Children with atopy are a special population, and atopy is often accompanied by airway hyperresponsiveness. In our study, we compared the clinical characteristics of children with atopy and HAdV pneumonia to children without atopy. We found that there was no difference in the duration of fever between the two groups. However, the eosinophil count in the atopic group was significantly higher than that in the non-atopic group, which was considered to be related to the fact that the children not allergens avoidance recently, because not all of the children in the atopic group had increased eosinophil count in blood. The eosinophil count in part of the children with atopy without HAdV infection is also higher, so we considered the higher eosinophil count not due to HAdV infection, but atopy. Considering the differences in clinical features and chest HRCT changes due to pneumonia severity after infection, we analyzed the clinical characteristics of children with mild and severe pneumonia respectively. In children with atopy (with or without HAdV infection) and mild pneumonia, the number of cases of severe cough or wheezing was significantly higher than that in those without atopy, and the number of patients with wheezing during hospitalisation was significantly different. Therefore, we concluded that after HAdV infection, children with atopy are more prone to severe coughing and wheezing than children without atopy. The reason for wheezing in children with atopy and HAdV pneumonia may be related to the exposure of the damaged airway epithelium neurons and increased airway sensitivity . Studies have shown that leukotriene E4 is strongly associated with episodes of acute wheezing in preschool children and that the levels of leukotriene E4 are higher in the airways of children with atopy than in those of children without atopy . In our study, we also found that the number of cases of wheezing in the atopic group with severe HAdV pneumonia was significantly higher than that in the atopic group without HAdV infection. The reason may be related to the characteristics of HAdV infection. Firstly, damage to the airway mucosa after HAdV infection and the release of inflammatory mediators can cause mucosal oedema of the bronchi and bronchioles, congestion, necrosis and shedding, necrotic obstruction of the lumen, and bronchial wall oedema and thickening, resulting in vasospasm and muscle contraction. As airway epithelial cells are damaged, their defence capacity is reduced, resulting in allergens invading the airway more easily . In contrast, toll-like receptors (TLR) and intracellular virus sensors such as protein-catalysed enzymes (protein kinase double-stranded RNA, PKR) in airway epithelial cells  induce MUC5AC production, leading to airway epithelial mucus hypersecretion and blockage of the lumen. After infection, HAdV can interact with the host cells and extensively participate in the functions of host cell proliferation, apoptosis, autophagy, and so on . Studies have shown that when HAdV infects respiratory epithelial cells, host cells develop adaptive autophagy, which enables immune evasion , leading to autophagy dysregulation in the host cells. HAdV can induce the activation of CD8+ T cells through the autophagy pathway, leading to microenvironmental changes in the lung tissue . In the airways of children with atopy, damaged neurons in the airway epithelia are exposed, increasing airway sensitivity  and leading to more serious epithelial injury, thus making patients more susceptible to wheezing.
The changes caused by HAdV pneumonia on the chest CT image include lung consolidation, patchy shadows, flocculent shadows, cluster shadows, air bronchograms, and lymph node enlargement. Its effects on the small airways include uneven inflation, mosaic sign, bronchial thickening, and bronchiectasis . In the current study, we compared children with HAdV pneumonia with and without atopy and found that the percentage of children with atopy and small airway lesions was more than that of children without atopy. We also compared the baseline characteristics and symptoms of children with pneumonia with and without small airway lesions. We found that in the small airway lesions group, the numbers of patients with atopy, severe infection, and a family or personal history of asthma were significantly higher than those in the group without small airway lesions. A family or personal history of asthma, atopy, severe infection, and HAdV infection were independent factors associated with the development of small airway lesions, based on chest HRCT findings.
Uneven inflation of the lungs is always found on chest CT in children with atopy, and children often experience coughing or wheezing which requires treatment after discharge. The changes in the lung parenchyma, such as lung consolidation, usually recover slowly after discharge and most small airway lesions require atomisation to recover; however, we observed that, even after 1 month, some children with atopy had small airway lesions on the chest CT. Some children were still intolerant to sports activities, had post-activity wheezing, and showed progression to bronchiolitis obliterans.
The small airway refers to the airway with an inner diameter ≤ 2 mm and is one of the smallest visible areas of the lungs. Most of the airways are referred to as bronchioles, belonging to the 12th–23rd branch of the airway . There are direct and indirect manifestations of small airway lesions on HRCT. The direct signs, including central lobular nodules, tree bud signs, and bronchiectasis, are caused by thickening of the bronchial wall or bronchiectasis . Indirect signs are caused by the obstruction of bronchioles and include mosaic sign and gas trapping . HRCT imaging of small airway lesions can detect the following: thickening of the bronchiole wall; tree bud sign; mosaic characteristics; and air retention. The mechanism for the development of small airway lesions in children with atopy may be eosinophilia and an abundance of CD4+ T lymphocytes in the small airways compared to that in the larger airways, which results in small airway inflammation . Small airway inflammation, airway remodelling, and matrix deposition eventually lead to increased airway resistance, similar to the pathophysiologic changes that occur in the small airways of patients with asthma . In our study, we found that the number of patients with small airway lesions during hospitalisation and after discharge was significantly higher in the atopic group with severe HAdV pneumonia than in the atopic group without HAdV infection. The reason may be that small airway lesions are also associated with persistent latent infection, attributed to the HAdV E1A genes. The adenovirus genome comprises linear double-stranded DNA, containing five early transcription units, namely E1A, E1B, E2, E3, and E4. The viral genome translocates to the host nucleus, and its transcription and expression initiate and facilitate viral replication. E1A is the earliest transcribed gene . Studies have demonstrated that the adenoviral E1A DNA and proteins persist in the lung tissue after viral replication stops in the acute infection phase; this enables the long-term expression of proteins without the need for replication of the entire virus. The main target cells are bronchial epithelial cells, alveolar epithelial cells, and submucosal cells . Studies have shown that enhanced expression of E1A genes can activate the mitogen-activated protein kinase (MAPK) signalling pathway, allowing HAdV to proliferate continuously in respiratory epithelial cells . Persistent latent infection of the lung tissue by E1A genes may lead to airway remodelling .
There are many limitations to our study. We only considered the influence of atopy on the clinical symptoms of children, and other confounding factors that may also affect the prognosis of children, such as co-infection with respiratory syncytial virus , mycoplasma infection, influenza , and mixed influenza infections, were not considered. In some patients with wheezing, the use of glucocorticoids to suppress immune responses may have also affected the prognosis of pneumonia, which was not considered in this study. The difference in the timing of treatment and virus typing in some patients with severe pneumonia may also affect their prognosis, which was not considered in this study . Therefore, our center will carry out relevant cohort studies in the future.