title: Persistent Lung Disease in Adults with NKX2.1 Mutation and Familial Neuroendocrine Cell Hyperplasia of Infancy.
abstract: Neuroendocrine cell hyperplasia of infancy (NEHI) is a diffuse lung disease that presents in infancy and improves during childhood. Long-term outcomes have not previously been described. In one familial cohort, we have reported that NEHI is associated with a heterozygous variant of NKX2.1/TTF1.
  
  
  
  Our objective was to determine whether pulmonary abnormalities persist in adults with NEHI, to aid in elucidating the natural history of this disease.
  
  
  
  Four adult relatives with heterozygous NKX2.1 mutation and with clinical histories compatible with NEHI enrolled in a prospective study that included questionnaires, pulmonary function tests, and chest computed tomography scans.
  
  
  
  Mild radiologic abnormalities including mosaicism were seen in all four cases. Three individuals had obstruction on pulmonary function tests, two had marked air trapping, and three had symptomatic impairments with exercise intolerance.
  
  
  
  Although clinical improvement occurs over time, NEHI may result in lifelong pulmonary abnormalities in some cases. Further studies are required to better describe the natural history of this disease and would be facilitated by additional delineation of genetic mechanisms to enable improved case identification.
authors.affiliation: 1 Division of Pulmonary Medicine, Department of Pediatrics.
authors.forename: Rebekah J
authors.initials: RJ
authors.lastname: Nevel
authors.affiliation: 2 Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, and.
authors.forename: Errine T
authors.initials: ET
authors.lastname: Garnett
authors.affiliation: 3 Department of Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: John A
authors.initials: JA
authors.lastname: Worrell
authors.affiliation: 4 Division of Pulmonary Medicine, University of Louisville, Louisville, Kentucky; and.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Morton
authors.affiliation: 5 Eudowood Neonatal Pulmonary Division, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Nogee
authors.affiliation: 2 Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, and.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.affiliation: 1 Division of Pulmonary Medicine, Department of Pediatrics.|2 Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, and.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Young
mesh_terms: D000328:Adult; D005192:Family Health; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007223:Infant; D008168:Lung / Q000503:physiopathology*; D017563:Lung Diseases, Interstitial / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055099:Neuroendocrine Cells / Q000473:pathology*; D011446:Prospective Studies; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D000074482:Thyroid Nuclear Factor 1 / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: C000614412:NKX2-1 protein, human; D000074482:Thyroid Nuclear Factor 1
keywords: childhood interstitial lung disease; neuroendocrine cell hyperplasia of infancy; thyroid transcription factor-1