Cystic Fibrosis in Pediatrics

1. Introduction
Cystic fibrosis is a genetic disease characterized by the production of abnormally thick mucus. This mucus builds up in the lungs and pancreas, leading to respiratory and digestive problems. Cystic fibrosis is a common life-limiting autosomal recessive genetic disorder in the Caucasian population. The disease was first described in the 1930s by Dr. Dorothy Andersen, although it wasn’t until 1989 that the defective gene that causes cystic fibrosis was identified. The gene, known as the cystic fibrosis transmembrane conductance regulator (CFTR) gene, was discovered by a team of scientists led by Dr. Lap-Chee Tsui. It is inherited as an autosomal recessive genetic disorder, which means that a child needs to inherit two copies of the defective gene, one from each parent, to develop cystic fibrosis. If both parents are carriers of the abnormal gene, there is a 25% chance that the child will have cystic fibrosis, a 50% chance that the child will be a carrier of the abnormal gene but will not have the condition, and a 25% chance that the child will not have the abnormal gene at all. The defective chloride channel protein that is produced as a result of the genetic mutation leads to the abnormally thick secretions associated with cystic fibrosis. These thick secretions have a big impact on the respiratory and digestive systems. In the respiratory tract, the thick mucus can cause airway obstruction and impair mucociliary clearance. This means that the mucus is not cleared effectively and is more likely to get infected with microorganisms such as bacteria or viruses. In the pancreas, the abnormally thick secretions can lead to blockages in the normal release of digestive enzymes that help to break down food and absorb nutrients. Over time, this disruption to the digestive process can lead to irreversible damage in the pancreas, resulting in cystic fibrosis related diabetes and malnutrition.
1.1 Definition of Cystic Fibrosis
Over 10,600 people in the UK have cystic fibrosis. The condition is most commonly diagnosed in children and young children, with around half of all people with cystic fibrosis in the UK being younger than 16 years old. However, due to advancements in treatment and care for cystic fibrosis in recent years, an increasing number of people diagnosed with the condition are living into adulthood. With improved treatments and care, life expectancy for someone with cystic fibrosis has also increased, with many people living well into their 30s, 40s, and some even into their 50s. However, in severe cases of cystic fibrosis where a lung transplant is required, the risk of transplant rejection and further complications can result in a shorter life expectancy.
In the vast majority of cases, cystic fibrosis is caused by a genetic mutation that a child inherits from both their mother and father. These mutations are found on a particular gene called the ‘cystic fibrosis transmembrane conductance regulator’ (CFTR) gene. Normally, the CFTR gene makes a protein that sits in the cell wall, which acts as a channel for the movement of salt in and out of the cells. This protein also helps control the movement of water in the cells, which keeps the mucus in the body’s passageways thin. However, mutations on the gene can cause the protein to act abnormally. This means that it cannot move salt and water to the surface of the cells as easily as it should, which results in the mucus in the body becoming thick and sticky.
Cystic fibrosis is an inherited disorder that causes severe damage to the lungs, digestive system, and other vital organs in the body. This damage is often a result of a build-up of thick, sticky mucus which can cause chronic and life-threatening infections and serious digestion problems. Over time, this build-up of mucus can cause scarring and fibrosis, hence the name cystic fibrosis. The name ‘cystic fibrosis’ refers to the scarring (fibrosis) and cyst formation within the internal organs, particularly the lungs. However, cystic fibrosis can affect several areas of the body, including the digestive system – where mucus can prevent the body from absorbing nutrients from food.
