Volume 95 Number 5, part 2
34. Brown ER, Stark A, Sosenko I, Lawson EE, and Avery ME: Bronchopulrrionary dysplasia: possible relationship tO pulmonary edema, J PEDIATR92:982, 1978. 35. Clarke TA, and Edwards DK: Pulmonary pseudocysts in newborn infants with respiratory distress syndrome, Am J Roentgenol (in press). 36. Moylan FMB, Kramer SK, Todres ID, and Shannon DC: Bronchopulmonary dysplasia and mechanical ventilation of R.D.S. (abst), Pediatr Res i0:465, 1976. 37. Hall RT, and Rhodes PG: Pneumothorax and pneumomediastinum in infants with idiopathic respiratory distress syndrome receiving continuous positive airway pressure, Pediatrics 55:493, 1975. 38. Edwards DK, Dyer WM, and Northway WH Jr: Twelve years' experience with bronchopulmonary dysplasia, Pediatrics 59:839, 1977. 39. Fitzhardinge PM: Follow-up studies in infants tieated by mechanical ventilation, Clin Perinatol 5:451, 1978. 40. Outerbridge EW, Nogrady MB, Beaudry PH, and Stern L: Idiopathic respiratory distress Ss,ndrome: recurrent respiratory illness in survivors, Am J Dis Child 123:99, 1972. 41. Geggel RL, Pereira GR, and Spackman TJ: Fractured ribs: unusual presentation of rickets in premature infants, J PEDIATR93:680, 1978. 42. Gutcher GR. and Chesney RW: Iatrogenic rickets as a complication of a total parenteral nutrition program, Clin Pediatr 17:817. 1978. 43. Auld PAM: Oxygen therapy for premature infants, J PEDIATR 78:705, 1971. 44. Hodgman JE, Mikity VG, Taiter D, and Cleland RS: Chronic respiratory distress in the premature infant: Wilson-Mikity syndrome, Pediatrics 44:179, 1969. 45. Wilson MG, and Mikity VG: A new form of respiratory disease in premature infants, J Dis Child 99:489, 1960.
Diagnosis" o f B P D
829
46. Mikity VG, and Taber P: Complications in the treatment of the respiratory distress syndrome: bronchopulmonary dysplasia,, oxygen toxicity, and the Wilson-Mikity syndrome, Pediatr Clin North Am 20:419, 1973. 47. Christie DL, O'Grady LR, and Mack DV: Incompetent lower esophageal sphincter and gastroesophageal reflux in recurrent acute pulmonary disease of infancy and childhood. J PEDIATR93:23, 1978. 48. Theros EG: Case Of the month from the AFIP, Radiology 89:524, 1967. 49. Whitley R J, Brasfield D, Reynolds DW, Stagno S, Tiller RE, and Alford CA: Protracted pneumonitis in young in~ fants associated with perinatally acquired cytomegaloviral infection; J PEDIATR89:16, 1976. 50. Swischuk LE: Bubbles in hyaline membrane disease. Dif ferentiation of three types, Radiology 122:417, 1977. 51. Magilner AD, Capitanio MA, Wertheimer l, and Burko H: Persistent localized intrapulm0nary interstitial emphysema: an observation in three infants, Radiology 111:379, 1974. 52. Stocker JT, and Madewell JE: Persistent interstitial pulmonary emphysema: another complication of the respiratory distress syndrome, Pediatrics 59:847, 1977. 53. Campbell RE: Intrapulmonary interstitial emphysema: a complication of hyaline membrane disease, Am J Roentgenol 110:449, 1970. 54. Harris H: Pulmonary pseudocysts in the newborn infant, Pediatrics 59:199, 1977. 55. Drew JH, Landau LI, Acton CM, Kent M, and Campbell PE: Pulmonary interstitial emphysema requiring lobectomy: complication of assisted ventilation, Arch Dis Child 53:424, 1978.
Clinical description of bronchopulmonary dysplasia M. T. Stahlman, M.D., Nashville, Tenn.
THE CHRONIC LUNG DISEASE.which may follow clinical hyaiine m e m b r a n e disease has a multifactorial pathogehesis. It is the result of a combination of deleterious events which are additive. The symptom complex starts almost invariably with clinical hyaline m e m b r a n e disease in premature infants, usually below 2,000 gm birth Weight. ! n the hours after birth, depending on the severity of the disease and its complications, infants who have
From the Department of Pediatrics, Vanderbilt University Medical School. Supported by a National Heart and Lung Institute Pulmonai'y SCOR Grant-HL 14214. Reprint address- Department of Pediatrics, VanderbiltUniversity Medical School Nashville, TN 37232.
