The Disease HCFA-TEAM June 15, 2023

The Disease


CF is a multisystem, life-threatening disease that affects many vital organs, mainly the lungs and pancreas.

The form and severity of symptoms vary from patient to patient due to the significant heterogeneity of gene mutations, which means that the disease manifests itself differently in each patient, depending on their genotype (genetic profile) and various other factors. The main symptoms concern the respiratory system, the digestive and gastrointestinal system, and the reproductive system.

Patients with Cystic Fibrosis, due to the lack or dysfunction of the CFTR protein, have very salty sweat, so in exceptionally high temperatures, especially in the summer months, they may experience episodes of dehydration due to a significant disturbance in electrolyte levels.

The complications of the respiratory system, which destroy the lungs over time, are considered critical for the survival of the patients, having the overwhelmingly most significant percentage among the causes of mortality of the disease. The symptoms usually presented by patients are continuous persistent cough, thick phlegm, difficulty breathing, wheezing, shortness of breath, bronchospasm, and hemoptysis. Patients also often develop respiratory infections, as thick sticky mucus builds up in the lungs, creating ideal conditions and environment for germs to survive and multiply.

Germs and bacteria, such as staphylococcus, pseudomonas aeruginosa, aspergillus, and mycobacteria, usually cause respiratory infections. These microbes typically settle permanently in the lungs of patients and are difficult to eradicate, creating a severe chronic problem. Also, patients often present with nasal polyps and sinusitis.

The accumulation of mucus in the pancreas blocks the passages that carry enzymes produced by the pancreas into the small intestine. Without the specific enzymes, the intestine cannot absorb the necessary nutrients from food, resulting in malabsorption, poor nutrition, and poor physical growth in patients.

Patients often experience loss of appetite, abdominal distension, constipation, chronic abdominal pain, chronic diarrhea, greasy and foul-smelling stools, steatorrhea, poor weight gain and growth, and intestinal obstruction, especially in neonates (meconium ileus). Pancreatitis can also occur many times. In the liver, thick mucus may block the bile duct, causing liver disease and severe liver problems such as cirrhosis.

Due to pancreatic insufficiency, insulin production stops or decreases in many patients. This results in the form of diabetes called Cystic Fibrosis Related Diabetes (CFRD). DMD is a different type of diabetes, which has features of both type 1 diabetes (known as juvenile diabetes) and type 2 diabetes (usually in older and overweight people).

The disease affects the patient’s fertility. 97-98% of men with Cystic Fibrosis have obstructive azoospermia and can only father a child through IVF. Women often produce vaginal mucus that is thicker than average, and it usually takes longer to get pregnant naturally.

The disease also affects other body systems, often causing bone diseases such as osteoporosis-osteopenia, joint pain, rheumatoid arthritis, thyroid complications, heart problems such as heart attack or heart failure, and various other complications.

What Is Cystic Fibrosis

Cystic Fibrosis-CF or mucoviscidosis is the most frequent, worldwide, hereditary disease within the white population. The condition is a genetic disorder, therefore non-contagious, and is one of the most common rare diseases.

Cystic Fibrosis is caused by a mutation of a gene on chromosome 7, which codes for the protein CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) that regulates the production of specific components of body fluids and secretions, such as sweat, mucus, and digestive juices.

Mutations in this gene produce thick, sticky, dehydrated fluid and mucus secretions in the lungs and other organs and glands (e.g., pancreas, liver, intestine). Viscous fluids and mucus build up in organs and clog pores and passages in the body.

Over time, the organs are damaged, gradually destroyed, and lead to failure, creating life-threatening problems for the patient, such as infections, respiratory failure, and poor nutrition. The diagnosis is usually made in infancy, as the symptoms manifest from the first months of the patient’s life.

It was not until 1989 that the gene associated with Cystic Fibrosis was identified, while to date, more than 2,100 mutations of the CFTR gene have been identified, with the most common being F508del or ΔF508.

Every year 1/2,000-2,500 children are born with Cystic Fibrosis, which affects more than 88,000 people worldwide. In Greece, the number of disease carriers is 500,000; according to the National Cystic Fibrosis Registry, the number of patients exceeds 800.

Life Expectancy

Cystic Fibrosis has a low life expectancy. In the 1960s, most patients died before age five, while in the 1980s, only 30% of patients made it to adulthood.

