Pulmonary Interstitial Emphysema 

Updated: Jun 25, 2019
Author: Abhay J Bhatt, MD, MBBS; Chief Editor: Muhammad Aslam, MD 

Overview

Pearls

Keep the following pearls in mind:

  • Pulmonary interstitial emphysema (PIE) is a common comorbidity of neonates that is mainly associated with the etiologic triad of prematurity, respiratory distress syndrome (RDS), and mechanical ventilation therapy.
  • PIE is mainly a radiologic and pathologic diagnosis. It is associated with few clinical signs, but a progressive, sometimes rapid, increase in O 2 requirements, CO 2 retention, or hypotension are suggestive of this diagnosis.
  • The reported incidence varies widely depending on various factors such as gestational age, use of surfactant therapy, and different modes of mechanical ventilation. In the postsurfactant era, the reported incidence is between 3% and 8%. Clinical research is needed, with a specific emphasis on the incidence of, and outcomes in, PIE in the current era of innovative ventilatory strategies.
  • Although prematurity—the primary risk factor for PIE—is nonmodifiable, attention must be given to judicial treatment of RDS with early administration of surfactant and optimal use of mechanical ventilator support. An often-used strategy is to reduce the inspiratory time and/or decrease pressure along with adjusting the positive-end expiratory pressure (PEEP) enough to stent the airway will allow better emptying of the alveoli during expiration. [1] Close clinical observation by monitoring oxygen need, work of breathing and perfusion status, as well as judicious analysis of blood gas and chest x-ray, are essential to determine an optimal PEEP for a particular infant.
  • Consequences of PIE can be other air leak syndromes, such as pneumomediastinum, pneumothorax, or penumopericardium, if not enough attention and management strategies are applied.
  • If PIE develops, various management strategies include lateral decubitus positioning, selective main bronchial intubation and occlusion, and lobectomy for unilateral cases. Studies has shown the benefit, safety, and effectiveness of high frequency jet and oscillatory ventilation; it is been shown to reduce the peak airway pressure (P IP) and mean airway pressure (MAP) requirements to achieve the same oxygenation and ventilation goals.

Background

Pulmonary interstitial emphysema (PIE) is a collection of gases outside of the normal air passages and inside the connective tissue of the peribronchovascular sheaths, interlobular septa, and visceral pleura. This condition develops when the most compliant portion of the terminal airway ruptures, allowing gas to escape into the interstitial space.[2] Pulmonary interstitial emphysema essentially, if not exclusively, occurs in preterm infants with immature lungs, usually after mechanical ventilation therapy,[3, 4, 5] but occasionally in the absence of mechanical ventilation.[6, 7, 8, 9] PIE is broadly classified under pulmonary air leak syndromes.

PIE is a radiographic and pathologic diagnosis (see image below and Workup). The introduction of surfactant and newer ventilator modalities has decreased the incidence of PIE. Its treatment of PIE is mainly preventive by using the minimum pressures or volume compatible with an acceptable gas exchange as well as early administration of selective surfactant, if indicated, to infants with respiratory distress syndrome (RDS). Therefore, minimizing the use of invasive ventilator support and favoring spontaneous ventilation under nasal continuous positive airway pressure (CPAP) is probably the best preventive measure. The principal therapies are lateral decubitus positioning, selective intubation, and occlusion of the contralateral bronchus, in conjunction with high-frequency or jet ventilation.[3, 4, 10] Intensive respiratory management is required to reduce morbidity and mortality in these patients.

This radiograph, obtained from a premature infant This radiograph, obtained from a premature infant at 26 weeks' gestation, shows characteristic radiographic changes of pulmonary interstitial emphysema (PIE) of the right lung.

See the Medscape Drugs & Diseases articles Imaging in Pulmonary Interstitial Emphysema, Respiratory Distress Syndrome, Respiratory Distress Syndrome Imaging, Bronchopulmonary Dysplasia, and Imaging in Bronchopulmonary Dysplasia for more information on these topics.

Pathophysiology

Pulmonary interstitial emphysema (PIE) is initiated when air ruptures from the alveolar air space and small airways into the perivascular tissue of the lung. Air leaks result from high intra-alveolar pressure more frequently due to mechanically applied pressure (insufflation), retention of large volumes of gas, and uneven ventilation, leading to rupture of the small airways or alveoli. Transpulmonary pressures that exceed the tensile strength of the noncartilaginous terminal airways and alveolar saccules can damage the respiratory epithelium. Loss of epithelial integrity permits air to enter the interstitium, causing pulmonary interstitial emphysema. The process often occurs in conjunction with respiratory distress syndrome (RDS).

