Cystic Fibrosis - Symptoms, Causes, Risk factors, Complications, Treatment & Prevention

Cystic fibrosis definition

Cystic fibrosis (CF) is a hereditary genetic disease that results in the accumulation of thick, sticky mucus which primarily affects the respiratory system (lungs), digestive system, and other organs of the body.

When individuals have CF, their mucus becomes extremely thick and sticky. People with cystic fibrosis have difficulty clearing this mucus from their lungs. It blocks the small airways and traps bacteria, leading to recurrent infections and obstructions, which can result in permanent lung damage as time passes.

Thick mucus in the digestive tract can impair the digestive enzymes flow from the pancreas to the small intestine, making it difficult to digest fats and absorb certain nutrients.

Cystic fibrosis disease is typically managed by a team of healthcare experts, primarily including a pulmonologist (lung specialist), because it primarily affects the lungs. Other specialists include a gastroenterologist who treats CF-related digestive issues, such as malabsorption and pancreatitis.

Cystic fibrosis prevalence

Prevalence of cystic fibrosis worldwide

A 2022 study found that an estimated 1,62,428 people globally have cystic fibrosis (CF), with 65% being identified and 12% receiving triple combination medications. Additionally, 57,076 people remain undiagnosed.

Prevalence of cystic fibrosis in India

In India, the prevalence of cystic fibrosis isn't well established, Only 600 people have been officially diagnosed with cystic fibrosis (CF), however this figure is far lower than the actual prevalence due to underdiagnosis and a lack of awareness. Approximately 19% to 34% of Indian CF patients carry the DF508 mutation, which is one of the most frequent genetic variants associated with CF.

Cystic fibrosis classification

Cystic fibrosis is often classified based on the mutations, severity, and presentation of the disease, particularly in terms of symptoms and how early or severe the disease manifests, including:

CFTR mutations can be classified as per mechanisms that disrupt CFTR function

• Class I mutations: Defective protein production 
• Class II mutations: Defective protein processing 
• Class III mutations: Defective regulation 
• Class IV mutations: Defective chloride conduction 
• Class V mutations: Reduced amounts of functional CFTR protein (less transcription)

These classes are classified based on the severity of the condition, such as:

• Class I, II and III usually lead to a classic (severe) CF phenotype with pancreatic insufficiency. 
• Class IV and V are mostly associated with a milder expression of the disease.

Cystic fibrosis symptoms

Signs and symptoms of cystic fibrosis typically appear in early childhood; however, they can also occur shortly after birth or later in adulthood. Some of the main symptoms of cystic fibrosis, according to the affected organ, are listed below:

Cystic fibrosis in lungs symptoms

There are many signs and symptoms of cystic fibrosis. Some are related to the respiratory system when the mucus clogs block airways. They are

• Ongoing chronic coughing 
• Shortness of breath
• Wheezing 
• Frequent sinus infections 
• Frequent lung infections
• Clubbing or enlargement of the fingertips and toes

Cystic fibrosis digestive system symptoms

Cystic fibrosis affects the digestive system. Many people experience digestive difficulties caused by the pancreas failing to function properly. Some common cystic fibrosis digestive symptoms include:

• Difficulty gaining weight 
• Poor growth
• Bowel obstructions
• Frequent greasy or oily bowel movements

Other cystic fibrosis symptoms in adults may include:

• Fertility problems 
• CF-related diabetes 
• Urinary Incontinence 
• Low bone mineral density 

Cystic fibrosis symptoms in kids include lung infections, salty-tasting skin, daily cough, at times with mucus, poor growth or slow weight gain even with a good appetite and shortness of breath, and trouble having a bowel movement.

Cystic fibrosis causes

Cystic fibrosis is only caused by a mutation in the gene called cystic fibrosis transmembrane conductance regulator (CFTR), which regulates the production of the CFTR protein. The following are the types of cystic fibrosis mutations that cause it:

Types of mutation in cystic fibrosis

There are about 2000 mutations in the CFTR gene that can cause cystic fibrosis. These mutations are grouped into five categories:

• Defective protein synthesis: This mutation fails to transform the genetic information into a protein product, resulting in a complete absence of the CFTR protein.

