Diagnosing cystic fibrosis: what are we sweating about?
- 1Department of Cystic Fibrosis, Royal Brompton Hospital, London, UK
- 2National Heart and Lung Institute, Imperial College, London, UK
- Correspondence to Dr Nicholas J Simmonds, Department of Cystic Fibrosis, Royal Brompton Hospital, London SW3 6NP, UK;
Contributors NJS wrote the first draft of the manuscript after discussion with AB; AB and NJS edited the subsequent drafts.
- Cystic fibrosis
- primary pulmonary hypertension
- pulmonary embolism
- asthma guidelines
- exhaled airway markers
- lung physiology
- paediatric asthma
- paediatric lung disease
Over the last few decades, the paradigm has shifted as cystic fibrosis (CF) is no longer a fatal disease of childhood and should be considered a chronic condition where survival into adulthood is expected. Median survival for current newborns is predicted to be at least 50 years and over 55% of patients in the UK are adults.1 Over these decades, our knowledge of the underlying pathophysiology has grown exponentially, from its original description in 1938 to the identification of the mutated gene (cystic fibrosis transmembrane conductance regulator, CFTR) in 1989.2 This has driven the development of effective therapies and brought about an increased understanding of the wide spectrum of diseases that result from abnormal CFTR function. During this time, the humble sweat test has remained at the heart of the diagnostic algorithm, with only modest changes from the original pilocarpine iontophoresis technique first described by Gibson and Cooke over half a century ago.3 Abnormal sweat electrolytes result from dysfunctional or absent CFTR protein in the epithelial cells of sweat glands.4 CFTR is widely distributed throughout the body and has many functions, such as encoding a cAMP-activated chloride channel and regulating transepithelial ion movement—a phenomenon identified by the measurement of potential difference across the nasal mucosa and later used as the basis of the nasal potential difference (NPD) diagnostic test.5 6
With the identification of the mutated gene and extensive knowledge of the associated basic defect, why is there still such a debate about the criteria for diagnosis and why do different diagnostic algorithms exist? When is CF atypical or non-classic and why introduce yet more terms—‘CFTR-related disorders’ and ‘CFTR-related metabolic syndrome’? Are these terms helpful …