41. Jahrgang Heft 09, September 2018

Cystic fibrosis: Basic science and epidemiology

Cystic fibrosis is the most common life-limiting genetic disease in the Caucasian population. The disease is caused by mutation in CFTR gene, located on the chromosome 7, which encodes a transmembrane chloride-channel and regulates water and anions transport. Failure or dysfunction of this channel results in a reduction of a chloride, water and bicarbonate flow and causes retention of body secretions. More than 2000 different mutations have been already identified and are usually divided in 6 different classes. Although the severity of this disease can be partly explained by mutation class and a residual rest function of the CFTR-channel (classes I to III result in a severe phenotype and classes IV to VI cause a mild disease), many other genetic and environmental protective factors can influence a course of the illness. A hallmark of the disease is retention of mucus leading to inflammation and chronic infection and to progressive destruction of lung tissue. Clinical symptoms of cystic fibrosis depend on age and on disease progression with malnutrition, failure to thrive and greasy stools being typical for infants and pulmonary symptoms developing in preschools and progressing into adulthood in older CF-patients. Pulmonary exacerbations and a severity of lung disease measured by lung function are the most important clinical outcome parameters, which help predict an occurrence of respiratory insufficiency. Many comorbidities of cystic fibrosis, including liver disease, diabetes, osteopenia and numerous complications, contribute to high burden of this severe disease. However, lung disease, with a development of respiratory failure, is the most important life-limiting issue for the majority of CF-patients.

Cystic fibrosis: Diagnostics

Cystic fibrosis is a systemic disease caused by mutation in a CFTR gene, which encodes a CFTR chloride channel, regulating anion and water transport. An early diagnosis of cystic fibrosis influences positively both somatic growth and lung function of young patients, two clinical parameters which have been shown to be important for future progression of the disease. Universal screening of newborn babies for cystic fibrosis was launched in Germany on 1 September 2016. Five of every 5000 screening tests yield findings requiring further evaluation and one test in 5 positive screened results ultimately leads to a diagnosis of cystic fibrosis. The gold standard for the confirmation of the CF diagnosis is a sweat test with measurement of chloride levels in sweat. If typical symptoms suggestive of cystic fibrosis are present, a confirmation diagnosis with a sweat test should be performed, despite of negative CF newborn-screening results. The sweat test should also be done in cases of azoospermia, bronchiectasis or polyposis nasi in adulthood, because symptoms of an atypical cystic fibrosis can also occur later in life.

Cystic fibrosis: Treatment

Therapy of cystic fibrosis should be started directly after the confirmation of the diagnosis, in the first weeks of life. The key therapy issues in infants and toddlers are: improvement of mucociliary clearance and treatment of malabsorption with pancreas enzymes and fat soluble vitamins. Later in life, treatment of respiratory exacerbations, comorbidities and extrapulmonary complications of cystic fibrosis are of major importance. Leading to respiratory failure the progressing pulmonary dysfunction is treated with oxygen and non-invasive ventilation, which can also be used as a bridging procedure for lung transplantation. For some years now, new causal therapies have been approved in Germany for a use in CF-patients with certain mutations. These new medications, CFTR-modulators, facilitate the trafficking of CFTR protein (correctors) to the cell surface or increase the activity of CFTR-channel function (potentiators). Several new substances, so called small molecules, focusing on restoring CFTR function are being developed and are currently tested in clinical trials.

Cystic fibrosis mother infected with a methicillin-resistant Staphylococcus aureus (MRSA)

A female cystic fibrosis-patient, infected with methicillin-resistant Staphylococcus aureus (MRSA), has underwent artificial insemination. The donor, her husband, carried cystic fibrosis transmembrane conductance regulator (CFTR) protein gene mutation. The pregnancy proceeded almost without any complications. The newborn baby inherited CF from its parents but was not infected with the MRSA. After birth, the mother suffered from a strong depression, showed a disturbed mother-child relationship originated from the anxiety that her baby could be infected with MRSA. Her treatment again MRSA didn’t get positive outcome. The mother-child relationship stabilized. Until now, one year after the birth, the child is not infected with MRSA.

Transdermal patches – risks and opportunities

The number of available drugs in transdermal application form is considerable and the prescription frequency increases. However, this not only harbors opportunities in therapy, but also risks as the results of a German patient survey in clinical practice show. Comprehensive patient information is essential. Checklists can help.