Abstract
Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current practice, a clinical and radiological approach is more and more preferred (NEHI syndrome). This national study aimed to address diagnosis and initial management of patients followed up for a NEHI pattern in pediatric centers for rare lung diseases (RespiRare, France). Data on neonatal and familial events, symptoms at diagnosis, explorations performed and results, and therapeutic management were collected by questionnaire. Fifty-four children were included (boys 63%). The mean onset of symptoms was 3.8 ± 2.6 months. The most frequent symptoms at diagnosis were tachypnea (100%), retraction (79.6%), crackles (66.7%), and hypoxemia (59.3%). The mean NEHI clinical score, evocative when ≥ 7/10, was 7.9 ± 1.4 (76% with a score ≥ 7). All chest CT-scans showed ground glass opacities evolving at least the middle lobe and the lingula. Lung biopsy was performed in 38.9% of the cases and was typical of NEHI in only 52.4%, even when the clinical presentation was typical. Initial treatments were oxygen (83.6%) and more curiously intravenous pulses of steroids (83.3%) and azithromycin (70.2%).
Conclusion: This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs.
What is Known: •Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy. | |
What is New: •In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively. •Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI. |
Similar content being viewed by others
Availability of data and materials
Data were anonymized but are available in an Excel file.
Code availability
Excel file was protected with a password.
Abbreviations
- BMI:
-
Body mass index
- chILD:
-
Childhood interstitial lung disease
- NEHI:
-
Neuroendocrine cell hyperplasia of infancy
References
Torrent-Vernetta A, Gaboli M, Castillo-Corullón S et al (2022) Incidence and prevalence of children’s diffuse lung disease in Spain. Arch Bronconeumol 58(1):22–29
Deterding RR, Pye C, Fan LL, Langston C (2005) Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia. Pediatr Pulmonol 40(2):157–165
Liptzin DR, Pickett K, Brinton JT et al (2020) Neuroendocrine cell hyperplasia of infancy. Clinical score and comorbidities. Ann Am Thorac Soc 17(6):724–728
Rauch D, Wetzke M, Reu S et al (2016) Persistent tachypnea of infancy. Usual and aberrant. Am J Respir Crit Care Med 193(4):438–447
Doan ML, Elidemir O, Dishop MK et al (2009) Serum KL-6 differentiates neuroendocrine cell hyperplasia of infancy from the inborn errors of surfactant metabolism. Thorax 64(8):677–681
Brody AS, Guillerman RP, Hay TC et al (2010) Neuroendocrine cell hyperplasia of infancy: diagnosis with high-resolution CT. Am J Roentgenol 194(1):238–244
Gomes VC, Silva MC, Maia Filho JH et al (2013) Diagnostic criteria and follow-up in neuroendocrine cell hyperplasia of infancy: a case series. J Bras Pneumol 39(5):569–578
Lukkarinen H, Pelkonen A, Lohi J et al (2013) Neuroendocrine cell hyperplasia of infancy: a prospective follow-up of nine children. Arch Dis Child 98(2):141–144
Popler J, Wagner BD, Tarro HL, Accurso FJ, Deterding RR (2013) Bronchoalveolar lavage fluid cytokine profiles in neuroendocrine cell hyperplasia of infancy and follicular bronchiolitis. Orphanet J Rare Dis 8:175
Caimmi S, Licari A, Caimmi D et al (2016) Neuroendocrine cell hyperplasia of infancy: an unusual cause of hypoxemia in children. Ital J Pediatr 42(1):84
Young LR, Deutsch GH, Bokulic RE, Brody AS, Nogee LM (2013) A mutation in TTF1/NKX2.1 is associated with familial neuroendocrine cell hyperplasia of infancy. Chest 144(4):1199–1206
Yancheva SG et al (2015) Bombesin staining in neuroendocrine cell hyperplasia of infancy (NEHI) and other childhood interstitial lung diseases (chILD). Histopathology 67(4):501–508
Jiramethee N, Erasmus D, Nogee L, Khoor A (2017) Pulmonary neuroendocrine cell hyperplasia associated with surfactant protein C gene mutation. Case Rep Pulmonol 2017:9541419
