Abnormal Pulmonary Bombesin Immunoreactive Cells in Wilson-Mikity Syndrome (Pulmonary Dysmaturity) and Bronchopulmonary Dysplasia

Abstract

Wilson-Mikity syndrome (WMS) is a disorder of uncertain origin. It is sometimes considered a variant of bronchopulmonary dysplasia (BPD), but it lacks the characteristic microscopic stigmata of destruction and fibrosis caused by the barotrauma and oxygen toxicity of ventilator support. Conventional clinical and autopsy studies of WMS have failed to identify the underlying pathophysiology. This study evaluated bombesin-containing pulmonary neuroendocrine (PNE) cells in eight WMS cases, seven cases of BPD, and five controls, using the immunoperoxidase technique. The PNE cells were quantified by established morphometric techniques. The percentage of airways containing PNE cells in WMS (mean, 85.56%) was similar to that in the controls (mean, 82.6%) but significantly greater than that in BPD (mean, 21.28%) (p < .001). Measurement of intraepithelial PNE cell cytoplasm within the bombesin-immunopositive airways demonstrated apparent PNE cell hyperplasia in both WMS and BPD. Prominent numbers of PNE cells were also present in the respiratory bronchioles and alveolar units in WMS. The increased PNE cells in WMS may reflect chronic hypoxia from hypoventilation and or autonomic dysfunction. The profile in BPD may reflect a similar pathophysiology but complicated by ventilator-induced injury to airway epithelium.

Ontogeny of Clara cell-specific protein and its mRNA: their association with neuroepithelial bodies in human fetal lung and in bronchopulmonary dysplasia.

“…Previous studies of the same material have shown that PNEC and NEBs are numerous in infants with advanced BPD (Johnson et al, 1988;Stahlman et al, 1985Stahlman et al, ,1987Stahlman and Gray, 1984). PNEC hyperplasia has been demonstrated in BPD in other studies as well (Gillan and Cutz, 1993;Johnson et al, 1982Johnson et al, ,1985. The increased numbers of NEBs in advanced BPD may reflect a response to chronic local hyp-oxia and/or increased production of growth factors such as bombesin.…”

Diagnostic Pathology of Diffuse Lung Disease in Children

“…Exclusion of other forms of chronic lung disease is also an important consideration, as airway neuroendocrine cell hyperplasia has been described as a secondary fi nding in a wide variety of pediatric lung disorders. [72][73][74][75][76][77][78] Some cases have mild airway-associated lymphoid hyperplasia, but signifi cant fi brosis is absent. The etiology of NEHI remains unknown and it has been suggested that this may be a developmental or genetic disorder due to familial descriptions of NEHI, or may also be a secondary reaction to prior airway injury, for example a postinfectious process or post-aspiration process.…”

Neuro-endocrine tumours of the lung. A review of relevant pathological and molecular data

“…Most cases are idiopathic ("diffuse idiopathic pulmonary NE cell hyperplasia," associated with obliterative bronchiolar fibrosis in the absence of known causes of interstitial or airway fibrosis or inflammation) [28], while others may be incidentally found in chronic bronchial inflammation [42], Langerhans cell hystiocytosis [2] or bronchopulmonary dysplasia [16].…”