Neuroendocrine cell hyperplasia of infancy (NEHI) is a rare lung condition affecting babies and young children, where an abnormal increase of special cells in the airways leads to breathing difficulties and low oxygen levels. While the condition was only identified and named in 2005, understanding how to support affected children through their early years has become increasingly important for families and healthcare teams.

How Medical Teams Support Children With NEHI

When a child is diagnosed with neuroendocrine cell hyperplasia of infancy, the focus of care shifts toward helping the young patient breathe more comfortably and grow well during the challenging early months and years. Treatment goals center on improving quality of life, maintaining adequate oxygen levels in the blood, and ensuring proper nutrition so that the child can develop normally despite the breathing challenges.^[1] Because NEHI mainly affects infants in their first two years of life, the approach to management depends heavily on how severe the symptoms are and how much the breathing difficulties interfere with daily activities like feeding and sleeping.^[2]

Unlike many lung conditions in children, NEHI generally does not respond to standard asthma medications or corticosteroids, which are drugs commonly used to reduce inflammation in the airways. This lack of response is actually an important clue that helps doctors distinguish NEHI from other, more common childhood breathing problems.^[1] Children with NEHI are often initially misdiagnosed with asthma or prolonged respiratory infections because the symptoms can look very similar, but the failure to improve with typical asthma treatments prompts doctors to look deeper for the true cause.^[1]

The understanding of NEHI is still evolving. There are no clinical trials currently testing specific drug treatments for this condition, and research into new therapies remains in very early stages. Medical societies have not yet established formal treatment guidelines beyond supportive care, which reflects how recently this disorder was recognized and how much remains to be learned about its underlying mechanisms.^[3]

Standard Supportive Care for NEHI

The cornerstone of treatment for neuroendocrine cell hyperplasia of infancy is what doctors call supportive care. This means that instead of trying to cure the condition or reduce the number of abnormal cells in the lungs, the medical team works to manage symptoms and support the child’s overall health while their body grows.^[1] The reality is that there are currently no medications proven to directly treat NEHI or reverse the excessive number of pulmonary neuroendocrine cells (PNECs), which are special cells normally found in the airways that help with lung development. In NEHI, these cells appear in much greater numbers than normal, though scientists still do not fully understand what role they play in causing the breathing problems.^[1]

Oxygen supplementation forms the most common medical intervention for children with NEHI. The amount of oxygen each child needs varies considerably from one patient to another. Some infants require oxygen around the clock, twenty-four hours a day, to keep their blood oxygen levels in a safe range. Others need supplemental oxygen only during sleep or when they become ill with a cold or other infection. Some children with milder forms of NEHI may not need any oxygen supplementation at all.^[1] The encouraging aspect of oxygen therapy in NEHI is that most patients gradually need less oxygen as they grow older. Many eventually outgrow the need for supplementation entirely as their lungs continue to develop and expand, even though the abnormal cells remain present.^[1]

Nutritional support represents another critical component of managing NEHI. Children with this condition often struggle with poor weight gain, a problem doctors refer to as failure to thrive. The reason for this difficulty stems from the increased effort required to breathe. Labored breathing burns significantly more calories than normal breathing, yet at the same time, the breathing difficulty can make feeding challenging and exhausting for infants.^[1] Additionally, many children with NEHI also experience gastroesophageal reflux (GERD), a condition where stomach contents flow back into the food pipe, which can further interfere with adequate nutrition.^[1] Optimizing the child’s nutritional status becomes essential for promoting adequate growth and supporting overall health during this critical developmental period.

Protection from respiratory infections forms the third pillar of supportive care. Common colds and influenza can be more severe in children with NEHI than in other children, potentially worsening breathing difficulties and increasing oxygen needs.^[1] For this reason, doctors recommend limiting the child’s exposure to respiratory infections as much as reasonably possible. Seasonal influenza vaccinations are strongly encouraged. Prevention strategies for Respiratory Syncytial Virus (RSV), another common virus that causes respiratory infections in young children, are also considered important protective measures.^[1]

The duration of active treatment varies from child to child, but generally continues throughout the infant and toddler years when symptoms are most severe. As children grow, particularly beyond age two, many experience gradual improvement in their symptoms. This improvement occurs not because the abnormal cells go away, but because the lungs continue to grow larger while the number of neuroendocrine cells stays the same. This means the abnormal cells have less impact on overall lung function as the child develops.^[6] Most children decrease their need for oxygen over time, with many eventually weaning off supplementation completely within two to seven years.^[6]

Current Research and Clinical Trials

At present, there are no active clinical trials testing new drug treatments specifically for neuroendocrine cell hyperplasia of infancy. The condition remains relatively rare and was only formally described and classified in 2005, which means scientific understanding of NEHI is still in relatively early stages.^[1] Over the past two decades since NEHI was first identified, several hundred cases have been reported and studied, but comprehensive research into potential treatments remains limited.^[3]

The absence of specific drug trials reflects several challenges inherent to NEHI research. First, the exact cause of the condition remains poorly understood. When a lung biopsy is examined with special bombesin staining, doctors can see the increased number of pulmonary neuroendocrine cells that define NEHI, but the role these cells play in causing the breathing problems remains unclear.^[1] Without understanding the fundamental mechanism of how NEHI causes symptoms, it becomes difficult to design targeted therapies that might address the underlying problem rather than just managing symptoms.

Some evidence suggests NEHI may have a genetic component, as the condition has been found to run in some families. This observation points toward a possible genetic basis for the disorder. However, despite this clue, researchers have not yet identified any specific gene abnormality linked to NEHI.^[1] If scientists could pinpoint genetic factors involved in NEHI, it might open pathways for developing gene-based diagnostic tests or even future gene therapies, though such possibilities remain theoretical at this stage.

Environmental factors may also influence the development of NEHI, but much more research is needed to answer questions about what external factors, if any, might trigger or contribute to the condition.^[1] The interplay between potential genetic susceptibility and environmental triggers represents an area where future research might provide important insights.

The relatively good natural prognosis of NEHI also affects the urgency and feasibility of drug trials. Because most children gradually improve as they grow, with many outgrowing the need for oxygen supplementation, there is less pressure to develop aggressive pharmaceutical interventions compared to conditions with worse outcomes. However, this does not diminish the importance of research, particularly for children with more severe forms of NEHI who face prolonged oxygen dependence and significant impacts on quality of life.

Most common treatment methods

• Oxygen supplementation
  • Provided in varying amounts depending on the child’s needs, ranging from 24-hour use to nighttime only or during illness
  • Most children gradually reduce their oxygen requirements as they grow
  • Many eventually discontinue oxygen supplementation entirely within two to seven years
• Nutritional support
  • Optimizing caloric intake to promote adequate growth and weight gain
  • Addressing failure to thrive caused by increased caloric expenditure from labored breathing
  • Managing gastroesophageal reflux when present to improve feeding tolerance
• Infection prevention
  • Limiting exposure to respiratory infections when possible
  • Seasonal influenza vaccinations
  • Respiratory Syncytial Virus prevention strategies
  • Prompt treatment of respiratory infections when they occur
• Monitoring and supportive care
  • Regular assessment of oxygen levels and breathing patterns
  • Growth monitoring to ensure adequate development
  • Adjustment of oxygen therapy as the child’s needs change