Cystic fibrosis is a genetic disorder that causes persistent lung infections and limits the ability to breathe over time. It is caused by a defective gene that causes the body to produce unusually thick, sticky mucus that clogs the lungs and obstructs the pancreas. The respiratory system is profoundly affected by cystic fibrosis.
What is cystic fibrosis?
Cystic fibrosis is an inherited disease caused by mutations in the CFTR gene. This gene encodes a protein called cystic fibrosis transmembrane conductance regulator which functions as a channel at the surface of cells that produce mucus, sweat and digestive juices. In people with CF, the malfunctioning CFTR protein causes secretions to become thick and sticky. Instead of acting as a lubricant, the secretions plug up tubes, ducts and passageways, especially in the lungs and pancreas.
This collection of thick mucus in the lungs allows bacteria to thrive and causes chronic lung infections. These chronic lung infections are responsible for most of the health problems, and disease associated with cystic fibrosis.
How does cystic fibrosis affect the respiratory system?
Cystic fibrosis has a profound effect on the entire respiratory system, including the upper and lower airways. Here are some of the key effects:
Increased mucus production
The main effect of cystic fibrosis on the respiratory system is increased mucus production. The defective CFTR protein causes mucus secretions to become abnormally thick and sticky. This mucus accumulates and clogs the airways, making breathing difficult.
Recurrent lung infections
The accumulated mucus in the airways provides an ideal environment for bacteria to grow. People with cystic fibrosis suffer from recurrent and persistent lung infections. The thick mucus blocks the airways and traps bacteria, allowing infections to become established. Common lung infections in CF include Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae.
Airway obstruction
The mucus accumulation and recurrent infections cause obstruction of the small and large airways. This makes it hard to breathe and causes shortness of breath. Airway obstruction also traps air in the lungs, leading to air trapping and hyperinflation.
Respiratory failure
Over many years, the persistent airway infections and inflammation cause progressive lung damage. This can eventually lead to respiratory failure, which is the most common cause of death in people with cystic fibrosis.
Other effects
Other respiratory effects of CF include:
– Bronchiectasis – permanent widening of the airways due to mucus plugging and infections
– Pneumothorax – collapsed lung due to air trapping and rupture of a lung bleb
– Hemoptysis – coughing up blood due to lung tissue damage
– Nasal polyps – growths in the nasal passages due to inflammation
– Sinus infections – mucus collection in the sinuses blocks drainage and causes infection
How does cystic fibrosis affect respiration?
The cycle of mucus accumulation, infections, and inflammation in CF lungs severely affects the process of respiration – the exchange of oxygen and carbon dioxide. Here’s how:
Impaired gas exchange
The mucus buildup and lung damage in cystic fibrosis makes it harder for oxygen to get across the airway walls into the bloodstream. At the same time, it is difficult for carbon dioxide to pass from the blood into the airways to be exhaled. This impaired gas exchange leads to oxygen deprivation and a buildup of carbon dioxide in the body.
Increased work of breathing
The increased mucus and infections cause narrowing of the airways in cystic fibrosis. This makes a person work harder to breathe – essentially, inhaling and exhaling requires more effort when the airways are obstructed. The increased work of breathing uses more energy and further increases the demand for oxygen.
Ventilation-perfusion mismatch
The airflow obstruction and mucus buildup makes ventilation (air reaching the alveoli) uneven. At the same time, mucus plugging and lung damage also makes blood perfusion (blood flow) to the alveoli uneven. This mismatch between ventilation and perfusion reduces the efficiency of gas exchange.
Hypoxemia and hypercapnia
Due to the impaired gas exchange and ventilation-perfusion mismatch, people with cystic fibrosis often have hypoxemia – low blood oxygen levels. They may also develop hypercapnia – a buildup of carbon dioxide in the blood. This state is called respiratory acidosis and further strains the body.
How are the lungs affected?
Cystic fibrosis has several effects on the lungs including mucus buildup, infections, inflammation, and long-term lung damage. Here is a more detailed look:
Mucus accumulation
In healthy people, mucus in the lungs traps debris and pathogens as part of the clearance mechanism. Coughing helps clear mucus upwards through the airways. In CF, defective mucus leads to thick secretions that are difficult to clear, causing mucus accumulation. This occurs in the small and large airways as well as in the alveoli.
Chronic infections
The abnormally thick mucus allows bacteria to become trapped and evade clearance from the airways. This leads to chronic airway infections, commonly from Pseudomonas aeruginosa, Staphylococcus aureus and Burkholderia cepacia. Chronic stimulation of the immune system causes persistent inflammation and lung damage.
Bronchiectasis
Repeated cycles of infection and inflammation cause permanent widening (dilation) of the bronchi and bronchioles – a condition known as bronchiectasis. This damaging process is localized to the pulmonary airways in cystic fibrosis. The affected bronchi are widened, thickened and inflamed.
Respiratory bronchiolitis
The smallest airways, called bronchioles, are also affected through a process known as respiratory bronchiolitis. Inflammation, fibrosis and mucus plugs within the bronchioles further impair airflow.
