Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

This week’s study is…

Case report: Three adult brothers with cystic fibrosis (delF508-delF508) maintain unusually preserved clinical profile in the absence of standard CF care

We previously published about this research in a story titled “The Unusual Clinical Profile of Three Brothers With Cystic Fibrosis Warrants A New Look at Standard CF Care” which can be found here. The study was originally published in the scientific research journal Respiratory Medicine Case Reports. You can view the full text of the study here.

What Happened?

This case study evaluated the condition of three brothers that were born with the rare disease cystic fibrosis. This disease causes a number of systemic symptoms, but the most defining characteristic of the disease is a decline in lung function, often triggered by persistent infections. This decline can be severe and often shortens the patient’s life considerably. However, these three brothers have attained early adulthood and, while receiving some treatment, have remained in remarkably stable condition compared to the average patient.

These brothers carry the most common form of the disease that is linked to the delF508 mutation. These brothers do not follow standard treatment guidelines for the disorder and have never attended a CF clinic. The only bacteria that the brother culture is Staphylococcus aureus, and the strain is sensitive to methicillin. The brothers are also homozygous for the delF508 mutation, which normally means that they would be expected to experience more serious disease and a more drastic decline in lung function. 

The first brother was 23 years old at the time of the study and was diagnosed with the disease at nine months old. Only a year later, his parents opted out of standard CF care. Since then, his only treatment was with prescription pancreatic enzymes (CREON 5/6) and he takes less than half the minimum suggested for his weight. His only sign of the disease is digital clubbing, and he played ice hockey actively growing up.

Brother two is 21 years old and was diagnosed at two weeks old; he never visited a CF clinic. He does not display digital clubbing and maintains a similar treatment regimen to the first brother. He has never received treatment with antibiotics. When sick with a respiratory virus, he often experiences a cough lasting longer than his other siblings, but it still resolves. He was an active athlete as well.

Brother three is 18 years old, was also diagnosed at two weeks, and also has never attended a CF clinic. He also maintains an identical CREON 5/6 regimen as his siblings. Much like the others, he also participated in athletics growing up and has never needed antibiotics.

It should be noted that the treatment regimen for the brothers is a bit more extensive than those noted above, but the other options are all well outside standard CF regimens and include a large number of nutritional supplements and vitamins.

About Cystic Fibrosis 

Cystic fibrosis is a type of genetic disorder which can have impacts throughout the body, but it is most characterized by the build-up of abnormally thick, sticky mucus in the lungs. This mucus becomes a fertile breeding ground and habitat for potentially infectious bacteria. Many patients must take antibiotics for much of their lives. This disorder is caused by mutations of the CFTR gene. Symptoms of cystic fibrosis include progressive decline in lung function, lung and sinus infections, coughing up mucus, fatty stool, poor growth, infertility in males, clubbed digits, and digestive problems. Treatment includes antibiotics and medications or procedures intended to maintain lung function. More useful treatments for the disorder have been introduced in recent years. Lung transplant is an option when lung function declines severely. Life expectancy ranges into the 40s and 50s with good care. To learn more about cystic fibrosis, click here.

Why Does it Matter?

The condition of these three brothers completely flies in the face of conventional wisdom and research surrounding cystic fibrosis. The average scientist would expect them to be in very poor shape considering how little of the recommended treatment they actually use. Their state is even more remarkable because they should have one of the most severe variants of the disorder.

The scientists on this report have proposed several theories as to why they haven’t seen normal progression:

1. They have mostly avoided the setting of the CF clinic. The act of visiting an in-person clinic increases a patient’s exposure to potential infections; a recent study revealed that Pseudomonas infection rates are higher in patients visiting in-person clinics versus those using telemedicine. This could have been a factor in early life, when infection controls were more lax compared to the COVID era.
2. The brothers may have benefitted from little to no use of antibiotics, despite the fact that they are normally a cornerstone of treatment. Antibiotics do not often discriminate and can destroy beneficial microbes such as those that populate the gut microbiome, which is important for immune system function. Antibiotic use can also promote the propagation of resistant bacterial strains. Preserving the gut microbiome could have been a major factor.
3. Other common cystic fibrosis drugs, like bronchodilators, were also avoided; these can bring down delF508 CFTR activation. They also avoided DNase, which has been linked to increased neutrophil elastase. They were also mostly not treated with chest percussive therapy (CPT), an approach that causes a large treatment burden and has limited benefit.
4. The brother’s regimen also included glutathione, which is deficient in CF and other respiratory illnesses. This supplementation in combination with their total regimen could have had a major impact on the brothers’ symptoms and progression. Exclusive breastfeeding could have also had a beneficial impact.
5. These brothers may have benefitted from the presence of modifier alleles that could have reduced the severity of their symptoms. So far a full genetic analysis of the brothers has not been performed.

Overall, the options for treatment in cystic fibrosis have improved greatly in recent years. However, this case study shines light on an alternative approach that has succeeded admirably so far. These cases indicate that the best approaches for treating cystic fibrosis aren’t so clear-cut after all.