Discussion

Influenza can cause signs and symptoms that are indistinguishable from some severe cases of the seasonal common cold. In general, a chest X-ray is the first paraclinical test that is performed for the assessment of respiratory involvement in patients with influenza. In the conditions that the chest X-ray shows the presence of questionable findings of respiratory involvement, a chest CT is requested. Also, it has been suggested that the chest CT is useful in evaluating complications or evidence of mixed infection, but this issue is open to discussion. So far, some studies have investigated the radiological features of influenza patients, especially in A-H1N1 cases. Marchiori et al. (2011) described the high-resolution CT features of fatal cases of influenza A-H1N1 virus-associated pneumonia 13. The predominant findings included areas of airspace consolidation and ground-glass opacities. Nicolini and co-workers (2011) reported unilateral or bilateral multifocal ground-glass opacities as the predominant feature in chest CTs obtained from influenza patients 14. In another study performed by Agarwal et al. (2009), patchy consolidations in the lower and central lung zones were reported as the main characteristic of A-H1N1 subjects 15. Also, Ajlan et al. (2009) stated that unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation are the crucial parameters that should be considered in influenza patients 16.
In our study, the rate of patchy infiltration detection, as a crucial parameter, was significantly different between the three types of investigated influenza strains (P<0.05). Patchy infiltration is considered as a poorly defined area of lung consolidation with scattered opacification seen on chest imaging. This clinical characteristic has been reported in many studies performed on the influenza disease. Rostami et al. (2011) studied the radiological characteristics of influenza A-H1N1 patients 17. In their survey performed in the Isfahan city of Iran, patchy infiltration was one of the most common thoracic CT findings in pandemic H1N1. The results of the present study are in agreement with the results of Rostami’s study. In another study, Elicker and co-workers (2010) reported the thoracic CT findings of novel influenza A-H1N1 infection in immunocompromised patients 18. In their study, some patients had atypical CT findings including focal lobar consolidation and patchy lower lobe consolidation with soft tissue centrilobular nodules. Such atypical findings may be indicative of a compromised immune status.
To date, a number of studies have reported the clinical features of various types of influenza, especially the A-H1N1 subtype. Walsh et al. (2002) described the clinical features of influenza-A infection in older hospitalized subjects 19. They stated that the presence of cough, fever, and severe illness are valuable in opting for respiratory isolation and designing antiviral trials for influenza patients. In 2009, Cao and co-workers listed the clinical features of influenza A-H1N1 patients 20. Based on their report, the most common symptoms of A-H1N1 influenza patients were fever and cough, which occurred in 67.4% and 69.5% of cases, respectively. In another survey, Hu et al. (2003) surveyed the clinical features of influenza A and B in younger patients and its association with myositis21. These researchers reported fever, cough, and rhinorrhea as the most common clinical manifestations, with benign acute childhood myositis being present in 5.5% and 33.9% of the type A and B patients, respectively. Irving and his colleagues (2011) conducted a study for the comparison of clinical manifestations of medically attended influenza-A and influenza-B in defined subjects over four seasons 10. They concluded that over four influenza seasons, clinical signs and symptoms were alike for cases with predominantly outpatient-attended influenza-A and influenza-B virus infections.
As previously mentioned, fever seems to be the most common influenza manifestation; Calitri et al. (2010), in their cross-sectional study, confirmed this among 2009 H1N1 influenza patients 22. In another study, Plessa et al. (2010) declared that fever was the most common symptom in pediatric patients with H1N1 influenza23. In our cross-sectional study, fever was present in most patients with various types of influenza. Notably, the fever temperature was significantly higher among influenza A-H3N2 subjects than A-H1N1 and B-H1N1 subjects (P<0.05). Kaji and co-workers (2003) investigated the differences in clinical features between A-H3N2, A-H1N1, and B influenza subjects in Japan 24. They reported that A-H3N2 influenza was more severe than A-H1N1 or B in terms of fever, leukopenia, and CRP level elevation. Our finding related to fever is in agreement with the Kaji et al. study.
Dynamic determination of inflammatory agents may offer important insights into individual alterations in the control of inflammation and risk for disorders. The CRP is produced by the liver in response to signaling by pro-inflammatory cytokines. A high level of plasma CRP is a marker of inflammation associated with a wide variety of disorders ranging from infection to malignancy 25,26. In recent years, the CRP level in patients with influenza has been of interest to researchers. Morton et al. (2017) suggested that CRP is a crucial parameter for determining the admission, observation, or discharge of H1N1 influenza patients 27. Based on their work, the CRP determinant was the most important predictor of safe discharge. In another survey, Li and co-workers found that CRP levels could indicate which febrile children under three months of age should undertake blood culture tests during influenza seasons 28. In the present study, we reported a significant difference between the levels of CRP in the three groups of influenza patients (P<0.05). Our results are consistent with those of Kaji et al., who reported a meaningful difference in CRP levels between A-H3N2, A-H1N1, and B influenza subjects in Japan.
For a probable diagnosis of influenza, many non-specific serological parameters have been suggested, such as lymphopenia, monocytosis, thrombocytopenia, and leukocytosis or leukopenia. The WBC count is one of the parameters that has frequently been investigated. In a survey of hospitalized subjects with A-H1N1 influenza during the first two months of its pandemic, leukopenia was observed in 20% of patients. Wiwanitkit et al. (2013) presented leukopenia and lymphopenia as important findings of influenza that can be verified through blood tests29. Soleimani and co-workers reported that the presentation of influenza in children is variable and A-H1N1 influenza may cause leucopenia and thrombocytopenia 30. As previously mentioned, Kaji et al (2003) reported that influenza A-H3N2 was more severe than A-H1N1 or B in terms of leukopenia24. In contrast, we did not find any meaningful difference between the numbers of WBC in the three groups under study.
This retrospective study was confronted with some limitations. Firstly, despite the use of the RT-PCR molecular technique for the definitive diagnosis of the influenza subtype, some of the features seen on CT scans could have been consequences of infections other than influenza. A second limitation was the lack of access to pathological samples of the patients’ lungs. As we know, the correlation between radiological and histopathological findings is a considerable issue in influenza. Finally, our study featured a relatively low number of patients, limiting its power.