William H. Northway

Late Pulmonary Sequelae of Bronchopulmonary Dysplasia

BACKGROUND Bronchopulmonary dysplasia is a chronic lung disease that often develops after mechanical ventilation in prematurely born infants with respiratory failure. It has become the most common form of chronic lung disease in infants in the United States. The long-term outcome for infants with bronchopulmonary dysplasia has not been determined. METHODS We studied the pulmonary function of 26 adolescents and young adults, born between 1964 and 1973, who had bronchopulmonary dysplasia in infancy. We compared the results with those in two control groups: 26 age-matched adolescents and young adults of similar birth weight and gestational age who had not undergone mechanical ventilation, and 53 age-matched normal subjects. RESULTS Sixty-eight percent of the subjects with bronchopulmonary dysplasia in infancy (17 of the 25 tested) had airway obstruction, including decreases in forced expiratory volume in one second, forced expiratory flow between 25 and 75 percent of vital capacity, and maximal expiratory flow velocity at 50 percent of vital capacity, as compared with both control groups (P less than 0.0001 for all comparisons). Twenty-four percent of the subjects with bronchopulmonary dysplasia in infancy had fixed airway obstruction, and 52 percent had reactive airway disease, as indicated by their responses to the administration of methacholine or a bronchodilator. Hyperinflation (an increased ratio of residual volume to total lung capacity) was more frequent in the subjects with a history of bronchopulmonary dysplasia than in either the matched cohort (P less than 0.0006) or the normal controls (P less than 0.0004). Six of the subjects who had bronchopulmonary dysplasia in infancy had severe pulmonary dysfunction or current symptoms of respiratory difficulty. CONCLUSIONS Most adolescents and young adults who had bronchopulmonary dysplasia in infancy have some degree of pulmonary dysfunction, consisting of airway obstruction, airway hyperreactivity, and hyperinflation. The clinical consequences of this dysfunction are not known.

Bronchopulmonary dysplasia: The pulmonary pathologic sequel of necrotizing bronchiolitis and pulmonary fibrosis

A light and electron microscopic study was carried out in 21 infants in whom the pathologic diagnosis of bronchopulmonary dysplasia had been made. All the infants except two had the respiratory distress syndrome at birth, and all 21 had been treated with respirator and oxygen therapy for various periods of time. The pathologic alterations observed in all the infants studied were primarily damage of the bronchial and bronchiolar ciliary apparatus and mucous membranes, severe necrotizing bronchiolitis, and marked bronchiolar and alveolar fibrosis. These changes were more pronounced in infants who survived the longest period of time. Such inflammatory and fibrotic changes are known to predispose to destruction of lung tissue, emphysema, and pulmonary hypertension. Six of these 21 infants developed symptoms and signs of cardiac atrial or ventricular stress, including cor pulmonale, prior to their demise. These infants were among those that survived the longest periods of time, had the longest exposure to supplemental oxygen, and showed histopathologically severe pulmonary fibrosis and emphysema.

Radiographic features of pulmonary oxygen toxicity in the newborn: Bronchopulmonary dysplasia.

A new syndrome of pulmonary disease following prolonged oxygen and respirator therapy of the respiratory distress syndrome of the newborn has recently been reported (13). This disease entity has been called bronchopulmonary dysplasia to emphasize the involvement of all the tissues of the developing lung in the pathologic process. It is believed to represent the toxic manifestations of 80–100 per cent oxygen (high O2) on the developing lung superimposed upon the healing phase of respiratory distress syndrome. Based on clinical, radiologic, and pathologic findings, bronchopulmonary dysplasia has been divided into four stages: Stage I: Clinically and radiographically resembles ordinary respiratory distress syndrome except for excessive mucosal necrosis (one to three days of age). Stage II: Characterized by marked radiopacity of the lungs, inability to be weaned from high O2, and cycles of alveolar injury and repair (four to ten days of age). Stage III: Radiographic cystic appearance of the lungs with respira...

Radiographic-pathologic correlation in bronchopulmonary dysplasia

THE CHEST RADIOGRAPH is an essential modality in 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.

On the origin of the membranous intraalveolar material in pulmonary alveolar proteinosis

Abstract A case of pulmonary alveolar proteinosis, studied by light and electron microscopy, showed evidence for increased secretion of lamellar bodies by granular pneumocytes, uptake of these lamellar bodies by alveolar macrophages and eventual disintegration of the macrophages. These findings are assumed to be the main events in the pathogenesis of this disease. The same sequence leading to a condition morphologically resembling alveolar proteinosis can be found in an experimental model using prolonged exposure of newborn mice to 100% oxygen. In both instances, the membranous component of the proteinaceous material (myeloid bodies) appeared to originate from the ingested lamellar bodies in lysosomes of alveolar macrophages. It is suggested that this conversion of lamellar bodies is a physiologic mode of inactivation of surfactant, and that pulmonary alveolar proteinosis represents a state in which the catabolic capacities of alveolar macrophages have been overstressed.

