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Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology
Pulmonary Interstitial Emphysema
Article Last Updated: May 22, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Abhay J Bhatt, MD, Department of Pediatrics, Division of Newborn Medicine, Assistant Professor, University of Mississippi Medical Center
Abhay J Bhatt is a member of the following medical societies: American Academy of Pediatrics
Coauthor(s):
Rita M Ryan, MD, Associate Professor of Pediatrics, Chief, Division of Neonatology, State University of New York at Buffalo; Chief, Division of Neonatology, Department of Pediatrics, Women's and Children's Hospital of Buffalo
Editors: Steven M Donn, MD, Professor of Pediatrics, Director, Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan Health System; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Brian S Carter, MD, FAAP, Professor of Pediatrics, Department of Pediatrics, Division of Neonatology, Vanderbilt University School of Medicine; Co-director, Pediatric Advance Comfort Team, Vanderbilt Children's Hospital; Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina; Neil N Finer, MD, Professor, Department of Pediatrics, University of California at San Diego School of Medicine; Program Director, Division of Neonatology, University of California San Diego Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
pulmonary interstitial emphysema, PIE, respiratory distress syndrome, RDS, meconium aspiration syndrome, MAS, amniotic fluid aspiration
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 secondary to alveolar and terminal bronchiolar rupture. PIE is more frequent in premature infants who require mechanical ventilation for severe lung disease. Once PIE is diagnosed, intensive respiratory management is required to reduce mortality and morbidity.
Pathophysiology
PIE often occurs in conjunction with respiratory distress syndrome (RDS), but other predisposing etiologic factors include meconium aspiration syndrome (MAS), amniotic fluid aspiration, and infection.
Positive pressure ventilation (PPV) and reduced lung compliance are significant predisposing factors. However, in extremely premature infants, PIE can occur at low mean airway pressure and probably reflects increased sensitivity of the underdeveloped lung to stretch. The process of PIE is initiated when air ruptures from the alveolar airspace and small airways into the perivascular tissue of the lung.
Infants with RDS have an initial increase in interstitial and perivascular fluid that declines rapidly over the first few days of life. This fluid may obstruct the movement of gas from ruptured alveoli or airways to the mediastinum, causing an increase of PIE. Another possible mechanism for entrapment of air in the interstitium is the increased amount of pulmonary connective tissue in the immature lung. The entrapment of air in the interstitium may result in a vicious cycle causing compression atelectasis of the adjacent lung, which 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. 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 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 may be located inside the pulmonary lymphatic network.
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 localize preferentially in any one of the 5 pulmonary lobes.
PIE compresses adjacent functional lung tissue and vascular structures and hinders both ventilation and pulmonary blood flow, resulting in impedance of oxygenation, ventilation, and blood pressure. This further compromises the already critically ill infant with a significant increase in mortality and morbidity. PIE can regress completely or decompress into adjacent spaces causing pneumomediastinum, pneumothorax, pneumopericardium, pneumoperitoneum, or subcutaneous emphysema.
Frequency
United States
The prevalence of PIE varies widely with the population studied. In a study by Gaylord et al, PIE developed in 3% of infants admitted to the neonatal intensive care unit (NICU). No specific data are available on the prevalence of PIE in the postsurfactant era; reported incidence of PIE in published clinical trials can be useful. In a randomized trial of surfactant replacement therapy at birth, in premature infants of 25-29 weeks' gestation, Kendig et al found PIE in 8 of 31 (26%) control neonates and 5 of 34 (15%) surfactant-treated neonates.
Another randomized controlled trial of prophylaxis versus treatment with bovine surfactant in neonates of less than 30 weeks' gestation included 2 of 62 (3%) early surfactant-treated, 5 of 60 (8%) late surfactant-treated, and 15 of 60 (25%) control neonates with PIE. Kattwinkel et al compared prophylactic surfactant administration versus the early treatment of RDS with calf lung surfactant in neonates of 29-32 weeks' gestation. Three of 627 neonates in the prophylaxis group and 3 of 621 neonates in the early treatment group developed PIE. This information suggests a higher incidence of PIE in more immature infants.
