[Abstract] Objective To analyze the X-ray and CT features of neonatal pulmonary hyaline membrane disease and improve the understanding and diagnosis of this disease. Methods We retrospectively analyzed the series of chest X-ray and CT manifestations of 34 cases of neonatal pulmonary hyaline membrane disease confirmed by comprehensive clinical diagnosis. Results: 11 cases of type I showed diffuse ground glass shadow in both lungs, including 8 cases with scattered microscopic nodular shadow and small nodules in both lungs, and 3 cases with scattered fine mesh nodular shadow; 15 cases of type II showed diffuse ground glass shadow in both lungs with scattered alveolar nodular shadow and patchy shadow in both lungs, 10 cases with bronchial inflation sign in the periphery of both lungs, and 13 cases with scattered fine mesh nodular shadow. The heart shadow and diaphragm shadow were slightly blurred in 6 cases; in 8 cases of type III, 5 cases showed diffuse ground glass shadow with scattered lamellar and large lamellar shadow and obvious bronchial inflation sign in both lungs, 3 cases showed “white lung” changes in both lungs, 2 cases showed a small amount of pleural pneumothorax, 1 case saw mild mediastinal emphysema, and the heart shadow and diaphragm shadow were blurred or disappeared in 8 cases. Among the 31 cases reviewed, 16 cases showed different degrees of rapid progression from type I to type III, and finally 3 cases had “white lung” in both lungs and died due to ineffective treatment; 15 children were treated promptly and their condition was stable or improved. Conclusion The X-ray and CT signs of neonatal pulmonary hyaline membrane disease have certain characteristics, and combined with its dynamic change characteristics and clinical data, the disease can be diagnosed timely and accurately. Lei Zhidan, Department of Radiology, Henan Provincial People’s Hospital
[Keywords] Neonatal; pulmonary hyaline membrane disease; radiography; body layer photography, x-ray computer
Neonatal pulmonary hyaline membrane disease (NHMD), also known as idiopathic respiratory distress syndrome (IRDS), is one of the major causes of death in newborns. It is a major cause of death in newborns, mostly in preterm infants, but also in newborns born by cesarean section and with a history of severe asphyxia during labor. We retrospectively analyzed the clinical and serial X-ray and CT data of 34 children with NHMD treated in our hospital from 2001 to 2006, and discussed the imaging features with the literature in order to improve the understanding and diagnosis of this disease.
1 Data and methods
1.1 Clinical data
There were 34 cases in this group, including 26 males and 8 females. 23 cases were preterm infants with gestational weeks of 28-35 weeks, 7 cases were delivered by cesarean section and all had a history of intrauterine distress, and 4 cases were obstructed infants with a history of severe asphyxia during labor. All the children had progressive dyspnea and shortness of breath of different degrees, 28 cases were accompanied by expiratory moaning, 30 cases had trigeminal signs, 27 cases had pallor or/and cyanosis, 34 cases had reduced breath sounds, and all 34 children had metabolic acidosis on blood gas analysis. All cases were confirmed by comprehensive clinical diagnosis. In all cases, the first imaging examination was performed within 2 to 36 hours after birth.
1.2 Examination methods
All 34 children had supine chest radiographs, 20 cases were conventional X-rays, 14 cases were CR films, and 31 cases had 2-4 follow-up chest radiographs after 4~72 hours. 10 severe cases had chest spiral CT scans, using Siemens’ double-row spiral CT with a matrix of 512×512, a layer thickness of 5mm, and a pitch factor of 1.0, ranging from the entrance of the thorax to the base of the lung, with a lung window and a mediastinal window, respectively. In three cases, HRCT was added with a layer thickness of 1 mm, layer interval of 10 mm, and bone algorithm reconstruction, and the lung window was used for observation.
1.3 Basis of staging and analysis method
1.3.1 Basis of staging
NHMD is divided into 3 types according to the severity of the lesion and the related imaging changes. Type I mainly consists of increased lung density with or without small nodules scattered in both lungs; type II mainly consists of diffuse ground glass shadow with alveolar nodular shadow or patchy shadow in both lungs, and may be accompanied by mild peripheral bronchial inflation sign; type III mainly consists of diffuse ground glass shadow with lamellar shadow, large lamellar shadow or even “white lung” in both lungs. Type III is mainly diffuse ground glass shadow with lamellar shadow, large lamellar shadow and even “white lung”, with obvious bronchial inflation sign.
