation, our two cases were characterized by a severe influenza syndrome with symptoms of high fever and cough, and radiological evidence of pneumonia. Radiologically, at the early acute phase these two cases of H5N1 viral pneumonia demonstrated regional ground glass opacities; then the virus affected the lungs further and lesions expanded rapidly in a few days, leading to disseminated exudation changes in both lungs. During the climax phase, majority of the pulmonary zones in both sides were involved. There was a secondary bacterial lung infection in both our cases, stressing the importance of radiological surveillance and also the preventive use of antibiotics. Following clinical recovery, H5N1 viral pneumonia demonstrated a slow absorption.
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For figures see original article at:
http://www.cmj.org/Periodical/PaperList.asp?id=LW201015566311809932