- Donate
- Understanding Rare Disease
- Living with a Rare Disease
- Community Support
- Advancing Research
- Driving Policy
- Get Involved
- Rare Disease News
- Resource Library
- About Us
- For Clinicians & Researchers
- For Patient Organizations
Last updated: 12/16/2024
Years published: 2024
NORD gratefully acknowledges Yarelis Machin, MD Candidate, American University of the Caribbean School of Medicine and Katiana Garagozlo, MD, Assistant Professor, University of South Florida Morsani College of Medicine, for the preparation of this report.
Summary
Neuroendocrine hyperplasia of infancy (NEHI), is a rare lung disease that affects children, typically presenting in the first two years of life. NEHI typically presents in otherwise healthy infants during the first months to the first year of life. It is characterized by persistent rapid and labored breathing (tachypnea), crackles and low oxygen levels (hypoxemia).1
The cause of NEHI is currently poorly understood.3,4 The prevalence is not well known, but it is considered a rare disease.5,6
The hallmark diagnostic features of NEHI on chest computed tomography (CT) include hyperinflation and ground-glass opacities in characteristic distributions, without other parenchymal abnormalities.2,7 While symptoms such as breathing difficulties and low oxygen levels tend to improve with time, they can persist for years, underscoring the importance of early diagnosis and long-term management.
Some patients undergo a lung biopsy which shows an increased number of pulmonary neuroendocrine cells (PNEC). The role of PNECs in NEHI is not well understood. Treatment is largely supportive including supplemental oxygen and ensuring the patient has adequate growth.1,8,9
Children with NEHI often present in the first year of life with:1,2,4,6,7
– Rapid, shallow breathing (tachypnea)
– Increased work of breathing, including retractions
– Low oxygen levels in the blood (hypoxemia)
– Crackling sounds (crackles) heard with a stethoscope
– Failure to gain weight (failure to thrive)
These symptoms can often be mistaken for more common conditions, leading to initial misdiagnoses of asthma or recurrent respiratory infections. Unlike asthma, wheezing is not a common symptom, and children with NEHI do not typically respond to asthma medications such as inhaled corticosteroids.
The cause of NEHI remains unknown, but there is evidence suggesting genetic factors may play a role. A change (variant) in the NKX2-1 gene was identified in a patient with NEHI, along with family members who had childhood lung disease, indicating a possible genetic link.3 While increased numbers of pulmonary neuroendocrine cells (PNECs) are found in NEHI patients, it is not clear whether these cells are directly involved in the development of the disease or serve as markers of the disorder.4 These cells play a role in oxygen sensing and lung epithelial regeneration, potentially contributing to disease symptoms. However, more research is needed to understand the full range of influences on NEHI.
NEHI is rare, but its exact prevalence remains unknown. Since its recognition in 2005, several case series have been reported, but there is still a lack of comprehensive data on the total number of affected individuals. A multicenter study involving the Children’s Interstitial and Diffuse Lung Disease Research Network (chILDRN) identified NEHI in 10% of children younger than two years of age who underwent lung biopsies.5 Additionally, the largest report to date collected 199 NEHI cases across 11 centers in the United States and Canada.6 Despite its rarity, NEHI may be underdiagnosed, which means that some children with NEHI are initially misdiagnosed as having other chronic lung conditions.
Doctors typically diagnose NEHI by looking at symptoms and using specialized tests. A high-resolution CT scan of the chest is a key tool. It can show characteristic patterns like ground-glass opacities (which look hazy on the scan) and air trapping, both of which are common in NEHI. Additionally, infant pulmonary function tests (PFTs) may help confirm the diagnosis by detecting signs of air trapping in the lungs.7
In most people, these noninvasive imaging and testing methods are enough to make a diagnosis of NEHI without needing more invasive procedures. However, if the imaging results are unclear or the symptoms are not typical of NEHI, doctors might need to do a lung biopsy. During this procedure, a small piece of lung tissue is removed and analyzed. The biopsy is stained with a special marker (called bombesin) to identify the increased presence of pulmonary neuroendocrine cells (PNECs). Since biopsies are more invasive, they are usually only done in cases where the noninvasive image tests are not conclusive. In most people, NEHI can now be confidently diagnosed through clinical symptoms and imaging tests alone.
There is no cure or specific treatment for NEHI, and management is primarily supportive.
Most of the affected children require supplemental oxygen to address low oxygen levels in the blood (hypoxemia) and nutritional support is often necessary to manage growth delays.1,8
The use of medications such as inhaled corticosteroids typically used for asthma, has not been found to be effective in NEHI.
Immunizations, including the influenza and pneumococcal vaccines are crucial in preventing further respiratory complications.
Genetic counseling may be recommended, especially in cases where familial lung disease is present
The Children’s Interstitial Lung Disease Research Network (chILDRN) has the mission to improve care for children with rare diffuse lung disease around the world through research, education and advocacy.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/
Show Your Stripes® this Rare Disease Day® with a gift to NORD
Your donation will help more than 30 million Americans with a rare disease navigate their diagnosis, receive financial assistance, and access the care and support they deserve. Make your tax-deductible gift today!