Neuroendocrine cell Hyperplasia of Infancy (NEHI)

Neuroendocrine cell Hyperplasia of Infancy (NEHI)

Lisa R. Young, MDDirector, Pediatric Rare Lung Diseases

ProgramCincinnati Children’s Hospital Medical Center

ChILD Foundation ConferenceJune 25, 2011

Chicago

Overview• What are the initial symptoms of

NEHI?

• How do we diagnose NEHI?

• How do we take care of children with NEHI?

• What happens to children with NEHI when they get older?

• Many more unknowns

NEHI is a relatively recently discovered disorder and we are still learning about it and teaching other doctors about it.

• Deterding RR, Fan LL, Morton R, Hay TC, Langston C. “Persistent tachypnea of infancy (PTI) – a new entity” Pediatr Pulmonol, 2001.

• Deterding RR, Pye C, Fan LL, et al. Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia. Pediatr Pulmonol, 2005.

• Typically presents in term infants in the first year (or months) of life

• Typical symptoms in early infancy are:• Tachypnea = fast breathing

• Retractions

• Crackles

• Hypoxia = low oxygen levels

• Failure to thrive / growth difficultiesDeterding et al. Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia. Pediatr Pulmonol. 2005; 40:157-165

NEHI Symptoms

We also sometimes see kids with proven NEHI who:

• were late preterm infants

• have wheezing

• have intermittent symptoms, more than chronic

• seemed well until they had an acute illness

• never need supplemental oxygen

• never have growth / feeding problems

NEHI Symptoms: An evolving spectrum

• Physicians must ‘rule-out’ other more common disorders first.

• But sometimes other more common problems can also complicate the picture.

• Reflux

• Acute infections, including viral illnesses

• Occasionally patients may be misdiagnosed with NEHI.

NEHI symptoms also overlap with many other causes of lung disease.

• Radiology studies

• Infant pulmonary function tests (infant PFTs)

• Lung biopsy

What are the tests that enable a confident diagnosis of NEHI?

The term ‘NEHI Syndrome’ has been proposed for children who have chest CTs suggesting NEHI but who have not had a biopsy for confirmation.

• May be:• Normal

• Hyperinflated

• Look like a viral infection or bronchiolitis

Chest x-rays in NEHI

Deterding et al, 2005

• May be diagnostic for NEHI in many cases

• Technical aspects of how the scan is done can be very important

• May be atypical in at least 1/5 of children proven to have NEHI by lung biopsy (Brody et al, AJR 2010)

Chest CT scans in NEHI

Chest HRCT findings in NEHI include geographic ground glass opacities, most prominent in the RML and

lingula, and significant air-trapping.

Importantly, no other significant abnormalities should be present.

Brody et al, AJR 2010

Examples of CT scans in NEHI

‘TYPICAL’ for NEHI NOT ‘TYPICAL’ for NEHI

Brody and Crotty, 2008; Brody et al, 2010; Young et al, 2010

Infant PFTs in NEHI

• May aid the diagnosis of NEHI in some cases

• Kerby et al (2009):• Mixed physiologic pattern in NEHI with air-

trapping• Distinct from other ILD

• Young et al (2010):• Severity of small airway obstruction on iPFT may

correlate with extent of neuroendocrine cells seen in the biopsy

• Other studies ongoing

Lung biopsies in NEHI

Example of normal lung structures when viewed under the microscope

Example of normal lung from a lung biopsy when viewed under the

microscope

Example of a normal bronchiole (“small air tube”) when viewed under the

microscope

Lung biopsies look nearly normal in NEHI. Bombesin staining identifies increased numbers

of neuroendocrine cells (NECs)

Bronchiole with NECs Neuroendocrine body (NEB)Provided by Gail Deutsch, MD

Where are the neuroendocrine cells?In NEHI, the NEC prominence is greatest in the distal respiratory bronchioles, and distinguishes NEHI cases from other disorders associated with NEC hyperplasia.

Young et al, 2010

NEHI: Variable numbers of neuroendocrine cells in different

airways

Deutsch et al, AJRCCM 2007

In NEHI, there is wide intra and inter-subject variability in NEC number, which does not

correlate with the imaging appearance of the region biopsied.

Young et al, Chest , 2010

How do we take care of children with NEHI?

• There are no proven medications.• Corticosteroids (Prednisone) do not help

in most cases.• Bronchodilators (breathing treatments)

don’t help most long-term.

How do we take care of children with NEHI?

• Supplemental oxygen when needed

• Nutritional support when needed

• Treat other problems as they arise, such as reflux or infections.

• Avoid injuries to the lung.• Flu shot each year• Synagis to try to prevent RSV?• Avoid cigarette smoke exposure

How do we take care of children with NEHI?

• Team approach• Different team members may be needed for different

kids and families.• Care coordination can be very important

• Psychosocial support for families

• Childcare and school considerations

How do we monitor children with NEHI?

• Monitoring of oxygen saturations

• Monitoring of growth

• Routine follow-up chest x-rays and repeat CT scans usually not helpful / not recommended. • May be needed if/when children are acutely ill or

clinical course is atypical.

• Infant PFTs may have a role.

• Improvement over time but variable speed

• May require supplemental oxygen for years

• Favorable long-term outcome

What happens to children with NEHI as they get older?

• At least some older children have with NEHI have abnormal PFTs and exercise intolerance.

• Some exacerbate with respiratory infection.

• Possible relationship to adult lung disorders is unknown.

WE NEED MORE DATA!THIS IS A BIG AREA WHERE THE REGISTRY CAN HELP.

What happens to children with NEHI as they get older?

Many unanswered questions about NEHI

• Why do children with NEHI often need supplemental oxygen?– What are the criteria for using oxygen in kids with NEHI?

Many unanswered questions about NEHI

• Why do children with NEHI have crackles?

Many unanswered questions about NEHI

• Does nutritional status and growth impact lung function in NEHI?

Many unanswered questions about NEHI

• Why do some children with NEHI have ‘atypical’ chest CTs and does it matter?

• Why are some children with NEHI ‘sicker’ than others?

How will we discover what causes NEHI and how to treat (or prevent) it?

Genetic basis?

What is the function of (or dysfunction) of neuroendocrine cells in NEHI?

Are other cells involved, and what happens in lung development in children with NEHI?

Acknowledgements

Rare Lung Diseases ProgramConnie Meeks, RNJackie Taylor, RD Allison Whisenhunt, MISWBrenda McMillan (coordinator)

Robert E. Wood, PhD, MDBruce Trapnell, MD

Pathology: Todd Boyd, DOGail Deutsch, MD (Seattle)

Radiology: Alan Brody, MDEric Crotty, MDMantosh Rattan, MD

Pediatric Surgery: Thomas Inge, MD, PhDInfant PFTs:

Jim Acton, MD (Missouri)Karen McDowell, MDBeth Koch, RRT

Children’s Interstitial Lung Disease Research Network