4 Discussion
The pathophysiology of pulmonary interstitial emphysema (PIE) is a result of air leakage into interstitium from alveolus due to disruption of the alveolar wall basement membrane, which may dissect along the bronchovascular bundles and radiates outwards to the periphery of the lung, mediastinum and pericardium. PIE included local persistant PIE and acute PIE, and diffuse persistent PIE[3, 4]. Diffuse persistent PIE is observed when small cysts are noted in all lobes of the lung[5], and acute IPE is lesser than 7 days in duration.
PIE is a rare condition that commonly affects newborn infants with a history of prematurity with positive pressure mechanical ventilation[9, 10]. However, it has also been reported rarely in both nonventilated infants and full-term infants[11, 12]. There have been only a few cases reported for PIE developing in unventilated neonates[3, 11, 12, 18, 20-22]. In our study, five full-term unventilated infants underwent surgical lobectomy were diagnosed with the PPIE. However, all the patients were diagnosed with PPIE with respiratory infection.
Chest CT sometimes may find air surrounding the bronchovascular bundles in patients with PIE[3]. A Multi-institutional research found that about 82% patients with PPIE had the characteristic CT findings with central lines and dots surrounded by radiolucency[23]. But Chest CT is not an effective diagnostic tool for PIE presenting as multiple cysts with various sized in one or more lobes of the lung[14]. Especially, CT showed cystic lung lesions mimicking CCAM[6]. When a patient with the absence of classical CT features, PIE should be differentiated from other cystic lung lesions, including CCAM, CLE, lymphangiectasia, a bronchogenic cyst, cystic lymphangioma, and diaphragmatic hernia. According to the CT findings and clinical features, CCAM was suspected in 66.7% (4/6) cases in present study. Besides, there was only one case that prenatal ultrasound found cystic lesions in the previous literature[24]. Messineo et al. reported a male infant suffered from type I CCAM at 20 weeks of gestation with ultrasound scanning, which was diagnosed with PIE after surgery[24]. The prenatal ultrasound did not find any lesions in the lung of six patients with prenatal ultrasound examination in present study, which indicates that the PPIE may be formed after birth.
Persistent PIE is pathologically characterized by irregular-shaped and multiloculated cysts of various sizes along the bronchovascular bundle. And the cysts are air-filled spaces in the parenchymal and composed of a thin band of fibrous connective tissue. The degree of the fibrosis may vary the duration of PIE. The uninucleated and/or multinucleated macrophages lining the cyst walls are the typical pathological features[7, 8]. The typical features of air cysts surrounding the bronchovascular bundles with fibrous tissue lining the uninucleated and/or multinucleated macrophages were both demonstrated among all 6 cases in our present study.
The differential pathologically diagnosis was made with other cystic lesions such as CCAM, PS, bronchogenic cyst, CLE, and cystic lymphangioma and so on. CCAM is characterized by a lack of communication between the lesion and the tracheobronchial tree and a proliferation of irregularly dilated terminal bronchiole-like structures[25]. PS is characterized with non-functioning lung tissue receives systemic arterial blood supply and does not communicate with the adjacent tracheobronchial tree[26]. Bronchogenic cyst is lined with pseudostratified columnar respiratory epithelium, cartilage plate, smooth muscle, and bronchial glands[27]. CLE showed lobar hyperinflation with overdistention of normally formed alveoli and without destruction of alveolar walls, aspiration pneumonia, infection, and proximal bronchial obstruction[28].
Standard treatment strategy for PIE has not yet been established. Surgical resection of PIE is controversial, and several studies have advocated a conservative medical approach[23, 29]. When it is difficulty in making the diagnosis, the absence of classical CT features, and nonsurgical options failed or progressive syndrome, or severe complications, surgery should be considered[30]. Jassal et al. reported a case illustrates that extensive bilateral PPIE associated with a persistent pneumomediastinum can resolve spontaneously thus demonstrating that conservative management without surgical intervention may be appropriate for some children[29]. Infants with PPIE and weighing less than 1000g are at significant risk of mortality and associated morbidity of PPIE[31].
The mechanism of production of PIE is the disruption of the alveolar wall basement membrane with subsequent dissection of air into the interstitial space. Given et al. [32] showed that PIE in bronchiolitis is thought to occur secondary to inflammation leading to mucosal edema, increased secretion and cellular debris, resulting in expiratory obstruction of the small airways, the resulting check-valve effect leads to hyperinflation then alveolar rupture. Another study[11] has demonstrated that pneumonia may contribute to the development of pulmonary air leaks by at least three mechanisms: firstly, air trapping from mechanical or check-valve obstruction within the bronchi by mucus and inflammatory exudates; Secondly, reduced strength or direct disruption of the alveolar lining from parenchymal inflammation or necrosis as commonly seen in necrotizing pneumonia, and thirdly, decreasing lung compliance.
There was obvious inflammatory reaction in present six rare cases. There are few reports of pulmonary air leakage with respiratory infection. There were just nine previous articles including 12 patients with PPIE with respiratory infection from a PubMed search[11-19]. Review of published literature of PIE with respiratory infection was showed inTable 3 . Gala et al. [16] did not mention the sex of the case, so there were seven females and four males, ranged from birth to 87 years. Only 50% (6/12) patients with PPIE were treated with surgery. 72.2% (8/11) were full-term, and 58.3% (7/12) without mechanical ventilation. There was pulmonary air leakage, pneumothorax (5/12 cases) and pneumomediastinum (2/12 cases). According to the previous reported PIE patients with respiratory infection, there were nine patients without certain infectious pathogens reported[11, 12, 14, 16-18], and the other three patients were infected by respiratory syncytial virus[13], Candida albicans[19], and respiratory sincitial virus[15], respectively. In our study, the common symptoms of the patients were cough, fever and expectoration. Special stains (acid fast stain, Gomori’s methenamine silver staining, and Giemsa) and TB-PCR did not find any identifiable organism or foreign material in our study. Streptococcus pneumonia was detected in patient No.1, whose infectious symptoms were present when surgery. Neisseria mucosa, Neisseria sicca, Prevotel lamelaninogenica, Prevotella histicola, and Fusobacterium nucleatum were detected in patient No.5, and all the bacteria were Gram-negative. Patient No.5 has suffered the disease Langerhans cell histiocytosis (LCH) in the left submandibular lymph node for 1 year, and has received the suggested chemotherapy treatment four times, and then she had suffered recurrent pneumonia for three months, so the detected infectious pathogens may be associated with the chemotherapy treatment for LCH. No infectious pathogen was detected in other 66.7% (4/6) cases with pneumonia prior to surgery, whose infectious symptoms were controlled with conventional anti-infective treatment before surgery.