DIPNECH
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

DIPNECH Patient Information


BACKGROUND INFORMATION    

    The acronym DIPNECH stands for Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (one of my goals is to find a new name that is less imposing and more positive!).  Loosely translated into regular English, it means that for unknown reasons there are cells (neuroendocrine cells) which are derived from primitive nerve-like cells ("neuro"), which produce hormones ("endocrine"), and which have spread out into the small airways of the lungs.  To understand the disease process of DIPNECH, you will need to understand certain terms:

      Bronchioles - these are the smallest airways that carry air directly to the air sacs of the lungs.  These very small and narrow airways are the place where neuroendocrine cells have invaded and are the part of your lungs where all the symptoms of DIPNECH occur.

     Neuroendocrine cells (NECs) - these cells are ordinarily quite rare and are mostly found in the lining of the intestine, although they are certainly found in other tissues as well (such as the lungs where they are called pulmonary neuroendocrine cells, PNCs). They release various chemicals and hormones that can have effects on the surrounding tissues.  You  may not have heard of any of these substances (serotonin, kallikrein, bombesin, ACTH and many others) but they have powerful effects on other tissues.  PNCs are known to be involved with healing injuries, and also may be sensitive to oxygen levels.  When there is injury to the lungs, the PNCs invade and release hormones that may assist in healing, but which may also lead to scarring and fibrosis.  No one knows why PNCs proliferate in the bronchioles of patients with DIPNECH but PNCs almost certainly contribute to the symptoms of coughing and shortness of breath.  They do this by narrowing the already narrow bronchioles, either by growing into the bronchioles or by creating scarring of the airways.  The coughing may be related to inflammation of the bronchioles which occurs because of the release of hormones and inflammatory substances.

    Carcinoid tumors - quite simply, these are large clusters of PNCs.  If the tumor is smaller than 5 mm, it is called a tumorlet. Carcinoids have some characteristics of a malignancy (known as a carcinoma) but often behave like a benign tumor, hence the term "carcinoid". They can be graded in three levels depending on how aggressive the cells look under a microscope, with Grade I being the most benign in appearance.  Grade I carcinoids are also called "typical" carcinoids.  The carcinoids of DIPNECH are virtually ALWAYS typical and do not act like cancers.  They do not spread to other parts of the body, or damage the surrounding lung tissue.  They do not come from other parts of the body either, but rather arise over time from the PNCs already present in the airways. A person with DIPNECH may have no tumors, just a few, or too many to count.  Carcinoid tumors that arise in the intestine are very different.  They secrete hormones that can cause unpleasant symptoms such as flushing, diarrhea, or high blood pressure. This is called Carcinoid Syndrome.  Carcinoids in DIPNECH do not cause Carcinoid Syndrome, but I believe that PNCs do release chemicals that create the inflammation of the bronchioles which then leads to scarring of the bronchioles as well as the coughing associated with DIPNECH.  Intestinal carcinoids can metastasize to other parts of the body such as the liver, however the carcinoids of DIPNECH do NOT metastasize. If you do research on the internet, do not confuse the carcinoid tumors of DIPNECH with intestinal carcinoids or any other neuroendocrine tumors.  They are DIFFERENT and more benign in nature.
 
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SYMPTOMS

    The most common symptoms of DIPNECH are cough, shortness of breath, and sometimes wheezing.  The coughing can be particularly persistent and problematic.  This is very similar to some other illnesses such as asthma and COPD.  Since regular x-rays may be completely normal in DIPNECH, patients are often misdiagnosed with asthma.  However, asthma medications such as inhaled steroids and bronchodilators will often have little or no apparent effect on the cough and shortness of breath.  Eventually, one or more areas of PNCs can grow into carcinoid tumors that are then visible on routine chest x-rays.  The carcinoid tumors do not appear to cause any symptoms in and of themselves. 

    Symptoms can go on for years or decades before the correct diagnosis is made, often when a carcinoid tumor shows up on a chest x-ray taken for some other reason.  A majority of patients with DIPNECH are women in their fourth or fifth decade of life at the time of diagnosis.  They tend to be non-smokers.  Although experience with DIPNECH is very limited at this time, it appears that a substantial proportion of patients with DIPNECH have either slow progression or no progression of their symptoms and underlying disease.  However, a few progress to severe small airway obstruction.

