Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• CFTR Modulator Therapy For Adults In Australia

  Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy in Adults has changed the management of cystic fibrosis (CF) from mainly treating complications to correcting part of the underlying protein defect. These medicines can improve CFTR channel activity, reduce thick airway secretions and support better lung function for people with eligible variants.

  The response is individual, however. Adult care still involves airway clearance, inhaled treatments, nutrition, infection surveillance and attention to diabetes, bone health and mental wellbeing. In Australia, treatment decisions also need to account for Therapeutic Goods Administration requirements, Pharmaceutical Benefits Scheme access and the practical realities of travelling between specialist centres in Sydney, Melbourne, Brisbane, Perth or regional areas.

  How CFTR Modulators Work

  CFTR modulators are oral medicines designed to improve the function, amount or stability of defective CFTR protein. Potentiators such as ivacaftor help the channel open more effectively, while correctors such as tezacaftor and elexacaftor help the protein fold and reach the cell surface.

  Combination therapy has broadened the number of adults who may benefit. Elexacaftor/tezacaftor/ivacaftor is commonly discussed for people with at least one eligible F508del variant, although prescribing depends on the person’s genetic result, age, clinical status and current regulatory and funding arrangements.

  Matching Treatment To Genetic Results

  A complete CFTR genotype is essential before therapy is selected. The same clinical diagnosis can arise from different variants, and some mutations produce little or no usable protein while others leave a partially functioning channel. Sweat chloride results and clinical history add useful context but do not replace molecular testing.

  Genetic reports should be interpreted by a CF physician or genetic specialist rather than treated as a simple positive-or-negative answer. Some adults diagnosed decades ago may need updated testing, particularly if their original report used older terminology. This is relevant in Australia, where records may be spread across a paediatric service, an adult centre and private pathology providers.

  Benefits For Adult Health

  Eligible adults may experience fewer pulmonary exacerbations, improved spirometry, better weight maintenance and greater exercise tolerance. Some people report less coughing and easier airway clearance within weeks, while others notice gradual gains over several months. These improvements can support employment, family life and participation in activities such as swimming or weekend sport.

  Modulators do not remove established bronchiectasis or guarantee freedom from infection. Chronic organisms, including Pseudomonas aeruginosa, may persist, and inhaled antibiotics or airway clearance may remain necessary. A change in cough should also be assessed carefully; it should not automatically be attributed to treatment when symptoms could reflect another infection. Current TB diagnostic updates illustrate why respiratory symptoms and drug-resistant infection require a structured assessment.

  Safety And Medicine Review

  Liver function testing is important before treatment and at intervals recommended by the product information and specialist team. People with previous liver disease, abnormal enzymes or a liver transplant may need closer monitoring. Rash, headache, abdominal symptoms and changes in mood or sleep should be reported, even when they appear mild.

  CFTR modulators interact with medicines processed through the CYP3A pathway. This includes some antifungals, macrolide antibiotics, anticonvulsants and herbal products such as St John’s wort. A pharmacist should review prescriptions, over-the-counter medicines and supplements. Pregnancy, breastfeeding and hormonal contraception also deserve a planned discussion rather than an assumption that treatment can continue unchanged.

  Access Within Australian Care

  Australian access is shaped by TGA registration, PBS arrangements, specialist prescribing and eligibility criteria, all of which can change. A person may need documentation of genotype, lung function, treatment history and monitoring capacity. CF centres can help clarify whether a medicine is funded, supplied through a specific pathway or subject to administrative approval.

  Distance affects continuity. Someone living near Cairns, Hobart or a remote Western Australian community may have fewer local services than a patient in Melbourne or Sydney. Telehealth can reduce travel for medication reviews, while blood tests and lung function measurements still need reliable local coordination. Adults should also plan for interstate travel, medicine storage and supply interruptions before holidays or work deployments.

  Monitoring The Real-World Response

  Baseline measurements commonly include spirometry, weight, oxygenation, liver enzymes, microbiology and a review of exacerbation frequency. Follow-up may show a meaningful rise in FEV1, but lung function is only one outcome. Fewer intravenous antibiotic courses, improved sleep, increased activity and reduced treatment burden may be equally important.

  A useful review compares results with the person’s own baseline rather than relying on a single number. Some adults have advanced lung disease and gain stability rather than a large spirometric improvement. Others may uncover previously silent complications, such as CF-related diabetes, when their health and appetite improve.

  Therapy type	Main action	Typical adult consideration
  Ivacaftor	Increases CFTR channel opening	Used for selected gating and residual-function variants
  Lumacaftor/ivacaftor	Helps protein processing and channel activity	May have respiratory or interaction concerns in some patients
  Tezacaftor/ivacaftor	Improves delivery and activity of CFTR protein	Eligibility depends closely on the variant
  Elexacaftor/tezacaftor/ivacaftor	Uses two correctors with a potentiator	Broad eligibility for selected genotypes, with liver and interaction monitoring

  Building A Sustainable Treatment Plan

  Starting a modulator is a shared decision involving the adult, CF physician, pharmacist, respiratory nurse, dietitian and, when needed, a hepatologist or endocrinologist. The plan should state when doses are taken, which foods are required for absorption, how blood tests will be arranged and what symptoms warrant urgent review. Fat-containing food is relevant for absorption of several regimens, so advice should fit the person’s usual diet rather than remain abstract.

  The immediate next step is to arrange a specialist medication review with the adult’s CF centre, bringing the latest CFTR genetic report, medication list and recent liver blood results.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)