0022-3476/79/110829 +06500.60/0 9 1979 The C. V. Mosby Co.
advancing hypoxemia and acidosis, both metabolic and respiratory, and who frequently also have have hypoglycemia, hypovolemia, and hypothermia, are warmed, given plasma expanders, buffers, and'glucose infusions. As the percent venous admixture increases, they are placed in increasing levels of inspired oxygen. Respiratory distress worsens, associated with sloughing of lining cells of respiratory bronchioles and alveolar ducts (Fig. 1), and the denuded areas fill with a fluid of high-protein content (Fig. 2). As correction measures proceed, pulmonary vasodilation replaces pulmonary vasoconstriction, and extensive capillary dilation occurs. Alveolar flooding may follow the overwhelming of the lymphatic system's ability to remove interstitial fluid, and a "white-out" may be seen
830
Workshop on BPD
The Journal of Pediatrics November 1979
Fig. I. Photomicrograph of lung from an infant of 30 weeks' gestation who died at 2 hours with hyaline membrane disease. The epithelium which lined terminal conducting airways has sloughed from its basement membrane and is aggregated in the air spaces. Pyknotic nuclei are present in the aggregates. Protein-rich fluid and a few erythrocytes fill some of the terminal airways. Arterioles are tightly constricted. Periodic acid-Schiff (original magnification: x 160). on x-ray study. If ventilatory assistance has not already been instituted, apnea or extreme respiratory distress makes it mandatory. Infants are usually intubated, placed on positive pressure ventilation, with positive end expiratory pressure added. Increasing levels of mean added airway pressure, in the presence of fluid filled the terminal conducting airways, frequently lead to advancing dissection of interstitial air, which migrates directly into peribronchial and perivascular lymphatics (Fig. 3). Pneum0mediastinum or extensive subpleural air may result, which frequently dissects into the pleural spaces as a frank tension pneumothorax (Fig. 4). Chest tubes are placed, often a number of times, for unilateral or bilateral removal o f air. High mean airway pressures are now needed for adequate ventilation, and high inspired oxygen levels are usually used. The addition of buffer for crises exaggerates the formation of pulmonary edema fluid, which no longer has a lymphatic space for its easy removal, since the lymphatic vessels are now air filled. If these events have not occurred during the initial management of the disease, the appearance of edema with a large left-to-right ductus Shunt on ihe third to fifth day of life may necessitate the use of high mean a~irway pressures, initiating air dissection. As time passes, the infant becomes oxygen dependent, since prolonged high inspired oxygen levels destroy existing Type I cells and they are replaced with Type II alveolar cells. Large portions of the capillary bed must remodel the damaged lung (Fig. 5). A diffusion barrier is
now created, leading to inability to decrease FI%. Carbon dioxide retention is common, associated with increasing dead space ventilation Of a false air space which is rapidly becoming permanent. Pressure damage can occur, especially to conducting airways and supporting tissues in alveolar junctional areas, with cellular proliferation both of epithelial layers and of connective tissue with excessive collagen production (Fig. 6). The lung becomes increasingly stiff and overdistended. The infant often acquires a low-grade infection with Pseudomonas aeruginosa or Aerobacter Klebsiella, both extremely difficult to eradicate, especially in an infant who is ventilator dependent With an endotracheal tube in place (Fig. 7). AdequNe nutrition is a dxfficult problem m such infants, and growth failure is common. The infant, now ventilator dependent or with great respiratory distress without it, hypercapnic, and oxygen dependent, although usually at medium range concentrations, develops persistent pulmonary hypertension, eardiomegaly due to cor pulmonale, and recurrent bouts of heart failure (Fig. 8)."~h6se may initially respond partially to digitalization and diuretic therapy, but eventually these measures become useless. The infant frequently dies with slow suffocation after several months of severe cardiopulmonary failure, with hypoxemia and CO~ retention resistant to the best efforts of ventilation and oxygenation (Fig. 9). Infants who are not so severely affected may survive, especially if they can be extubated early and if they avoid secondary infection. They often have recurrent bouts of
Volume 95 Number 5, part 2
Diagnosis of BPD
83 1
Fig. 2. Photomicrograph of lung from an infant o f 28 weeks' gestation who died at 30 hours with severe hyaline membrane disease. Y-shaped alveolar duct system is denuded of epithelium, lined with early membrane material, and filled with protein-rich fluid. Small arterioles are tightly constricted and some pulmonary capillaries are grossly overdistended with blood (C). Hematoxylin and eosin (original magnification: • 80).
