Cystic Fibrosis Treatment in Delhi, India

Cystic fibrosis (CF) is a genetic disorder that primarily affects the respiratory and digestive systems. It is caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which leads to the production of thick and sticky mucus. This abnormal mucus can clog the airways in the lungs and cause respiratory and digestive problems such as the following.

• Respiratory issues: The thick mucus in the airways can lead to frequent lung infections, difficulty breathing, persistent coughing, and reduced lung function over time. Chronic respiratory problems can result in lung damage.
• Digestive problems: The thick mucus can also affect the digestive system, causing issues with the pancreas and preventing digestive enzymes from reaching the small intestine. This can lead to problems with nutrient absorption, malnutrition, and digestive symptoms like diarrhoea and greasy stools.
• Sweat gland abnormalities: People with cystic fibrosis often have higher levels of salt in their sweat. This characteristic is used in the diagnosis of the condition through a sweat test.
• Other manifestations: Cystic fibrosis can affect other organs and systems in the body, leading to complications such as liver disease, diabetes, and reproductive issues.

Cystic fibrosis is an autosomal recessive genetic disorder, meaning that an individual must inherit a mutated copy of the CFTR gene from both parents to develop the condition. Carriers, who have one mutated copy and one normal copy of the gene, typically do not show symptoms but are carriers of this condition which means there’s a chance that they can pass the mutated gene to their children.

Causes

Cystic fibrosis arises from a genetic mutation affecting the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This mutation alters the function of a protein responsible for regulating salt movement in and out of cells. Consequently, thick and sticky mucus accumulates in the respiratory, digestive, and reproductive systems, accompanied by an increase in salt levels in sweat. The specific type of gene mutation is linked to the severity of the condition, with various defects possible.

For the disease to manifest, children must inherit one mutated copy of the gene from each parent. In cases where children inherit only one copy, they become carriers of the gene without developing cystic fibrosis. These carriers, however, have the potential to pass the gene to their own offspring.

Risk factors

Cystic fibrosis is primarily an inherited disorder, and a family history of the condition constitutes a significant risk factor. While cystic fibrosis can affect individuals of all races, it is more prevalent in individuals of Northern European descent, particularly those of white ethnicity. Therefore, genetic predisposition plays a crucial role in the occurrence of cystic fibrosis, and individuals with a familial connection to the disorder are at an increased risk of being carriers or having affected children.

The symptoms of cystic fibrosis (CF) can vary widely among individuals, and the severity of symptoms is influenced by the specific mutations in the CFTR gene. Common symptoms of cystic fibrosis include:

Respiratory Symptoms

• Persistent coughing
• Frequent lung infections, such as pneumonia or bronchitis
• Difficulty breathing or shortness of breath
• Reduced exercise tolerance
• Wheezing

Digestive Symptoms

• Pancreatic insufficiency, leading to difficulty digesting food and absorbing nutrients
• Malnutrition and poor growth, especially in children
• Foul-smelling, greasy stools
• Abdominal pain.

Other Symptoms

• Clubbing of fingers and toes (enlargement of the fingertips and toes)
• Nasal polyps
• Sinus infections.
• Infertility in males due to the absence or blockage of the vas deferens

The diagnosis of cystic fibrosis (CF) involves a combination of clinical assessments, genetic testing, and specialised laboratory tests. Early and accurate diagnosis is essential for implementing

appropriate medical interventions and management strategies. The diagnostic process typically includes the following components:

Newborn Screening

In many countries, newborns are screened for cystic fibrosis shortly after birth. This involves testing a small blood sample to identify elevated levels of immunoreactive trypsinogen (IRT), a substance that may indicate the presence of CF.

Genetic Testing

Genetic testing is a key component of CF diagnosis. It involves analysing DNA to identify mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This testing helps confirm the presence of CF and determine the specific gene mutations involved.

Sweat Test

The sweat test is a definitive diagnostic tool for cystic fibrosis. It measures the concentration of salt in sweat, which is typically elevated in individuals with CF. The test involves stimulating sweat production on a small area of the skin, collecting the sweat, and analysing its salt content.

Clinical Evaluation

A thorough clinical assessment by healthcare professionals is crucial. This includes a review of the patient's medical history, physical examination, and evaluation of symptoms such as respiratory and digestive issues.

Imaging Studies

Chest X-rays or other imaging studies may be performed to assess the condition of the lungs and detect any signs of respiratory complications associated with cystic fibrosis.

Lung Function Tests

Lung or pulmonary function tests (PFTs) use a device called a spirometer to measure lung capacity and airflow, which, in turn, helps assess respiratory function. These tests are important for monitoring lung health and determining the severity of lung involvement in CF.

Sputum Culture

In this procedure, the healthcare provider collects a sample of the individual's sputum (saliva and mucus) and examines it for the presence of bacteria. Commonly, bacteria such as Pseudomonas are identified, particularly in individuals with cystic fibrosis.

Nasal Potential Difference (NPD)

This test involves using a voltmeter along with electrodes positioned inside the individual's nose and one external to it. The goal is to measure the electrical activity resulting from the transfer of ions in solution across nasal tissue. The test employs three different types of solutions during the process.

