Cystic fibrosis and primary ciliary dyskinesia: Clinical sciences

Cystic fibrosis and primary ciliary dyskinesia are distinct autosomal recessive disorders, both of which are associated with recurrent respiratory infections and chronic bronchiectasis.

Cystic fibrosis, or CF for short, is associated with a mutation of the cystic fibrosis transmembrane conductance regulator, or CFTR, gene coding for the CFTR protein. Normally, the CFTR protein acts as a channel that controls the flow of chloride and water in and out of tissues as needed to regulate viscosity of secretions. In CF, these channels are dysfunctional, resulting in abnormally viscous secretions that are thick and sticky. This primarily impairs airway clearance and increases the risk of respiratory infection.

On the flip side, primary ciliary dyskinesia, or PCD for short, is associated with abnormal ciliary movement, which can also lead to poor airway clearance and chronic respiratory infections.

Now, if your patient presents with a chief concern suggesting cystic fibrosis or primary ciliary dyskinesia, first perform an ABCDE assessment to determine if the patient is unstable or stable. If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access, and begin continuous vital sign monitoring, including respiratory rate, pulse oximetry, and cardiac monitoring. Finally, if needed, don’t forget to provide supplemental oxygen.

Now, let’s go back to the ABCDE assessment and take a look at stable patients. In this case, first obtain a focused history and physical exam, which will help you differentiate between CF and PCD.

First, let’s start with cystic fibrosis! CF primarily affects organs with secretory functions, like the lungs, gastrointestinal tract, and pancreas. Normally, these secretions are thin, but a defect in a chloride channel leads to thick mucus secretions that can congest the airways and GI ducts.

Newborns with CF commonly present with meconium ileus or prolonged jaundice. Additionally, you may identify a positive newborn screen or a positive family history of CF. In infants and older children, there’s typically a history of chronic cough, and chronic sinus and pulmonary infections, as well as chronic constipation or recurrent pancreatitis. Moreover, pancreatitis typically results in fat malabsorption, which is associated with bulky, greasy, foul-smelling stools!

In addition to fat malabsorption, impaired pancreas function also results in protein malabsorption, so your physical exam will typically reveal an underweight patient. Other important physical exam findings include nasal polyps, digital clubbing, and even hepatomegaly. Finally, pulmonary auscultation might reveal signs of lung involvement, like crackles or rhonchi.

Now here’s a high-yield fact! Individuals with CF have an increased risk of infertility due to several mechanisms. Biologically male patients often have congenital absence of the vas deferens; while biologically female patients can experience secondary amenorrhea, as well as hyperviscous reproductive tract mucus, both of which impair fertility.

The presence of these findings should make you suspect cystic fibrosis, so your next step is to order a sweat chloride test. The sweat chloride test, also known as quantitative pilocarpine iontophoresis, uses pilocarpine and electrical stimulation to stimulate production of a sufficient amount of sweat for the measurement of chloride content. Because a CFTR mutation results in excessive chloride losses, elevated sweat chloride is highly suggestive of CF.

Now, if the sweat chloride test is less than 30 millimoles per liter, the test is negative, and CF is unlikely, so you should consider alternative diagnoses. However, if the result is intermediate, meaning it’s between 30 and 59 millimoles per liter, you should order genetic testing. The presence of two CF mutations confirms the diagnosis of cystic fibrosis. Finally, if the sweat chloride test is positive, meaning above 60 millimoles per liter, repeat the test to confirm the result. If the second sweat chloride test is also positive, you can diagnose cystic fibrosis without genetic testing.

Alright, now let’s move on and discuss treatment! Medical management of patients with cystic fibrosis includes identifying and preventing respiratory infection, providing nutritional support, treating complications, surveillance, and genetic counseling.

The cornerstone of management is airway clearance therapy, so you should provide it at least once daily. Chest physiotherapy techniques include manual chest percussion and postural drainage; or in older children, high-frequency chest wall oscillation devices like vests. Additionally, you can use nebulized hypertonic saline or rhDNase to reduce the viscosity of respiratory secretions and improve airway clearance.

As far as respiratory infections go, you should promptly identify and treat any pulmonary exacerbations or infections. Consider adding nebulized tobramycin if cultures grow Pseudomonas, and don’t forget routine immunizations, as well as pneumococcal and influenza vaccines if the patient meets age criteria. Finally, you can consider adding daily azithromycin, to reduce chronic airway inflammation.

Now let’s discuss nutritional support for children with CF, which is often necessary due to pancreatic exocrine insufficiency and malabsorption. First, you’ll need to monitor your patient’s growth closely and ensure that caloric intake is sufficient to maintain an adequate weight-for-age or body mass index. If your patient has pancreatic insufficiency, supplement with pancreatic enzyme replacement therapy and fat-soluble vitamins, including vitamins A, D, E, and K. Finally, provide oral salt supplementation for all children under 2 years of age and for those exposed to warm climates, to reduce sodium and chloride losses through sweat.

Next, individuals with CF often develop complications that require additional treatment. For example, if your patient has CF-related diabetes, they may require treatment with insulin, and if they have cholestasis from CF-related liver disease, you should consider ursodiol. Finally, some patients with CF who have pansinusitis or nasal polyposis can use nasal saline irrigation to improve mucus clearance and nasal corticosteroids to decrease inflammation. In severe cases, consider consulting your surgery team for possible polypectomy.

All patients with CF should have regular surveillance, including a baseline chest X-ray, and follow-up X-rays every other year to monitor disease progression. Also, be sure to follow quarterly oropharyngeal cultures to monitor for respiratory pathogens, such as MRSA, Pseudomonas, Burkholderia cepacia, Aspergillus fumigatus, and Mycobacterium avium complex. In addition, order annual liver function tests and an oral glucose tolerance test to screen for CF-related liver disease and diabetes.