Other predisposing etiologic factors include meconium aspiration syndrome (MAS), amniotic fluid aspiration, and infection (which can include chorioamnionitis[11]  or congenital pneumonia). The highest incidence of PIE in tiny infants has been observed when intrauterine pneumonia complicates the respiratory distress syndrome (RDS). It is also been reported with respiratory syncytial virus (RSV) infection or other bronchiolitis in term infants which can be mimicked by congenital cystic adenomatoid malformation.[3, 12]

Positive pressure ventilation (PPV) and reduced lung compliance are significant predisposing factors. Studies have shown that hyperventilation and overinflation of the lungs increase the loss of surface active phospholipids.[13] However, in extremely premature infants, PIE can occur at low mean airway pressure and probably reflects the underdeveloped lung’s increased sensitivity to stretch. PIE has been rarely reported in the absence of mechanical ventilation or continuous positive airway pressure (CPAP).[7, 8] Incorrect positioning of endotracheal tube may be responsible for localized PIE.[14]

Infants with RDS have an initial increase in interstitial and perivascular fluid that rapidly declines over the first few days of life. This fluid may obstruct the movement of gas from ruptured alveoli or airways to the mediastinum, thereby causing an increase of PIE. This occurs more commonly in preterm infants due to the structural immaturity of the lung, mainly owing to a lack of elastic tissue and the presence of large interstitium as a result of poor alveolation. The entrapment of air in the interstitium may initiate a vicious cycle in which compression atelectasis of the adjacent lung then necessitates a further increase in ventilatory pressure with still more escape of air into the interstitial tissues.

Plenat et al described two topographic varieties of air leak: intrapulmonary pneumatosis and intrapleural pneumatosis.[15] In the intrapulmonary type, which is more common in premature infants, the air remains trapped inside the lung and frequently appears on the surface of the lung, bulging under the pleura in the area of interlobular septa. This phenomenon develops with high frequency on the costal surface and the anterior and inferior edges, but it can involve all of the pulmonary areas. In the intrapleural variety, which is more common in more mature infants with compliant lungs, the abnormal air pockets are confined to the visceral pleura, often affecting the mediastinal pleura. The air of PIE can be located inside the pulmonary lymphatic network.[16]

The extent of PIE can vary. It can present as an isolated interstitial bubble, several slits, lesions involving the entire portion of one lung, or diffuse involvement of both lungs. PIE does not preferentially localize in any one of the five pulmonary lobes.

PIE compresses adjacent functional lung tissue and vascular structures and hinders both ventilation and pulmonary blood flow, thus impeding oxygenation, ventilation, and blood pressure. This further compromises the already critically ill infant and significantly increases morbidity and mortality. PIE can completely regress or decompress into adjacent spaces, causing pneumomediastinum, pneumothorax, pneumopericardium, pneumoperitoneum, or subcutaneous emphysema.[17]

Etiology

Risk factors for pulmonary interstitial emphysema (PIE) include the following:

  • Prematurity
  • Respiratory distress syndrome (RDS)
  • Meconium aspiration syndrome (MAS)
  • Amniotic fluid aspiration
  • Infection: Exposure to chorioamnionitis, neonatal sepsis, or pneumonia,
  • Low Apgar score or need for positive pressure ventilation (PPV) during resuscitation at birth
  • Use of high peak airway pressures on mechanical ventilation therapy in the first week of life
  • Incorrect positioning of the endotracheal tube in one bronchus
  • Antenatal exposure to magnesium sulfate [18] : More investigation is needed

Independent risk factors for PIE in preterm infants include higher oxygen requirements during resuscitation as well as greater need for surfactant and higher ventilatory pressures before confirmation of the diagnosis.[5]

Epidemiology

United States data

The prevalence of pulmonary interstitial emphysema (PIE) widely varies with the population studied. In a report by Gaylord et al, PIE developed in 3% of infants admitted to the neonatal intensive care unit (NICU).[20]

In a retrospective case-controlled study, 11 (24%) of 45 extremely low birth weight infants developed PIE.[18] This study was done in the present era of tocolysis, antenatal steroids, and postnatal surfactant administration; however, all infants included in the study were treated with a conventional ventilator in the assist-control mode before the onset of PIE.