Intestinal Current Measurement (ICM)

For this test, a biopsy of rectal tissue is required. The collected tissue is induced to secrete chloride, and the amount of secretion is then measured.

Early detection allows for timely intervention and improves the quality of life for individuals with CF. So it is important to prioritise routine screenings and genetic testing, particularly in newborns, to identify cystic fibrosis at the earliest stages. This proactive approach not only facilitates swift medical intervention but also opens avenues for comprehensive care and support tailored to the unique needs of individuals with CF.

While there's no cure for cystic fibrosis, treatment aims to manage symptoms, improve quality of life, and slow disease progression. Here are some common treatment options:

Medications

• Bronchodilators: These medications help relax the muscles around the airways, making it easier to breathe.
• Mucolytics: Drugs such as dornase alfa (Pulmozyme) thin the mucus, making it easier to clear from the airways.
• Antibiotics: Used to treat lung infections, which are common in individuals with cystic fibrosis.
• CFTR Modulators: Drugs like ivacaftor (Kalydeco), lumacaftor/ivacaftor (Orkambi), tezacaftor/ivacaftor (Symdeko), and ivacaftor/tezacaftor/ivacaftor (Trikafta) target specific defects in the CFTR protein, helping improve its function.
• Pancreatic Enzyme Replacements: To aid in digestion and nutrient absorption due to pancreatic insufficiency.
• Vitamin Supplements: Particularly fat-soluble vitamins (A, D, E, and K), as CF can lead to malabsorption.

Airway Clearance Techniques (ACTs)

ACTs are physical techniques and devices designed to help individuals clear the thick, sticky mucus from their airways. These techniques promote better lung function, reduce the risk of infections, and improve overall respiratory health. Examples include chest physiotherapy, postural drainage, breathing exercises, PEP therapy, HFCWO, and exercise.

Lung transplantation

For individuals with advanced lung disease that does not respond to other treatments, lung transplantation may be considered. This involves replacing one or both diseased lungs with healthy donor lungs to improve respiratory function and quality of life.

Exercise and physical therapy

Regular physical activity and exercise play a crucial role in cystic fibrosis management. Exercise helps improve lung function, cardiovascular health, and overall fitness. Physical therapy techniques such as chest physiotherapy, breathing exercises, and postural drainage are also vital for maintaining optimal respiratory health.

Nutritional support

Nutritional support is essential in cystic fibrosis management due to malabsorption and increased energy needs. This category includes dietary interventions such as a high-calorie, high-protein diet, pancreatic enzyme replacements, vitamin and mineral supplements, and, in severe cases, tube feeding or intravenous nutrition.

Psychosocial support

Living with cystic fibrosis can be challenging, both physically and emotionally. Psychosocial support services such as counselling, support groups, and educational resources help individuals and families cope with the emotional and psychological aspects of the condition.

The treatment plan for cystic fibrosis is often tailored to each individual's specific needs and may evolve over time as the condition progresses. Close collaboration between patients, caregivers, and healthcare providers is essential for optimal management and improving quality of life.

While advancements in treatment have improved life expectancy for individuals with CF, the condition still presents several potential complications. These complications can arise due to the buildup of thick mucus in the lungs and the malfunctioning of the pancreas.

Respiratory Complications

• Chronic lung infections: Individuals with CF are prone to recurrent and chronic lung infections, often caused by bacteria such as Pseudomonas aeruginosa and
• Staphylococcus aureus: These infections can lead to inflammation, airway damage, and progressive lung function decline.
• Bronchiectasis: Chronic inflammation and infection can cause irreversible widening and scarring of the airways (bronchiectasis), leading to further mucus accumulation and impaired lung function.
• Pulmonary exacerbations: Periods of acute worsening of respiratory symptoms, characterised by increased cough, sputum production, shortness of breath, and fatigue. Pulmonary exacerbations require prompt treatment with antibiotics and airway clearance techniques.
• Respiratory failure: Advanced lung disease can lead to respiratory failure, where the lungs can no longer provide adequate oxygen to the body's tissues. This may necessitate interventions such as supplemental oxygen therapy or mechanical ventilation.

Gastrointestinal Complications

• Pancreatic insufficiency: The majority of individuals with CF develop pancreatic insufficiency, where the pancreas fails to produce enough digestive enzymes to break down food properly. This leads to malabsorption of nutrients, malnutrition, and vitamin deficiencies.
• Meconium ileus: Newborns with CF may develop intestinal obstruction shortly after birth due to thick, sticky meconium (the first stool) blocking the intestines. This condition requires immediate medical intervention.
• Distal Intestinal Obstruction Syndrome (DIOS): Similar to meconium ileus, DIOS is a condition where thickened mucus obstructs the intestines, leading to abdominal pain, bloating, and constipation.
• Liver disease: CF-related liver disease can manifest as liver cirrhosis, liver enlargement, or bile duct obstruction, leading to jaundice, abdominal pain, and abnormal liver function tests.