Radiologic and histologic investigation of pulmonary oxygen toxicity in newborn guinea pigs.

The hypothesis that pulmonary oxygen toxicity is radiographically demonstrable was tested by serially radiographing 23 newborn guinea pigs maintained in a 96 to 100% oxygen environment at normal atmospheric pressure. All animals died in the increased-oxygen environment by six and one-half days. Nineteen showed characteristic radiologic progression of disease to death. Graded histologic changes in the lungs, particularly at the bronchiolar level, correlated strongly with the duration of 96 to 100% oxygen exposure (correlation coefficient, 0.90, P < 0.001). Duration of life in 96 to 100% oxygen was directly related to birth weight, but not to sex. Seventeen control newborn guinea pigs maintained in room air showed no radiologic evidence of disease and minimal histologic changes.

Sonographic detection of congenital pancreatic cysts in the newborn: Report of a case and review of the literature

A case of congenital pancreatic cysts detected antenatally by ultrasound is presented. This is the second case detected antenatally. Congenital pancreatic cysts should be included in the differential diagnosis of upper abdominal cystic masses in the fetus and newborn infant.

The Effect of Dexamethasone on Chronic Pulmonary Oxygen Toxicity in Infant Mice

ABSTRACT: The effect of dexamethasone (0.1, 1, and 5 mg/kg/d given subcutaneously from d 14-18) was tested in infant mice continuously exposed from birth to either humidified air or 80% oxygen. Dexamethasone significantly decreased lung wet wt (p<0.01), lung water (p<0.021), lung dry wt, protein, and DNA (p<0.001) in both airand oxygen-exposed animals. Dexamethasone, however, had no effect on lung compliance measured after animals were killed on d 18. It also had no effect on the increase in the blood-air barrier thickness or decrease in the blood-air exchange surface area seen in the 80% oxygen-exposed mice. Dexamethasone decreased thymus gland wt (p<0.001), body wt gain (p<0.001), brain wt (p<0.001), and lung lymphocytes (p<0.05) in both air- and oxygenexposed animals. The effect of 1 mg/kg and 5 mg/kg of the drug could not be differentiated. During the 4 d of drug administration, one air- and one oxygen-exposed animal died; both received 5 mg/kg/d of dexamethasone; microscopic and culture evidence of infection was not found. If dexamethasone causes similar effects in human infants with bronchopulmonary dysplasia, it should be used with great caution even for short-term clinical management.

Prologue: Advances in Bronchopulmonary Dysplasia

It has been 42 years since our first published report of bronchopulmonary dysplasia (BPD) 1 ; it is still a problem for premature infants. The original goal of using mechanical ventilation to treat premature infants with respiratory distress syndrome and respiratory failure was to decrease the significant mortality. During the ensuing decades, a decrease in mortality has indeed occurred. Once recognized, it was hoped that a reduction of supplemental oxygen concentrations and ventilatory pressure would eliminate or decrease the incidence of BPD. This has, for the most part, been achieved in the 33 week gestational age infants originally described. Advances in neonatal care and respiratory therapy since 1967 have resulted in the successful ventilation of increasingly more immature infants. As a result the original radiographic picture and pathology have been modified. The understanding of the growth and development of the extremely premature lung and the genetic, intrauterine, biochemical, and infectious factors that influence the susceptibility and severity of BPD has also advanced. This has led to improvements in prevention strategies and both ventilatory and non-ventilatory treatment of BPD. Unfortunately, it has not eliminated BPD or led to a more precise diagnosis. The chest radiographic changes are much more subtle and are seldom used in the diagnosis. Infants are now delivered while their lungs are in the late canalicular to early saccular stage of development. It has yet to be determined whether there is an oxygen concentration or ventilator pressure below which these treatments are non-injurious. Prevention of premature delivery remains an elusive and persistent problem. The long-term pulmonary function of premature infants with or without BPD surviving beyond adolescence to older adulthood is also unknown. Whereas some of the original premature infants with BPD displayed persistent pulmonary dysfunction as adolescents, it is not known if these changes regressed, persisted, or exacerbated in older adulthood. These original infants were less premature than today’s neonatal intensive care unit population. They also were treated with higher concentrations of supplemental oxygen, and higher ventilator pressures than are currently used, and prior to the widespread use of antenatal corticosteroids and surfactant therapy. The persistence of BPD in more immature premature infants indicates the need for long-term clinical and pulmonary function testing. Physicians who deal with these patients as adults will need to be aware of their possible late pulmonary disability. Knowledge of the evolving pulmonary function of infants born very prematurely might best be obtained if pediatric and adult oriented pulmonologists combine their interest and talents. We should not forget, however, that the continuing morbidity from BPD is the result of the successful application of modern neonatal intensive care to very premature infants to improve their survival.

Portal vein gas complicating Hirschsprung's disease with enterocolitis

Summary A case is reported of neonatal Hirschsprungs disease complicated by necrotizing enterocolitis and gas in the portal venous system. Several factors which could lead to the accumulation of portal venous gas in such a patient are discussed.