Respiratory conditions

Cystic Fibrosis

A multisystem genetic disease transformed by modern therapy.

For patients & health professionals
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Authorship & review
Dr Sean James Ledger, BSc Physio (Hons) MSc PhD FHEA
Director and Principal Physiotherapist
Ahpra registration PHY0002298174
Version
1.0
Last updated
12 August 2026
Next review
12 August 2027
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Part 1 · In plain language

Cystic fibrosis (CF) is an inherited condition that makes mucus in the lungs and digestive system thick and sticky, leading to repeated chest infections and problems absorbing food. It is present from birth and affects several parts of the body, so care involves a specialist team. Daily airway clearance, nebulised medicines, enzymes with meals and good nutrition are central, and newer "modulator" drugs have transformed outcomes for many people. With modern treatment, people with CF are living longer, fuller lives. This page explains CF and how it is managed.

Definition

Cystic fibrosis is an autosomal recessive multisystem disease caused by pathogenic variants in the CFTR gene (cystic fibrosis transmembrane conductance regulator), which encodes a chloride and bicarbonate channel on epithelial surfaces. Loss of CFTR function results in thick, dehydrated secretions affecting the airways, pancreas, intestine, hepatobiliary system, sweat glands, and reproductive tract.1

Pathophysiology

In the airway, impaired chloride and bicarbonate secretion leads to dehydration of the airway surface liquid, reduced mucociliary clearance, chronic bacterial colonisation, and a relentless cycle of infection, inflammation, and progressive bronchiectasis. Similar mechanisms produce ductal obstruction in the pancreas (causing exocrine and endocrine insufficiency), biliary system, and male reproductive tract.

Co-morbidities

Common co-morbidities include CF-related diabetes (CFRD), pancreatic exocrine insufficiency, CFTR-related liver disease, osteopenia and osteoporosis, gastro-oesophageal reflux, chronic rhinosinusitis with nasal polyposis, distal intestinal obstruction syndrome (DIOS), male infertility (CBAVD), and mental health conditions.

Prevalence

CF affects approximately 1 in 2,500 to 1 in 3,500 live births in people of European ancestry. In Australia, there are approximately 3,500 people living with CF, the majority of whom are now adults due to dramatic improvements in survival. Cystic Fibrosis Australia maintains the Australian Cystic Fibrosis Data Registry.

Causes

CF is caused by pathogenic variants in CFTR on chromosome 7. Over 2,000 variants have been described, of which approximately 400 are known to be disease-causing. F508del is the most common pathogenic variant, accounting for around 70% of CF alleles in Australia. The pattern of inheritance is autosomal recessive.

Symptoms

Typical features include persistent productive cough, recurrent chest infections, breathlessness on exertion, finger clubbing, failure to thrive in children, steatorrhoea and abdominal symptoms (from pancreatic insufficiency), male infertility, and salty-tasting skin. Symptom burden is highly variable depending on genotype, age, modifiers and access to treatment.

Newborn screening and diagnosis pathway

Newborn screening for CF has been universal in Australia since 2018. Babies with a positive screen are referred for confirmatory sweat chloride testing and CFTR genetic analysis. Adults may present with milder phenotypes (e.g. CFTR-related disease, late-diagnosis CF) and warrant testing in the presence of bronchiectasis, infertility, recurrent pancreatitis, or chronic sinusitis.

Diagnosis

Importance of a diagnosis

Early diagnosis enables prompt commencement of airway clearance, pancreatic enzyme replacement, nutritional optimisation, and (where indicated) CFTR modulator therapy. It also enables family screening and genetic counselling.

How is it diagnosed?

CF is diagnosed by a combination of clinical features (or positive newborn screen) plus evidence of CFTR dysfunction, demonstrated by: a sweat chloride ≥60 mmol/L on two occasions, identification of two disease-causing CFTR variants, or abnormal nasal potential difference measurement. Sweat chloride is the cornerstone investigation.

Radiology

HRCT shows bronchiectasis (typically upper-lobe predominant in adults), bronchial wall thickening, mucous plugging, mosaic attenuation, and tree-in-bud nodules. Chest X-ray underestimates disease severity. Annual or periodic imaging is used to monitor structural progression.

Lung function

Spirometry is the principal monitoring tool. FEV1 percent predicted is the most widely used measure of disease severity, although the lung clearance index (LCI) is more sensitive to early disease, particularly in children. Lung function is monitored at every routine review.

