Variation in the bombesin staining of pulmonary neuroendocrine cells in pediatric pulmonary disorders—A useful marker for airway maturity

Abstract

Objectives Pulmonary neuroendocrine cells (NEC) increase with age due to pulmonary maturity. The aim of this study was to determine whether open lung biopsies from patients with interstitial lung diseases have increased pulmonary NEC compared with neuroendocrine cell hyperplasia of infancy (NEHI). Our second aim was to assess pulmonary NECs in the lung autopsy of children without lung disease who died from different causes. Methods Lung tissue of 5 infants with NEHI; 21 patients with pediatric interstitial lung disease (chILD); 17 lung autopsies of infants at varying age without lung disease were included. The percentage of the airways containing neuroendocrine cells, the average percentage of neuroendocrine cells (NECs) per airway, and the number of neuroendocrine bodies (NEBs) in each case were analyzed. Results The mean percentage of the airways containing neuroendocrine cells were 95% in the NEHI group, 30% in the chILD group, 89% under Intrauterine 37 weeks, 70% between intrauterine 37 to 40 weeks, 52% at postnatal 4 days to 6 months of autopsy ages. In the NEHI group, diffuse NE cell distribution and large NEBs were noticed in the lung biopsy. In the chILD group, neuroendocrine cells were dispersed, did not form clusters and NE cells showed solitary distribution. In the lung autopsy group, linear NE cells were detected at younger aged fetuses and solitary distribution of NE cells was detected with the older increasing age. Conclusions Our findings confirm that NECs are seen in many other childhood interstitial lung diseases; NE cell hyperplasia may be a marker of decreased pulmonary development and NE cells decrease with the increasing age of the fetus during Intrauterine life.

Upregulation of neuropeptides and infant obstructive airway disorder in post-RSV wheezing and NEHI

“…A bombesin-induced airflow limitation at that level is consistent with the clinical presentation, i.e. small airway obstruction and air-trapping 7,18 .…”

“…As previously mentioned, abnormalities in the number, distribution and function of pulmonary NEC have been documented in a number of different pediatric lung disorders that include PH 3,18 . In normal lungs the relative density of nerve fibers increases during childhood in the arteries of the respiratory unit.…”

“…After birth, pulmonary NEC decrease and often disappear with lung maturation by 1-2 years of age 15 . This may not be the case in conditions of pathology, such as pediatric PH, BPD, SIDS, CCHS and CF 3,[15][16][17][18] . Acute or persistent hypoxia and injury to the airways, features of some of these disorders, are recognized stimuli that can activate pulmonary NEC inducing release of bioactive neuropeptides, such as bombesin, which can modulate lung damage, as shown in premature infants with BPD, or trigger smooth muscle contraction, as shown in NEHI 3,9,[15][16][17][18] .…”

“…Acute or persistent hypoxia and injury to the airways, features of some of these disorders, are recognized stimuli that can activate pulmonary NEC inducing release of bioactive neuropeptides, such as bombesin, which can modulate lung damage, as shown in premature infants with BPD, or trigger smooth muscle contraction, as shown in NEHI 3,9,[15][16][17][18] . In this latter disorder, a predominant abundance of pulmonary bombesin-positive NEC in small airways and distal bronchiole has been described as the characteristic finding [18][19][20] . A bombesin-induced airflow limitation at that level is consistent with the clinical presentation, i.e.…”

“…Pulmonary NEC may play a proinflammatory role via production of neuropeptides in these pathologies and possibly, as will be reviewed in the next two paragraphs, in respiratory virus-induced airway diseases. These latter disorders are characterized by inflammation, release of oxygen radicals, injury to airway structures, and, clinically by acute hypoxia, all stimuli that can activate pulmonary NEC causing release of bioactive neuropeptides [16][17][18]25,30 .…”