Cystic Fibrosis: Symptoms, Causes & Modern Treatment

What Is Cystic Fibrosis?

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR gene that affects the movement of salt and water in cells, resulting in thick, sticky mucus that clogs the airways and blocks digestive enzymes. It primarily affects the lungs, pancreas, liver, and intestines.

Cystic fibrosis is one of the most common life-shortening genetic conditions, affecting approximately 70,000 to 100,000 people worldwide. The condition is inherited in an autosomal recessive pattern, meaning a child must inherit a defective copy of the CFTR gene from both parents to develop CF. People who carry only one defective gene are called carriers and typically do not have symptoms.

The CFTR (cystic fibrosis transmembrane conductance regulator) protein normally functions as a channel that allows chloride ions to move in and out of cells. When this protein is defective or absent, the balance of salt and water on cell surfaces is disrupted, leading to the production of abnormally thick, sticky mucus throughout the body.

While CF has historically been considered a childhood disease with poor prognosis, advances in treatment have transformed it into a chronic condition that many people manage well into adulthood. The development of CFTR modulator therapies, which target the underlying protein defect, has been particularly revolutionary in improving outcomes for many patients.

How CF Affects the Body

The thick mucus produced in cystic fibrosis affects multiple organ systems, though the lungs and digestive system are most significantly impacted. In the lungs, the sticky mucus clogs the airways, making it difficult to breathe and creating an environment where bacteria can thrive, leading to chronic infections. Over time, repeated infections cause progressive lung damage.

In the digestive system, the thick mucus blocks the ducts of the pancreas, preventing digestive enzymes from reaching the intestines. Without these enzymes, the body cannot properly break down and absorb nutrients from food, particularly fats and proteins. This leads to poor weight gain and nutritional deficiencies despite a healthy appetite.

Genetic Inheritance Pattern

Cystic fibrosis follows an autosomal recessive inheritance pattern. This means that both parents must be carriers of a CFTR gene mutation for a child to have CF. When both parents are carriers, each pregnancy has a 25% chance of resulting in a child with CF, a 50% chance of the child being a carrier like the parents, and a 25% chance of the child inheriting no mutated genes.

More than 2,000 different mutations in the CFTR gene have been identified, though some are much more common than others. The most frequent mutation, called F508del, accounts for approximately 70% of CF cases worldwide. The specific mutations a person has affect how severe their disease is and which treatments may be effective.

What Are the Symptoms of Cystic Fibrosis?

Cystic fibrosis symptoms include persistent cough with thick mucus, frequent lung infections, wheezing, shortness of breath, poor weight gain despite good appetite, salty-tasting skin, and greasy, bulky stools. Symptoms typically appear in infancy or early childhood, though some people are not diagnosed until adulthood.

The symptoms of cystic fibrosis can vary significantly between individuals, even those with the same genetic mutations. Some people have severe symptoms from infancy, while others may have milder manifestations that are not recognized until adolescence or adulthood. The variability in symptoms depends partly on the specific CFTR mutations and partly on other genetic and environmental factors.

Most cases of CF are now identified through newborn screening before symptoms appear, allowing early treatment. However, understanding the symptoms remains important for diagnosis in areas without screening programs and for recognizing disease progression.

Respiratory Symptoms

The respiratory system is typically the most affected organ system in cystic fibrosis. The thick, sticky mucus that characterizes CF clogs the airways, creating a cycle of infection, inflammation, and progressive lung damage that drives most of the disease's morbidity and mortality.

• Persistent cough: Often productive with thick, sticky mucus that is difficult to clear
• Frequent lung infections: Recurrent pneumonia and bronchitis caused by bacteria that thrive in the thick mucus
• Wheezing and shortness of breath: Resulting from airway obstruction and inflammation
• Exercise intolerance: Difficulty participating in physical activities due to reduced lung function
• Nasal polyps: Soft, noncancerous growths in the nasal passages that can cause congestion
• Chronic sinusitis: Persistent inflammation and infection of the sinuses

Digestive Symptoms

Digestive problems are the second major category of CF symptoms, caused by thick mucus blocking the pancreatic ducts and affecting the intestines. Approximately 85-90% of people with CF have pancreatic insufficiency, meaning their pancreas cannot produce enough digestive enzymes.