• Defective protein processing: This malfunction causes the CFTR protein to undergo abnormal post-translational processing. As a result, CFTR cannot be moved to the proper cellular site.

• Disordered regulation: This malfunction leads to decreased protein activity in response to intracellular signals. As a result, protein channels are completely non-functionally formed in the cell.

• Defective chloride conductance: This malfunction occurs when the protein is generated and properly located on the cell surface, but CFTR Protein works slowly because the rate of chloride ion flow decreased than normal.

• Accelerated channel turnover: This malfunction occurs when there is insufficient CFTR protein in the cellular membrane due to fast breakdown by cellular processes.

The result of all mutations indicates that the production of CFTR protein does not function properly and disturbs the movement of salt and water in the cells. These changes lead to the buildup of thick mucus in the lungs, digestive system, and other organs in the body. 

Cystic fibrosis inheritance pattern

Everyone inherits two CFTR genes, one from the mother and the other from the father. Children who inherit a CFTR gene with a mutation from both parents will develop cystic fibrosis.

A cystic fibrosis carrier is a person who inherits a mutant CFTR gene from one parent and a normal CFTR gene from the other parent. Cystic fibrosis carriers can pass the mutant CFTR gene to their children. Cystic fibrosis gene carriers are normally healthy but may experience mild symptoms.

Cystic fibrosis risk factors

Identifying and addressing these cystic fibrosis risk factors, helps in the diagnosis and management. The following are the cystic fibrosis risk factors:



• Family history: One of the leading risk factors for cystic fibrosis (CF) is having a family history of the condition, which means it is inherited when both parents carry the faulty CF genes as it can be passed to the next generation.
• Cystic fibrosis genetics: Cystic fibrosis is an autosomal recessive disease, meaning individuals must inherit two defective copies of the CFTR gene, one from each parent, to develop the condition.
• Ethnicity: CF can affect anyone, and the specific gene mutations that cause CF also differ according to geographic region and ethnic background. Some ethnicities have a higher carrier rate of the cystic fibrosis gene mutation, which increases the risk of passing on the condition.
  

Cystic fibrosis complications

Long-term complications of cystic fibrosis can arise when the condition is left untreated, which are listed below:

• Diabetes: Cystic fibrosis causes diabetes because the mucus buildup results in inflammation and scarring of the pancreas, which prevents it from producing sufficient insulin, resulting in increased blood glucose levels.

• Cardiovascular (heart) disease: Cardiac dysfunction in CF is not only a complication of pulmonary hypertension. It is caused by the destruction of lung parenchyma and additional factors, including CFTR gene polymorphism, systemic inflammation, hypoxia-induced myocardial damage, diabetic cardiomyopathy, and a lack of certain essential trophic factors, such as proteins or molecules that promote the survival, growth, and differentiation of cells.

• Colorectal cancer: Colorectal cancer is a complication of CF, but the exact cause is not fully understood. Cystic fibrosis affects the digestive system, leading to thick mucus, causing intestinal blockages, rectal prolapse and inflammation. This inflammation may increase the risk of colorectal cancer.

• Pneumonia: Pneumonia is a complication of cystic fibrosis because the mucus in the lungs is thicker, sticky, and more difficult to clear, leading to the trapping of microorganisms such as bacteria, viruses, or, in rare cases, fungi, resulting in a high likelihood of repeated chest infections.

• Infertility: Men with cystic fibrosis have a congenital bilateral absence of the vas deferens (CBAVD), a condition called azoospermia in cystic fibrosis (male infertility in cystic fibrosis) where the sperm tubes are absent, which prevents sperm from passing from the testicles to the urethra. 

• Osteoporosis and arthritis: Some of the factors that contribute to bone disease in the cystic fibrosis population include decreased absorption of fat-soluble vitamins (particularly D and K) due to pancreatic insufficiency, delayed puberty because of altered sex hormone production, chronic inflammation, a lack of physical activity, glucocorticoid treatment, and intrinsic hyper-resorptive bone physiology (imbalance in the bone remodeling process). In other studies, 75 percent of adult individuals with CF had osteopenia (loss of bone density) or osteoporosis.

