Managing cystic fibrosis in primary care
Dr Michael Lim, a senior consultant at the Paediatric Pulmonary and Sleep Division, National University Hospital, Singapore, speaks to Roshini Claire Anthony on the rare disease that is cystic fibrosis.
Cystic fibrosis (CF) is a multisystem autosomal recessive genetic condition that results in an accumulation of mucus in various organs. It is one of the most common life-limiting genetic conditions in the Western World, with an incidence of about 1 in 2,500 births among Caucasians. There is no detailed information on the prevalence of cystic fibrosis in Asia and available data is mostly based on case reports or case series, with an estimated prevalence in East Asia of around 1 in every 100,000–350,000 people.
More than 2,000 CF gene mutations have been identified. CF is inherited genetically and is caused by a gene defect on the long arm of chromosome 7. The gene defect codes for an abnormal protein known as the cystic fibrosis transmembrane regulating (CFTR) protein. This results in viscid secretions in tubular structures mainly within the lung, sinuses, liver, and pancreas.
CF is an uncommon disease in Singapore. There are a small number of local and foreign patients who have their condition managed at tertiary centres here. Nevertheless, GPs can play an important role in the management of patients with CF, as part of a shared-care model with specialist centres.
While CF is very uncommon in Singapore, it remains an important differential diagnosis for any patient presenting with a chronic wet cough that does not improve with time. In countries with predominant Caucasian populations, screening for CF after birth is routine, and most patients with CF are now diagnosed through newborn screening. CF newborn screening is not routine in Singapore due to the low incidence, although it is offered as a choice to families of babies with a higher chance of inheriting the disease. The diagnosis is confirmed by an investigation called a sweat test which either measures the concentration of chloride that is excreted in sweat, or the electrical conductivity of sweat.
Screening for CF in the newborn period allows for early diagnosis, often when the child is still asymptomatic. A heel prick test at 2–3 days of age is carried out, and the dried blood sample is tested for immunoreactive trypsinogen (IRT) levels. Those with an elevated IRT result are then tested for a panel of common CF mutations. Confirmation of CF diagnosis is then done by sweat testing. Early diagnosis of CF also allows for early intervention, and potential improvement in clinical outcomes in the long term.
It should be noted that CF mutations in Asians are not necessarily represented by common CF mutation panels offered by screening laboratories, so further genetic testing may be required to define the mutation. For example, the p.F508del mutation is the most common CF mutation, occurring in approximately 70 percent of Caucasian patients, but is uncommon amongst Asian CF patients.
As screening is done at around 2–3 days of life, the opportunity will lie with the paediatrician caring for the newborn to offer screening. However, among older patients, if the diagnosis is suspected clinically at the GP surgery, prompt referral to a specialist centre for review and sweat testing is crucial.
Due to its rarity, there is a lack of experience in diagnosing and managing patients with CF in primary care. Patients with a chronic wet cough or recurrent chest infections with no clear reason for the symptoms should have CF considered as a potential diagnosis. A referral to a tertiary paediatric centre for further review and sweat testing should be made to confirm or exclude the diagnosis.
The treatment of patients with CF requires a multidisciplinary approach. Patients with CF should always be managed in partnership with a specialist team right from the time of diagnosis and treatment should be individualized to each patient.
There is no cure for CF, but treatment is aimed at easing symptoms and reducing complications. Treatment goals include preventing and treating infections that occur in the lungs, carrying out airway clearance techniques to loosen and remove mucus from the lungs, providing adequate nutrition and pancreatic enzyme replacement therapy, treating and preventing intestinal blockage, and monitoring and treating the various complications that can arise from CF.
In the past, GPs have not been an established part of the multidisciplinary team managing patients with CF, due in part to a lack of clear opportunity for their involvement. Moreover, most GPs in Singapore will not encounter a single CF case in their career. However, for GPs who do encounter patients with CF, they can potentially play a crucial role in their patients’ management. The standard of care is for patients with CF to be assessed regularly (usually every 3 months) at specialist centres. Treatment burden is high for patients with CF due to the multisystemic nature of the disease, and adherence to therapy is a challenge. GPs can play a role in encouraging and monitoring treatment compliance. GPs can also make a significant impact by helping patients with CF maintain an adequate body mass index, and promoting good general health including exercise. GPs should also be aware of potential complications that patients with CF can present with, such as an acute pneumothorax presenting with breathlessness, so as not to merely attribute the presenting symptoms to an infective exacerbation.
As patients with CF now live longer, they share the same health risks as the general population. GPs remain a crucial point of medical contact for patients with CF in the community. GPs should continue to provide standard medical care to these patients, and ensure that routine immunizations are adhered to, with emphasis on pneumococcal and annual influenza vaccinations.
The main challenge for GPs in Singapore is a lack of experience with dealing with CF both due to the rarity of the condition as well as its primary management at tertiary centres. It is a complex medical condition with complications and challenges unique to this disease.
Because of its low incidence in Singapore, patients presenting with chronic cough or failure to thrive would not have CF as a main differential diagnosis, as there are other more common conditions to consider as potential diagnoses. If the suspicion of CF is raised, a prompt referral to a specialist centre is important for further work-up.
Managing CF-related complications
Patients with CF are prone to recurrent lung infections and exacerbations of pulmonary symptoms such as increased cough. Regular chest physiotherapy with muco-active treatments such as hypertonic saline nebulization and prophylactic antibiotics are important for patients with CF. Patients with advanced lung disease may require oxygen or non-invasive ventilation.
Patients with CF also suffer from nutritional deficiency. For example, many suffer from pancreatic insufficiency and require pancreatic enzyme supplementation to aid absorption. These patients require a high-fat, high-calorie diet. They are also prone to constipation and intestinal obstruction. Patients with CF are also at risk of CF-related liver disease or diabetes, osteopenia, and osteoporosis. Most male patients with CF are infertile. Patients with CF and their families may need psychological support as they grapple with a chronic medical condition with many potential complications.
A common misconception is that CF is limited to the lungs. It is a multisystemic disease, and other organs in the body, such as the pancreas and liver, can also be affected. It can also lead to diabetes and infertility in men. CF can present differently at different ages, such as meconium ileus in the newborn, failure to thrive, and recurrent pneumonia in the older child.
Because CF most commonly affects Caucasians, there is also the misconception that it only affects Caucasians. In fact, all races can be carriers of the CF gene, and therefore inherit the condition. For example, in Singapore, we have patients with CF of Chinese, Malay, and Indian descent.
CF is a complex multi-organ disease which requires care from a specialist multidisciplinary team. GPs can play an important role in the ongoing management of patients with CF in the community, in partnership with specialist centres managing this condition. Any suspicion of CF in patients with chronic cough or recurrent chest infections, or failure to thrive, should prompt an early referral to a specialist centre. As CF is a genetic condition, one cannot prevent the condition. However, early diagnosis and intervention can improve long-term outcomes and improve life expectancy.