The reported incidence of PIE in published clinical trials can be useful. In a randomized trial of surfactant replacement therapy at birth in premature infants born at 25-29 weeks' gestation, Kendig et al reported PIE in 8 (26%) of 31 control neonates, and in 5 (15%) of 34 surfactant-treated neonates.[21]

Another randomized controlled trial of prophylaxis versus treatment with bovine surfactant in neonates with respiratory distress syndrome (RDS) born at less than 30 weeks' gestation included 2 (3%) of 62 early surfactant-treated neonates, 5 (8%) of 60 late surfactant-treated neonates, and 15 (25%) of 60 control neonates with PIE.[22]

Kattwinkel et al compared prophylactic surfactant administration versus the early treatment of RDS with calf lung surfactant in neonates born at 29-32 weeks' gestation; 3 of 627 neonates in the prophylaxis group and 3 of 621 neonates in the early treatment group developed PIE.[23]  This information suggests a higher incidence of PIE in more immature infants as well as those administered with late surfactant therapy.

International data

Studies reflecting the international frequency of PIE demonstrated that 2-3% of all infants in NICUs develop this condition.[11, 24] When limiting the study population to premature infants, the frequency increases to 20-30%, with the highest frequencies occurring in infants weighing less than 1000 g.[25]  A trial that compared high-frequency positive pressure mechanical ventilation (HFPPV) with conventional ventilation revealed a 25.8 % and 6.5% incidence of PIE in the respective groups.[26]

In another study of low birth weight infants, the incidence of PIE was 42% in infants with a birth weight of 500-799 g, 29% in those with a birth weight of 800-899 g, and 20% in those with a birth weight of 900-999 g.[27]  Unfortunately, minimal information is available about the prevalence of PIE in the postsurfactant era.

In a prospective multicenter trial comparing early high-frequency oscillatory ventilation (HFOV) and conventional ventilation in preterm infants of fewer than 30 weeks' gestation with RDS, 15 (11%) of 139 infants in the high-frequency group and 15 (11%) of 134 infants in the conventional group developed PIE.[24]

Sex- and age-related demographics

In a study by Plenat et al, PIE developed about equally in both sexes (21 males, 18 females).[15]  Although these data also included cases with intrapleural pneumatosis, no relationship between sex and type of interstitial pneumatosis was noted.

PIE is more common in infants of lower gestational age, and it usually occurs within the first weeks of life. That is, development of PIE within the first 24-48 hours after birth is often associated with extreme prematurity, very low birth weight, perinatal asphyxia, and/or neonatal sepsis—and frequently indicates a grave prognosis.

Prognosis

Pulmonary interstitial emphysema (PIE) can predispose an infant to other air leaks. In a study by Greenough et al, 31 of 41 infants with PIE developed pneumothorax, compared to 41 of 169 infants without PIE.[8] In addition, 21 of 41 babies with PIE developed intraventricular hemorrhage (IVH), compared to 39 of 169 among infants without PIE.

PIE may not resolve for 2-3 weeks; therefore, it can increase the duration of mechanical ventilation support as well as the incidence of bronchopulmonary dysplasia (BPD). Some infants may develop chronic lobar emphysema, which may require surgical lobectomies.[19]

In a study in the postsurfactant era, 4 of 11 infants with PIE developed severe IVH (grade 2 or higher) compared to 4 of 34 infants without PIE. Additionally, PIE remained significantly associated with death (odds ratio, 14.4; 95% confidence interval, 1-208; P = 0.05).[18]

Long-term follow-up data are scarce. Gaylord et al demonstrated a high (54%) incidence of chronic lung disease in survivors of PIE compared to their nursery's overall incidence of 32%.[20]  In addition, 19% of the infants with PIE developed chronic lobar emphysema; of these babies, 50% received surgical lobectomies.