1.3.2 Analysis method
The imaging data of 34 children were analyzed, categorized and summarized by two senior radiologists who were unaware of the results, and their imaging signs and dynamic changes were recorded. Then three radiologists compared them with the clinical data and combined with the literature to summarize the imaging features of the disease.
2 Results
2.1 Staging and imaging signs of NHMD
2.1.1 Common imaging features of NHMD
All 34 children had symmetrical and non-collapsed thorax, normal heart shadow shape and size, and no fluid accumulation in bilateral chest cavities.
2.1.2 Imaging signs of each type of NHMD
In 11 cases of type I, all of them showed diffuse ground glass shadow in both lungs, and the density of ground glass shadow in each lobe was relatively uniform. 8 cases of type I were accompanied by scattered microscopic nodules and small nodules in both lungs, and the nodules were mainly distributed in the peripheral part of the lung lobes, with some nodule edges clear and some blurred. 3 cases were accompanied by fine mesh nodules scattered in the periphery of the middle and lower lungs bilaterally.
In type II, 15 cases showed diffuse ground glass shadow with scattered alveolar nodular shadow and patchy shadow in both lungs, and the alveolar nodular shadow and patchy shadow were distributed according to lobe segments. 10 cases showed bronchial inflations in the periphery of both lungs with dilated and short-tipped bronchial endings. 13 cases showed scattered fine mesh nodular shadow, mainly in the peripheral part of lung lobes. 6 cases showed mild blurring of cardiac shadow and diaphragm shadow.
In 8 cases of type III, 5 cases showed diffuse ground glass shadow with scattered lamellar and large lamellar shadows in both lungs and obvious bronchial inflations with short bald dendrites and marked dilatation of the inflated bronchi, which appeared as vesicular and irregularly dilated bronchial shadows on CT. The heart shadow and diaphragm shadow were blurred or even disappeared in 8 patients.
2.2 Dynamic changes of NHMD
Among the 31 cases reviewed, 16 cases showed different degrees of rapid development from type I to type III within 1-4 days, and 13 cases gradually improved after receiving a clearer diagnosis and treatment, while 3 cases with “white lung” in both lungs eventually died after treatment failed; 15 cases were diagnosed and treated promptly and their condition was stable and gradually improved.
3 Discussion
3.1 Overview
The etiology of neonatal pulmonary hyaline membrane disease is currently considered to be mainly related to prematurity, cesarean section and perinatal asphyxia [1. 2]. 23 of the 34 children in this group were born prematurely, 7 were born by cesarean section and 4 had a history of severe asphyxia, which is consistent with literature reports. The above etiology can cause a decrease or lack of alveolar surface active substance synthesis in neonates, which leads to ineffective retention of residual air in the lungs after expiration, progressive expiratory alveolar atrophy, causing pulmonary ventilation and ventilatory dysfunction, as well as excessive dilatation of alveolar ducts, respiratory fine bronchi and terminal fine bronchi due to high inhalation pressure, hypoxia, acidosis causing pulmonary small artery spasm, and inadequate pulmonary perfusion, followed by damage to pulmonary capillary endothelial cells and pulmonary capillary bronchial mucosa, plasma protein extravasation, covering the alveolar wall and the surface of the terminal airways to form
The plasma protein exudates and forms a fibrinous hyaline membrane on the alveolar wall and the surface of the terminal airways [2. 3. 4]. Clinically, children present with progressive dyspnea, expiratory moaning, aspiration concavity, pallor, cyanosis, and respiratory failure. Blood gas analysis is often metabolic acidosis. Because of the many complications, rapid progression and high mortality [2. 3. 5], early and correct diagnosis is required.
3. 2 Grading of NHMD
In the classification of NHMD, most scholars classify NHMD into grade I-IV according to Rame’s classification [6-8], and some classify it into mild, moderate and severe [2. 5], both of which have played a positive role in the application of NHMD. However, in practice, both methods have shortcomings. The former is difficult to grasp because the fine-grained shadow and dot shadow of grade I and II are not easily distinguished on X-ray, while the latter classifies grade I and II as mild and grade III and IV as moderate to severe, respectively, and fails to reflect the severity of the lesion exactly based on the state of air cavity inflation or collapse. The author believes that the extent of ground glass shadow and lamellar shadow in the lung reflects the degree of air cavity inflation or collapse in the lung, and the state of air cavity inflation or collapse in the lung is the anatomical basis for the degree of lung ventilation and gas exchange, so the extent of ground glass shadow and lamellar shadow is closely related to the severity of clinical symptoms. Therefore, the author classifies the disease into type I, II and III mainly based on the extent of the ground glass shadow and lamellar shadow and the severity of the lesion.