1.2 Prevalence in Pediatrics
Cystic fibrosis is one of the most common life-threatening genetic disorders in the Caucasian population, with a prevalence of approximately 1 in 2000 to 3000 live births. However, the incidence and prevalence of cystic fibrosis varies according to the geographical location and the ethnicity of the population. As most of the patients with cystic fibrosis are diagnosed and managed in the pediatric setting, it is important to understand the prevalence of this genetic condition in the pediatric population all around the world. Cystic fibrosis is a genetic disorder, and it is inherited in an autosomal recessive pattern. This means that both copies of the CFTR gene in each cell must have mutations or damages in order for the genetic instructions not to make a functional cystic fibrosis transmembrane conductance regulator and result in the symptoms of cystic fibrosis. The typical life expectancy of patients with cystic fibrosis has been increasing over the past few decades. However, it is still a severely life-limiting condition. The median predicted age of survival in the United States is around 40 years old. It is a distressing fact that the majority of the cystic fibrosis patients will eventually succumb to the chronic diseases, in particular the respiratory complications from the disease. This genetic disorder does not affect just the respiratory system, making the symptom control in cystic fibrosis even more challenging. With the help of the advance in the diagnostic and screening methods, newborn screening for cystic fibrosis is nowadays widely available and implemented in many countries with high prevalence of cystic fibrosis. Early diagnosis allows early management and intervention that will significantly improve the long-term outcome of the disease, particularly in preventing the damages to the lung and the malnutrition that arise from the disease. However, it is also essential to bear in mind the potential psychological and social harm that may be brought to the family when the diagnosis of cystic fibrosis is made in their newborn baby. Every family deserves to be given adequate support and genetic counseling when long-term genetic condition like cystic fibrosis is diagnosed.
1.3 Etiology and Genetic Basis
Prenatal testing for cystic fibrosis is also available and can be performed as early as the ninth week of pregnancy using a chorionic villus sampling technique, or from the sixteenth week using an amniocentesis. Such tests are particularly useful for identifying couples at risk of giving birth to a child with cystic fibrosis. The identification of two CFTR mutations through newborn screening allows for prompt initiation of both medical management and genetic counseling, which are key in preventing serious complications and improving the long-term prognosis for children with cystic fibrosis.
Cystic fibrosis is inherited in an autosomal recessive manner, meaning that a child must inherit two copies of the faulty CFTR gene – one from each parent – in order to develop the condition. If both parents are carriers of a CFTR mutation, there is a 25% chance with each pregnancy that the child will be affected by cystic fibrosis. Carriers of a single copy of a mutated CFTR gene do not have the condition themselves, but they can still pass the faulty gene onto their children.
Cystic fibrosis is a monogenic autosomal recessive condition caused by mutations in the CFTR gene. This gene provides instructions for the formation of a protein called cystic fibrosis transmembrane conductance regulator (CFTR), which regulates the movement of chloride and sodium ions in and out of cells. There are over 1,700 identified mutations in the CFTR gene, which can result in a wide variety of clinical presentations of cystic fibrosis. The most common mutation, affecting approximately 70% of patients with cystic fibrosis, is the deletion of phenylalanine at position 508 on the CFTR protein. This mutation leads to a faulty CFTR protein that is unable to fold correctly and reach the cell surface, resulting in disrupted ion transport and subsequently leading to the characteristic thick, sticky mucus found in the lungs and digestive system of patients.
2. Clinical Presentation
2.1 Respiratory Symptoms
2.1.1 Chronic Cough
2.1.2 Recurrent Chest Infections
2.1.3 Wheezing and Shortness of Breath
2.2 Gastrointestinal Symptoms
2.2.1 Failure to Thrive
2.2.2 Steatorrhea and Malabsorption
2.2.3 Meconium Ileus
3. Diagnostic Evaluation
3.1 Sweat Chloride Test
3.2 Genetic Testing
3.3 Pulmonary Function Tests
4. Management and Treatment
4.1 Pharmacological Interventions
4.1.1 Pancreatic Enzyme Replacement Therapy
4.1.2 Bronchodilators and Mucolytics
4.1.3 Antibiotics for Infections
4.2 Nutritional Support
4.2.1 High-Calorie Diet
4.2.2 Vitamin and Mineral Supplementation
4.2.3 Enteral Tube Feeding
4.3 Physiotherapy and Airway Clearance Techniques
4.3.1 Chest Physiotherapy
4.3.2 Positive Expiratory Pressure Devices
4.3.3 Flutter Valve and Acapella Devices
5. Complications and Prognosis
5.1 Respiratory Complications
5.1.1 Chronic Lung Infections
5.1.2 Bronchiectasis
5.1.3 Pneumothorax
5.2 Gastrointestinal Complications
5.2.1 Intestinal Obstruction
5.2.2 Rectal Prolapse
5.2.3 Liver Disease
5.3 Prognosis and Life Expectancy