Sputum pathology

Regular sputum surveillance is essential. Pathogens commonly isolated include S. aureus (including MRSA), H. influenzae, P. aeruginosa, Burkholderia cepacia complex, Stenotrophomonas, and NTM (particularly M. abscessus, which has major implications for transplantation eligibility).

Investigations for related complications

Annual screening includes oral glucose tolerance test for CFRD from age 10, liver function tests and ultrasound, DXA for bone health, fat-soluble vitamin levels (A, D, E, K), and assessment of nutritional status. Sinus assessment, fertility counselling, and mental health screening are also incorporated into routine care.

Management

Management and goals

Goals are to maintain lung function, minimise exacerbations, support nutrition and growth, treat extra-pulmonary complications, support psychological wellbeing, and extend healthy life expectancy. Care is delivered through multidisciplinary CF centres.2

Treatment options

Core treatment includes:

Identifying an exacerbation

A pulmonary exacerbation is recognised by an increase in cough, sputum volume or purulence, breathlessness, fatigue, reduced appetite or weight loss, a drop in FEV1 (typically ≥10%), or new findings on examination. Early recognition and treatment are key to preserving lung function.

Action plan

A written action plan specifies the patient’s usual symptoms, signs of an exacerbation, when to intensify airway clearance, when to obtain a sputum sample, when to initiate or escalate antibiotics, and clear criteria for contacting the CF team or attending hospital.

Medications

Medications for CF

CFTR modulators are now the cornerstone for genotype-eligible patients and have transformed outcomes. Other classes include mucolytics (dornase alfa, hypertonic saline), inhaled antibiotics (tobramycin, colistin, aztreonam), bronchodilators, pancreatic enzymes, fat-soluble vitamins, and antibiotics for acute and chronic infection. Insulin is used in CFRD.

Correct use of medications

Adherence is the strongest determinant of outcome. Time should be invested in inhaler and nebuliser technique, enzyme dose adjustment with meals, and recognition of side-effects. Patients should be supported with reminder systems, structured review of the daily medication routine, and adherence-focused conversations.

Order of medications

For airway clearance, the recommended sequence is:

  1. Bronchodilator
  2. Hypertonic saline
  3. Airway clearance therapy
  4. Dornase alfa (timing per local CF centre protocol — usually 30 minutes before airway clearance, or separately)
  5. Inhaled antibiotic (after airways are cleared)
  6. Inhaled corticosteroid (if indicated)

Multi-system manifestations

Pancreatic insufficiency and CF-related diabetes

Pancreatic exocrine insufficiency affects around 85% of people with CF and requires lifelong PERT with meals and snacks, plus fat-soluble vitamin supplementation. CFRD develops in around 20% of adolescents and 50% of adults; it is distinct from type 1 and type 2 diabetes and requires insulin therapy, not oral agents.

CFTR-related liver disease

A spectrum of hepatobiliary disease occurs, from mild abnormalities of liver enzymes to focal biliary cirrhosis and portal hypertension. Annual screening is required. Ursodeoxycholic acid may be used; advanced disease may require liver transplantation.

Sinonasal disease

Chronic rhinosinusitis and nasal polyposis are highly prevalent. Saline irrigation, intranasal corticosteroids, dornase alfa irrigation, and endoscopic sinus surgery may be required.

Reproductive health and fertility

Congenital bilateral absence of the vas deferens (CBAVD) causes infertility in approximately 98% of men with CF, although spermatogenesis is preserved and assisted reproduction is usually successful. Women with CF have largely preserved fertility but require pre-conception counselling, especially around CFTR modulators in pregnancy.

Bone disease and musculoskeletal

CF bone disease results from chronic inflammation, malabsorption, low vitamin D, corticosteroid use, and reduced weight-bearing activity. DXA screening is recommended. Weight-bearing exercise, vitamin D and calcium, and bisphosphonates where indicated form the management approach.

Living with cystic fibrosis

Nutrition

Historically a high-energy, high-fat, high-salt diet was recommended to maintain growth and lung function. With CFTR modulators, weight gain is now common and dietary advice is increasingly individualised. Dietitian input is essential at every life stage.

Sleep

Sleep disturbance is common from cough, nocturnal symptoms, and treatment burden. Sleep-disordered breathing should be considered, particularly in advanced disease where nocturnal hypoxaemia and hypoventilation may occur.

Travel

Travel is generally well tolerated. Patients should carry a clinician letter, a complete supply of medications, prescriptions, equipment (nebulisers and chargers), and consider in-flight oxygen assessment in advanced disease. Cross-infection precautions are important when meeting other people with CF.