The mortality rate associated with PIE is reported to be as high as 53-67%.[20, 25] Lower mortality rates of 24% and 38% reported in other studies could result from differences in population selection.[8, 11] Morisot et al reported an 80% mortality rate with PIE in infants with a birth weight of fewer than 1600 g and severe respiratory distress syndrome.[28]

The early appearance of PIE (< 48 h after birth) is associated with increased mortality. However, this may reflect the severity of the underlying parenchymal disease.[11, 28]

Complications

Potential complications of PIE include the following:

  • Respiratory insufficiency
  • Other air leaks (eg, pneumomediastinum, pneumothorax, pneumopericardium, pneumoperitoneum, subcutaneous emphysema [rare])
  • Massive air embolism
  • Chronic lung disease of prematurity
  • IVH
  • Periventricular leukomalacia
  • Death
 

Presentation

History and Physical Examination

History

Pulmonary interstitial emphysema (PIE) is a radiographic and pathologic diagnosis. PIE is associated with few clinical signs, but a progressive, sometimes rapid, increase in oxygen (O2) requirements, carbon dioxide (CO2) retention or hypotension are suggestive of this diagnosis.

Alternatively, the infant can present with the signs of one of the complications of PIE, such as pneumothorax. Occasionally, PIE becomes apparent following reexpansion of a collapsed lung after drainage of a pneumothorax.

Physical examination

No specific signs of PIE are reported. There may be overinflation of the chest wall and crepitations on auscultation on the affected side. A characteristic sound of crushing styrofoam or walking on dry snow signals PIE.

 

DDx

Diagnostic Considerations

The roentgenologic appearance of pulmonary interstitial emphysema (PIE) can be confused with the following[29] :

  • Air bronchograms in respiratory distress syndrome (RDS)
  • Aspiration pneumonia
  • Pulmonary edema
  • Distended airways in patients on mechanical ventilatory support

Other differential diagnosis of persistent pulmonary interstitial emphysema includes the following:

Differential Diagnoses

 

Workup

Approach Considerations

 

 

Radiography

Pulmonary interstitial emphysema (PIE) is a radiographic and pathologic diagnosis. However, obtain blood gases in affected infants to ensure adequate gas exchange.

The classic radiologic appearance of PIE often provides a clear diagnosis. PIE is best visualized in the anteroposterior supine projection. This condition has two basic radiographic appearances, linear or cystlike radiolucencies, although both types often appear together.

Linear radiolucencies are coarse and nonbranching, measure from 3 to 8 mm, and vary in width but rarely exceed 2 mm. Cystlike radiolucencies are small, ranging from 1 to 4 mm in diameter; although generally round, they may also appear oval or slightly lobulated.

The disorganized, haphazard distribution of PIE in localized areas is unlike the anatomically organized pattern of the air bronchogram. The air bronchogram is a classic radiographic sign of respiratory distress syndrome (RDS), which should not be confused with PIE.

In RDS, long, smooth, branching, linear radiolucencies decrease in caliber from the hilum and frequently disappear at the lung periphery. PIE should be suspected when coarse radiolucencies appear in the lung periphery or when the lucencies do not branch in a pattern consistent with the normal bronchial tree.

In some infants receiving mechanical ventilation therapy, the distended airways and alveoli have a somewhat similar radiographic appearance to that of PIE. Over time, this either progresses to a classic radiographic picture of PIE or resolves very rapidly as the ventilator settings are lowered.

Rarely, PIE can be misinterpreted as a normally aerated lung surrounded by exudate, as in an aspiration syndrome or pulmonary edema.[29]

The first radiograph below shows a right-sided pneumothorax and PIE. Interstitial air prevents collapse of the underlying lung by a tension pneumothorax. In such cases, extreme caution is required during drainage of the pneumothorax to avoid perforation of the underlying lung.

This radiograph shows pneumothorax and pulmonary i This radiograph shows pneumothorax and pulmonary interstitial emphysema (PIE) on the right side. Interstitial air prevents collapse of the underlying lung by a tension pneumothorax. In such cases, extreme caution is required during drainage of a pneumothorax to avoid perforation of the underlying lung.
This radiograph, obtained from a 1-day-old prematu This radiograph, obtained from a 1-day-old premature infant at 24 weeks' gestation, shows bilateral pulmonary interstitial emphysema (PIE). Linear radiolucencies extending up to the lung periphery are visible.
This radiograph, obtained from a premature infant This radiograph, obtained from a premature infant at 26 weeks' gestation, shows characteristic radiographic changes of pulmonary interstitial emphysema (PIE) of the right lung.