3.3 Imaging features of NHMD
3.3.1 Ground glass shadow Due to alveolar atrophy, filling of alveolar septum and air cavity with plasma protein-rich fluid, resulting in reduced air cavity inflation, deformation of lung structure and interstitial thickening, resulting in increased lung density [11], when the alveoli are not completely filled with fluid or completely collapsed, the lung density is only mildly increased and appears as ground glass shadow. The presence of this sign in 32 of the 34 cases in this group, which were present in types I-III, indicates that the lack of surface active substance and the resulting alveolar atrophy and plasma protein extravasation are the main signs of the disease throughout its course, and thus the ground glass shadow is the main sign of the disease and reflects its pathological features to some extent.
3.3.2 Micronodules, small nodules, and alveolar nodules Due to collapse or complete filling of the alveolar cavity, primary lobules, and alveoli, the lung density at the level of the alveolar cavity, primary lobules, and alveoli may increase and appear as nodular shadows of corresponding size, while the thickening of the mass at the same time appears as tiny nodules on their axial images. These structures are mainly located in the peripheral part of the lung, and therefore the nodules are located in the peripheral part of the lung. In the present group of children, 23 nodular shadows were mainly scattered in the peripheral parts of both lungs of type I and II, reflecting that the lesions mainly damaged the peripheral interstitium and parenchyma of the lungs, and the damage was only mild to moderate.
3.3.3 Fine reticulum nodular shadow Among the 34 children, fine reticulum nodular shadow was seen in 16 cases because of thickening of the alveolar septa due to plasma protein-rich fluid and fibrous hyaline membranes in the alveolar wall, and when these thickened interstitium existed in the ground glass shadow and were not obscured by solid or collapsed lung tissue, they appeared as fine reticulum nodular shadow, thus reflecting a mild to moderate degree of lung damage. The 16 children with fine mesh nodules were all type I-II and had fewer lamellar shadows, further suggesting that fine mesh nodules are a common sign of mild to moderate disease.
3.3.4 Patchy, lamellar, and large lamellar shadows were seen in 23 of the 34 children in this group, with patchy, lamellar, and large lamellar shadows, and even “white lung” changes, distributed by lobe and lung segment, mainly in cases of type II and III, reflecting alveolar collapse or/and complete filling of the alveoli with plasma-rich proteins occurring at the level of lobules, lung subsegments, lung segments, and even the entire lung. The extent of the lamellar shadows reflects the severity of the disease, as they are mainly semilamellar in type II and large lamellar shadows are mainly seen in children with type III.
3.3.5 Bronchial dilatation The bronchial dilatation below the peripheral or terminal fine bronchi in 15 cases in this group is seen in the form of short-tipped thin or short bald dendritic bronchial shadow, which appears as vesicular and irregularly dilated bronchial shadow on CT, because the atrophy of the alveoli or the filling with fluid is the result of the decrease of the gas exchange function of the body and the compensatory overinflation of the small airways with gas exchange function in order to maintain normal gas exchange, thus passive dilatation. Therefore, most scholars believe that the inflatable bronchial sign is a characteristic imaging sign of this disease [2. 4-10], but this sign was seen in only 15 children in our group. 3.3.6 Other signs
3.3.6 Other signs The thorax of all 34 children was symmetrical without collapse, indicating that the lung volume of the disease was normal because although alveolar atrophy could cause a reduction in lung volume, it was compensated by the inflatable and dilated fine bronchi, so the overall lung volume was normal. 14 children had blurred or absent heart shadow and diaphragm surface because the solid shadows near the heart and diaphragm surface were in close contact with them and obscured them or because of the peripheral interstitial effect or partial volume effect. Two cases of pneumothorax and one case of mediastinal emphysema were the result of alveolar or fine bronchial destruction, especially fine bronchial destruction of gas into the thoracic cavity or interstitium.
3.4 Dynamic changes of NHMD Among the 31 cases reviewed, the imaging changes of 16 children who did not receive timely diagnosis and treatment developed rapidly from type I to type III within 1-4 days, and 3 of the 8 patients with type III died of “white lung”, thus indicating that the disease progressed rapidly and the greater the extent of the lesion, the more serious the disease.