Pneumothorax
The weakened, obstructed airways are prone to forming blebs or blisters that can rupture and collapse the lung – known as a pneumothorax. This causes sudden shortness of breath and pain.
Respiratory failure
The cumulative effects of recurrent infections combined with bronchiectasis and respiratory bronchiolitis cause progressive loss of lung function over time. Eventually, end-stage lung disease leads to respiratory failure.
How are the upper airways affected?
Although the lung effects of CF are most severe, the upper airways are also impacted by increased mucus production.
Sinusitis
The paranasal sinuses become congested with mucus in people with CF. This mucus stasis allows bacterial infections to establish and become chronic. Sinusitis symptoms include facial pain, headaches, and nasal discharge.
Nasal polyps
Chronic inflammation due to sinus infections can cause abnormal tissue growths called nasal polyps. These noncancerous growths obstruct sinus drainage and airflow through the nasal passages.
Middle ear infections
Eustachian tubes can get clogged with mucus and become infected, leading to recurrent middle ear infections. This may cause ear pain, temporary hearing loss, and discharge.
Diagnosing lung and respiratory involvement
Doctors use several tests to assess the extent of lung and respiratory involvement in cystic fibrosis:
Imaging tests
– Chest X-ray: Shows bronchial wall thickening, mucus plugging, bronchiectasis, and other lung damage.
– CT scan: Provides more detailed views of lung involvement to identify early changes.
– MRI: Useful for imaging details of lung damage without radiation exposure.
Lung function tests
– Spirometry: Measures airflow obstruction by tracking inhalation and exhalation.
– Plethysmography: Measures lung volumes and detects air trapping.
– Lung diffusion capacity: Assesses how well gases are exchanged in the lungs.
Other tests
– Exercise testing: Checks oxygen saturation during exertion.
– Sleep study: Monitors oxygen levels during sleep and detects nighttime hypoxemia.
– Cough swabs: Collect mucus samples to identify lung bacteria.
Blood tests
– Arterial blood gas: Detects hypoxemia and respiratory acidosis.
– Complete blood count: Checks for elevated white blood cells due to infection.
How is cystic fibrosis treated?
While there is no cure for cystic fibrosis, treatments aim to manage symptoms and prevent and treat complications. Respiratory treatments include:
Airway clearance
Methods to loosen and clear mucus:
– Chest physiotherapy
– Breathing techniques
– Devices that vibrate the chest wall
– Inhaled hypertonic saline
Mucolytics
Medications that thin mucus such as:
– Dornase alfa (Pulmozyme®)
– Inhaled hypertonic saline
Bronchodilators
Drugs that open airways:
– Albuterol
– Ipratropium
Anti-inflammatory drugs
Reducing inflammation in the airways:
– Inhaled corticosteroids
– Oral corticosteroids during exacerbations
– Nonsteroidal anti-inflammatory drugs
Antibiotics
Oral, intravenous, or inhaled antibiotics to treat lung infections. May be used chronically to suppress infections.
Lung transplant
For end-stage lung disease, a lung transplant may be considered. This can significantly improve quality of life.
Other treatments
– Vaccines: Annual influenza vaccine, pneumonia vaccines
– Oxygen therapy
– Noninvasive ventilation
What is the life expectancy for cystic fibrosis?
In the past, cystic fibrosis had a very poor prognosis and most people did not survive childhood. Thanks to advances in diagnosis and treatment, the median life expectancy has now improved significantly:
– In 2019, the median survival age was estimated to be close to 44 years according to the Cystic Fibrosis Foundation.
– Median predicted survival age increased from 27 years in 1986 to over 43 years in 2016 per the US Cystic Fibrosis Foundation patient registry.
– With continued improvements in treatments, people with CF are living longer. Some are now living well into their 50s and beyond.
– Lung transplantation can extend survival in suitable candidates. The median survival post lung transplant is over 8 years.
– Poor nutritional status, female gender, severe genotype, and colonization with certain bacteria at an early age are associated with worse prognosis.
So while cystic fibrosis remains a severe, chronic disease, the prognosis is now significantly better compared to several decades ago thanks to a multidisciplinary approach to care.
Conclusion
Cystic fibrosis has a profound impact on the respiratory system leading to increased mucus production, recurrent infections, airway obstruction, and eventual respiratory failure in most patients. The thick mucus impairs clearance mechanisms and allows bacteria to become trapped in the airways.
Chronic airway infection and inflammation causes bronchiectasis, respiratory bronchiolitis, and progressive lung damage over time. Impaired gas exchange leads to problems with oxygenation and ventilation. Besides the lung effects, the upper airways are also affected by sinus infections and nasal polyps.
With advances in therapies to improve mucus clearance and treat infections, survival has improved significantly for cystic fibrosis. However, most patients eventually develop severe respiratory impairment leading to respiratory failure. Lung transplantation may be an option for suitable candidates with end-stage lung disease. Ongoing research aims to develop treatments that target the underlying defect in CFTR to improve mucus abnormalities and lung function.