As a 40-year-old who lives with cystic fibrosis (CF), Zachary Schulz, PhD, EdS, MPH, is said to be among the reputed “last generation” of patients — those born before the advent of drugs that target the disease’s underlying genetic defect. The moniker has led him to wonder if it’s become just as difficult for clinicians to characterize this patient cohort as it has been to help people survive the challenging diagnosis. “It’s nonsense. We’re supposed to be dead,” said Schulz, a senior lecturer of history at Auburn University, Auburn, Alabama, who teaches health humanities and holds a master’s in public health, which lends to his unique perspective as a patient and student of the chronic condition. “We’re discovering that the pediatric lung disease we were born with is now becoming this ‘weird’ disease where we don’t know what’s going on anymore. We’re adults now. Where do we go from here?”
According to pulmonologists and other clinicians who help patients with CF to manage their conditions, the future for the estimated 2500 patients born with CF each year will likely still be dependent on reducing the severity of commonly acquired CF-related infections and ultimately treating them when they are infected.
Infection Control and Management
The threat of acute and chronic infections is essentially unavoidable for those who live with CF, but there are strategies for reducing severity for all age groups. As a baseline, the Cystic Fibrosis Foundation (CFF) recommends patients receive respiratory cultures quarterly, although more can be necessary during exacerbations or other signs of changing health status.
A variety of oral, inhaled, and intravenous antibiotics can be considered, but not all antibiotics are created equal, said Peter Polos, MD, PhD, a board-certified pulmonologist and medical advisor at Lindus Health, a full-service, end-to-end clinical trial provider for life science companies based in Boston.
“Any treatment decision should be driven by severity, patient history, and pathogen,” he explained. For example, someone with an initial presentation of mild symptoms could warrant an oral antibiotic with a bronchodilator to keep the airways open so that mucus doesn’t become too thick and escalate a productive environment for bacteria.
Many clinicians will also use an antibiotic gel so that pathogens are not inhaled to set up infection, said Polos. “And then we’re doing what these patients are used to — chest physiotherapy and hydration,” he said. “Some patients will also do postural therapy if they’re trying to drain secretions out of their lungs. There’s a variety of techniques that are patient specific and clinical setting specific.”
At Phoenix Children’s Hospital, Pheonix, Michelle M. Ratkiewicz, DO, pulmonology specialist, said that when using cultures as a guide, the tendency is to turn to antibiotics more quickly, especially for pediatric patients. “If we know that the patient typically grows methicillin-resistant Staphylococcus aureus [MRSA] or Pseudomonas aeruginosa, our treatment is going to be dictated by those chronic cultures,” she said. “We might choose a different antibiotic than you might choose for a standard community-acquired infection. And our duration of treatment tends to be slightly longer, particularly in the setting of bronchiectasis or lower-airway damage. We also have a lower threshold to treat CF with antibiotics if symptoms following a viral infection are lasting longer, are more severe, or fall outside the usual course of a viral infection. We may suspect that bacterial infection is more active.”
In the setting of infection, Ratkiewicz said she will increase the intensity of treatment. “Typically, we’ll do a more frequent therapy vest, or if the patient uses a positive expiratory pressure device, we always recommend doing extra in the setting of an illness,” she said. “We also will sometimes augment aerosol treatments. Some patients use dornase alfa or hypertonic saline all the time. Some patients just use that when they’re sick or use it more frequently when they’re sick. But we always step up the frequency and intensity of their airway clearance beyond what they do at baseline in the setting of a viral infection or a bacterial infection. And that should be true for adults and pediatric patients.”
Attempting to dodge infections can invoke generalized tactics that are promoted to any segment of the public, with advice including hand hygiene, routine vaccinations, avoidance of sick contacts, and not sharing personal items. However, there are approaches to better protect the particularly susceptible CF population within these parameters. “Some important ways to prevent infections are to use contact precautions, including gowns and gloves, within medical settings,” said Anthony J. Fischer MD, PhD, a pulmonologist at University of Iowa Health Care. “This can protect people from acquiring antibiotic-resistant microbes that they are most prone to. Another important step is to ensure nebulizers and other respiratory equipment is properly sanitized daily.”
Polos noted there are points of emphasis to make on infections control. “Often, companies have suggested regimens for how to clean equipment that are specific for the device,” he explained. “But you can accomplish infection control by the basics of soapy warm water and then rinsing the equipment well and letting it dry properly.”