3.5 Differential diagnosis
3.5.1 Neonatal wet lung mainly presents with diffuse ground glass, nodular, and patchy shadows, but it does not have fine bronchial dilatation, and lamellar shadows, especially large lamellar shadows, are rare, and the lesions improve rapidly in 3-4 days, and progression is very rare.
3.5.2 Acute interstitial pneumonia is mainly characterized by rapid progression from ground glass and patchy shadows to reticular shadows, bronchiectasis, destruction of lung structures, and honeycombing [14], but the former is less rapid than the latter in comparison with NHMD, where bronchiectasis can occur at any one or more bronchial levels from 2 to 23, and where there is a reduction in lung volume and honeycombing is common, whereas the latter has normal lung volume.
3.5.3 Neonatal acute respiratory distress syndrome is an acute respiratory distress that occurs in newborns after severe infection, shock, or surgery, and is characterized by normal or hyperinflation, increased lung texture, lamellar shadowing, large lamellar shadowing, and “white lung” on X-ray, but ground glass shadowing and inflatable bronchial signs are less common. Therefore, it is not difficult to differentiate it from NHMD with medical history.
In conclusion, I believe that the signs and rapid dynamic changes of ground glass shadow, lamellar shadow, nodular shadow, reticular shadow, bronchial dilatation and normal lung volume reflect the pathological characteristics of NHMD and are indispensable imaging manifestations in the whole process of NHMD development.
References
1. Wang Y, Wang HY, Guo ZC. Analysis of factors in the development of pulmonary hyaline membrane disease in preterm infants[J]. Journal of Neonatology, 2000, 15(2):59-60.
2. Wang LS, Hu KF, Bao JQ, et al. A controlled X-ray and pathological study of neonatal pulmonary hyaline membrane disease (with analysis of 9 cases) [J]. Radiology Practice, 2003, 18(4): 274-276.
3. Yang QN, Zhu JX, Zhang ZD. Clinicopathological diagnosis of neonatal pulmonary hyaline membrane disease [J]. Journal of Shanghai Second Medical University, 2003, 23: 102-103, 106.
4. Literat A, Su F, Norwicki M, et al. Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (NHMD) [J]. Life-Sci, 2001, 70(3): 253-267.
5. Zang D, Xu JM, Wen Feiqiu, et al. X-ray diagnosis and clinical analysis of neonatal pulmonary hyaline membrane disease[J]. Chinese Journal of Practical Pediatrics, 2004, 19(7): 428-429.
6. Zhang Xinxian. X-ray analysis of 67 cases of neonatal pulmonary hyaline membrane disease. Journal of Xuzhou Medical College, 2003,23(4): 360-361.
7. Northway WH JR. Bronchopulmonary dysploasia and research in diagnostic radiology[J]. AJR, 1991, 156: 681-687.
8. Feng R D, Lin Y Q, Ah J Y, et al. Imaging analysis of neonatal pulmonary hyaline membrane disease[J]. Journal of Practical Medical Imaging, 2004, 5(1): 25-26.
9. Howling SJ, Northway WH JR, Hansell DM, et al. Pulmonary sequelae of bronchopulmonary dysploasia survivors:high-resolution CT findings[J]. AJR, 2000, 174: 1323-1326.
10. Marini C, Bulleri A, Cambi L, et al. The neonatal respiratory insu fficieney syndrome: the role of the chest radiogram[J]. Radiol Med(Torino), 1997, 94: 463-467.
11. Lei ZD, Lu YS, Jia WL, et al. Clinical significance of lung density inhomogeneity in the imaging diagnosis of lung diseases[J]. Journal of Practical Diagnosis and Therapy, 2006, 20(2): 125-126.
12. Wu S. B. X-ray diagnosis of lung in premature infants [J]. Chinese Journal of Medical Imaging, 14(6): 430-432.
13. Liang Xiumei, Gou Zhengquan. Clinical X-ray diagnosis of pulmonary hyaline membrane disease in neonates (with X-ray and pathological analysis of 4 cases)[J]. Journal of Practical Radiology, 2003, 19(12):1150-1152.
14. Lei ZD, Ge YF, Wen ZJ, et al. Imaging diagnosis of acute interstitial pneumonia [J]. Journal of Practical Diagnosis and Therapy, 2005, 19(11): 799-800, 802.