A New Form of Respiratory Disease in Premature Infants

Wilson, Miriam G.; Mikity, Victor G.

doi:10.1001/archpedi.1960.02070030491011

Cited by 72 publications

(61 citation statements)

References 3 publications

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“…Although enlarged alveoli were reminiscent of those seen in CLD/BPD, there was more variation in size and many were exceptionally large, round, and cyst-like. Simplified and enlarged alveoli as seen in this infant may also be observed in Wilson-Mikity syndrome (20,21), Down syndrome (22), primary pulmonary hypoplasia, and in association with other congenital abnormalities (23). Wilson-Mikity syndrome was described in preterm infants before the use of mechanical ventilation.…”

Section: Discussionmentioning

confidence: 54%

Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome

Galambos

Levy

Cannon

et al. 2010

Am J Respir Crit Care Med

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Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12-21.3 haploid deletion encompassing the TTF-1 gene locus who had cerebral dysgenesis, thyroidal dysfunction, and respiratory insufficiency. The clinical course was notable for mild hyaline membrane disease, continuous ventilatory support, and symmetrically distributed pulmonary cysts by imaging. He developed pneumonia and respiratory failure and died at 8 months. Pathologically, the lungs had grossly visible emphysematous changes with ''cysts'' up to 2 mm in diameter. The airway generations and radial alveolar count were diminished. In addition to acute bacterial pneumonia, there was focally alveolar septal fibrosis, pneumocyte hypertrophy, and clusters of airspace macrophages. Ultrastructurally, type II pneumocytes had numerous lamellar bodies, and alveolar spaces contained fragments of type II pneumocytes and extruded lamellar bodies. Although immunoreactivity for surfactant protein SP-A and ABCA3 was diminished, that for SP-B and proSP-C was robust, although irregularly distributed, corresponding to the distribution of type II pneumocytes. Immunoreactivity for TTF-1 protein was readily detected. In summation, we document abnormal airway and alveolar morphogenesis and altered expression of surfactant-associated proteins, which may explain the respiratory difficulties encountered in TTF-1 haploinsufficiency. These findings are consistent with experimental evidence documenting the important role of TTF-1 in pulmonary morphogenesis and surfactant metabolism.Keywords: alveolar growth abnormality; cerebral dysgenesis; thyroid transcription factor-1; bronchopulmonary dysplasia; surfactant protein Thyroid transcription factor-1 (TTF-1, also known as TITF-1, NKX2-1, or TEBP), a member of the NKx2 homeodomain transcription factor family, is essential for the morphogenesis of thyroid, lungs, and brain (3).TTF-1 knockout mice fail to develop these organs and die at birth, whereas the heterozygous mice reach term (4).TTF-1 haploinsufficiency in humans is responsible for a rare syndrome (TTF-1 deficiency syndrome) characterized by neurological, thyroidal, and pulmonary dysfunction (5-9). In a recent series that also reviewed the clinical and pathologic findings of 46 patients with TTF-1 deficiency, pulmonary disease occurred in 54%, with ''infant respiratory distress syndrome'' being the most common (7). The pulmonary pathology has been described briefly in one patient, whereas only one other case report illustrates the pathologic findings (10, 11).We identified an infant with cerebral dysgenesis, thyroidal dysfunction, respiratory insufficiency, and a karyotype showing a 14q13-21.3 deletion encompassing the TTF-1 gene locus. The infant died at 8 months with pneumonia and respiratory insufficiency. We describe his pulmonary pathology, incl...

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Section: Discussionmentioning

confidence: 54%

Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome

Galambos

Levy

Cannon

et al. 2010

Am J Respir Crit Care Med

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“…1). The radiographic findings resembled those seen in Wilson-Mikity syndrome (31). However, according to the original description, the clinical course of Wilson-Mikity syndrome is generally very mild, with a low FiO 2 , no need for respiratory support, delayed onset of respiratory symptoms and radiographic abnormalities, and death usually being due to nonrespiratory problems in fatal cases (25,32).…”

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confidence: 86%

Plasma KL-6 Predicts the Development and Outcome of Bronchopulmonary Dysplasia

et al. 2006

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Circulating KL-6 is a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium. Our preliminary study suggested the usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To confirm the diagnostic value of KL-6 for BPD as well as to determine the reference range, we conducted a larger prospective study in 135 preterm infants Ͻ32 wk GA. Among the infants without oxygen dependence at a postconceptional age of 36 wk, the plasma KL-6 level showed no significant association with GA at any time. Among 42 infants Ͻ28 wk GA, plasma KL-6 levels were significantly higher in those with moderate/ severe BPD compared with those with no/mild BPD. A plasma level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of moderate/severe BPD Ͻ28 wk GA (positive predictive value of 83% and 80%, respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6 objectively reflects the severity of pulmonary injury irrespective of the treatment or the radiographic changes. Therefore, not only as a good marker, measurement of KL-6 may also help to provide new insights into the pathogenesis of BPD.

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“…We were convinced that the dose was enough to exhibit affects on lungs of newborn rats similar to postnatal administration, because the dose of postnatal DXM was so much lower than that of clinical use for CLD (15)(16)(17), i.e. 3.3-12.5 g·kg Ϫ1 ·d Ϫ1 versus 0.5 mg·kg Ϫ1 ·d Ϫ1 (18,19).…”

Section: Antenatal Dexamethasone and Rat Lungsmentioning

confidence: 99%

Antenatal Dexamethasone Administration Impairs Normal Postnatal Lung Growth in Rats

et al. 2001

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Our purpose was to determine the influences of antenatal dexamethasone administration on neonatal lung development in rats. Dexamethasone (0.4 mg/kg maternal body weight per day) was administered i.p. on the 21st d (group 1) or on the 20th and 21st d (group 2) of gestation in Sprague Dawley rats with timed pregnancies. After natural deliveries, the lungs of the pups 1-60 d of age were removed and processed for morphometric analysis. In 60-d-old pups, groups 1 and 2 both showed a lower numerical density of alveoli and a larger mean alveolar radius than control pups. Antenatal administration of dexamethasone to rats impairs the normal postnatal lung growth. Some aspects of the use of antenatal glucocorticoid therapy in humans may require reconsideration. Antenatal glucocorticoid therapy, including the administration of DXM and betamethasone, is widely used in the perinatal care of premature infants (1-3) The effects of antenatal glucocorticoid therapy include a reduction in the severity of respiratory distress syndrome, reductions in the incidences of several other complications associated with prematurity (hypotension, intracranial hemorrhage, etc.), and a reduction in mortality. In animal experiments, glucocorticoid administration appears to accelerate not only the establishment of the surfactant system, but also the activities of antioxidant enzymes (4) and, via surfactant-independent mechanisms, an increase in alveolar wall compliance (5).The growth of the lung during the human perinatal period consists of several phases (6): 1) the establishment of a surfactant system, 2) an increase in the number of alveoli through division of the existing alveoli (alveolarization), and 3) alveolar wall thinning and capillary fusion (microvascular maturation). The latter two phases are accompanied by structural changes. Alveolarization occurs mainly between the 35th wk of gestation and approximately the third postnatal year. Microvascular maturation begins after birth and is completed by 5 y of age. Alveolarization is said to occur only in the presence of immature thick septa (6).These three phases of lung growth have been observed in most mammals (6), but the times at which the phases occur differ among species. For example, the pulmonary ultrastructure of newborn rats corresponds to that of humans at about the 28th wk of gestation. In other words, rats are born before the process of alveolarization has begun. Alveolarization in the rat lung takes place predominantly within the first 2 wk of life, with microvascular maturation occurring during the third wk (7).Postnatal administration of DXM (1 g/d, i.e. 3.3-12.5 g·kg Ϫ1 ·d Ϫ1 , from d 2 to 15) is known to impair subsequent alveolarization in rats (8,9) During the first 2 wk, DXM accelerates microvascular maturation and suppresses alveolarization. One week after drug withdrawal, the trend toward precocious maturation is reversed. The alveolar wall returns to a more immature state, and a delayed burst of alveolarization begins. At d 60, the lungs appear emphysematous, with l...

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A New Form of Respiratory Disease in Premature Infants

Cited by 72 publications

References 3 publications

Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome

Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome

Plasma KL-6 Predicts the Development and Outcome of Bronchopulmonary Dysplasia

Antenatal Dexamethasone Administration Impairs Normal Postnatal Lung Growth in Rats

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