Computed tomography (CT) scanning of the chest can be a helpful diagnostic tool if doubt about the diagnosis remains, particularly in persistent cases and if surgical interventions are being considered. A round or linear soft-tissue component seen in the wall of or within the air-containing spaces is a key to making the correct diagnosis.[30]  In addition, the presence of subpleural PIE, in which there is an interstitial air collection in the subpleural region of the lungs excluding the bronchovascular bundle, on CT scan suggests single or multiple alveolar rupture(s) as an origin of pneumomediastinal air.[2]  

See the Medscape Drugs & Diseases articles Imaging in Pulmonary Interstitial Emphysema, Respiratory Distress Syndrome Imaging, and Imaging in Bronchopulmonary Dysplasia for more information on these topics.

Histologic Findings

The histology of pulmonary interstitial emphysema (PIE) has been well described by Plenat et al.[15]  Interstitial slits are preferentially located in the perivenous topography.

Occasionally, the peribronchial arterial or arteriolar sheaths are involved. Air dissects through a plane just next to the arterial or arteriolar face, opposite the bronchus, which is pushed into adjoining parenchyma. Most often, the bronchoarterial solidarity is respected.

Seldom, air can dissect arterioles and bronchioles and isolate them from the adjacent lobules. On the periphery of interstitial slits, the small vessels are compressed but never ruptured, whereas the collagen fibers are constantly broken and squeezed together.

 

Treatment

Approach Considerations

Admission/transfer to a neonatal intensive care unit (NICU) is indicated for infants with pulmonary interstitial emphysema (PIE). A thoracentesis set should be readily available due to the possibility of air leak, including pneumothorax and pneumopericardium.

Different treatment modalities have been used to manage PIE, with variable success.

Although the primary risk factor for PIE, prematurity, is rarely preventable, attention should be given to the use of as little mechanical ventilatory support as is necessary for the infant's very fragile lungs. An often-used strategy is to reduce the inspiratory time and/or decrease pressure along with adjusting the positive-end expiratory pressure (PEEP) enough to stent the airway will allow better emptying of the alveoli during expiration.[1] Close clinical observation by monitoring oxygen need, work of breathing and perfusion status, as well as judicious analysis of blood gas and chest x-ray, are essential to determine an optimal PEEP for a particular infant.

Because pneumothorax is a known complication of PIE, anticipatory guidance for this possibility should be provided for all those caring for the infant. Appropriate personnel should be readily available to address this complication.

In addition to pulmonary treatment, the overall importance of appropriate nutritional management of these ill newborns cannot be overstressed. Most of these infants are treated with total parenteral nutrition, and their nutritional needs require diligent attention.

All infants with PIE need to be under the care of a neonatologist. In some cases, pediatric pulmonology and pediatric surgery consultations are appropriate.

Lateral Decubitus Positioning

Lateral decubitus positioning is a conservative approach that has been used successfully in infants with pulmonary interstitial emphysema (PIE), and it is most effective in infants with unilateral PIE. In different case studies of lateral decubitus positioning as a treatment of unilateral PIE in infants, PIE resolved in 48 hours to 6 days with minimal recurrence and a low failure rate. Thus, lateral decubitus positioning should be considered as an early first-line therapy in the management of unilateral PIE; it has also been used successfully for patients with bilateral PIE when one side is more significantly affected.

Place the infant in the lateral decubitus position, with the affected lung dependent. This therapy can result in plugging of dependent airways and improved oxygenation of the nondependent lung. The latter allows for an overall decrease in ventilatory settings. The combination of the above factors helps in resolving PIE.[31]

Selective Main Bronchial Intubation and Occlusion

Many case reports detail successful treatment of infants with severe localized pulmonary interstitial emphysema (PIE) by selective intubation of the contralateral bronchus.[32, 33, 34]  This maneuver decompresses the overdistended lung tissue and avoids exposing it to high positive inflationary pressures. Selective bronchial intubation of the right main bronchus is not a difficult procedure; the left side may be more difficult.

This procedure uses an endotracheal tube of the same diameter as for a regular intubation. However, the tube is inserted 2-4 cm beyond its usual position. It is introduced with the bevel on the end of the tube positioned so that the long part of the tube is toward the bronchus to be intubated. This increases the chance of the tube entering the correct bronchus as it is advanced into the airway. Turning the infant's head to the left or right moves the tip of the endotracheal tube to the contralateral side of the trachea and may help in selective tube placement.