Although Cystic Fibrosis is progressive and requires daily care, today, many patients can attend school, study, and work. Their quality of life is significantly improved compared to previous decades, while their life expectancy has increased and reaches up to 40 years, while some patients will live past the age of 50.

Based on mathematical models, it is estimated that by 2040 the proportion of children and adult patients will be 25%-75%, as children who receive new innovative treatments in time and from an early age are expected to have a life expectancy almost equivalent to that of the healthy people.

How Cystic Fibrosis is Inherited?

Cystic Fibrosis-CF is a genetic disorder, therefore non-contagious, from which patients suffer from birth. Patients have inherited two abnormal Cystic Fibrosis genes, one from each of their parents. People who carry a single pathological gene are called carriers of the disease and are considered perfectly healthy. In Greece, there are more than 500,000 operators, a number that is equivalent to 4-5% of the country’s general population.

An individual must inherit two non-functioning CF genes – one from each parent – to have CF. If both parents are carriers there is a 1 in 4 (25 percent) chance that both will pass on the non-functioning gene, which would result in a pregnancy affected with cystic fibrosis. Mendel’s rule determines the probability of the occurrence of the disease for each child:


  • In the usual case of two carrier parents, for each child, there is a 25% chance of having the disease, a 50% chance of being a carrier, and a 25% chance of not even carrying the gene.
  • From a parent who does not carry the gene at all and a carrier parent, there is no chance of a child being born with the disease, but each child has a 50% chance of being a carrier.
  • From a patient parent and a carrier parent, each child has a 50% chance of having the disease and a 50% chance of being a carrier.

It was not until 1989 that the gene associated with Cystic Fibrosis was identified, and to date, more than 2,100 mutations of the CFTR gene have been identified.

The most frequent gene mutation observed in Greece is the one characterized as F508del or ΔF508, which is considered one of the most severe mutations in symptoms. It has an incidence of approximately 70% in North America, 70-80% in northern European countries, and 30-54% in southern European countries, while in our country, its frequency is 53% of patients. In Greece, the number of patients exceeds 800.

It is estimated that every year 1/2,000-2,500 children are born with Cystic Fibrosis and a total of 50-60 children per year in Greece (one child per week). Therefore, 4-5% of the general population, i.e., one (1) in 20 to 25 people, is considered a carrier of the pathological gene. Today, more than 500,000 Greeks are carriers of the disease, equivalent to 4-5% of the country’s general population.

In comparison, although in Greece and other Mediterranean countries, Mediterranean Anemia shows twice the percentage of carriers (8-10%), due to the information and the extensive program of prenatal control that has been implemented in the last 20 years, the births of sick children do not exceed five (5) every year. Therefore, from the point of view of the birth of new sufferers, Cystic Fibrosis is by far the most widespread hereditary disease in Greece.

Cystic Fibrosis Milestones

The first mention of the disease appears in 1705 in a folklore book, stating that "a child with a salty taste is bewitched."


In a book of Children's Songs and Games published in Switzerland, the medieval saying is included: "Woe to the child whose forehead is kissed with a salty taste because he is bewitched and will soon die."


Dr. Dorothy Andersen first describes the mysterious disease that kills children as "Cystic Fibrosis of the Pancreas."


A modern comprehensive treatment plan for patients is proposed for the first time


The first double lung transplant in patients with Cystic Fibrosis is performed.


Cystic Fibrosis gene discovered in Canada by Lap-Chee Tsui, Francis Collins, and Jack Riordan.


First inhaled mucolytic drug designed explicitly for Cystic Fibrosis approved.


The first inhaled antibiotic for Cystic Fibrosis is approved.


The first meeting of the European Cystic Fibrosis Community (ECFS) physician group with the EurocareCF research group to create the European CF Patient Registry takes place.


The first innovative CFTR Modulator treatment that targets the causes of the disease is approved.


The 4th consecutive innovative CFTR Modulator treatment is approved in America, which addresses 90% of patients worldwide and has spectacular results by "freezing" the disease.


Evidence on the impact of covid-19 on CF patients is being studied and published.


Cystic Fibrosis Gene Therapy and Bacteriophage Therapy Clinical Trials Underway.