The earliest references to Cystic Fibrosis (CF) can be dated back as far as the 17th century when European folklore pronounced, “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die”. At that time, it was widely believed that an infant with a salty brow was cursed by witches, and they would likely die soon. Despite this early reference, CF has remained relatively poorly understood until quite recently.

CF was not recognised as a specific disease entity until 1938 when it was described in literature as “cystic fibrosis of the pancreas” by an American pathologist after many careful autopsy studies of malnourished infants. Ten years later, during an extreme heatwave, a paediatrician noticed an excess of sodium and chloride in the sweat of infants with CF. This discovery led to the development of the sweat test for diagnosis in 1959.

Genetic pathologist Dr Anja Ravine explains that the sweat test remains an important diagnostic or verifying test for CF today, although detection of a pathogenic CFTR variant within each of the two gene alleles now often serves the same purpose.

“CF is a recessively inherited genetic condition that causes salty and thickened secretions. In infants and children, it is these thickened, salty secretions in the pancreas, lungs, and skin sweat glands, which are most noticeable clinically. Long before CF was properly identified or understood, physicians knew that salty skin in a baby was a sign of serious illness with a poor outcome. Even now, often the first CF symptom parents notice is a salty taste when they kiss their baby. We know now that this is because the faulty gene responsible for CF is important for removing salt from cells, and people with CF also tend to have two to five times the normal amount of salt in their sweat.

“Developed over 60 years ago, the sweat test is an important diagnostic test for CF. Performed by a trained technician, the test measures the concentration of chloride in the sweat and can be done for anyone older than 48 hours. There are no needles involved so the test is painless and lasts less than one hour. Once the sweat has been collected, the sample is evaluated in an experienced and appropriately credentialled laboratory,” said Dr Ravine.

In the 1950s, it was recognised that early diagnosis for CF resulted in better patient outcomes. However, at that stage, there was no newborn screening (NBS) test for CF and clinical diagnosis often occurred late when children were in poor physical health.

“In 1979 New Zealand scientists developed a test for CF which measures immunoreactive trypsin (IRT) in dried blood spots. This was followed by the first nationwide NBS program for CF which began in New Zealand in 1981. NBS screening was also introduced in Australia in NSW 1981, with all states and territories screening for the condition by 1999. The first improvement to the screening test was made in 1989 when it was found that CF was caused by inactivating gene variants within the CFTR gene. A more comprehensive massively parallel sequencing-based approach was later introduced, which now detects many dozens of known severe-disease causing variants across the gene.

“Like all other NBS blood spot tests, CF NBS is completed during the first few days of life and has become a standard of care, transforming the routine method for diagnosing the disease. By diagnosing CF early through its inclusion in the routine NBS program, the quality and longevity of life for those affected is now much improved and the gains continue,” said Dr Ravine.