Cystic Fibrosis Week at the ATS

Although cystic fibrosis (CF) is the most common life-shortening disease in Caucasians, it affects people of many different ethnic backgrounds.  Thirty thousand people in the U.S. and 70,000 people worldwide have CF.  While the majority of morbidity and mortality of CF is due to the lung disease, CF affects many other organs including the sinuses, liver, pancreas, intestines, sweat glands, bones, and reproductive organs. The median survival in CF has increased from 28 years in the early 1990s to approximately 40 years in 2014.  This improvement in survival is due to advances in research with respect to knowledge about underlying disease processes and the development of improved therapeutics.  Despite this remarkable improvement in survival over the past 25 years, further advances are necessary to change CF from a disease that people die from to a disease that people live with.

The American Thoracic Society (ATS) has worked with the Cystic Fibrosis Foundation to improve the lives of people with CF.  The ATS is committed to the CF community and to fighting this disease.  The ATS has promoted awareness of CF and augmented the advocacy work done by the Cystic Fibrosis Foundation.  At the ATS International Conference, groundbreaking results of basic science research and clinical trials in CF are presented each spring.  ATS journals help to disseminate knowledge about CF by serving as a publication outlet for CF research.  The ATS also funds grants to individual investigators who study CF.  In these days of difficult federal funding opportunities, the impact of this cannot be minimized.  That CF is highlighted in a Lung Disease Week at the ATS only confirms this commitment.  The hope is that spotlighting the advances made in CF in the laboratory and in the clinic will help to increase awareness about CF in the general population and to build enthusiasm to further support research funding for CF that will eventually relegate this disease to the medical history books.

Beth Sufian and James F. Chmiel

Beth Sufian, JD
Director, CF Legal Information Hotline
Cystic Fibrosis Foundation

James F. Chmiel, M.D., M.P.H.Director and Chief Executive
Ohio Clinical Trials Collaborative
Professor of Pediatrics
Case Western Reserve University School of Medicine
Board of Director, American Thoracic Society

About CF

Cystic Fibrosis (CF), the most common life-limiting disease in Caucasians, is an autosomal recessive disease, which means that for an individual to have cystic fibrosis, he/she must inherit one cystic fibrosis mutation from each parent.  Nearly 2000 cystic fibrosis mutations have been described. Cystic Fibrosis occurs in approximately 1 in 3,400 live births in the U.S.  It affects approximately 30,000 people in the U.S. and 70,000 people worldwide.  In the U.S., approximately 1 in 29 people carry one cystic fibrosis mutation.  Survival in cystic fibrosis has improved dramatically.  In the 1940s, most children with cystic fibrosis did not live to see their first birthday.  Today the survival is approximately 40 years.  For the first time in history there are now more adults with cystic fibrosis than children.  While this is an impressive accomplishment, there is still much work to be done.

Cystic Fibrosis mutations cause an abnormality in a chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR), which is expressed on the surface of cells located in the lungs, sinuses, liver, pancreas, intestines, sweat glands, and reproductive organs.  Because the channel is defective, chloride cannot move normally between the cell and its environment.  This often causes the secretions in these organs to become thick and sticky, thus creating an obstruction.  The lungs seem to be exquisitely sensitive to the abnormal movement of chloride.  The airways in the lungs of a person with cystic fibrosis will become blocked by mucus.  The mucus eventually becomes infected by bacteria which incite a strong inflammatory response.  Instead of eliminating the bacteria, the inflammatory response actually damages the lungs and ultimately causes most of the morbidity and mortality of the disease. Treatment of cystic fibrosis lung disease involves the administration of chest physiotherapy, mucus thinners, and mucus hydrators to relieve the obstructed airways, antibiotics to treat the chronic bacterial infection, and anti-inflammatory drugs to reduce the exaggerated inflammatory response.  Active clinical trials are ongoing in all of these areas.

People with cystic fibrosis also have issues with their gastrointestinal system.  Most people with cystic fibrosis do not make adequate enzymes to digest food properly.  Without treatment, they will not absorb essential fats, proteins, carbohydrates, vitamins, and minerals.  This then leads to nutritional deficiencies and growth failure.  In order to treat this, people with cystic fibrosis have to ingest enzyme capsules with each meal and snack and take extra vitamins.  These therapies allow most people to gain weight and grow adequately.

Diagnosing cystic fibrosis early in life prior to the onset of permanent lung damage is imperative.  Previously the diagnosis was not made until a child presented with symptoms, typically poor growth and nutrition and recurrent respiratory symptoms.  Now, all 50 states have newborn screening programs in place for cystic fibrosis.  This has significantly reduced the age of diagnosis.  Newborn screening is confirmed by genetic testing and sweat chloride measurement.  Since the advent of newborn screening, it is rare to see a baby with cystic fibrosis present with severe protein-calorie malnutrition that frequently occurred in the past.  Early diagnosis is also important so that novel therapies that have been developed to correct the abnormal chloride channel can be initiated early in life. CFTR modulators that are specific for a patient’s mutations are just now becoming increasingly available. These modulators are known as potentiators and correctors. These drug increase the amount of functional CFTR on the surface of cells.  One potentiator, ivacaftor, and one corrector, lumacaftor, are currently available to patients. These drugs have been associated with improved lung function, improved weight gain, decreased pulmonary exacerbations and decreased sweat chloride concentrations in clinical trials. There are many more potentiators and correctors being investigated in clinical trials and in the laboratories. In addition to potentiators and correctors, drugs that stabilize CFTR and amplify CFTR are also being evaluated in clinical trial.  The hope is that specific CFTR modulators will be developed to address all cystic fibrosis mutations.

People with cystic fibrosis must take many medications and perform many therapies in order to maintain their health.  These treatments must be done several times every day.  It is not unusual for a person with cystic fibrosis to do therapies for more than 2 hours per day and swallow dozens of pills.  This treatment burden significantly impacts a person’s quality of life.  It is not uncommon for a person with cystic fibrosis to experience depression.  We as healthcare providers are just now beginning to realize this, and we have recently begun screening for depression in our patients during clinical visits so that the appropriate treatment may be prescribed.  However, as new therapies become available, it will be important for the cystic fibrosis community to determine what therapies are really pertinent to a given patient so that a health care provider can work with each patient to develop an individualized treatment plan.  Reducing treatment burden while improving quality of life may ultimately have the greatest impact upon an individual’s mental health.

Four Facts About Cystic Fibrosis

  1. Cystic fibrosis (CF) is an inherited chronic disease that leads to life-threatening lung infections and digestive problems. It is a rare disease, affecting 30,000 children and adults in the United States (70,000 worldwide). Currently, there is no cure for the disease and the median predicted age of survival is in the late 30s and rising.
  2. More than 10 million Americans are symptomless carriers of the defective CF gene.
  3. All babies born in the United States are screened for CF at birth as part of newborn screening (NBS).
  4. Ivacaftor (Kalydeco™), the first therapy targeting the basic defect in CF, was approved by the U.S. Food and Drug Administration in 2012.

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