Fig. 3. Chest radiograph of a 13-day-old infant with severe hyaline membrane disease treated with positive pressure ventilation. Disseminated interstitial air is present in both lungs, most marked on the right where overdistention is prominent. A chest tube was placed for drainage of a right pneumothorax.
Fig. 4. Chest radiograph of a 3-day-old infant with hyaline membrane disease showing massive tension pneumothorax in the left side of the chest and interstitial air dissection in the right, with subpleural air collection and pneumomediastinum.
832
Workshop on B P D
The Journal of Pediatrics November 1979
Fig. 5. Electron micrograph of lung from an infant born at 34 weeks' gestation who lived 7 days. Hyaline membrane disease is in a regenerating phase. The airway (A) has been relined with alveolar Type II cells filled with large lamellar bodies. Active capillary invasion has stretched the epithelium of a Type cell over an endothelial surface which has approximated the airway (arrow head). A basement membrane can be followed between epithelial and endothelial cells and between epithelium and interstitium (arrows). Uranyl acetate and lead citrate (original magnification: x 3,275).
Fig. 6. Photomicrograph of it~ng from an 11-day-old inthnt who had disseminated interstitial air dissection following respirator treatment for severe hyaline membrane disease. A small muscular artery is surrounded by lymphatic channels dilated with air. Adjacent to this is a bronchiole (B) whose lining has undergone squamous metaplasia. Hematoxylin and eosin (original magnification: x 65).
Volume 95 Number 5, part 2
Diagnosis of BPD
833
Fig. 7. Photomicrograph of the terminal airways of infant lung seen in Fig. 6, showing protein containing edema fluid, round cell and polymorphonuclear leukocyte accumulation associated with infection with Pseudomonas aeruginosa. Hematoxylin and eosin (original magnification: x 160).
Fig. 8. Chest radiograph of same infant as in Fig. 4, now 7 weeks of age. Infant was still ventilator and oxygen dependent, with superimposed chronic Pseudomonas aeruginosa pneumonia. Cardiomegaly is also apparent.
Fig. 9. Chest radiograph of same infant as in Figs. 4 and 8, now 6 months of age during terminal hospitalization. Right lung is grossly overdistended, with depression of the right diaphram, and is essentially functionless, except as dead space. Left lung is also distended. There are dense fibrotic scarred areas around the hilum. The heart is enlarged.
834
Workshop on BPD
wheezing and severe respiratory distress, clinically resembling bronchiofitis. Frank pneumonia may occur, requiring repeated hospitalizations. These bouts of acute pulmonary insufficiency, which are superimposed on varying levels of chronic pulmonary impairment, usually gradually decrease in frequency an d severity after the
The Journal of Pediatrics November 1979 second year of fife. As the originally involved areas scar around the hilum, new formed lung units may allow relatively normal pulmonary function throughout childhood. The eventual outcome of these children is not known.
Radiographic-pathologic correlation in bronchopulmonary dysplasia David K. Edwards, M.D.,* San Diego, Calif., Thomas V. Colby, M.D., and William H. Northway, Jr., M.D., Stanford, Calif.
THE CHEST RADIOGRAPH is an essential modality in
T a b l e i. Independent radiographic and pathologic staging
the diagnosis and monitoring of patients with bronchopulmonary dysplasia. 1 Some authors have questioned the degree of correlation of the radiographic staging of BPD with the pathologic staging of the diseaseY 3 Determining this correlation could facilitate attempts to establish prognosis, using changes in the chest radiograph as one of the clinical markers. The purpose of this study was to compare retrospectively the radiographic staging of BPD with the histopathologic staging of changes in the lungs of a series of patients with respiratory distress syndrome who died after receiving mechanically assisted ventilation and supplemental oxygen therapy.
of BPD in 142 autopsied patients
MATERIALS
AND METHODS
S t u d y group. Among 299 consecutive infants with RDS treated at Stanford University Hospital with assisted ventilation for at least 24 hours, 158 patients died. Adequate autopsy histologic sections of lungs were available for 142 of these patients; this group of patients is the basis of this report. All patients in this series were born between January, 1962, and December, 1973, and have been described elsewhere. 4 R a d i o g r a p h i c e v a l u a t i o n . All chest radiographs were examined by two of us (D. E. and W. N.), working together, without knowledge of the patients' clinical course or pathologic findings. Each patient was staged for BPD (I to IV) 5 using the final available film. The patient's age at the last film was noted and subsequently c o m p a r e d with the age at death obtained from the medical record.
