Pulmonology Coding Alert

Researchers are concerned about causing further harm.

When app developers discover a security flaw, they alter the code and deliver an update to fix the problem on your mobile device. Researchers are using a similar idea to find a cure for cystic fibrosis (CF).

Read on to learn how corrected DNA may be the key to curing cystic fibrosis.

Gene Therapy is a Tool for Tackling CF

Patients suffering from cystic fibrosis, coded to E84.- (Cystic fibrosis), may soon experience relief from the disorder. Providers are using gene therapy to place a correct version of the cystic fibrosis transmembrane conductance regulator (CFTR) gene inside the patient’s body, so it can provide the blueprint for cells to make normal CFTR proteins. The mutated genes will still be in the patient’s body, but the corrected version is what the body’s cells will look to when producing the proteins.

“It’s a great time to be optimistic. This is a new technology that’s showing promise, not just for cystic fibrosis, but all other genetic diseases and CF is going to lead the charge once again,” says Mitchell Drumm, PhD, vice chair of Translational Research, director of The Research Institute for Children’s Health, Connie and Jim Brown Professor in Cystic Fibrosis Research, and professor in the Department of Genetics and Genome Sciences at Case Western Reserve University in Cleveland, Ohio.

The Cystic Fibrosis Foundation lists three different versions of gene therapy currently tested by researchers:

• Integrating gene therapy: This method involves using a piece of DNA that holds the correct version of the CFTR gene. Providers deliver the DNA into the patient’s cells,where the new CFTR gene becomes a permanent fixture of the person’s genome.
• Non-integrating gene therapy: Similar to integrating gene therapy, non-integrating gene therapy contains a piece of DNA with the correct CFTR gene. Conversely, the new DNA stays separated from the patient’s genome. The patient’s cells can utilize the correct version of the CFTR gene to produce normal CFTR proteins, but the gene doesn’t disturb the rest of the genome.
• RNA therapy: Ribonucleic acid (RNA) is essentially a working copy of your body’s DNA that cells use to build proteins. With RNA therapy, scientists give the patient’s cells the RNA with the correct CFTR gene directly. These corrected working copies help the body produce normal CFTR proteins. Plus, the RNA doesn’t disrupt the patient’s genome.

No concrete solution: Drumm indicates many types of mutations don’t make any protein, so there isn’t a single answer as to what therapy would work best. “In many cases, it is a single A, T, C, or G that is changed and may be amenable to the various gene editing strategies; but in others, it may involve thousands of base pairs of the gene and the technologies to circumvent or repair those will be quite different,” Drumm says.

Find out how Gene Therapy Administration Works

Patients who suffer from diminished lung function due to cystic fibrosis, such as E84.0 (Cystic fibrosis with pulmonary manifestations), could experience significant relief from gene therapy. Since the lungs are one of the organs severely affected by cystic fibrosis, researchers are focusing their efforts on the task of delivering gene therapy to lung cells. This is proving to be an immense challenge due to the lungs’ natural defenses, which are mucus and the cell membrane.

If the gene-corrected DNA can get through the thick mucus layer of a CF patient’s lung, it will still need to enter through the cell’s protective membrane. For DNA to move through the cell membrane, the genes will require a special coating.

Two methods researchers are testing to introduce correct DNA into cells are chemical coatings and viruses. DNA packaged inside a lipid coating forms a liposome, which can then fuse with the cell’s membrane to allow the DNA to transfer into the cell. Scientists also are testing whether viruses are a viable option. This method involves packaging DNA inside a protein coating to allow the DNA to enter the patient’s cells. However, the viral components can cause inflammation, which could cause the patient to suffer more instead of providing relief.

Would Gene Therapy Change E/M Visits?

Scenario: A 12-year-old patient visits your pulmonology practice with chronic sinus and lung infections. They’re experiencing shortness of breath, a persistent cough with thick sputum, and wheezing when breathing. The pulmonologist orders 81223 (CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; full gene sequence), which reveals the patient has a mutation of the CFTR gene, so the physician diagnoses them with CF with pulmonary manifestations due to the thick mucus.

In this scenario, you’ll assign E84.0 to code the patient’s diagnosis. The physician may additionally order antibiotics, a steroid inhaler, nonsteroid anti-inflammatory drugs (NSAIDs), or a bronchodilator as treatment depending on the severity of the patient’s condition.

But what types of CPT^® codes would you assign for the procedure, if any of the gene therapies mentioned above become viable options in future? If a gene therapy option is in the Food and Drug Administration’s (FDA) approval process, the procedure will receive a Category III CPT^® code. Category III CPT^® codes are new and emerging codes assigned by the American Medical Association (AMA) for tracking purposes, and contain four numerical digits followed by a T. In that scenario, you’ll assign the appropriate Category III code depending on the gene therapy treatment ordered by the physician.

Additionally, as effective as the different therapies mentioned could be in treating CF, evaluation and management (E/M) visits will still need to occur. “It is hard to tell if the E/M visits or their frequency would change in the future. Physicians would still need to assess the patients’ condition despite undergoing gene therapy,” says Carol Pohlig, BSN, RN, CPC, manager, Coding & Education in the Department of Medicine at the Hospital of the University of Pennsylvania in Philadelphia. CF can cause severe organ damage and scarring in patients, and gene therapy can’t fix permanent harm that occurred before treatment. “Patients who have sustained lung damage would still need to be monitored,” Pohlig says.

Calculate the Risk of Complications

One of the biggest hurdles to implementing gene therapy in CF patients is “optimizing the editing process and making sure we do no damage,” Drumm says. Researchers can repair several mutations with different strategies with cells grown in a dish, but to fix enough cells in an entire person? The efficiencies just aren’t there yet.

Safety is another component researchers are coming to terms with. “There is always the possibility for what we call ‘off-target’ effects, where we end up damaging a person’s DNA at an unintended site and causing problems, such as cancer. This looks to be less and less of an issue as the technologies progress and evolve, but it is always something we need to keep in mind,” Drumm says.