Neuroendocrine cell hyperplasia of infancy (NEHI)
- Lisa R Young, MD
Lisa R Young, MD
- Associate Professor of Pediatrics and Medicine
- Vanderbilt University School of Medicine
Neuroendocrine cell hyperplasia of infancy (NEHI), previously known as persistent tachypnea of infancy, is a rare lung disease first described in 2005 . The etiology is unknown, but genetic mechanisms may play a role. NEHI typically presents in otherwise healthy infants during the first months to year of life with persistent tachypnea, crackles, and hypoxemia. In addition to these chronic clinical features, NEHI is defined by chest computed tomography (CT) findings of hyperinflation and ground-glass opacities in a characteristic geographic distribution and lung biopsy findings demonstrating prominence of bombesin-positive neuroendocrine cells in the distal airways. NEHI may be diagnosed based on high-resolution CT (HRCT) and clinical findings in many cases, but lung biopsy is still needed in others. Pulmonary symptoms and hypoxemia tend to improve with time, but may persist for years.
The clinical presentation, diagnosis, and treatment of NEHI is discussed in this topic review. The characteristics and diagnosis of other interstitial lung diseases of infancy and childhood are discussed separately. (See "Classification of diffuse lung disease (interstitial lung disease) in infants and children" and "Approach to the infant and child with diffuse lung disease (interstitial lung disease)".)
The incidence and prevalence of NEHI are unknown, but it is clearly rare. Available data derive from small to moderate-sized case series. The original report of this disorder in 2005 included 15 cases from two referral centers . In an 11-center study reported by the Children's Interstitial Lung Disease Research Network in North America (CHILDRN), NEHI cases (n = 18) represented 10 percent of all lung biopsies from children less than two years of age . A study from a large referral center identified 19 cases (14 percent) from among 138 lung biopsy cases accrued over a 10-year period . Twenty-three NEHI cases were included in a separate study testing chest high-resolution computed tomography (HRCT) diagnostic criteria . The largest report to date includes 37 cases in a manuscript focusing on infant pulmonary function testing (PFT). Importantly, there is a significant overlap of cases included in all of these publications, making the total number of NEHI cases in North America unknown at this time. Additional published cases have now been reported from Finland (n = 9), Brazil (n = 12), the United Kingdom (n = 7), and single cases from China and Poland, as well as cases from Australia, New Zealand, Ecuador, Spain, Germany, France, Mexico, and Japan .
It is suspected that the prevalence of NEHI may be greater than currently estimated. At a pediatric center that was not a historic referral center or included in the above studies, there were 8 cases (8.3 percent) of NEHI out of 93 cases of childhood interstitial lung disease (ILD) identified through a retrospective review. Most of these NEHI cases were not previously recognized, and the patients had been diagnosed with other specific or nonspecific types of chronic lung disease .
In the original series of 15 cases reported by Deterding et al, there was a slight male predominance . This pattern has been observed in some, but not all, subsequent reports.
- Deterding RR, Pye C, Fan LL, Langston C. Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia. Pediatr Pulmonol 2005; 40:157.
- Deutsch GH, Young LR, Deterding RR, et al. Diffuse lung disease in young children: application of a novel classification scheme. Am J Respir Crit Care Med 2007; 176:1120.
- Young LR, Brody AS, Inge TH, et al. Neuroendocrine cell distribution and frequency distinguish neuroendocrine cell hyperplasia of infancy from other pulmonary disorders. Chest 2011; 139:1060.
- Brody AS, Guillerman RP, Hay TC, et al. Neuroendocrine cell hyperplasia of infancy: diagnosis with high-resolution CT. AJR Am J Roentgenol 2010; 194:238.
- Lisa R Young, MD - Personal experience and correspondence from the Children's Interstitial and Diffuse Lung Disease [chILD] Foundation.
- Soares JJ, Deutsch GH, Moore PE, et al. Childhood interstitial lung diseases: an 18-year retrospective analysis. Pediatrics 2013; 132:684.
- Young LR, Deutsch GH, Bokulic RE, et al. A mutation in TTF1/NKX2.1 is associated with familial neuroendocrine cell hyperplasia of infancy. Chest 2013; 144:1199.
- Cutz E, Yeger H, Pan J. Pulmonary neuroendocrine cell system in pediatric lung disease-recent advances. Pediatr Dev Pathol 2007; 10:419.
- O'Connor MG, Wurth M, Young LR. Rare Becomes More Common: Recognizing Neuroendocrine Cell Hyperplasia of Infancy in Everyday Pulmonary Consultations. Ann Am Thorac Soc 2015; 12:1730.
- Gomes VC, Silva MC, Maia Filho JH, et al. Diagnostic criteria and follow-up in neuroendocrine cell hyperplasia of infancy: a case series. J Bras Pneumol 2013; 39:569.
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- Popler J, Wagner BD, Tarro HL, et al. Bronchoalveolar lavage fluid cytokine profiles in neuroendocrine cell hyperplasia of infancy and follicular bronchiolitis. Orphanet J Rare Dis 2013; 8:175.
- Langston C, Patterson K, Dishop MK, et al. A protocol for the handling of tissue obtained by operative lung biopsy: recommendations of the chILD pathology co-operative group. Pediatr Dev Pathol 2006; 9:173.
- Yancheva SG, Velani A, Rice A, et al. Bombesin staining in neuroendocrine cell hyperplasia of infancy (NEHI) and other childhood interstitial lung diseases (chILD). Histopathology 2015; 67:501.
- Hamvas A, Deterding RR, Wert SE, et al. Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1. Chest 2013; 144:794.
- Purcell HN, Whisenhunt A, Cheng J, et al. "A remarkable experience of god, shaping us as a family": parents' use of faith following child's rare disease diagnosis. J Health Care Chaplain 2015; 21:25.
- Houin PR, Deterding RR, Young LR. Exacerbations in neuroendocrine cell hyperplasia of infancy are characterized by increased air trapping. Pediatr Pulmonol 2016; 51:E9.