International
Studies reflecting international frequency demonstrated that 2-3% of all infants in NICUs develop PIE. When limiting the population studied to premature infants, this frequency increases to 20-30%, with the highest frequencies occurring in infants weighing fewer than 1000 g. In another study of low birth weight infants, the incidence of PIE was 42% in infants with birth weight of 500-799 g, 29% in those with birth weight of 800-899 g, and 20% in those with birth weight of 900-999 g. Minimal information is available about the prevalence of PIE in the postsurfactant era. In a recent 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 of 139 (11%) infants in the high-frequency group and 15 of 134 (11%) infants in the conventional group developed PIE.
Mortality/Morbidity
The mortality rate associated with PIE is reported to be as high as 53-67%. Lower mortality rates of 24% and 39% reported in other studies could result from differences in population selection. Morisot et al reported an 80% mortality rate with PIE in infants with birth weight of fewer than 1600 g and severe RDS. The early appearance of PIE (<48 h after birth) is associated with increased mortality, but this may reflect the severity of the underlying parenchymal disease. In survivors, morbidity also is high. 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. 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 length of time of mechanical ventilation and the incidence of bronchopulmonary dysplasia. Some infants may develop chronic lobar emphysema, which may require surgical lobectomies. No specific mortality and morbidity data concerning PIE in the postsurfactant era are available.
Sex
In a study by Plenat et al, PIE developed equally in both sexes (21 males, 18 females). Although these data also included cases with intrapleural pneumatosis, no relationship between sex and type of interstitial pneumatosis exists.
Age
PIE is more frequent in infants of lower gestational age. PIE usually occurs within the first weeks of life. Development of PIE within the first 24-48 hours after birth often is associated with extreme prematurity, very low birth weight, perinatal asphyxia, and/or neonatal sepsis and frequently indicates a grave prognosis.
History
Pulmonary interstitial emphysema (PIE) is a radiographic and pathologic diagnosis. In most cases, the discovery of PIE may be preceded by a decline in the baby's clinical condition. Hypotension and difficulty in oxygenation and ventilation can suggest the development of PIE. Alternatively, the baby can present with the signs of one of the complications of PIE, such as pneumothorax. Sometimes, PIE becomes apparent following reexpansion of a collapsed lung after drainage of a pneumothorax.
Physical
No specific signs of PIE exist. Overinflation of the chest wall and crepitations on auscultation on the affected side may be present.
Causes
- Risk factors
- Prematurity
- Respiratory distress syndrome
- Meconium aspiration syndrome
- Amniotic fluid aspiration
- Infection - Neonatal sepsis, pneumonia, or both
- Low Apgar score or need for PPV during resuscitation at birth
- Use of high peak airway pressures on mechanical ventilation
- Incorrect positioning of the endotracheal tube in one bronchus
Other Problems to be Considered
The roentgenologic appearance of pulmonary interstitial emphysema can be confused with the following: Air-bronchogram in RDS
Aspiration pneumonia
Pulmonary edema
Distended airways in patients on a ventilator
Lab Studies
- Blood gases should be obtained to ensure adequate gas exchange.
Imaging Studies
- Chest radiograph (see Images 1-3)
- The classic radiologic appearance of pulmonary interstitial emphysema (PIE) often provides a clear diagnosis. PIE is best visualized in the anteroposterior supine projection. PIE has two basic radiographic appearances, linear and cystlike radiolucencies, although both types often appear together.
- Linear radiolucencies are coarse and nonbranching, measure from 3-8 mm, and vary in width but rarely exceed 2 mm.
- Small cystlike radiolucencies extend in diameter from 1-4 mm, and, though generally round, they may appear oval or slightly lobulated.
- 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 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 patients receiving mechanical ventilation, distended airways and alveoli have a somewhat similar appearance to that of PIE on radiographs. Over time, it either progresses to a classic radiographic picture of PIE or resolves very rapidly as ventilator settings are decreased.
- PIE rarely can be misinterpreted as normally aerated lung surrounded by exudate as in an aspiration syndrome or pulmonary edema.
Histologic Findings
The histology of PIE is well described by Plenat et al. Their histologic study demonstrates interstitial slits preferentially located in perivenous topography. Sometimes, 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. The bronchoarterial solidarity most often 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, while the collagen fibers constantly are broken and squeezed together.
Medical Care
Different treatment modalities have been used to manage pulmonary interstitial emphysema (PIE), with variable success.
- Lateral decubitus positioning
- This conservative approach has been used with success and is most effective in infants with unilateral PIE. The infant is placed in the lateral decubitus position with the affected lung in a dependent position. This therapy can result in plugging of dependent airways and improved oxygenation of the nondependent lung. The latter allows for overall decreased ventilatory settings. The combination of the above factors helps in resolution of PIE.
- In different case studies of lateral decubitus position as a treatment of unilateral PIE in infants, PIE resolved in 48 hours to 6 days with minimal recurrence and a low failure rate. Lateral decubitus positioning should be considered as an early first-line therapy in the management of unilateral PIE. Lateral decubitus positioning has been used successfully for patients with bilateral PIE when one side is affected more significantly.
- Selective main bronchial intubation and occlusion
- Many case reports exist of successful treatment of severe localized PIE in infants with selective intubation of the contralateral bronchus to decompress the overdistended lung tissue and to avoid 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. The endotracheal tube of the same diameter as for a regular intubation 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 entering the correct bronchus as the tube 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 have 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 0.5 cm above the tip of the oblique distal end. With the side with the elliptical hole directed to the left lung, left selective bronchus intubation can be accomplished easily and repeatedly. 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 also can be considered.
- Potential complications of the selective intubation/ventilation are atelectasis in the affected lung, injury to bronchial mucosa with subsequent scarring and stenosis, acute hypoventilation or hypoxemia if ventilating one lung is inadequate, excessive secretions, hyperinflation of the intubated or nonoccluded lung, upper lobe collapse when intubating the right lung, and bradycardia. Despite potential risks, selective bronchial intubation is a desirable alternative to lobectomy in a persistent, severe, localized PIE causing mediastinal shift and compression atelectasis and not responding to conservative management. This procedure should be attempted before any surgical intervention.
- High-frequency ventilation
- Keszler et al studied use of high-frequency jet ventilation (HFJV) in 144 newborns with PIE. They concluded that HFJV was safe and more effective than rapid-rate conventional ventilation in the treatment of newborns with PIE. With HFJV, similar oxygenation and ventilation was obtained at lower peak and mean airway pressures, suggesting that in infants with PIE a reduction in the amount of air leaking into the interstitial spaces would occur.
- Similar effects can be achieved by use of HFOV.
- In a study by Clark et al, 27 low birth weight infants who developed PIE and respiratory failure while on conventional ventilation were treated with HFOV. 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, while nonsurvivors progressively developed chronic respiratory insufficiency with continued PIE from which recovery was not possible. Overall survival in nonseptic patients was 80%.
- They found HFOV to be effective in the treatment of PIE and hypothesized that interstitial air leak is decreased during HFOV because adequate ventilation is provided at lower peak distal airway pressures. Although this mode of ventilation has inherent risks, it can be a very effective tool in experienced hands for the treatment of severe diffuse PIE. 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.
- Other treatment modalities
- Case reports and/or case series describe different approaches for the management of PIE, including 3-day course of dexamethasone (0.5 mg/kg/d), chest physiotherapy with intermittent 100% oxygen in localized and persistent compressive PIE, artificial pneumothorax, and multiple pleurotomies.
- Despite success claimed by the authors, the efficacy of these treatment modalities seems questionable. With advancements in respiratory care, these treatment modalities rarely are used.
Surgical Care
Lobectomy is indicated in a small number of patients with localized PIE when spontaneous regression is not occurring and medical management has failed. Although clear guidelines for surgical intervention are difficult to establish, it should be reserved for infants in whom the risks of recurring complications outweigh those of surgery. It seems most helpful in infants who develop severe lobar emphysema.
Consultations
All infants with PIE need to be under the care of a neonatologist. In some cases, pediatric pulmonology and pediatric surgery consultations are appropriate.
Diet
The overall importance of appropriate nutritional management of ill newborns cannot be overstressed. Most of these infants are treated with total parenteral nutrition and require diligent attention.
Further Inpatient Care
- Admission/transfer to a NICU is indicated.
- Keep a thoracentesis set handy and keep the possibility of air leak, including pneumothorax and pneumopericardium, in mind.
Further Outpatient Care
- 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 IVH and periventricular leukomalacia (PVL), which also increase the risks of developmental delay in these infants.
- Patients with chronic lung disease may need pediatric pulmonology follow-up care.
Deterrence/Prevention
- Surfactant
- Four of the 5 randomized controlled trials for the prophylactic use of surfactant in premature infants with RDS noted a significant reduction in the incidence of PIE. Metaanalysis of the different trials suggests that prophylactic administration of surfactant leads to significant reduction in the risk of PIE.
- Metaanalysis of early surfactant replacement therapy with brief ventilation compared with later, selective surfactant replacement and continued mechanical ventilation suggests a trend towards a decreased incidence of air leak syndromes in premature infants in the early surfactant group. Early surfactant treatment, less invasive ventilatory support, or both could be responsible factors for the observed beneficial trend.
- High-frequency ventilation
- In a study comparing high-frequency positive pressure ventilation (HFPPV) to conventional ventilation, Pohlandt et al reported a reduction in the risk of PIE with HFPPV. Review of different trials of elective HFOV versus conventional ventilation for acute pulmonary dysfunction in preterm infants suggests an increase in the incidence of air leak syndromes including but not limited to PIE in the HFOV group.
- A recent prospective randomized multicenter study of HFOV versus conventional ventilation in premature infants with RDS showed no difference in the incidence of PIE. Limited data regarding rescue HFOV for pulmonary dysfunction in the preterm infant also showed no difference in the rate of PIE.
- Cochrane reviews of trials of elective HFJV versus conventional ventilation for RDS demonstrated no significant difference in the incidence of air leak syndrome in the individual trials or in the overall analysis.
- In summary, current literature suggests that elective or rescue high-frequency ventilation does not prevent the development of PIE.
- Other considerations
- Different modes of conventional ventilation: No significant difference in the rate of PIE was found either in pooled analysis within subgroups or overall pooled analysis of trials comparing volume-targeted versus pressure-limited ventilation in the neonate.
- Avoid use of high peak inspiratory pressure (PIP).
- Be careful (watch manometer) during manual ventilation.
Complications
- Death
- Respiratory insufficiency
- Other air leaks
- Pneumomediastinum
- Pneumothorax
- Pneumopericardium
- Pneumoperitoneum
- Subcutaneous emphysema (rare)
- Massive air embolism
- Chronic lung disease (CLD) of prematurity
- Intraventricular hemorrhage
- Periventricular leukomalacia
Prognosis
- Long-term follow-up data are scarce.
- Gaylord et al demonstrated a high (54%) incidence of CLD in survivors of PIE compared with their nursery's overall incidence of 32%. In addition, 19% of the infants developed chronic lobar emphysema; 50% received surgical lobectomies.
Medical/Legal Pitfalls
- Although the primary risk factor for pulmonary interstitial emphysema, prematurity, is rarely preventable, attention should be given to the use of as little mechanical ventilatory support as is necessary for the patient's very fragile lungs.
- Because pneumothorax is a known complication, 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.
| Media file 1:
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. |
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Media type: X-RAY
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| Media file 2:
This radiograph, obtained from a premature infant at 26 weeks' gestation, shows characteristic radiographic changes of pulmonary interstitial emphysema (PIE) of the right lung. |
 | View Full Size Image | |
Media type: X-RAY
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| Media file 3:
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. |
 | View Full Size Image | |
Media type: X-RAY
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Pulmonary Interstitial Emphysema excerpt Article Last Updated: May 22, 2006
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