Cystic fibrosis and primary ciliary dyskinesia: Clinical sciences

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Introduction0:00–1:09

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.

Unstable patient1:09–1:40

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.

Stable patient1:40–1:58

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!

Cystic Fibrosis1:58–3:45

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.

Cystic Fibrosis - diagnosis3:45–4:56

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!

Cystic Fibrosis - treatment4:56–8:28

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.Finally, be sure to offer genetic counseling to your patient and their family members.Before we move on, here’s a clinical pearl!
There are now CFTR modulators, which represent a true game changer for the treatment of CF. These medications can improve production and function of the defective CFTR protein.
But here’s the catch! Since there are various mutation possibilities, the first step is to obtain genetic testing to see if the patient has a responsive mutation that qualifies for this agent.Aright, now that we are done with cystic fibrosis, let’s switch gears and discuss primary ciliary dyskinesia.

Primary Ciliary Dyskinesia8:28–10:08

Even though CF and PCD share some similar clinical features, there are a few distinct manifestations that set PCD apart!
In the immediate newborn period, infants with PCD may develop unexplained respiratory distress, whereas older infants and children typically report a chronic productive cough and nasal congestion.
Most patients also experience chronic sinusitis and respiratory infections, as well as recurrent acute otitis media with or without hearing loss.
Physical exam findings can reveal nasal polyps, digital clubbing, and sometimes, middle ear effusions are visible. Don’t be alarmed if you hear heart sounds in the right hemithorax, or if you palpate the liver on the left side!
These findings indicate situs inversus, which is a laterality defect. Here’s a high-yield fact!
Half of patients with PCD also have a condition called Kartagener syndrome, which consists of the triad of pansinusitis, bronchiectasis, and situs inversus.
Also, similarly to CF, individuals with PCD have an increased risk of infertility, but in this case, the mechanism is different; biologically male patients with PCD have immotile sperm, while biologically female patients have abnormal ciliary motion involving both the fallopian tubes and endometrium, which in turn leads to impaired transportation and implantation of the embryo.
Alright, at this point, you should suspect PCD, so your next step is to confirm or rule out the diagnosis with testing. As an initial step, assess your patient’s ability to perform nasal nitric oxide testing.If capable, proceed with the testing and if the result is normal or elevated, PCD is unlikely, so you should consider alternative diagnoses.

Primary Ciliary Dyskinesia - diagnosis10:08–11:24

However, if nasal nitric oxide concentrations are low, move on to confirmatory testing, which can involve either nasociliary brushing or biopsy for electron microscopy or video microscopy.
Alternatively, you can order extended gene panel testing. Similarly, if your patient is unable to complete nasal nitric oxide testing or if testing is unavailable, again, proceed with confirmatory testing.Now, if electron microscopy reveals ultrastructural ciliary defects, video microscopy shows an abnormal ciliary waveform, or genetic testing identifies mutations in PCD-associated genes, any one of these findings confirms the diagnosis of PCD.
Alright, let’s move on to treatment, which is focused on the management of respiratory complications. Just like for CF, airway clearance therapy is the hallmark of PCD management, which primarily relies on chest physiotherapy and regular physical exercise.

Primary Ciliary Dyskinesia - treatment11:24–12:54

You can also consider nebulized hypertonic saline or rhDNase to reduce the viscosity of respiratory secretions and improve airway clearance.As far as respiratory infections go, you’ll need to promptly identify and treat any respiratory infections.
These are most commonly caused by pathogens like Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae; in some cases, you might see infection with Pseudomonas.
As a preventative measure, make sure your patient receives all routine childhood immunizations, as well as pneumococcal and annual influenza vaccines, and advise them to avoid passive and active tobacco smoke exposure.
Next, if your patient has recurrent otitis media, consult your surgery team for possible pressure equalization tube placement.For routine surveillance, annually, order a high-resolution CT of the chest to monitor for the development of bronchiectasis.
Also order regular sputum cultures to monitor your patient’s respiratory pathogens and guide antibiotic therapy when needed.Finally, be sure to offer genetic counseling to your patient and their family members.Alright, as a quick recap… When a patient presents with a chief concern suggesting CF or PCD, review the details from the history and physical examination.

Review12:54–14:07

If you suspect CF, order a sweat chloride test or genetic testing. Once you confirm the diagnosis proceed with management, which primarily relies on regular airway clearance therapy, tailored antibiotics as needed, immunizations, and anti-inflammatory medications.
Also, provide nutritional support, including pancreatic enzymes, fat-soluble vitamins, and salt supplementation; and don’t forget to treat complications like diabetes and liver disease.
On the flip side, if you suspect PCD, perform nasal nitric oxide screening and confirm the diagnosis with a nasociliary specimen or genetic testing.
Once you confirm PCD, treatment is primarily based on regular airway clearance therapy, tailored antibiotics as needed, and immunizations.
Finally, in both CF and PCD patients, provide routine surveillance and genetic counseling.
Cystic fibrosis and primary ciliary dyskinesia | Osmosis