Pulmonary interstitial emphysema (PIE) is a rare, abnormal pathology that occurs more commonly in neonates but can be seen in adults as well. The increased air pressure within the alveoli and alveolar airspaces can disrupt the adjacent lung interstitial tissue, damaging the lung structure and causing linear and cystic spaces that can be complicated with air leaks. The leaked air is collected outside normal air passages and inside the interstitium or bronchovascular complexes. Premature infants with pulmonary interstitial emphysema can develop respiratory distress syndrome. The critical goal is to be able to maintain sufficient gas exchange. Without adequate gas exchange, lungs will be damaged, resulting in prolonged hypoxia, respiratory acidosis, and pulmonary hypoperfusion.
PIE is a diagnosis based on imaging and histopathology. Administration of surfactant and high-frequency ventilation has been shown to decrease the incidence of PIE in premature infants. The latest management of infants with respiratory distress syndrome is prophylaxis with synthetic surfactant and continuous positive airway pressure, possibly without mechanical ventilation.
Neonatal etiologies include:
Other causes in adults include:
Pulmonary interstitial emphysema (PIE) occurs more commonly in premature infants within the first few weeks of birth. Premature infants that develop PIE within 48 hours of life usually have a grave prognosis. These infants may have associated low birth weight, premature birth, perinatal asphyxia, and sepsis. In old studies, there was no difference in the development of PIE among different sexes. A retrospective study showed that out of the extremely premature infants on ventilators who were treated with antenatal steroids, tocolysis, and postnatal surfactant administration, 24% had developed PIE later in their hospital course.
The prevalence of the pathology depends on which population is studied, whether it is patients with low birth rates versus respiratory distress syndrome versus other etiologies. In one study, infants with respiratory distress syndrome born prematurely at less than 30 weeks, PIE occurred in 3% of neonates treated early with the surfactant, 8% of neonates treated with surfactant late, and 25% of neonates that served as control.
A different study that compared surfactant administration as prophylaxis versus early treatment in premature infants showed that there was a higher incidence of PIE in premature infants and those treated with surfactant late. Premature infants born 25 to 29 weeks of gestation that were randomly treated with surfactant at birth resulted in PIE in 15% of the treated infants and 26% of the control infants.
Premature infants weighing less than 1000g at birth showed the highest frequencies of developing PIE. Infants that weighted 500 to 799g had an incidence of 42% of PIE, infants weighing 800 to 899g had an incidence of 29%, and infants weighing 900 to 999g had an incidence of 20%.
The pathophysiology of pulmonary interstitial emphysema (PIE) revealed the alveolar hyperdistention and bronchial duct gland ectasia formation resulting in tissue rupture. Some causes of air leaks and alveolar rupture are from insufflation (mechanical ventilation or positive pressure ventilation), uneven ventilation, and reduce lung compliance, especially since the lungs are underdeveloped and very sensitive to stretch.
The increased transpulmonary pressure being higher than the tensile strength of the alveolar and airways will injure the respiratory epithelium. The injury to the epithelium is where the air will enter the interstitium from and the air leak into the perivascular tissue of the lung due to the high intra-alveolar pressure. The air will also leak into the pleural connective tissue of the peribronchovascular sheaths, interlobular septa, and visceral pleura. The air is then trapped in the interstitium, which causes compression atelectasis of the adjacent lung. The infant will then have associated respiratory distress syndrome. Surface active phospholipids are also lost from hyperinflation and overinflation.
Two common types of air leaks are intrapulmonary pneumatosis and intrapleural pneumatosis. Intrapulmonary pneumatosis is much more common. The air trapped inside the lung is underneath the pleura in the interlobular septa. Intrapleural pneumatosis occurs more commonly in mature infants with normal lungs. The abnormal air pockets are within the visceral pleura and affect mediastinal pleura.
The complications of PIE vary from an isolated interstitial bubble to lesions of unilateral lung or lesions bilaterally. It damages the functional tissue and vascular structure with fibrotic and inflammatory changes. The pathology also results in fibroblast foci with organizing and interstitial pneumonia, granulomatous disease, and sometimes lymphangiectasia. This prevents both ventilation and perfusion, affecting the systemic oxygenation and perfusion of the rest of the body, which increases morbidity and mortality of the infant. The resolution of PIE can be spontaneous, or it can result in pneumomediastinum, pneumothorax, or subcutaneous emphysema. Air can also leak into the pericardium or peritoneum.
Autopsy of a previous case revealed bilateral pleural hyperinflation that stayed inflated even after the thoracic cavity was opened. There were many mucus plugs but no effusions in the pleura or pericardium. Histologically, the autopsy revealed thickening of the airway and basement membrane, along with inflammation of airway lumens and eosinophils, mimicking asthma. The airways were filled with mucus exudates. Case series revealed hyperdistention and revealed signs of alveolar tear, parabronchial and perivascular widening, and connective tissue tearing all pointing towards pulmonary interstitial emphysema.
Pulmonary interstitial emphysema (PIE) is a diagnosis made mainly from imaging and histopathology; however, few clinical signs in history can suggest this diagnosis. It is crucial to consider the risk factors for PIE, which are mainly premature birth and low birth weight. Some nonspecific clinical signs in both adults and infants that are associated with PIE are increased oxygen requirements, which can progressively and rapidly increase carbon dioxide retention.
There are no physical exam findings specifically to help make the diagnosis. If PIE has already progressed, there can be signs of air leaks, so upon physical exam, it is important to monitor for air leaks such as decreased breath sounds, crepitus heard on the affected side, or over-inflation of the chest wall.
Pulmonary interstitial emphysema (PIE) is partially a radiologic diagnosis. On imaging, PIE shows the lung parenchyma filled with a mix of spherical cystic, linear, and oval air containing lucencies. Early changes appear to be linear but slowly progresses to the more cystic formation in the interstitium. Linear radiolucencies are about 3-8 mm long and less than 2 mm in width. Cystic-like radiolucencies measure 1-4 mm in diameter. During inspiration, the lung volumes may increase, but premature lungs have decreased lung compliance resulting in hyperdistended lungs on imaging.
Air leaks can also be seen on imaging. With air leaks, the air in the interstitium is full of large volumes of air, which reduces the gas exchange between the vascular bed and airspaces due to the increased distance. Pneumothorax can form if subpleural cysts end up rupturing. The air leak compresses on the heart from the increased intrathoracic pressures and results in decreased venous return to the heart. Other findings seen on imaging are linear gas collections in the periphery. This is usually seen with increased demand for respiratory support and increased lung volumes, which are diagnostic markers for PIE.
Sometimes early bronchopulmonary dysplasia can be seen in the setting of partial bronchia obstructions. Histopathological findings in infants with bronchopulmonary dysplasia can show PIE, even if not seen on imaging. A previous case study revealed a CT completed before the autopsy, which showed pleural wall thickening and constricted airways. Imaging showed pulmonary hyperinflation and localized interstitial emphysema.
PIE can sometimes be seen on the anteroposterior supine chest X-ray, but it requires sequential studies to see the disease progression. There may be some difficulty differentiating lucent bronchiole overdistention from PIE, but airways that are distended are also round and uniform. PIE tends to be more elliptical of various sizes in the bronchovascular bundles. The radiolucencies are not consistent with the normal bronchial tree. PIE can sometimes be misinterpreted as pulmonary edema or aspiration syndrome if the normally aerated lung seems surrounded by exudate. Air bronchograms are signs of respiratory distress syndrome, not PIE. It can also be mistaken if an infant is on a mechanical ventilator, the airways and alveoli can appear similarly distended as in PIE. If a chest X-ray is unable to differentiate, then a CT scan would be the next step for diagnostic imaging.
Infants with pulmonary interstitial emphysema (PIE) are treated in neonatal ICU as these patients are critically ill and can develop complications such as pneumothorax, pneumopericardium, and require mechanical ventilation. They may also need invasive procedures such as thoracentesis, chest tubes, along with vitals monitoring closely. There are a few approaches for the management of PIE; however, success rates vary. A high number of PIE infants tend to be premature. Firstly, the use of surfactant in premature infants (<30 to 32 weeks) may reduce PIE development by preventing the occurrence of respiratory distress syndrome. Secondly, if mechanical ventilation is avoidable, then it should be avoided because high oxygen pressure can damage the infant's underdeveloped lungs. CPAP should be attempted first, although it can also cause PIE. Ventilator settings should be focused on reduced inspiratory time, prolong expiratory time, and decreased pressure while adjusting PEEP. This should allow the airway to empty upon expiration properly. These infants require close monitoring of vitals, oxygen, blood gas, and nutrition.
There are a few preventive measures to prevent PIE. The prophylactic surfactant can be administered in preterm infants who are at risk of respiratory failure as it has shown to decrease risk. It has been observed that the incidence of air leaks is reduced in premature infants if the surfactant is administrated early with brief ventilation.
A more conservative approach is lateral decubitus positioning. It is more effective in infants with unilateral PIE and has been successful. One case study showed that with this approach, unilateral PIE had resolved within 2 to 6 days. There are low failure rates and minimal recurrence. Lateral decubitus positioning helps with bilateral PIE if one side is affected more significantly. The lung that is not affected will have improved oxygen, which will decrease the ventilator settings.
Surfactant is used in premature infants for prophylactic and management of respiratory distress syndrome. Surfactant is available as natural or synthetic and administrated through intratracheal administration. Surfactant helps decrease the surface tension between air and alveolar surface, so it prevents the collapse of the alveoli upon expiration.
Natural surfactants are normally derived from animals, more commonly bovine then porcine. It has been found to very similar to human surfactants. There has been success in using them. Some obstacles with surfactant use are that efficiency is inconsistent; there is a risk of pathogen contamination, lack of cost-effectiveness, and possible anaphylactic shock reaction. Currently used surfactants are the following: Survanta is made of bovine lung extract, beractant is made of porcine lung extract, and calfactant is a bovine broncho-alveolar extract.