• Liver diseases: Cystic fibrosis can cause liver impairment by accumulating mucus and blocking bile ducts. This prevents bile from leaving the liver and results in inflammation and scarring (fibrosis), which in turn results in abnormal liver function.

• Pneumothorax: The main cause of pneumothorax in CF is the damage and structural changes in the lungs, which make it easier for air to leak into the chest.

• Malnutrition: Cystic fibrosis causes malnutrition because the condition causes thick mucus to obstruct the pancreas and prevents digestive enzymes from reaching the intestine, known as malabsorption, which makes it difficult for CF patients to absorb nutrients and digest food.
  

Cystic fibrosis diagnosis

Cystic fibrosis diagnosis usually involves a single test or a combination of tests performed by a healthcare professional to confirm the presence of the disease:

• Medical history
• Physical examination
• Newborn screening
• Newborn blood spot test
• Confirming cystic fibrosis
• Sweat test 
• Genetic test
• Screening and preconceptional diagnosis of cystic fibrosis 
• Cystic fibrosis carrier testing
• Prenatal cystic fibrosis screening
• Chorionic villus sampling (CVS)
• Amniocentesis 
• Chest x-ray
• Sputum culture
• Stool test
  

Cystic fibrosis treatment

Cystic fibrosis treatments help in managing symptoms and slow down lung damage as it has no cure. As a result of various treatment options, many cystic fibrosis people are living healthier lives. Below are some of the cystic fibrosis treatment options:



Conservative management (non-surgical treatments)

• Airway clearance techniques
• PEP therapy
• High‐pressure PEP therapy
• Active cycle of breathing techniques
• Autogenic drainage
• Airway oscillating devices
• Cystic fibrosis medications
• Antibiotics
• Anti-inflammatory medicines
• Bronchodilators 
• CFTR modulators
• Mucus thinners
• Breathing support
• Oxygen therapy
• Pulmonary rehabilitation 
• Gene therapy
• Dietary management 
• Exercise

Cystic fibrosis Surgical management

• Ventilator support 
• Extracorporeal membrane oxygenation (ECMO)
• Lung transplant

Cystic fibrosis prevention

Cystic fibrosis is a genetic condition; hence, it cannot be prevented. However, one can reduce the risk of passing it to the child by taking the following genetic tests to detect mutated CFTR genes before and during pregnancy. If someone is planning on becoming a parent, as mentioned. The following are some of the genetic screening and counselling techniques that can help to manage the risk: 

Cystic fibrosis Genetic Counseling

• Preconceptional test: It is done before pregnancy to determine whether an individual (or couple) is a carrier of the CFTR gene mutations that cause cystic fibrosis

• Prenatal test: It is performed during pregnancy and can identify whether a fetus is at risk for CF.

• Genetic counselling for cystic fibrosis patients: Genetic counsellors are medical professionals qualified in both genetics and counselling as well as they provide emotional support to CF patients and help them to understand what it is, what causes it, its inheritance and what diagnostic tests can help to detect mutated genes, finding the risk of passing this condition to the child.
  

Cystic fibrosis patient education

Preventing the spread of transmissible infections in CF patients: It is a top priority in caring for individuals with cystic fibrosis (CF). The following are some preventive measures that help avoid infections in cystic fibrosis patients: 

• Following hand hygiene
• Maintaining segregation
• Using facemasks 
• Enhanced adherence (encouraging and helping patients stick to their prescribed medications, therapies, or lifestyle changes).

Difference between Pulmonary fibrosis vs Cystic fibrosis

Pulmonary fibrosis vs cystic fibrosis

Pulmonary fibrosis and cystic fibrosis are both disorders that can impair the lungs and make breathing difficult, but they differ in several ways, as detailed below:

Difference between COPD and cystic fibrosis

COPD vs cystic fibrosis​

Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are both lung disorders that cause airway blockage and inflammation, although they differ in various ways, including: