Maternal smoking and pulmonary neuroendocrine cells in sudden infant death syndrome.

BACKGROUND: Maternal smoking is a well-recognized risk factor for sudden infant death syndrome (SIDS), but the precise mechanism is unknown. We tested a hypothesis that maternal smoking affects pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs), which are innervated PNEC clusters and presumed airway chemoreceptors. METHODS: Lung sections from infants who died of SIDS and whose mothers smoked during pregnancy (n = 22), infants who died of SIDS and whose mothers were nonsmokers (n = 17), and age-matched control infants (n = 15) who died of other causes were immunostained for bombesin (a PNEC and NEB marker) and assessed morphometrically. RESULTS: The frequency of PNEC (the percentage of airway epithelium immunoreactive for bombesin) was increased up to twofold in the lungs of infants who died of SIDS (7.7 +/- 0.4%) compared with controls (4.9 +/- 0.4%), as was the frequency (40 +/- 3.5 vs 23 +/- 3.7/cm2) and size (748 +/- 46.5 vs 491 +/- 25.8 microns2) of NEBs. In infants who died of SIDS and who were born to smoking mothers, PNEC frequency was increased significantly compared with that in those born to nonsmoking mothers, but the frequency and size of NEBs were not significantly different between the two groups. CONCLUSION: Our findings suggest that maternal smoking potentiates hyperplasia of the PNEC system in the lungs of infants who die of SIDS and that a dysfunction of these cells may contribute to the pathophysiology of SIDS.

Sudden death in infants under one year of age.

Clinical and postmortem findings on 126 consecutive cases of sudden infant deaths occurring in Metropolitan Toronto over a 42-month period were reviewed and classified. Of these cases, 101 were diagnosed as sudden infant death syndrome (SIDS), the other 25 as due to other causes. The SIDS cases were classified into three groups: A-1 (39%), infants born at term who died between 2 weeks and 6 months of age and in whom clinical and autopsy findings were negative; A-2 (4%), same as A-1, except that the infants were born prematurely (< 36 weeks of gestation); and B (57%), infants with miscellaneous minor clinical and pathological findings not directly related to or responsible for death. The most common findings in group B were clinical and/or pathological signs of minor respiratory infection. These findings were prevalent in older SIDS infants (> 10 weeks at death), with up to 80% concordance between clinical and pathological indices of respiratory infection. Group B also included cases with minor congenital abnormalities, drug use by mother, and other miscellaneous findings. This report defines the clinicopathological features of SIDS infants and describes the spectrum of findings associated with the syndrome. It is suggested that by applying uniform criteria for definition and classification of SIDS a more reliable data base can be obtained, facilitating research into the causes and pathogenesis of SIDS.

Genetic aspects of immotile cilia syndrome.

The genetics of the immotile cilia syndrome has been analyzed in a series of 46 affected individuals from 38 families. Both sexes were equally affected: there were 20 males and 26 females in this series. All patients had upper and lower respiratory disease with chronic sinusitis, otitis, and chronic cough from early childhood. Bronchiectasis was common in older children and adults. Situs inversus occurred randomly, affecting 11 males and 15 females. Biopsies of nasal and bronchial mucosa from these subjects have been investigated by electron microscopy and identified as having specific ultrastructural defects of respiratory tract cilia including deficiencies in outer dynein arms (19), inner dynein arms (3), both inner and outer dynein arms (15), radial spoke defect (5); and microtubular transposition anomaly (4). Segregation analysis of proband sibships was consistent with autosomal recessive inheritance. However, the different ultrastructural defects that underly the immotile cilia syndrome involve presumably different genetic determinants, and the different types have not been analyzed separately. Examination of paternal age and birth order gave no evidence of new autosomal dominant mutation in the series.

Cystic fibrosis in Ontario.

The incidence of cystic fibrosis in Ontario, Canada has been determined from clinical data, from the cystic fibrosis database of the Hospital for Sick Children, Toronto, and from population statistics in the Province of Ontario. The survey included 420 confirmed cases of cystic fibrosis born during the period 1966-1980. The mean incidence during this period was one in 2,927. In the last 5-year period, a decline was noted in incidence that may have reflected in part the effectiveness of early diagnosis and genetic counseling in affected families. During the period of the survey, over 60% of cases were diagnosed within the first year of life, 74% by age 2 years, and 90% by age 5 years. Clinical diagnosis in the first year of life was more common in males (65%) than in females (54%), a consistent finding during the period of the survey. The incidence of meconium ileus was 15.7% of ascertained cases of cystic fibrosis, with similar incidences in males (16.4%) and females (14.4%). Although survival has not been the subject of this survey, mortality in the neonatal period was significantly higher in males than in females with cystic fibrosis.

Genital mycoplasma infection. Intrauterine infection: pathologic study of the fetus and placenta.

Mycoplasma infection was present in the fetuses from three spontaneous abortions and in one second-trimester newborn. Gross examination revealed in most cases a severely infected placenta and membranes, with a fetus of normal appearance. The fetal infection presumably followed placental involvement and appeared to have been acquired shortly prior to delivery. Genital mycoplasmas, Ureaplasma urealyticum or Mycoplasma hominis, were isolated from the placentas and the fetal tissues, and from the genital tracts of the mothers. Isolation of mycoplasmas from the liver indicated that bloodstream dissemination of these organisms occurred in the fetus. In the fetus, the pathologic changes were variable. Lesions were identified in the lung by scanning electron microscopy of the bronchial tree in two cases and were accompanied by interstitial pneumonia. An abnormally dilated left ventricle suggestive of cardiomyopathy was observed in one case.

Cystic fibrosis: effects of serum factors on mucus secretion.

The effects of serum from children with cystic fibrosis and from normal children on the mucus-secreting, ciliated epithelium have been investigated in vitro using explanted tissue from rabbit lung. By optical and scanning electron microscopy, a sequence of structural changes is observed after incubation with cystic fibrosis serum; this sequence does not occur with normal serum. The earliest changes involve swelling of the goblet cells, with subsequent discharge of mucus onto the epithelial surface. This is followed by disruption of the normally rapid and synchronized ciliary activity. Mucus gradually extends over the surface entangling cilia. Finally, some shedding of ciliated cells occurs from the epithelium. These findings suggest that factors in cystic fibrosis serum cause discharge of mucus leading to a disturbance of the normal ciliary activity in the rabbit lung. It is postulated that such changes result in dysfunction of the mucociliary clearance mechanism and that this dysfunction may be a contributory factor to the pathogenesis of lung disease.