    Therefore, the most common clinical presentation of DIPNECH would be a middle-aged woman who has had a persistent cough for a decade.  She would have sought medical help and most likely would have been told she had asthma or COPD, however the usual inhalers would have had little or no effect.  She would typically have shortness of breath with exertion.  Routine x-rays might show hyperinflation but little else.  If pulmonary functions were done they would show obstructive airway disease. 


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TESTS and DIAGNOSIS
 
    The diagnosis of DIPNECH is based on the presence of areas in the lungs where the bronchioles are invaded by pulmonary neuroendocrine cells (PNCs).  In DIPNECH there are patches of the lungs which are normal, and other patches where the bronchioles are affected.  In the past, the diagnosis was usually made when a tumor was seen on a regular X-ray, and a biopsy showed the tumor to be a carcinoid.  Special staining of the tissues around the carcinoid tumor would reveal the presence of PNCs in the bronchioles.  In the past five years or so, a new type of CT scanning is available called high resolution computerized tomography (HRCT). There are fairly consistent findings on HRCT that, in conjunction with a typical history, may be sufficient to make the diagnosis of DIPNECH.  However, the gold standard for diagnosis of DIPNECH remains biopsy of lung tissue, which involves obtaining a piece of lung for analysis.  This can be accomplished by several means.  A fiber-optic bronchoscope ("bronchoscopy") is a small tube that can be led down to the small airways by going through the trachea and bronchi, thus reaching the lungs for biopsy.  Video-assisted thoracoscopic surgery ("VATS") involves getting a piece of tissue through a small incision in the chest wall.  Finally, lung tissue can be removed as part of a regular surgical procedure called a thoracotomy.

    There are a variety of other tests which might need to be done to help with the diagnosis of DIPNECH.  Chromogranin A is a substance released by carcinoid tumors and which can be measured in the blood.  Its level may correlate to the total amount of carcinoid tumor present in the body.  5-HIAA is a chemical that is derived from serotonin (a hormone produced by carcinoids), and may be elevated in the urine when carcinoids are present.  It is usually measured by collecting urine for 24 hours. Another blood test that might be done is a neuron specific enolase (NSE).  This is a screening test for certain types of lung cancers but it is NOT elevated in DIPNECH.  It would be ordered by your doctor as a screening test to make sure you don't have a lung cancer.

    A PET scan is a way of finding tumors in the body, and measuring whether those tumors are actively growing.  A DIPNECH carcinoid will be evident on PET scanning but there will not be any other tumors elsewhere in the body.  A more specific scanning test for the presence of carcinoid tumors would be an octreotide scan.  Plain X-rays of the chest will probably not show anything other than any fairly large carcinoid tumors which may be present.

    Pulmonary function tests (PFTs) are a very important way of measuring how your lungs and airways are working.  Since patients with DIPNECH often have significant obstruction of their small airways (bronchioles), they usually will be followed with PFTs to monitor their progress.  One of the more important measures of obstruction is the FEV1, which is reported as a % of expected value for one's age.  
    
    PNCs can sometimes be found in the vicinity of certain types of lung injury, such as bronchiectasis or lung cancers.  This is not DIPNECH.  In DIPNECH, the PNCs are proliferating into the bronchioles for no apparent reason.  When carcinoid tumors appear, they are arising from the PNCs which are already present.

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TREATMENT

    Sadly, at this time there is no known or proven treatment for DIPNECH.  However, there are some things to consider.  I would strongly recommend that anyone with a chronic lung condition such as DIPNECH be vaccinated against preventable infections such as influenza, pneumonia and whooping cough.  Catching one of these deadly infections could be disastrous if you already have compromised airways.  The flu vaccine should be the injectable (or "killed" virus) type of vaccine, not the nose spray.  Pneumonia can in some cases be prevented with a pneumococcal conjugate vaccine, and whooping cough is prevented with a vaccine called TdaP.

    You should have your oxygen levels checked while awake and while asleep.  Some patients with DIPNECH have low blood oxygen levels leading to symptoms like fatigue and headaches.  This can easily be corrected by receiving an oxygen supplement.  There is a possibility that PNCs may sense low levels of oxygen, and that this may cause them to release their chemicals that lead to more inflammation.