Nutritional Complications

• Malnutrition: Due to pancreatic insufficiency and malabsorption, individuals with CF are at risk of malnutrition, weight loss, and growth failure. Maintaining adequate nutrition is essential for growth, development, and overall health.
• Vitamin deficiencies: Malabsorption can lead to deficiencies in fat-soluble vitamins (A, D, E, and K) and other nutrients, requiring supplementation to prevent complications such as osteoporosis, vision problems, and clotting disorders.

Other Complications

• Diabetes: CF-related diabetes (CFRD) is a common complication characterised by impaired glucose tolerance or insulin insufficiency. It requires careful monitoring and management to prevent long-term complications.
• Bone health issues: CF-related bone disease, including osteopenia and osteoporosis, can occur due to malnutrition, vitamin deficiencies, chronic inflammation, and steroid use. This increases the risk of fractures and skeletal abnormalities.

Managing these complications requires a multidisciplinary approach involving healthcare providers specialising in pulmonology, gastroenterology, nutrition, endocrinology, and other relevant fields.

Unfortunately, cystic fibrosis (CF) cannot be prevented, however, there are some strategies that can be considered:

• Genetic counselling and testing: Individuals with a family history of CF or concerns about their risk can consult a genetic counsellor. They can provide information about CF, discuss family history, and offer genetic testing options. This can help individuals understand their carrier status and make informed decisions about family planning.
• Carrier screening: Couples planning to have children can undergo carrier screening to determine if they carry a CF gene. If both partners are carriers, their children have a 25% chance of inheriting CF, a 50% chance of being carriers, and a 25% chance of being neither carriers nor having CF. This information can help couples make informed reproductive decisions.
• Prenatal testing: If an individual is pregnant and knows they or their partner are carriers, prenatal testing can be done to determine if the foetus has CF. This allows couples to prepare for the possibility of having a child with CF and make informed decisions about their pregnancy.

While preventing CF itself is not currently possible, research is ongoing to explore potential avenues for prevention in the future. These include:

• Gene therapy: This involves introducing a healthy copy of the CFTR gene into cells to correct the underlying genetic defect. While still in the early stages of development, gene therapy holds promise for potentially preventing or treating CF in the future.
• Preimplantation genetic diagnosis (PGD): This technique allows couples undergoing in vitro fertilisation (IVF) to select embryos free of the CF gene for implantation. However, PGD raises ethical concerns and is not widely available.

It's important to remember that these are future possibilities and not currently available options for preventing CF. If someone has concerns about CF or their risk of having a child with CF, it's crucial to consult with a healthcare professional or genetic counsellor for personalised guidance and support.

Why is a high-calorie, high-fat diet suggested for people with cystic fibrosis (CF)?

A high-calorie, high-fat diet is recommended for individuals with CF because they often have difficulty absorbing nutrients due to pancreatic insufficiency. The extra calories and fat help compensate for poor absorption, promote weight gain, and support overall growth and development.

How do I take care of myself if I have cystic fibrosis?

Taking care of yourself with cystic fibrosis involves adhering to a comprehensive treatment plan prescribed by your healthcare team. This includes medications, airway clearance techniques, nutritional support, regular exercise, and attending routine medical appointments for monitoring and management of the condition.

Is cystic fibrosis contagious?

No, cystic fibrosis is not contagious. It is a genetic disorder caused by inheriting two faulty copies of the CFTR gene, one from each parent.

Can you get cystic fibrosis at any age?

No, cystic fibrosis is a genetic condition that is present from birth. It is inherited when both parents are carriers of the faulty CFTR gene and pass it on to their child.

Is cystic fibrosis a terminal illness?

While cystic fibrosis significantly impacts life expectancy and quality of life, it is not necessarily considered a terminal illness. Advances in medical care and treatment options have improved outcomes for individuals with CF, with many living well into adulthood. However, it is still a serious and life-limiting condition that requires ongoing management.

What is the best treatment for cystic fibrosis?

The best treatment for cystic fibrosis depends on individual patient needs and the expertise of the healthcare team. Treatment typically includes a combination of medications, airway clearance techniques, nutritional support, and regular monitoring by specialists in pulmonology, gastroenterology, and other relevant fields.

Who treats cystic fibrosis?

Cystic fibrosis is treated by a multidisciplinary team of healthcare professionals, including pulmonologists, gastroenterologists, nutritionists, respiratory therapists, genetic counsellors, and other specialists as needed. These professionals work together to develop and implement a comprehensive treatment plan tailored to the individual needs of each patient.

What type of genetic disorder is cystic fibrosis?

Cystic fibrosis is an autosomal recessive genetic disorder. This means that a person must inherit two copies of the faulty CFTR gene, one from each parent, to develop the condition. Individuals who inherit only one faulty copy of the gene are carriers and typically do not have symptoms of the disease.

Is there a permanent cure for cystic fibrosis?

As of now, there is no permanent cure for cystic fibrosis. However, research into potential treatments, including gene therapy and CFTR modulator drugs, is ongoing and holds promise for improving outcomes and quality of life for individuals with CF.

Reviewed by Dr. Vivek Nangia, Principal Director & Head - Pulmonology on 11-Mar-2024.