A few synthetic surfactants have been studied to be therapeutic and better than natural surfactants. Colfosceril palmitate only contains phospholipids and is protein-free. Lucinactant is one of the newer surfactants that contain protein and have been studied to be better and more effective.
High-frequency positive pressure ventilation has been proven to be a preventive measure of air leaks and PIE when compared to conventional mechanical ventilation in some studies. Still, data is limited, and others have proven to be no different. Other studies have shown that elective or preventive high-frequency ventilation might not help in the development of PIE.
If an infant is in severe respiratory distress, there have been cases that have successively treated infants with selective intubation of contralateral bronchus of patients affected by PIE. This allows the over-distended lung tissue to decompress. That lung will also be prevented from being exposed to high positive oxygen pressures. Selective bronchial intubation of the left side bronchus is more complicated than the right side because the endotracheal tube needs to be inserted an additional 2 to 4 cm as compared to the right. Upon intubation, the bevel must be directed toward the bronchus of choice to increase the chance of intubating the correct bronchus.
Another method that may help with intubation is turning the infant's head contralateral to the side of intubation, which may help with the intubation of the bronchus of choice. Small fibrotic bronchoscope or intubation under fluoroscopy can be done. The possible complications to be aware of are atelectasis, hyperinflation of the intubated lung, upper lung collapse, acute hypoventilation or hypoxemia, injury to bronchial mucosa, or bradycardia. This is preferred over lobectomy.
A study found that high-frequency oscillatory ventilation is better compared to rapid-rate ventilation. These settings were found to be safe and effective for PIE in infants. These settings resulted in similar oxygenation as rapid rate ventilation with lower peak and mean airway pressures. This prevented any air leaks into the mediastinum and interstitial spaces, whereas conventional ventilation had resulted in respiratory failure in patients that had PIE. Eighty percent of the infants survived with high-frequency ventilation and required a low fraction of inspired oxygen, while treated for PIE. These patients must be closely monitored because high-frequency oscillatory ventilation can exacerbate gas trapping and airway collapse. Even transitioning to low-frequency oscillatory ventilation has shown improvements in both unilateral and bilateral PIE.
Lobectomy is considered one of the last resort therapies due to its being an invasive procedure. Lobectomies are considered when medical management fails, and spontaneous resolution does not occur. This is considered in infants who have severe emphysema as previous results are successful.
Other Methods of Management
Few other rare case reports of other methods of management have included artificial pneumothorax, chest physiotherapy with oxygen therapy, steroid treatment, ECMO, and even nitric oxide treatment. However, these treatments are questionable and not commonly used.
Pulmonary interstitial emphysema (PIE) is a radiologic and histopathologic diagnosis. The following must be ruled out which can usually be achieved by CT scan of the chest:
Diagnosis of pulmonary interstitial emphysema (PIE) is ultimately a poor prognosis. Studies have shown high mortality rates of 53 to 67%. Studies of infants with PIE with a low birth weight of fewer than 1600 grams and severe respiratory distress syndrome have grave prognosis with a reported mortality of 80%. PIE is known to cause air leaks such as pneumothorax and mediastinal emphysema, which also increases mortality. If PIE appears early, it is associated with increased mortality due to severe underlying parenchymal disease.
It takes a few weeks for PIE to resolve with proper management; however, this leads to prolonged mechanical ventilator use and complications associated with prolonged ventilator use, such as bronchopulmonary dysplasia or chronic lobar emphysema. These may require surgical lobectomies. One study showed that 54% of PIE survivors developed chronic lung emphysema, and 50% of these infants required surgical lobectomies. Studies showed that infants with PIE also developed intraventricular hemorrhage and that PIE was still strongly associated with death.
Pulmonary interstitial emphysema (PIE) is a severe disease. The following complications are associated with it.
Post-treatment monitoring is necessary for premature infants. Complications to monitor are periventricular leukomalacia, intraventricular hemorrhage, and developmental delay. Infants can develop chronic lung disease and need to follow a pulmonologist. Literature is unclear regarding if chronic lung disease will benefit from bronchodilator treatment.
Management of pulmonary interstitial emphysema (PIE) is multidisciplinary teamwork. The following specialties are involved in the care of such patients.
Preventive measures during pregnancy must be discussed in infants that are high-risk for pulmonary interstitial emphysema (PIE).
Keep the following pearls in mind:
With premature infants that are high risk for pulmonary interstitial emphysema (PIE), they must be monitored closely in NICU. These infants need a strong interprofessional team to coordinate the care among pediatricians, pulmonologists, intensivists, and surgeons. CPAP and synthetic surfactants are currently the latest management for the prevention of PIE in patients with respiratory distress syndrome. Patients must be monitored closely by pediatricians and pulmonologist after recovery for any long-term effects. With appropriate communication, the management of these critical patients can be done on time.
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