cystic fibrosis notes

Cystic fibrosis is a genetically transmitted disorder and is considered the most common lethal genetic disease, affecting roughly 40,000 individuals in the U.S.
Primarily diagnosed in children, with some mutations identified later (in early adulthood) due to over 1,700 different mutations of the CF gene.
CF primarily affects the exocrine glands, including sweat glands, mammary glands, mucus glands in airways, salivary glands, and reproductive glands.
The most common mutation, Delta F508, affects about 70-75% of CF patients, and average life expectancy has improved significantly from 10 years in 1980 to about 38-40 years now.

At birth, infants typically appear normal with normal lung function. Changes often arise in early childhood, around 2-3 years of age.
Key alterations in the lungs include:
- Bronchial Gland Hypertrophy: Bronchial glands that produce mucus increase in size.
- Goblet Cell Overgrowth: An increase in goblet cells leads to the production of thick, sticky mucus.
- Mucociliary Escalator Dysfunction: Thick mucus disrupts the function, leading to mucus retention and blockage of airways, potentially causing air trapping and consolidation.
- Chronic Bacterial Infections: Due to defective mucus clearance, bacterial infections in the lungs are common, contributing to long-term lung damage.

CF is categorized as an autosomal recessive genetic disorder, which means both parents must pass on the defective gene for a child to have the disease.
The gene responsible for CF is located on chromosome 7 and affects transmembrane conductance regulator (CFTR) functionality, impacting salt and water movement across cell membranes.
Delta F508 is the most prevalent mutation, highlighting the need for targeted therapies in patients with this specific mutation.

The malfunction of the CFTR gene leads to reduced chloride ion transport, causing water to be drawn into cells and leading to dehydrated, thickened mucus within the airways.
This thick mucus impairs cilia function (which typically help move mucus and pathogens out of the lungs), resulting in an increased susceptibility to respiratory infections.
Complications also extend to the pancreas, liver, and other organs, as exocrine function is compromised, leading to difficulties in fat and protein digestion.

Diagnosis involves meeting two of several criteria, including genetic testing to identify CF mutations and sweat chloride tests to measure salt levels in sweat (a hallmark of CF).
For infants, a heel prick test checks for CF immediately after birth, gaining widespread acceptance since 2011 in the U.S.

Lungs: Progressive lung issues lead to chronic lung infections, bronchiectasis, and eventually respiratory failure being a common cause of mortality.
Pancreas: Patients often suffer from malnutrition due to insufficient enzyme production causing poor digestion and absorption of nutrients.
Gastrointestinal Symptoms: Cystic fibrosis can lead to meconium plugs (obstruction of the intestines in infants) and fatty, sticky stools due to pancreatic insufficiency.
Sweat Glands: CF patients excrete salt at much higher concentrations leading to salty skin, which was historically recognized as a sign of the disease.
Reproductive System: Male patients typically face infertility due to non-development of reproductive structures, while female patients may have thickened cervical mucus impacting fertility.

Airway Clearance Techniques: Includes chest physiotherapy, postural drainage, and devices like the Vest to help clear mucus.
Medications: Include bronchodilators, mucolytics (like acetylcysteine), hypertonic saline, and enzyme supplements for digestion. Recently developed modulator therapies address specific genetic mutations (e.g., Trikafta for Delta F508).
Transplants: Lung transplants may be an option, but they do not cure CF or reverse the genetic defect, and patients often experience rejection leading to poor long-term outcomes.

Individuals with CF are at high risk for respiratory infections from bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus, necessitating careful monitoring and antibiotics to manage infections.
Bronchiectasis is often associated with CF, characterized by irreversible airway enlargement and chronic cough with copious, foul-smelling sputum.
Management involves aggressive treatment of infections and potentially surgical interventions depending on the severity of bronchiectasis.