Lelii M, Patria MF, Pinzani R et al (2017) Role of high-resolution chest computed tomography in a child with persistent tachypnoea and intercostal retractions: a case report of neuroendocrine cell hyperplasia. Int J Environ Res Public Health 14(10):1133
Liptzin DR, Hawkins SMM, Wagner BD, Deterding RR (2018) Sleeping chILD: neuroendocrine cell hyperplasia of infancy and polysomnography. Pediatr Pulmonol 53(7):917–920
Nevel RJ, Garnett ET, Schaudies DA, Young LR (2018) Growth trajectories and oxygen use in neuroendocrine cell hyperplasia of infancy. Pediatr Pulmonol 53(5):656–663
Deterding RR, Wagner BD, Harris JK, DeBoer EM (2019) Pulmonary aptamer signatures in children’s interstitial and diffuse lung disease. Am J Respir Crit Care Med 200(12):1496–1504
Spielberg DR, Brody AS, Baker LM, Woods JC, Towe CT (2019) Ground-glass burden as a biomarker in neuroendocrine cell hyperplasia of infancy. Pediatr Pulmonol 54(6):822–827
Seidl E, Carlens J, Schwerk N et al (2020) Persistent tachypnea of infancy: follow up at school age. Pediatr Pulmonol 55(11):3119–3125
Urbankowska E, Urbankowski T, Drobczynski L et al (2020) Lung ultrasound-a new diagnostic modality in persistent tachypnea of infancy. Pediatr Pulmonol 55(4):1028–1036
Wang X, Huang R, Zhang GY, Huang YH, Zheng XR, Liu CT (2020) Clinical features of neuroendocrine cell hyperplasia of infancy. Zhongguo Dang Dai Er Ke Za Zhi 22(3):257–261
Balinotti JE, Maffey A, Colom A et al (2021) Clinical, functional, and computed tomography finidings in a cohort of patients with neuroendocrine cell hyperplasia of infancy. Pediatr Pulmonol 56(6):1681–1686
Breuer O, Cohen-Cymberknoh M, Picard E et al (2021) The use of infant pulmonary function tests in the diagnosis of neuroendocrine cell hyperplasia of infancy. Chest 160(4):1397–1405
Marczak H, Peradzynska J, Seidl E et al (2021) The improved clinical course of persistent tachypnea of infancy with inhaled bronchodilators and corticosteroids. Pediatr Pulmonol 56(12):3952–3959
Young LR, Brody AS, Inge TH et al (2011) Neuroendocrine cell distribution and frequency distinguish neuroendocrine cell hyperplasia of infancy from other pulmonary disorders. Chest 139(5):1060–1071
Emiraliogliu N, Orhan D, Cinel G et al (2020) Variation in the bombesin staining of pulmonary neuroendocrine cells in pediatric pulmonary disorders-a useful marker for airway maturity. Pediatr Pulmonol 55(9):2383–2388
Bush A, Cunningham S, de Blic J et al (2015) European protocols for the diagnosis and initial treatment of interstitial lung disease in children. Thorax 70(11):1078–1084
Deterding RR (2010) Infants and young children with children’s interstitial lung disease. Pediatr Allergy Immunol 23(1):25–31
Nathan N, Taam RA, Epaud R et al (2012) A national internet-linked based database for pediatric interstitial lung diseases: the French network. Orphanet J Rare Dis 7:40
Jo HE, Glaspole IN, Levin KC et al (2016) Clinical impact of the interstitial lung disease multidisciplinary service. Respirology 21(8):1438–1444
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by C Fabre, C Thumerelle, M Dervaux, N Nathan, and JC Dubus. The first draft of the manuscript was written by C Fabre, C Thumerelle, M Dervaux, J Mazenq, N Nathan, and JC Dubus and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval
This is an observational study. The Comité d’éthique de la recherche de la Société Française de Pédiatrie (CER_SFP_2020_123) and the Commission Nationale de l’Informatique et des Libertés (CNIL 2219327) gave their consents.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Conflict of interest
The authors declare no competing interests.
Additional information
Communicated by Peter de Winter
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Fabre, C., Thumerelle, C., Dervaux, M. et al. French national cohort of neuroendocrine cell hyperplasia of infancy (FRENCHI) study: diagnosis and initial management. Eur J Pediatr 181, 3067–3073 (2022). https://doi.org/10.1007/s00431-022-04510-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-022-04510-y