    Steroids are medicines that, among other things, reduce inflammation.  In DIPNECH it is believed that the PNCs are causing inflammation to the bronchioles.  Therefore there may be some benefit to using steroid medications although they are certainly not a cure. They can be administered either by mouth or as an inhaler. The latter can be used over long periods of time.  Short courses of oral steroids might be of some benefit to help you through illnesses such as colds where there might be worsening of your symptoms from increased mucus production in your chest.  There are some risks to taking steroids, like any medicine, so you should discuss this carefully with your doctor.

    Bronchodilators, such as albuterol, probably would not be helpful in DIPNECH.  These medicines are meant to open up the bronchioles in diseases like asthma where the airway constriction is reversible.  In DIPNECH the small airways are irreversibly constricted due to the presence of the PNCs in the airways, and to scarring.  However, airway dilation can be measured with PFTs, and if it can be shown that the airways are opened by a bronchodilator, such as albuterol, then they might be helpful.

    There is a medicine called Sandostatin (the generic name is octreotide) that is used to prevent Carcinoid Syndrome in patients with intestinal carcinoids.  In this illness, the carcinoids release hormones that cause flushing and diarrhea, as noted above.  The carcinoids in DIPNECH have not been reported to cause classic Carcinoid Syndrome, but there is no doubt that they do release substances that are causing symptoms such as cough.  It may be that octreotide will inhibit the PNCs enough to at least diminish coughing, and several DIPNECH patients, including my wife, have reported improvement in their coughing with octreotide.  Long term studies need to be done on this.

    Surgery may be one of the few treatments that offer a chance for some improvement.  When a diseased portion of the lung is removed, such as when a carcinoid tumor is resected, the surrounding healthy lung expands and may improve overall pulmonary function.  This has been reported in the medical literature on DIPNECH.  My wife's FEV1 went from 29% of predicted to 35% of predicted after she underwent a thoracotomy for removal of a 5 cm (2 inch) carcinoid in her right upper lobe.  Finally, there are a few patients with DIPNECH who progress to severe airway obstruction.  In this case there needs to be consideration of lung transplantation.

    Finally, I would like to point out that the carcinoids that occur in the context of DIPNECH are not typical cancers.  The carcinoids should not be treated with the chemotherapy agents that are used for other types of carcinoid tumors.

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REASONS for HOPE   

    
It is my hope that the information presented above will help you understand your condition better.  As a physician, and the husband of a wonderful wife who happens to have DIPNECH, I have learned that knowledge imparts a sense of control over one's destiny and highlights the path of healing, both physically and emotionally.  I believe that if more information can be shared by patients and physicians, then a better understanding of DIPNECH will be found and perhaps some more effective treatments.  Along these lines I hope to have a blog site for DIPNECH up and running in the next few days.  The second and third pages of this website will provide information for physicians to learn about DIPNECH, and will give patients with DIPNECH an opportunity to share their stories.  I am aware of some interesting developments.  National Jewish Hospital in Denver has been contacting patients with DIPNECH in order to obtain DNA samples in order to try to detect genetic markers for DIPNECH.  In addition, a review of DIPNECH was published by the Mayo Clinic in Phoenix this year, and the authors are calling for a national database on DIPNECH, which is precisely the sort of effort it will take to understand this illness.

    If any reader would like to contact me about any aspect of DIPNECH, you can use my email address for this site which is dipnechhubby@dipnech.com .  I will check my email peridically and will absolutely respond to all inquiries.

    Finally, as an example of what can be done, I would like to draw your attention to a website for an illness called lymphangioleiomyomatosis (LAM).  This is a rare illness involving smooth muscle cells in the lungs which only affects women.  It has surprising similarities to DIPNECH.  Twenty years ago it was essentially unheard of by the medical community, but through the work of a few people, there is now a foundation for it that has raised $20 million dollars for research, and is now sponsoring the first clinical trials for a new drug that poses some promise for treatment.  The website is www.thelamfoundation.org and I would invite you to visit it as an example of what can be done.  I would welcome anyone who wants to help with updating my DIPNECH website to write to me at my email address.

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