Prognosis

Median predicted survival has risen dramatically in recent decades and now exceeds 50 years in many high-income countries. Outcomes are further transformed by CFTR modulators. Prognosis is influenced by genotype, lung function trajectory, nutritional status, and complications such as Pseudomonas, M. abscessus, and CFRD.

Anxiety, depression and transition to adult care

Mental health disorders are over-represented in CF. The International Committee on Mental Health in CF recommends annual screening for anxiety and depression. Transition from paediatric to adult care occurs in late adolescence and requires structured support to maintain engagement and adherence.

Role of the physiotherapist

The physiotherapist is a core member of the CF multidisciplinary team across the lifespan. They prescribe and progress daily airway clearance, use exercise both as a clearance technique and to build fitness, and continually review technique and adherence as needs change (including in the CFTR-modulator era). They also support musculoskeletal health, breathlessness management, and education for the person and their family.8,9,10

Warning signs

Call 000 nowCoughing up a large volume of fresh blood, or sudden severe one-sided chest pain with breathlessness — which may mean a lung has collapsed. Both are recognised complications of cystic fibrosis and both are emergencies.
Emergency department todayFever with worsening breathlessness or a new oxygen requirement, or severe abdominal pain with vomiting and no bowel motions, which may be distal intestinal obstruction syndrome.
Same-day medical assessmentA rise in cough or sputum volume, a change in sputum colour, unintended weight loss, or a fall in your home spirometry readings. These are the signs of an exacerbation and treatment is more effective started early.

Part 1 · References

  1. Southern KW, Addy C, Bell SC, et al. Standards for the care of people with cystic fibrosis: establishing and maintaining health. J Cyst Fibros 2024;23(1):12–28.
  2. Cystic Fibrosis Foundation. Infection prevention and control guideline for cystic fibrosis: 2013 update. Infect Control Hosp Epidemiol 2014;35(S1):s1–s67.
  3. Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med 2019;381(19):1809–1819.
  4. Heijerman HGM, McKone EF, Downey DG, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet 2019;394(10212):1940–1948.
  5. Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med 1994;331(10):637–642.
  6. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006;354(3):229–240.
  7. Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999;340(1):23–30.
  8. Wilson LM, Morrison L, Robinson KA. Airway clearance techniques for cystic fibrosis: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev 2019;(1):CD011231.
  9. Davies JC, Sermet-Gaudelus I, Naehrlich L, et al. Airway clearance in the era of highly effective CFTR modulators: rethinking the daily regimen. J Cyst Fibros 2023;22(4):595–603.
  10. Radtke T, Smith S, Nevitt SJ, Hebestreit H, Kriemler S. Physical activity and exercise training in cystic fibrosis. Cochrane Database Syst Rev 2022;(8):CD002768.

References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines are living documents — verify against the latest version before clinical use.

Drug pipelineFor the full therapeutic history, the approved agents and their pivotal trials, and what is in phase 2 and 3 now, see The Cystic Fibrosis Drug Pipeline →
How we treat this at the clinic

Clearing mucus well is a skill rather than a machine. We match a technique to your lungs and your routine, then coach it until you can do it at home on a bad morning.

Airway Clearance Therapy →
Part 2 of 2

Clinical evidence

Part 1 covers the same condition without the technical detail. What follows is the evidence base behind it, written for clinicians — the literature, the reasoning and the gaps.

For clinicians: this summary supports clinical reasoning and is not a protocol. Check current guidelines and local policy before applying it, and read it alongside the key references and guidelines directory.

Framing. CF care has been reorganised twice over: first by mucoactive and inhaled antibiotic therapy, and now by highly effective CFTR modulators. Elexacaftor–tezacaftor–ivacaftor produced large, sustained gains in FEV1, sweat chloride, quality of life and exacerbation rate in both heterozygous and homozygous Phe508del populations, and the resulting reduction in sputum burden is changing what physiotherapy is for — from daily secretion clearance toward exercise, musculoskeletal health, adherence and long-term function.1,2

Established therapy

  • Dornase alfa (rhDNase) improved lung function and reduced exacerbations — a CF-specific benefit that does not transfer to bronchiectasis of other cause.3
  • Hypertonic saline 7% improved lung function and reduced exacerbations over 48 weeks and remains a standard adjunct to clearance.4
  • Inhaled tobramycin improves lung function and reduces hospitalisation in chronic Pseudomonas aeruginosa infection.5
  • Airway clearance techniques improve short-term sputum transport with no technique demonstrating consistent superiority; the Cochrane conclusion is that choice should follow patient preference, age and adherence.6
  • Exercise training improves exercise capacity, lung function and quality of life, with the Cochrane review supporting it as a core component of care rather than an adjunct.7