From the Departments of RadtolOgy and Pediatrics, University of California at San Diego, and the Departments of Pathology, Radiology and Pediatrics, Stanford University Medical Center. *Reprint address: Departmentof Radiology, University Hospital, 225 Dickinson St., San Diego, CA 92103.
Pathologic stage Radiographic stage I I to II II
II to III III IV
I
l
Il
l
Iil
21
39
11
3
2
2
--~
6 --
10 3
--
4
1
l
lv 4 --
8 1 I0 17
Abbreviations used BPD: bronchopulmonary dysplasia RDS: respiratory distress syndrome P a t h o l o g i c e v a l u a t i o n . Hematoxylin and eosin stained sections of lung (both lungs in most instances) from all patients were examined by one of us (T. C.) without knowledge of clinical history, radiographic findings, or prior autopsy re~ort. The histologic variables examined were adapted-f~om those of Rosan 1' 2 and included changes (if any) in bronchiolar mucosa, pulmonary interstitium, lymphatics, and inflation pattern. The presence and extent of yellow pigment (hematoidin), bronchiolitis obliterans, hyaline membranes, hemorrhage, alveolar infiltrates (excluding areas of obvious pneumonia), and interstitial and peribronchial smooth muscle proliferation wer~ also noted. These histologic variables were graded in severity from 0 to 4. A synthesis of all variables in an individual patient resulted in a pathologic stage of BPD from I to IV, as described by Rosan. 2 Staging was necessarily somewhat subjective because different variables were often of different severity in the same patient. D a t a analysis. Following independent interpretation of
6022-3476/79/110834+ 03500.30/0 9 1979 The C. V. Mosby Co.
34. Brown ER, Stark A, Sosenko I, Lawson EE, and Avery ME: Bronchopulrrionary dysplasia: possible relationship tO pulmonary edema, J PEDIATR92:982, 1978. 35. Clarke TA, and Edwards DK: Pulmonary pseudocysts in newborn infants with respiratory distress syndrome, Am J Roentgenol (in press). 36. Moylan FMB, Kramer SK, Todres ID, and Shannon DC: Bronchopulmonary dysplasia and mechanical ventilation of R.D.S. (abst), Pediatr Res i0:465, 1976. 37. Hall RT, and Rhodes PG: Pneumothorax and pneumomediastinum in infants with idiopathic respiratory distress syndrome receiving continuous positive airway pressure, Pediatrics 55:493, 1975. 38. Edwards DK, Dyer WM, and Northway WH Jr: Twelve years' experience with bronchopulmonary dysplasia, Pediatrics 59:839, 1977. 39. Fitzhardinge PM: Follow-up studies in infants tieated by mechanical ventilation, Clin Perinatol 5:451, 1978. 40. Outerbridge EW, Nogrady MB, Beaudry PH, and Stern L: Idiopathic respiratory distress Ss,ndrome: recurrent respiratory illness in survivors, Am J Dis Child 123:99, 1972. 41. Geggel RL, Pereira GR, and Spackman TJ: Fractured ribs: unusual presentation of rickets in premature infants, J PEDIATR93:680, 1978. 42. Gutcher GR. and Chesney RW: Iatrogenic rickets as a complication of a total parenteral nutrition program, Clin Pediatr 17:817. 1978. 43. Auld PAM: Oxygen therapy for premature infants, J PEDIATR 78:705, 1971. 44. Hodgman JE, Mikity VG, Taiter D, and Cleland RS: Chronic respiratory distress in the premature infant: Wilson-Mikity syndrome, Pediatrics 44:179, 1969. 45. Wilson MG, and Mikity VG: A new form of respiratory disease in premature infants, J Dis Child 99:489, 1960.