Weintraub et al described a method for left selective bronchus intubation using a regular Portex endotracheal tube in which an elliptical hole 1 cm in length has been cut through half the circumference about 0.5 cm above the tip of the oblique distal end.[34]  By directing the side with the elliptical hole to the left lung, left selective bronchus intubation can be easily and repeatedly accomplished.

Another method of selective intubation is the use of a small fiberoptic bronchoscope to direct the endotracheal tube tip into the desired bronchus. Selective intubation under fluoroscopy can also be considered.

Potential complications of selective intubation/ventilation include the following:

  • Atelectasis in the affected lung
  • Injury to the bronchial mucosa, with subsequent scarring and stenosis
  • Acute hypoventilation or hypoxemia if ventilating one lung is inadequate
  • Excessive secretions
  • Hyperinflation of the intubated (nonoccluded) lung
  • Upper lobe collapse when intubating the right lung
  • Bradycardia

Despite the potential risks, selective bronchial intubation is a desirable alternative to lobectomy in a patient with persistent, severe localized PIE that is causing a mediastinal shift and compression atelectasis that is refractory to conservative management. This procedure should be attempted before any surgical intervention.

High-Frequency Ventilation

Keszler et al found that high-frequency ventilation was safe and more effective than rapid-rate conventional ventilation in the treatment of newborns with pulmonary interstitial emphysema (PIE).[35]  In their study of 144 newborns with PIE, the use of high-frequency ventilation resulted in similar oxygenation and ventilation obtained at lower peak and mean airway pressures. These results suggested that less air would leak into the interstitial spaces in these infants.

Similar effects can be achieved by use of high-frequency oscillatory ventilation (HFOV). A study by Clark et al demonstrated the efficacy of HFOV in 27 low birth weight infants who developed PIE and respiratory failure while on conventional ventilation.[36]  Overall survival in nonseptic patients was 80%. Surviving patients showed continued improvement in oxygenation and ventilation at an increasingly lower fraction of inspired oxygen (FiO2) and proximal airway pressure with resolution of PIE, whereas nonsurvivors progressively developed chronic respiratory insufficiency with continued PIE from which recovery was not possible.[36]

The investigators hypothesized that interstitial air leak is decreased during HFOV because adequate ventilation is provided at lower peak distal airway pressures.[36] Although this mode of ventilation has inherent risks, it can be a very effective tool for experienced clinicians to treat severe diffuse PIE. Note that care must be taken in smaller infants who require a high amplitude to ventilate, because the active exhalation during HFOV may cause small airway collapse and exacerbate gas trapping.

Squires et al also found that low oscillatory frequency of HFOV had some benefits for preterm infants with severe PIE.[37] After transition to low-frequency HFOV, physiologic responses were seen in both unilateral and bilateral PIE, in particular a rapid and sustained improvement in oxygenation in the bilateral group.[37]

Lobectomy

Lobectomy is indicated in a small number of patients with localized pulmonary interstitial emphysema (PIE) in whom spontaneous regression is not occurring and medical management has failed.[38, 39, 40] However, a case report exists of the spontaneous resolution of diffuse persistent PIE with pneumomediastinum, supporting the consideration of a nonsurgical approach in a stable infant with persistent PIE.[41] Thus, clear guidelines for surgical intervention in PIE are difficult to establish. In general, lobectomy should be reserved for infants in whom the risks of recurring complications outweigh those of surgery. Lobectomy seems most helpful in infants who develop severe lobar emphysema.

Other Treatment Modalities

Case reports and/or case series describe a variety of other approaches for the management of pulmonary interstitial emphysema (PIE), including the following:

  • A 3-day course of dexamethasone (0.5 mg/kg/d) [42] or hydrocortisone (2 mg/kg/day) [10]
  • Chest physiotherapy with intermittent 100% oxygen in localized and persistent compressive PIE [43]
  • Artificial pneumothorax [44, 45]
  • Multiple pleurotomies [46]
  • Heliox with inhaled nitric oxide [47]
  • Percutaneous catheter insertion [4]

Despite the success claimed by the authors of these reports, the efficacy of the treatment modalities they discussed seem questionable. With advancements in respiratory care, these treatment modalities are rarely used.

Prevention of Pulmonary Interstitial Emphysema

Surfactant

Prophylactic surfactant administration to infants (< 30-32 weeks' gestation) judged to be at risk of developing respiratory distress syndrome (RDS) compared with selective use of surfactant in infants with established RDS has been demonstrated to decrease the risk of PIE.[48]

Meta-analysis of early surfactant replacement therapy with brief ventilation compared with later, selective surfactant replacement and continued mechanical ventilation suggests a trend toward a reduced incidence of air leak syndromes in premature infants in the early surfactant group.[49] Early surfactant treatment, less invasive ventilatory support, or both could be responsible factors for the observed beneficial trend.[49]

According to one report, in infants with RDS, multiple doses of animal-derived surfactant extract resulted in greater improvements in oxygenation and ventilatory requirements, a decreased risk of pneumothorax, and a trend toward improved survival.[50]

High-frequency ventilation

In a study comparing high-frequency positive pressure ventilation (HFPPV) to conventional mechanical ventilation (CMV), Pohlandt et al reported a reduction in the risk of PIE with HFPPV.[51]  A meta-analysis by Greenough et al demonstrated that, compared to CMV, HFPPV was associated with a reduction in the risk of air leak, primarily pneumothorax, but not for PIE (typical relative risk [RR] for pneumothorax was 0.69; 95% confidence interval [CI]: 0.51-0.93).[52]

A review of different trials of elective high-frequency oscillatory ventilation (HFOV) versus CMV for acute pulmonary dysfunction in preterm infants suggested there may be an increase in the incidence of air leak syndromes, including but not limited to PIE in the HFOV group.[53]

In contrast, a prospective randomized multicenter study of HFOV versus CMV in premature infants with RDS showed no difference in the incidence of PIE.[24] Limited data regarding rescue HFOV for pulmonary dysfunction in the preterm infant also showed no difference in the rate of PIE.[54]  Similarly, Cochrane reviews of trials of elective high-frequency jet ventilation (HFJV) versus CMV for RDS demonstrated no significant difference in the incidence of air leak syndrome in the individual trials or in the overall analysis.[55]

In summary, the available literature suggests elective or rescue high-frequency ventilation does not prevent the development of PIE.

Other considerations

Different modes of CMV do not appear to affect the risk of PIE. Goel at al showed that the rate of PIE was significantly less while delivering nasal continuous positive airway pressure (CPAP) in the mask group as compared to cannula group (4.9% vs 17.5%; RR: 0.28, 95% CI: 0.08-0.96; P = 0.03).[56]

Although data are limited on the benefit of volume-targeted ventilation strategies, some data appear to be promising regarding volume-targeted ventilation to prevent PIE. Stefanescu et al reported that rates of PIE were lower among infants treated with volume guarantee pressure support ventilation versus pressure-controlled ventilation (odds ratio: 0.6; 95% confidence limits: 0.4, 0.8).[57] However, McCallion et al found no significant difference in the rate of PIE either in a pooled analysis within subgroups or the overall pooled analysis of trials comparing volume-targeted versus pressure-limited ventilation in the neonate.[58]

Avoid the use of high peak inspiratory pressure (PIP). Carefully monitor the PIP (watch the manometer) during manual ventilation.

Long-Term Monitoring

Monitoring for physical and psychomotor development in a neonatal follow-up care program or equivalent program is important, because most infants with pulmonary interstitial emphysema (PIE) are premature and are at risk for developmental delay. In addition, PIE has been associated with increased risks of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), which also raise the risks of developmental delay in these infants.

Patients with chronic lung disease (CLD) may need pediatric pulmonology follow-up care. Note that the available literature remains unclear regarding the role of bronchodilator agents in preventing or treating CLD in preterm infants; in addition, no specific trials appear to have studied the use of these agents for managing CLD in this population.[59]

 

Medication

Medication Summary

The principal therapies for pulmonary interstitial emphysema (PIE) are lateral decubitus positioning, selective intubation, occlusion of the contralateral bronchus, and high-frequency ventilation. However, administration of surfactant to premature infants (< 30-32 weeks' gestation) judged to be at risk of developing respiratory distress syndrome may reduce the risk of PIE development.

Lung Surfactants

Class Summary

These agents prevent the alveoli from collapsing during expiration that results from deficient or ineffective endogenous lung surfactant in neonates. There are two different kinds: Natural and Synthetic.  It is for intratracheal administration only. Surfactant prevents alveoli from collapsing during expiration by lowering the surface tension between air and alveolar surfaces. Surfactant  is used for prophylaxis and treatment of respiratory distress syndrome (RDS) in premature infants.