The modulator era

  • Sputum production falls substantially on highly effective modulator therapy, and many patients question the need for continued daily clearance — a genuine clinical dilemma being tested prospectively rather than one to resolve by assertion.1,8
  • The problem set is shifting: weight gain and metabolic health, musculoskeletal pain, pelvic floor dysfunction, mental health and preserved-but-not-normal exercise capacity are increasingly the presenting issues.8,9
  • Standards of care continue to specify individualised airway clearance, annual physiotherapy review, exercise prescription and adherence support for all patients, including those on modulators.9,10

Physiotherapy implications

  • Sequence nebulised therapy: bronchodilator → hypertonic saline → airway clearance → inhaled antibiotic last, so the antibiotic deposits on cleared airways; dornase alfa is given per the unit's protocol, typically at least 30 minutes before clearance.
  • Do not unilaterally stop clearance on modulator therapy. De-escalation is a CF-team decision with objective follow-up; a reasonable interim position is to individualise frequency against symptoms, sputum, spirometry and exacerbation history.8
  • Prescribe exercise as treatment, including resistance work for bone and muscle health, and use it as a clearance adjunct rather than a replacement.7
  • Screen routinely for urinary incontinence — highly prevalent in women with CF, frequently unreported, and a direct cause of suppressed coughing and huffing.9
  • Infection control is non-negotiable: single-patient equipment, taught cleaning and drying, segregation and no cross-attendance of patients with transmissible organisms.10
  • Escalate frank haemoptysis (defer percussion and head-down positions until assessed), pneumothorax symptoms, and any acute drop in exercise tolerance or spirometry.

Clinical reasoning

  • Failure to clear is usually a regimen problem — timing, hydration, adherence, technique drift — before it is a device problem.
  • Distinguish a true exacerbation (increased cough and sputum, weight loss, fatigue, spirometry fall) from post-viral variation; the first needs the CF team.
  • Musculoskeletal chest and back pain is common and interferes with clearance and exercise; treat it rather than working around it.
  • Adherence over decades is the central determinant of outcome, so the shortest effective regimen the patient will actually do beats the theoretically optimal one they will not.

Evidence gaps

  • Whether, when and how far daily airway clearance can safely be reduced on highly effective modulator therapy is the major open question in CF physiotherapy.8
  • No trial establishes optimal clearance technique, dose or duration in the modulator era.6
  • Long-term musculoskeletal, metabolic and reproductive consequences of modulator therapy are only beginning to be described.
  • Care of the ageing CF population — now the majority — has almost no dedicated rehabilitation evidence.
Drug pipelineFor the full therapeutic history, the approved agents and their pivotal trials, and what is in phase 2 and 3 now, see The Cystic Fibrosis Drug Pipeline →

References for the clinical evidence summary

  1. Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med 2019;381(19):1809–1819.
  2. Heijerman HGM, McKone EF, Downey DG, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet 2019;394(10212):1940–1948.
  3. Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med 1994;331(10):637–642.
  4. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006;354(3):229–240.
  5. Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999;340(1):23–30.
  6. Wilson LM, Morrison L, Robinson KA. Airway clearance techniques for cystic fibrosis: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev 2019;(1):CD011231.
  7. Radtke T, Smith S, Nevitt SJ, Hebestreit H, Kriemler S. Physical activity and exercise training in cystic fibrosis. Cochrane Database Syst Rev 2022;(8):CD002768.
  8. Davies JC, Sermet-Gaudelus I, Naehrlich L, et al. Airway clearance in the era of highly effective CFTR modulators: rethinking the daily regimen. J Cyst Fibros 2023;22(4):595–603.
  9. Southern KW, Addy C, Bell SC, et al. Standards for the care of people with cystic fibrosis: establishing and maintaining health. J Cyst Fibros 2024;23(1):12–28.
  10. Cystic Fibrosis Foundation. Infection prevention and control guideline for cystic fibrosis: 2013 update. Infect Control Hosp Epidemiol 2014;35(S1):s1–s67.
Important: This page is general information, not medical advice. If your breathing or symptoms change suddenly or severely, seek urgent medical care. For personalised assessment, contact Inspire Clinic.

Corrections: If something on this page is wrong, out of date or unclear, we want to know. Email reception@inspireclinic.au with the page name and what you believe is incorrect. Substantive corrections are made promptly, and the guide’s version and last-updated date are changed to reflect it.