Diagnosis" o f B P D
829
46. Mikity VG, and Taber P: Complications in the treatment of the respiratory distress syndrome: bronchopulmonary dysplasia,, oxygen toxicity, and the Wilson-Mikity syndrome, Pediatr Clin North Am 20:419, 1973. 47. Christie DL, O'Grady LR, and Mack DV: Incompetent lower esophageal sphincter and gastroesophageal reflux in recurrent acute pulmonary disease of infancy and childhood. J PEDIATR93:23, 1978. 48. Theros EG: Case Of the month from the AFIP, Radiology 89:524, 1967. 49. Whitley R J, Brasfield D, Reynolds DW, Stagno S, Tiller RE, and Alford CA: Protracted pneumonitis in young in~ fants associated with perinatally acquired cytomegaloviral infection; J PEDIATR89:16, 1976. 50. Swischuk LE: Bubbles in hyaline membrane disease. Dif ferentiation of three types, Radiology 122:417, 1977. 51. Magilner AD, Capitanio MA, Wertheimer l, and Burko H: Persistent localized intrapulm0nary interstitial emphysema: an observation in three infants, Radiology 111:379, 1974. 52. Stocker JT, and Madewell JE: Persistent interstitial pulmonary emphysema: another complication of the respiratory distress syndrome, Pediatrics 59:847, 1977. 53. Campbell RE: Intrapulmonary interstitial emphysema: a complication of hyaline membrane disease, Am J Roentgenol 110:449, 1970. 54. Harris H: Pulmonary pseudocysts in the newborn infant, Pediatrics 59:199, 1977. 55. Drew JH, Landau LI, Acton CM, Kent M, and Campbell PE: Pulmonary interstitial emphysema requiring lobectomy: complication of assisted ventilation, Arch Dis Child 53:424, 1978.
Clinical description of bronchopulmonary dysplasia M. T. Stahlman, M.D., Nashville, Tenn.
THE CHRONIC LUNG DISEASE.which may follow clinical hyaiine m e m b r a n e disease has a multifactorial pathogehesis. It is the result of a combination of deleterious events which are additive. The symptom complex starts almost invariably with clinical hyaline m e m b r a n e disease in premature infants, usually below 2,000 gm birth Weight. ! n the hours after birth, depending on the severity of the disease and its complications, infants who have
From the Department of Pediatrics, Vanderbilt University Medical School. Supported by a National Heart and Lung Institute Pulmonai'y SCOR Grant-HL 14214. Reprint address- Department of Pediatrics, VanderbiltUniversity Medical School Nashville, TN 37232.
0022-3476/79/110829 +06500.60/0 9 1979 The C. V. Mosby Co.
advancing hypoxemia and acidosis, both metabolic and respiratory, and who frequently also have have hypoglycemia, hypovolemia, and hypothermia, are warmed, given plasma expanders, buffers, and'glucose infusions. As the percent venous admixture increases, they are placed in increasing levels of inspired oxygen. Respiratory distress worsens, associated with sloughing of lining cells of respiratory bronchioles and alveolar ducts (Fig. 1), and the denuded areas fill with a fluid of high-protein content (Fig. 2). As correction measures proceed, pulmonary vasodilation replaces pulmonary vasoconstriction, and extensive capillary dilation occurs. Alveolar flooding may follow the overwhelming of the lymphatic system's ability to remove interstitial fluid, and a "white-out" may be seen
830
Workshop on BPD
The Journal of Pediatrics November 1979
Fig. I. Photomicrograph of lung from an infant of 30 weeks' gestation who died at 2 hours with hyaline membrane disease. The epithelium which lined terminal conducting airways has sloughed from its basement membrane and is aggregated in the air spaces. Pyknotic nuclei are present in the aggregates. Protein-rich fluid and a few erythrocytes fill some of the terminal airways. Arterioles are tightly constricted. Periodic acid-Schiff (original magnification: x 160). on x-ray study. If ventilatory assistance has not already been instituted, apnea or extreme respiratory distress makes it mandatory. Infants are usually intubated, placed on positive pressure ventilation, with positive end expiratory pressure added. Increasing levels of mean added airway pressure, in the presence of fluid filled the terminal conducting airways, frequently lead to advancing dissection of interstitial air, which migrates directly into peribronchial and perivascular lymphatics (Fig. 3). Pneum0mediastinum or extensive subpleural air may result, which frequently dissects into the pleural spaces as a frank tension pneumothorax (Fig. 4). Chest tubes are placed, often a number of times, for unilateral or bilateral removal o f air. High mean airway pressures are now needed for adequate ventilation, and high inspired oxygen levels are usually used. The addition of buffer for crises exaggerates the formation of pulmonary edema fluid, which no longer has a lymphatic space for its easy removal, since the lymphatic vessels are now air filled. If these events have not occurred during the initial management of the disease, the appearance of edema with a large left-to-right ductus Shunt on ihe third to fifth day of life may necessitate the use of high mean a~irway pressures, initiating air dissection. As time passes, the infant becomes oxygen dependent, since prolonged high inspired oxygen levels destroy existing Type I cells and they are replaced with Type II alveolar cells. Large portions of the capillary bed must remodel the damaged lung (Fig. 5). A diffusion barrier is
