Integrating Primary Care into the Management of Cystic Fibrosis

Abstract

Over the last 50 years, cystic fibrosis has radically transformed from a fatal disease of infancy to a chronic disease of adulthood. By 2025 it is estimated that 70% of individuals with cystic fibrosis (iwCF) will be cared for in adult clinics. We believe the role of a dedicated primary care provider (PCP) for preventative care will be crucial for the longevity of iwCF. There are various models for incorporating primary care medicine into CF management, but no universally accepted standard exists. Ideally, the PCP and pulmonologist practice in a patientcentered medical home, given the growing evidence that these care models are associated with improved quality-of-life measures, mental health, and disease-specific outcomes. To improve engagement with primary care in CF, there needs to be a shift in education at the undergraduate medical education and provider training levels. Increasing the knowledge of CF-related illness is vital in fostering a close relationship between the PCP and their patient. To meet this need, primary care doctors will need tools and practical experiences in managing this rare condition. This can start being addressed by providing ample opportunities for the inclusion of PCPs into subspecialty clinics and through engagement with community providers through readily available didactics, seminars, and open lines of communication. As PCPs and CF clinicians, we feel that shifting the domain of preventative care to the expertise of a primary care physician will allow for a more CF-specific focus in subspecialty clinics and help prevent these vital health maintenance tasks from being overlooked, altogether advancing the health and well-being of iwCF.

Introduction

Over the last 50 years, cystic fibrosis (CF) has radically transformed from a fatal disease of infancy to a chronic disease of adulthood, primarily through advancement in targeted therapeutics. ¹ Individuals with CF (iwCF) in developed countries can expect to live well into their fifth decade. ¹ Many pursue higher education and various professions and also raise families. By 2025 it is estimated that 70% of the roughly 40 000 iwCF in the United States will be cared for by adult providers.^2,3 As clinicians with backgrounds in primary care and pulmonary medicine who care for iwCF, we anticipate that there will be an enhanced need for primary care physician (PCP) engagement, particularly regarding the current and evolving preventative care measures needed for this unique population. This commentary will provide relevant background on diagnosing and treating cystic fibrosis, current preventative screening measures, and potential models for delivering primary care to this group.

Background

CF is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane receptor (CFTR) gene. To date, nearly 2000 mutations of the CFTR gene have been identified, the most common of which is F508del (p.Phe508del), which is present in at least one allele in roughly 85% of iwCF. ⁴ mutations impact the encoded CFTR protein in various ways and are classified into 6 categories of mutations characterized by absent, reduced, or dysfunctional amounts of an epithelial transmembrane protein responsible for chloride and bicarbonate exchange. ⁵

CF is fundamentally a disease of impaired mucus clearance. In childhood, the most notable symptoms are recurrent sinus and pulmonary infections and impaired exocrine pancreatic function from blocked pancreatic ducts, leading to malnutrition and steatosis. During adolescence and adulthood, a progressive decline in lung function often occurs due to recurrent pulmonary infections. In addition, individuals can develop endocrine pancreatic dysfunction leading to the destruction of islet cells, causing impaired insulin secretion and insulin resistance, referred to as CF-related diabetes.

Screening and Diagnosis

Primary care providers already play a critical role in diagnosing CF, which can occur at any stage of life. Most iwCF are diagnosed through newborn screening (NBS), performed routinely in the United States since 2010. ⁶ If the newborn screen is positive, the infant should be referred to a CF specialty clinic to undergo sweat chloride skin testing. A sweat chloride value >60 mmol/L is diagnostic and considered the gold standard for diagnosis at all ages. This multistep screening algorithm has a sensitivity approaching 95%. ⁷ A recent study found that roughly 65% of Canadian PCPs have reported notifying a family of a positive NBS and report they place significant importance on their involvement in disclosing these results but have moderately low confidence in doing so. ⁸ This highlights the need for more effective education strategies and support structures for primary providers surrounding CF.

Treatment

The treatment of CF has dramatically changed over the last 2 decades and is the primary driver for improved survival. The main pillars of treatment currently focus on (1) thinning of mucus in the respiratory tract (with the use of nebulized hypertonic saline and dornase alpha), (2) clearance of mucus from the airway (via chest physiotherapy using vibratory and oscillatory devices, manual maneuvers, huff cough, and other techniques), (3) aggressive treatment of pulmonary infections especially from pseudomonas and staphylococcus aureus (including suppressive treatment with nebulized or inhaled antibiotics for pseudomonas), (4) restoration of CFTR protein function through oral therapies, commonly referred to as modulators, (5) the restoration of impaired exocrine pancreatic function through the use of supplemental pancreatic enzymes (pancrelipase or CREON), and (6) high-fat and high-calorie diets to prevent malnutrition. ¹

In 2019, the American Food and Drug Administration approved a combination medication containing 3 modulators: elexacaftor, ivacaftor, and tezacaftor (Trikafta). This medication is approved for nearly 90% of CF mutations and significantly improves CFTR function in these groups. So far, it has been shown to improve lung function, reduce the number of pulmonary exacerbations, increase body mass index, and improve quality of life. ⁹

Primary and Preventative Care in CF

Primary care providers have reported low comfort with caring for iwCF. ¹⁰ In the pediatric literature, there is evidence that in more rural areas or regions without a multidisciplinary CF clinic, PCPs are more likely to refer patients to pulmonologists, even for non-CF-related care. This has been shown to overburden the subspecialty clinics and make it difficult for patients to access their physicians for acute care needs. ¹¹ A similar phenomenon is observed among adults needing care with other chronic medical conditions, particularly those with lower incomes or limited access to healthcare. ¹² In a 2008 study of PCPs, half the internists surveyed felt primary care for individuals with child-onset chronic illness should be delegated to an adult subspecialist. ¹⁰ This may explain, in part, our anecdotal experience of patients preferentially seeking out non-CF-related medical care needs like cancer screening and non-CF-related disease management within our CF specialty clinic, with some iwCF lacking a PCP altogether.

We believe the role of a dedicated PCP will be crucial for the continued progress in health and quality-of-life outcomes, particularly related to preventative care. Preventive maintenance by a PCP spans many domains, including but not limited to vaccinations, screenings for cancer, osteoporosis, sexually transmitted infections, depression, diabetes, atherosclerotic and cardiovascular disease, Hepatitis C, and Human Immunodeficiency Virus.

The CF Foundation currently requires annual or quarterly screening from accredited CF clinics for certain conditions like CF-related diabetes, osteoporosis, liver disease, mycobacterial disease, and allergic bronchopulmonary aspergillosis (ABPA); however, there are no requirements for most other age-specific preventive healthcare screening measures, which will become ever more pertinent to the longevity of iwCF. A PCP-led preventive care screening strategy can enhance compliance with guidelines while minimizing replication of effort, inconvenience, and cost. ¹³

Current and Future Screening and Preventative Care Measures

Here we outline standard screening and preventative care considerations in CF that would be ideal for shifting to the domain of a PCP. The PCP must be familiar with the need for annual diabetes screening done for non-diabetic iwCF with glucose tolerance tests rather than fasting glucose or hemoglobin A1C. Additionally, individuals with CFRD should undergo yearly screening for microvascular complications, as is done in the general population, through dilated retinal exams and urine albumin-to-creatinine ratios. ¹⁴

There is a 5 to 10-fold increased risk of colon cancer among iwCF compared to the general population. ¹⁵ Colon cancer screening for iwCF begins at age 40 with a colonoscopy. It is repeated every 5 years at a minimum. Those who have undergone solid organ transplantation may start screening earlier at the age of 30. ¹⁵

Osteoporosis risk is significantly higher in iwCF. Screening for osteoporosis should be undertaken using dual-energy x-ray absorptiometry (DEXA) once by age 18. Screening should continue every 1 to 5 years based on T and Z scores. Interestingly, screening rates for osteoporosis fall short even among CF programs. ¹⁶ Thus, it is crucial to have a comprehensive approach that is PCP driven to shore up gaps in routine care.

Newer concerns unique to older iwCF that are not routinely within the scope of a CF clinic include age-related preventative care, such as screening for elevated cholesterol, abdominal aortic aneurysm, gynecologic and breast cancers, and prostate cancer, among many others. A yearly visit with a PCP also provides the opportunity for counseling on various elements that may not be factored in at a subspecialty visit, such as in-depth family planning, particularly with the increased number of pregnancies in women with the use of triple-drug modulators. ¹⁷

Enhancing Primary Care Providers’ Role in CF

Comfort with caring for iwCF has been directly linked to the volume of patients cared for, outweighing other factors like access to ancillary services and subspecialists. ¹⁰ We believe that PCPs should be embedded into CF care teams. Several models for incorporating PCPs into the routine care of iwCF are already in use, but no universally accepted standard exists. Ideally, the PCP and pulmonologist practice together in a patient-centered medical home (PCMH) for both pediatric and adult patients. This model typically relies upon a general practitioner (pediatrician, internist, family medicine, or advanced practice provider) and pulmonologist leading multidisciplinary teams with appropriate subspecialists, providing both primary care and specialty services to patients. This model has yet to be explicitly studied in CF-related outcomes; however, some North American CF centers utilize a similar structure. There is growing evidence that these care models are associated with improved quality-of-life measures, mental health, and disease-specific outcomes like glycemic control in diabetes, cholesterol reduction in cardiovascular disease, and reduced hospitalizations in other chronic disease states. ¹⁸

The PCMH model is not feasible for every center or patient, especially those in more rural settings. Telemedicine can address this gap by facilitating interactions between patients and providers, PCPs, and specialty clinics. Within CF, telehealth visits have been shown to enhance access to care, adherence to therapies, detection of pulmonary exacerbations, and mental health. ¹⁹ Telemedicine may be well suited for PCPs in CF care and enhance lines of communication between practices. One example of implementing this is creating an annual visit that includes all patient care team members, including the PCP, in a virtual format. This would allow the patient and care team members to engage regardless of their distances and could be blended into the workflow of the PCP’s clinic schedule that day. This has not been explicitly studied in CF, but examples of similar and effective use of this technology to engage PCPs with specialty teams have demonstrated improved patient-centered outcomes, cost-effectiveness, and provider satisfaction in other chronic disease processes. ²⁰

Conclusion

The community of CF patients, providers, and researchers have pioneered novel management strategies that have prolonged the lives of many individuals with this disease. The models used in CF care have also had ripple effects in promoting improvements in the management strategies for other chronic childhood diseases. In our practice, we have seen growth in the burden of non-CF-related conditions like hypertension and obesity and an increased need for routine preventative screening as patients live longer. Anecdotally we find that many of our patients preferentially seek care at our specialty clinic, and some do not regularly engage with a PCP.

As we enter a new era of CF management, the role of primary care medicine will become increasingly relied upon to provide multimodal care to the aging population of iwCF. To meet this moment, PCPs will need tools and practical experiences in managing this rare condition. We advocate for including and recruiting PCPs into subspecialty clinics and through engagement with community providers through readily available didactics, seminars, and telemedicine opportunities. As PCPs and CF clinicians, we feel that sharing the domain of preventative care with the expertise of a PCP will provide improved health and well-being for older iwCF. To demonstrate that these efforts are practical and effective, we must closely monitor outcomes data and patient and provider perspectives related to real-world experiences and ongoing needs assessments.