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.