Natural Sufactant

Beractant (Survanta®), Poractant (Curosurf®), Calfactant (Infasurf®)

It is derived from animals. It has been considered the superior subtype, due to its greater efficacy in mimicking the action of human surfactant. The value between the two subtypes has yet to be fully elucidated. Bovine samples are most commonly used followed by porcine extracts. Despite the positive findings when natural surfactant is administered, there are a number of drawbacks, including the lack of cost-effectiveness, inconsistent efficacy, possible anaphylactic shock reaction, and risk of pathogen contamination. It is important to note that the pathogenic risks have not been identified on a clinical level.

Beractant (Survanta®) is animal surfactant derived from minced bovine lung extract, with the added products of DPPC, palmitic acid and tripalmitin.

Poractant (Curosurf®) is derived from minced porcine lungs.

Calfactant (Infasurf®) is another bovine surfactant extracted by broncho-alveolar lavage

Synthetic surfactants

Exosurf®, Lucinactant (Surfaxin®)

It is produced synthetically in laboratory.  Previous synthetic surfactant only contained phospholipids, with colfosceril palmitate (Exosurf®) the most commonly trialled protein-free synthetic surfactant The prime factor has been the development of protein-containing synthetic surfactant. It had been shown that its therapeutic effect was inferior to that of natural surfactant. The rise of protein-containing synthetic surfactant, such as lucinactant (Surfaxin®), has offered scientists a new avenue to further expand upon our advancement in surfactant as its action has been hypothesised to be as effective as, or even better than, natural surfactant.

 

Questions & Answers

Overview

What are pearls regarding pulmonary interstitial emphysema (PIE)?

What is pulmonary interstitial emphysema (PIE)?

What is the pathophysiology of pulmonary interstitial emphysema (PIE)?

Which factors increase the risk of pulmonary interstitial emphysema (PIE)?

What is the prevalence of pulmonary interstitial emphysema (PIE) in the US?

What is the global prevalence of pulmonary interstitial emphysema (PIE)?

What are the sexual predilections of pulmonary interstitial emphysema (PIE)?

Which infants are at highest risk for pulmonary interstitial emphysema (PIE)?

What is the prognosis of pulmonary interstitial emphysema (PIE)?

What are the possible complications of pulmonary interstitial emphysema (PIE)?

Presentation

Which clinical history findings are characteristic of pulmonary interstitial emphysema (PIE)?

Which physical findings are characteristic of pulmonary interstitial emphysema (PIE)?

DDX

Which conditions are included in the differential diagnoses of pulmonary interstitial emphysema (PIE)?

What are the differential diagnoses for Pulmonary Interstitial Emphysema?

Workup

What is the role of radiography in the workup of pulmonary interstitial emphysema (PIE)?

Which histologic findings are characteristic of pulmonary interstitial emphysema (PIE)?

Treatment

How is pulmonary interstitial emphysema (PIE) treated?

Which specialist consultations are beneficial to infants with pulmonary interstitial emphysema (PIE)?

What is the role of lateral decubitus positioning in the treatment of pulmonary interstitial emphysema (PIE)?

What is the role of bronchial intubation in the treatment of pulmonary interstitial emphysema (PIE)?

What are the possible complications of bronchial intubation in pulmonary interstitial emphysema (PIE)?

What is the role of high-frequency ventilation (HFV) in the treatment of pulmonary interstitial emphysema (PIE)?

What is the role of lobectomy in the treatment of pulmonary interstitial emphysema (PIE)?

Which novel therapies have been used in the treatment of pulmonary interstitial emphysema (PIE)?

What is the role of surfactant replacement therapy in the prevention of pulmonary interstitial emphysema (PIE)?

What is the role of high-frequency positive pressure ventilation (HFPPV) in the prevention of pulmonary interstitial emphysema (PIE)?

What is the role of conventional ventilation (CMV) in the prevention of pulmonary interstitial emphysema (PIE)?

What is included in long-term monitoring of pulmonary interstitial emphysema (PIE)?

Medications

What is the role of medications in the treatment of pulmonary interstitial emphysema (PIE)?

Which medications in the drug class Synthetic surfactants are used in the treatment of Pulmonary Interstitial Emphysema?

Which medications in the drug class Natural Sufactant are used in the treatment of Pulmonary Interstitial Emphysema?

Which medications in the drug class Lung Surfactants are used in the treatment of Pulmonary Interstitial Emphysema?