• Poor weight gain and growth: Despite eating normally or even more than normal
• Greasy, bulky, foul-smelling stools: Called steatorrhea, caused by malabsorption of fats
• Frequent bowel movements: Due to malabsorption and altered gut motility
• Abdominal pain and bloating: From gas, constipation, or intestinal blockage
• Intestinal blockage: Can occur at birth (meconium ileus) or later (distal intestinal obstruction syndrome)
• Rectal prolapse: When straining to pass stool causes the rectum to protrude

Symptoms in Infants and Children

In infants, cystic fibrosis may first be suspected when a baby fails to pass stool in the first day or two of life (meconium ileus), which occurs in about 15-20% of newborns with CF. Other early signs include poor weight gain despite a good appetite, bulky and greasy stools, and a persistent cough.

Parents often notice that their child's skin tastes unusually salty when they kiss them - this is due to the elevated salt content in sweat that is characteristic of CF. Children may also have a swollen belly due to malabsorption and gas, and enlarged cheeks from using their sucking muscles more intensely due to difficulty feeding.

Symptoms in Adults

Some people with milder forms of CF may not be diagnosed until adolescence or adulthood. In these cases, the presenting symptoms are often chronic respiratory infections, nasal polyps, chronic sinusitis, or infertility. Men with CF are typically infertile due to absence of the vas deferens (the tube that carries sperm), and this may be discovered during fertility evaluation.

Adults may also present with pancreatitis (inflammation of the pancreas), liver disease, or CF-related diabetes. The diagnosis of CF in adulthood is becoming less common as newborn screening programs expand, but it still occurs in populations without universal screening.

How Is Cystic Fibrosis Diagnosed?

Cystic fibrosis is diagnosed through newborn screening (IRT blood test), confirmed by sweat chloride testing (the gold standard - chloride above 60 mmol/L is diagnostic), and genetic testing to identify specific CFTR mutations. Early diagnosis through screening allows treatment to begin before significant lung damage occurs.

The diagnostic approach to cystic fibrosis has evolved significantly with the implementation of newborn screening programs in many countries. Today, most cases are identified shortly after birth, before symptoms develop. This early diagnosis is crucial because starting treatment early can prevent or delay lung damage and improve long-term outcomes.

Diagnosis of CF requires both clinical evidence of the disease (symptoms or positive newborn screen) and laboratory evidence of CFTR dysfunction (abnormal sweat test or identification of CF-causing mutations). In some cases, particularly with milder or atypical presentations, diagnosis may be challenging and require specialized evaluation at a CF center.

Newborn Screening

Newborn screening for CF is now performed in most developed countries and is expanding worldwide. The screening typically measures immunoreactive trypsinogen (IRT), an enzyme produced by the pancreas. Elevated IRT levels in newborns suggest possible CF and warrant further testing. Some screening programs also include genetic testing for common CFTR mutations.

It is important to understand that a positive newborn screen does not mean the baby definitely has CF - it means further testing is needed. Approximately 10-15% of babies with positive screens are ultimately diagnosed with CF after confirmatory testing.

Sweat Chloride Test

The sweat chloride test is the gold standard for diagnosing cystic fibrosis. This painless test measures the concentration of chloride in sweat. Because the CFTR protein normally moves chloride out of sweat gland cells, people with CF have abnormally high chloride levels in their sweat.

The test involves applying a chemical called pilocarpine to a small area of skin (usually the forearm) along with a mild electrical current to stimulate sweating. The sweat is collected for about 30 minutes and then analyzed. Results are interpreted as follows:

• Chloride above 60 mmol/L: Diagnostic for cystic fibrosis
• Chloride 30-59 mmol/L: Intermediate - may indicate CF or carrier status, requires genetic testing
• Chloride below 30 mmol/L: Makes CF unlikely (though not impossible in rare cases)

Genetic Testing

Genetic testing identifies specific mutations in the CFTR gene. This is important for several reasons: it confirms the diagnosis when sweat test results are borderline, it identifies the specific mutations which affects treatment decisions (particularly for CFTR modulator therapy), and it provides information for family planning and genetic counseling.

Standard panels test for the most common CFTR mutations. If these are negative but CF is still suspected, expanded sequencing of the entire CFTR gene may be performed. Identifying both mutations is not always possible, as some are rare or uncharacterized.

Additional Diagnostic Tests

Once CF is diagnosed, additional tests help assess the extent of organ involvement and establish baselines for monitoring. These typically include pulmonary function tests (spirometry), chest X-ray or CT scan, sputum cultures to identify lung bacteria, fecal elastase to assess pancreatic function, and liver function tests.

When Should You Seek Medical Care?

Seek immediate medical care if you or your child with CF experiences severe breathing difficulties, coughing up blood (more than a few tablespoons), severe chest pain, high fever with respiratory symptoms, or signs of intestinal blockage. Regular CF center visits are essential for routine care.

People with cystic fibrosis require regular, ongoing medical care at specialized CF centers. However, certain situations require urgent or emergency attention. It is crucial for patients and families to recognize warning signs that indicate a need for immediate medical evaluation.

Signs of Pulmonary Exacerbation

A pulmonary exacerbation is a worsening of lung symptoms that may require intensified treatment, including IV antibiotics. Contact your CF care team if you notice increased cough, changes in sputum color or amount, decreased energy or appetite, weight loss, decreased lung function, or fever.

Routine Care Requirements

People with CF should have regular appointments at an accredited CF center, typically every 1-3 months. These visits include lung function testing, sputum cultures, nutritional assessment, and review of treatment regimens. Annual comprehensive evaluations include blood tests, imaging studies, and screening for complications such as CF-related diabetes.

How Is Cystic Fibrosis Treated?

CF treatment includes CFTR modulator drugs (like Trikafta) that address the underlying defect, airway clearance techniques, inhaled medications, pancreatic enzyme supplements, nutritional support, and antibiotics for infections. Treatment is lifelong and requires daily management, but has dramatically improved outcomes.

Treatment for cystic fibrosis has two main goals: addressing the underlying CFTR protein defect (now possible with CFTR modulators) and managing the symptoms and complications of the disease. Treatment is complex and time-consuming, often requiring several hours of daily therapy, but adherence to treatment regimens is strongly associated with better outcomes.

Care should be coordinated by an accredited CF center with a multidisciplinary team including pulmonologists, gastroenterologists, dietitians, respiratory therapists, social workers, and other specialists. This team approach has been shown to significantly improve survival and quality of life.

CFTR Modulator Therapy

CFTR modulators are breakthrough medications that target the underlying cause of CF by improving the function of the defective CFTR protein. These drugs have transformed CF care and significantly improved outcomes for eligible patients.

Trikafta (elexacaftor/tezacaftor/ivacaftor) is the most effective and widely used CFTR modulator, approved for patients aged 2 and older with at least one F508del mutation (approximately 90% of CF patients). Studies show Trikafta improves lung function by 10-15 percentage points and reduces pulmonary exacerbations by 63%.

Other CFTR modulators include:

• Kalydeco (ivacaftor): For specific gating mutations
• Orkambi (lumacaftor/ivacaftor): For F508del homozygotes
• Symdeko (tezacaftor/ivacaftor): For certain mutations

Airway Clearance Therapy

Airway clearance techniques help loosen and remove the thick mucus from the lungs. This is a cornerstone of CF management and typically needs to be performed 1-4 times daily. The time commitment is significant (often 20-40 minutes per session), but consistent airway clearance helps maintain lung function and reduce infections.

Methods include:

• Chest physiotherapy (CPT): Manual percussion and postural drainage
• Positive expiratory pressure (PEP) devices: Create resistance during exhalation
• Oscillating PEP devices: Such as Acapella, Flutter, or Aerobika
• High-frequency chest wall oscillation (vest therapy): An inflatable vest that vibrates the chest
• Active cycle of breathing techniques: Specific breathing exercises
• Autogenic drainage: Controlled breathing at different lung volumes

Inhaled Medications

Several inhaled medications are used in CF treatment, typically administered via nebulizer before or after airway clearance:

• Bronchodilators: Open the airways before other treatments
• Dornase alfa (Pulmozyme): Breaks down DNA in mucus, making it thinner
• Hypertonic saline: Draws water into the airways to thin mucus
• Inhaled antibiotics: Such as tobramycin or aztreonam for chronic Pseudomonas infection

Nutritional Management

Good nutrition is essential for people with CF, as they need more calories than average due to the energy required for breathing and fighting infections, combined with poor nutrient absorption. CF centers typically recommend a high-calorie, high-fat diet with adequate protein.

Pancreatic enzyme replacement therapy (PERT) is necessary for the 85-90% of CF patients with pancreatic insufficiency. Enzyme capsules are taken with every meal and snack to help digest fats and proteins. The dose is adjusted based on the amount and type of food eaten.

Fat-soluble vitamin supplements (A, D, E, and K) are routinely prescribed because these vitamins are poorly absorbed without sufficient fat digestion. Some patients may require salt supplements, especially in hot weather or during exercise.

Treating Infections

Lung infections are treated with antibiotics based on sputum culture results. For mild exacerbations, oral antibiotics may be sufficient. More severe exacerbations often require IV antibiotics, either in the hospital or at home with proper support. Chronic infections with organisms like Pseudomonas aeruginosa may require long-term inhaled antibiotics.

Lung Transplantation

For patients with severe, end-stage lung disease who are not responding adequately to medical therapy, lung transplantation may be an option. This is a major decision with significant risks and benefits. Post-transplant, patients must take immunosuppressive medications for life and remain susceptible to rejection and infection. However, successful transplantation can dramatically improve quality of life and extend survival.

How Does Cystic Fibrosis Affect Daily Life?

Living with CF requires significant daily management including airway clearance (1-4 times daily), taking multiple medications, maintaining high-calorie nutrition, and attending regular medical appointments. Despite these demands, many people with CF lead full, active lives including careers, relationships, and families.

The daily treatment burden for CF is substantial. A typical day may include morning and evening airway clearance sessions (20-40 minutes each), nebulized medications (15-30 minutes per session), oral medications, enzyme capsules with every meal and snack, and attention to nutrition and hydration. This can add up to 2-4 hours of treatment time daily.

Despite these challenges, many people with CF live full and productive lives. With modern treatments, especially CFTR modulators, more people with CF are attending college, building careers, getting married, and having children. However, the disease does require ongoing attention and can impact various aspects of life.

Physical Activity and Exercise

Physical activity is strongly encouraged for people with CF. Exercise helps clear mucus from the lungs, improves cardiovascular fitness, strengthens respiratory muscles, and enhances overall well-being. Most people with CF can participate in sports and physical activities, though some modifications may be needed based on lung function and endurance.

Mental Health Considerations

Living with a chronic, life-shortening illness can take a psychological toll. Rates of anxiety and depression are higher in people with CF and their caregivers compared to the general population. CF centers typically screen for mental health concerns and can provide referrals to psychologists or psychiatrists experienced in chronic illness.

Support from family, friends, and other people with CF can be invaluable. Patient advocacy organizations offer resources, support groups, and connections with the CF community. However, people with CF should generally avoid in-person contact with each other due to infection risk.

Education and Career

Most children with CF attend regular schools and can participate fully in academics. Some accommodations may be needed, such as time for treatments, access to snacks, and flexibility for medical appointments. Many adults with CF complete higher education and have successful careers, though job choices may be influenced by factors like health insurance needs and physical demands.

Relationships and Family Planning

CF does not prevent meaningful relationships, and many people with CF get married or have long-term partners. When considering having children, genetic counseling is recommended. While most men with CF are infertile due to absent vas deferens, they can often father biological children through testicular sperm extraction and in vitro fertilization. Women with CF can become pregnant naturally, though fertility may be reduced. Pregnancy requires careful planning and monitoring by both CF and obstetric specialists.

What Complications Can Occur?

CF complications include bronchiectasis (permanent airway damage), CF-related diabetes (affecting 40-50% of adults), liver disease, osteoporosis, sinus disease, and male infertility. Regular screening and early treatment of complications are essential parts of CF care.

As people with CF live longer, managing complications becomes an increasingly important aspect of care. Many complications can be prevented or effectively managed with appropriate screening and treatment.

CF-Related Diabetes (CFRD)

CF-related diabetes affects approximately 40-50% of adults with CF. It has features of both type 1 and type 2 diabetes and is caused by damage to the insulin-producing cells in the pancreas. CFRD is associated with worse lung function and nutrition, so screening begins in adolescence and insulin treatment is started when diagnosed.

Liver Disease

About 5-10% of people with CF develop significant liver disease, which can progress to cirrhosis. Regular liver function monitoring is part of routine CF care. In severe cases, liver transplantation may be needed.

Bone Disease

People with CF are at increased risk for osteoporosis due to vitamin D deficiency, malnutrition, chronic inflammation, and some medications. Bone density monitoring and treatment with calcium, vitamin D, and sometimes bone-strengthening medications are part of CF care.

Sinus Disease

Chronic sinusitis and nasal polyps are common in CF. These may require medical treatment or surgery. Nasal symptoms can significantly impact quality of life and should be addressed.

What Is the Life Expectancy for Cystic Fibrosis?

Life expectancy for CF has improved dramatically from early childhood death in the 1950s to a median predicted survival of over 50 years today. With CFTR modulators and continued advances in care, people diagnosed today are expected to have even better outcomes.

The prognosis for cystic fibrosis has improved remarkably over the past several decades. In the 1950s, most children with CF did not survive to attend elementary school. Today, the median predicted survival age exceeds 50 years, and babies born with CF today are expected to live even longer as treatments continue to improve.

The introduction of CFTR modulators, particularly Trikafta, has further accelerated improvements in outcomes. Early data suggest these medications may significantly extend life expectancy for eligible patients, though long-term studies are still ongoing.

Factors associated with better outcomes include early diagnosis, consistent treatment adherence, care at accredited CF centers, maintaining good nutrition, and eligibility for CFTR modulator therapy. While CF remains a serious, life-shortening condition, the outlook continues to improve.