now created, leading to inability to decrease FI%. Carbon dioxide retention is common, associated with increasing dead space ventilation Of a false air space which is rapidly becoming permanent. Pressure damage can occur, especially to conducting airways and supporting tissues in alveolar junctional areas, with cellular proliferation both of epithelial layers and of connective tissue with excessive collagen production (Fig. 6). The lung becomes increasingly stiff and overdistended. The infant often acquires a low-grade infection with Pseudomonas aeruginosa or Aerobacter Klebsiella, both extremely difficult to eradicate, especially in an infant who is ventilator dependent With an endotracheal tube in place (Fig. 7). AdequNe nutrition is a dxfficult problem m such infants, and growth failure is common. The infant, now ventilator dependent or with great respiratory distress without it, hypercapnic, and oxygen dependent, although usually at medium range concentrations, develops persistent pulmonary hypertension, eardiomegaly due to cor pulmonale, and recurrent bouts of heart failure (Fig. 8)."~h6se may initially respond partially to digitalization and diuretic therapy, but eventually these measures become useless. The infant frequently dies with slow suffocation after several months of severe cardiopulmonary failure, with hypoxemia and CO~ retention resistant to the best efforts of ventilation and oxygenation (Fig. 9). Infants who are not so severely affected may survive, especially if they can be extubated early and if they avoid secondary infection. They often have recurrent bouts of
Volume 95 Number 5, part 2
Diagnosis of BPD
83 1
Fig. 2. Photomicrograph of lung from an infant o f 28 weeks' gestation who died at 30 hours with severe hyaline membrane disease. Y-shaped alveolar duct system is denuded of epithelium, lined with early membrane material, and filled with protein-rich fluid. Small arterioles are tightly constricted and some pulmonary capillaries are grossly overdistended with blood (C). Hematoxylin and eosin (original magnification: • 80).
Fig. 3. Chest radiograph of a 13-day-old infant with severe hyaline membrane disease treated with positive pressure ventilation. Disseminated interstitial air is present in both lungs, most marked on the right where overdistention is prominent. A chest tube was placed for drainage of a right pneumothorax.
Fig. 4. Chest radiograph of a 3-day-old infant with hyaline membrane disease showing massive tension pneumothorax in the left side of the chest and interstitial air dissection in the right, with subpleural air collection and pneumomediastinum.
832
Workshop on B P D
The Journal of Pediatrics November 1979
Fig. 5. Electron micrograph of lung from an infant born at 34 weeks' gestation who lived 7 days. Hyaline membrane disease is in a regenerating phase. The airway (A) has been relined with alveolar Type II cells filled with large lamellar bodies. Active capillary invasion has stretched the epithelium of a Type cell over an endothelial surface which has approximated the airway (arrow head). A basement membrane can be followed between epithelial and endothelial cells and between epithelium and interstitium (arrows). Uranyl acetate and lead citrate (original magnification: x 3,275).
Fig. 6. Photomicrograph of it~ng from an 11-day-old inthnt who had disseminated interstitial air dissection following respirator treatment for severe hyaline membrane disease. A small muscular artery is surrounded by lymphatic channels dilated with air. Adjacent to this is a bronchiole (B) whose lining has undergone squamous metaplasia. Hematoxylin and eosin (original magnification: x 65).
Volume 95 Number 5, part 2
Diagnosis of BPD
833
Fig. 7. Photomicrograph of the terminal airways of infant lung seen in Fig. 6, showing protein containing edema fluid, round cell and polymorphonuclear leukocyte accumulation associated with infection with Pseudomonas aeruginosa. Hematoxylin and eosin (original magnification: x 160).
Fig. 8. Chest radiograph of same infant as in Fig. 4, now 7 weeks of age. Infant was still ventilator and oxygen dependent, with superimposed chronic Pseudomonas aeruginosa pneumonia. Cardiomegaly is also apparent.
Fig. 9. Chest radiograph of same infant as in Figs. 4 and 8, now 6 months of age during terminal hospitalization. Right lung is grossly overdistended, with depression of the right diaphram, and is essentially functionless, except as dead space. Left lung is also distended. There are dense fibrotic scarred areas around the hilum. The heart is enlarged.
834
Workshop on BPD
wheezing and severe respiratory distress, clinically resembling bronchiofitis. Frank pneumonia may occur, requiring repeated hospitalizations. These bouts of acute pulmonary insufficiency, which are superimposed on varying levels of chronic pulmonary impairment, usually gradually decrease in frequency an d severity after the
The Journal of Pediatrics November 1979 second year of fife. As the originally involved areas scar around the hilum, new formed lung units may allow relatively normal pulmonary function throughout childhood. The eventual outcome of these children is not known.
Radiographic-pathologic correlation in bronchopulmonary dysplasia David K. Edwards, M.D.,* San Diego, Calif., Thomas V. Colby, M.D., and William H. Northway, Jr., M.D., Stanford, Calif.
THE CHEST RADIOGRAPH is an essential modality in
T a b l e i. Independent radiographic and pathologic staging
the diagnosis and monitoring of patients with bronchopulmonary dysplasia. 1 Some authors have questioned the degree of correlation of the radiographic staging of BPD with the pathologic staging of the diseaseY 3 Determining this correlation could facilitate attempts to establish prognosis, using changes in the chest radiograph as one of the clinical markers. The purpose of this study was to compare retrospectively the radiographic staging of BPD with the histopathologic staging of changes in the lungs of a series of patients with respiratory distress syndrome who died after receiving mechanically assisted ventilation and supplemental oxygen therapy.
of BPD in 142 autopsied patients
MATERIALS
AND METHODS
S t u d y group. Among 299 consecutive infants with RDS treated at Stanford University Hospital with assisted ventilation for at least 24 hours, 158 patients died. Adequate autopsy histologic sections of lungs were available for 142 of these patients; this group of patients is the basis of this report. All patients in this series were born between January, 1962, and December, 1973, and have been described elsewhere. 4 R a d i o g r a p h i c e v a l u a t i o n . All chest radiographs were examined by two of us (D. E. and W. N.), working together, without knowledge of the patients' clinical course or pathologic findings. Each patient was staged for BPD (I to IV) 5 using the final available film. The patient's age at the last film was noted and subsequently c o m p a r e d with the age at death obtained from the medical record.
From the Departments of RadtolOgy and Pediatrics, University of California at San Diego, and the Departments of Pathology, Radiology and Pediatrics, Stanford University Medical Center. *Reprint address: Departmentof Radiology, University Hospital, 225 Dickinson St., San Diego, CA 92103.
Pathologic stage Radiographic stage I I to II II
II to III III IV
I
l
Il
l
Iil
21
39
11
3
2
2
--~
6 --
10 3
--
4
1
l
lv 4 --
8 1 I0 17
Abbreviations used BPD: bronchopulmonary dysplasia RDS: respiratory distress syndrome P a t h o l o g i c e v a l u a t i o n . Hematoxylin and eosin stained sections of lung (both lungs in most instances) from all patients were examined by one of us (T. C.) without knowledge of clinical history, radiographic findings, or prior autopsy re~ort. The histologic variables examined were adapted-f~om those of Rosan 1' 2 and included changes (if any) in bronchiolar mucosa, pulmonary interstitium, lymphatics, and inflation pattern. The presence and extent of yellow pigment (hematoidin), bronchiolitis obliterans, hyaline membranes, hemorrhage, alveolar infiltrates (excluding areas of obvious pneumonia), and interstitial and peribronchial smooth muscle proliferation wer~ also noted. These histologic variables were graded in severity from 0 to 4. A synthesis of all variables in an individual patient resulted in a pathologic stage of BPD from I to IV, as described by Rosan. 2 Staging was necessarily somewhat subjective because different variables were often of different severity in the same patient. D a t a analysis. Following independent interpretation of
6022-3476/79/110834+ 03500.30/0 9 1979 The C. V. Mosby Co.