As far as infection control for patients who are washing their hands with soap and water, “we generally say 20-30 seconds of good scrubbing of the back and the front of your hands, as well as between your fingers, and rinsing with warm water. If they’re using hand sanitizers, use those that give about 60 percent alcohol.”
Ratkiewicz also recommends that patients with CF refrain from certain indoor and outdoor environmental triggers and activities that can lead to more frequent exposure to bacteria, such as hot tubs, stagnant bodies of water, humidifiers, and gardening due to an abundance of soil and water. “Fortunately, chlorinated swimming pools and the ocean are safe,” she said.
Maintaining Multidisciplinary Best Practices
With the benefit of potentially initiating CF transmembrane conductance regulator modulator therapy earlier in a patient’s treatment continuum, many providers are not seeing a severity of lung disease that had become expected previously. Still, there are necessary precautions that are best served through a multidisciplinary care team.
“All people with CF should receive routine care at a center accredited by the CFF,” Ratkiewicz suggested. “Patients are more likely to have comorbidities such as diabetes, osteoporosis, and significant sinus disease that may require additional therapies or subspecialty involvement.” Ratkiewicz’s team includes physicians, nurse practitioners, dietitians, respiratory therapists, social workers, pharmacists, physical therapists, and psychologists. “We’re diligent about adhering to the clinical care guidelines by the CFF that dictate frequency of screening tests, monitoring lung function, and surveillance cultures. People with CF really shouldn’t be getting care at a general pulmonary clinic or a place that doesn’t have experience with CF,” said Ratkiewicz.
Inside her clinic, Ratkiewicz follows strict protocol that requires patients to not share elevators or restrooms and to be seen without spending time in a waiting room. Everyone also has the option of wearing purple CF identity badges that help others to distance. All rooms are disinfected between visits, with extra consideration given to multi-use equipment. Ratkiewicz also urges that patients with CF not share classrooms, day camps, or sports teams, except for siblings. She said it’s important to be increasingly mindful of these types of precautions to reduce the potential of complacency as modalities improve.
“Some people refer to CF as an ‘invisible disease’ because patients might outwardly appear healthy, but they really need more attention,” she said. “There’s less significant lung disease today, but that is not universal. We see adults who are healthy and stable, and pediatrics who have as much lung disease as some adults might have. CF is not ‘one-size-fits-all.’”
Schulz can attest to that. Born with the most common Delta F508 mutation, he began taking a modulator in 2015 and has always displayed low expressivity. He does carry pulmonary scar damage from an early-age infection and has colonized MRSA, but his cardiovascular status is excellent, allowing for regular bike rides.“My capacity for spirometry testing is well within the 100th-110th percentiles,” he said. “I feel healthier than I think most do. I don’t have joint issues. My resting heart rate is 56. My blood pressure is about 114 over 64. I don’t produce a lot of sputum anymore with the modulator. My main display of cystic fibrosis is a lack of pancreatic enzymes.”
This all ranks in stark contrast to that of his older brother Eric, who was born with the same mutation but passed away several years ago. “Hewas a standard case,” said Schulz. “Constant exacerbations. Nebulizer tents that weren’t good for mold growth. Heavy steroid use by the end of his life to control inflammation. Lack of weight gain. We were involved in studies while he was alive on how siblings with the same mutation could have significant differences in expressivity.”
Potential of Evolving Care
There’s enlightening research ongoing to potentially improve future CF management, said Ratkiewicz. Notable examples include compounds to help disrupt biofilm and studies to help better detect bacterial infections through exhaled breath. “Many patients don’t produce sputum because they’re so much healthier on modulator therapy,” she said. “Using detecting compounds and exhaled breath that could detect viral or bacterial infections could be very helpful in identifying infections early and allowing us to treat them more effectively. Clustered regularly interspaced short palindromic repeats and mRNA technologies are also being explored as potential treatment options, and studies are underway on bacteriophage therapy, specialized viral particles that replicate inside bacteria and kill bacteria in a specific way.”
Current literature shows no routine use of biologics for CF, according to Ratkiewicz, with the most common use being for those with poorly controlled asthma or allergic bronchopulmonary aspergillosis, an allergic response to Aspergillus in the airways. “But it’s an interesting concept,” she said. She’s also encouraged by an increased rate of parents choosing to deliver babies born with CF since the more widespread use of modulator therapy beginning in 2019. “And that is because people are living longer,” she said. “We’re seeing many adults living very productive and healthy lives. More people are pursuing higher education, working full time, and we really expect that to continue to get better.”
Schulz, Ratkiewicz, Fischer, and Polos reported no relevant financial relationships.