01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Defective CFTR-mediated chloride and bicarbonate transport produces dehydrated secretions and altered host defence. In the lung this causes mucus retention, infection and bronchiectatic damage; in the pancreas it commonly causes exocrine insufficiency. Phenotype varies greatly by genotype and modifier factors, so current lung function alone does not describe the total burden or future risk.
Care is delivered by a recognised multidisciplinary CF centre incorporating respiratory medicine, nursing, physiotherapy, dietetics, pharmacy, psychology and relevant diabetes, gastroenterology, hepatology, fertility and transplant services. Annual review is comprehensive, while acute treatment is informed by the patient's own culture and resistance record, vascular access, allergies and previous response.
Highly effective modulator therapy can improve lung function, weight and attack frequency, but introduces drug interactions and liver monitoring and may alter insulin, nutritional and reproductive needs. Treatment remains a shared decision: simplify burden where evidence permits, yet do not discontinue airway, infection or complication surveillance without the CF team.
Key points
- Cystic fibrosis is an autosomal-recessive CFTR disorder affecting airway mucus, pancreas, gut, liver, sinuses, sweat and reproduction; modern modulator therapy changes but does not erase multisystem surveillance.
- Adolescents should move through a planned, developmentally appropriate transition to a specialist adult CF centre, with increasing autonomy, medicines competence and attention to education, work and mental health.
- A late diagnosis remains possible in adults with bronchiectasis, recurrent pancreatitis, malabsorption, male infertility or characteristic organisms; use sweat chloride and CFTR testing through a specialist pathway.
- Respiratory treatment combines individual airway clearance, exercise, mucoactive therapy and culture-led antimicrobial plans; do not copy non-CF bronchiectasis regimens into CF without the centre's protocol.
- CFTR modulators are genotype and product specific. NICE TA988 recommends elexacaftor–tezacaftor–ivacaftor plus ivacaftor for eligible people with at least one F508del mutation within the marketing authorisation.
- Pancreatic enzyme replacement is taken with fat-containing food and adjusted by symptoms, growth or weight and specialist dietetic review; excessive dosing is unsafe.
- Screen proactively for CF-related diabetes, liver disease, low bone density, kidney toxicity, nutritional deficiency, fertility needs and treatment-related anxiety or depression.
- People with CF should not be placed together casually in clinics or wards because cross-infection with transmissible bacteria and NTM remains a material safety concern.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
CFTR variants
Biallelic pathogenic CFTR variants impair epithelial chloride and bicarbonate transport, with genotype influencing residual protein function and treatment eligibility.
Autosomal recessive inheritance
Disease occurs when a person inherits an affected allele from each carrier parent; siblings may be affected while parents are usually clinically well.
Modifier influences
Other genes, airway infections, treatment access, nutrition and environmental exposures shape severity beyond the CFTR genotype alone.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Dehydrated secretions
Defective ion transport reduces airway-surface hydration and alters mucus properties across respiratory, pancreatic, biliary and reproductive epithelia.
- 2Impaired mucociliary clearance
Viscous airway mucus traps organisms but is poorly transported, initiating persistent infection and neutrophilic inflammation, with effects that increase as the pathological process progresses.
- 3Progressive bronchiectasis
Repeated infection and protease-rich inflammation damage bronchial walls, producing dilatation, mucus plugging and worsening airflow obstruction.
- 4Duct obstruction
Thick secretions block pancreatic and biliary ducts, causing maldigestion, nutritional deficiency, diabetes and liver complications in susceptible people.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Increased cough, sputum, breathlessness, fatigue, reduced appetite or weight and a fall in spirometry may occur without fever. Severity and prior Pseudomonas, Burkholderia, MRSA or NTM history shape urgent treatment.
A large fresh bleed, sudden unilateral pleuritic pain, marked desaturation or acute respiratory distress requires immediate imaging, airway assessment and CF-respiratory escalation; suspend forceful clearance until reviewed.
Colicky right-lower-quadrant pain, distension, reduced stool and a palpable caecal mass suggest partial DIOS; bilious vomiting, peritonism or complete obstruction requires surgical and CF gastroenterology assessment.
Weight loss, declining lung function, fatigue or recurrent infection may precede classic osmotic symptoms. HbA1c alone can miss early post-prandial hyperglycaemia, so the centre follows a dedicated screening pathway.
An adult with diffuse bronchiectasis, recurrent pancreatitis, chronic sinus disease, salt-loss episodes or obstructive azoospermia may have CF despite survival without a childhood label or an incomplete mutation panel.
Missed therapy may reflect time, mood, side effects, health literacy, work or embarrassment rather than refusal. Confidential adolescent review and routine psychological assessment help reveal solvable barriers.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Sweat chloride in an accredited pathwayFirst step - Why
- Assess CFTR dysfunction in a person with a compatible phenotype or newborn-screen follow-up.
- Interpretation and limitations
- Interpret age-appropriate values with clinical features and genotype. Intermediate or discordant results require repeat and specialist functional or genomic assessment; one normal test does not settle every atypical presentation.
- 02
CFTR genotyping - Why
- Support diagnosis, reproductive counselling and eligibility for mutation-specific modulator treatment.
- Interpretation and limitations
- A limited panel may miss rare variants. Classify variants through the specialist genetics service and never infer drug responsiveness from an unvalidated sequence result.
- 03
Respiratory culture and spirometry - Why
- Track airway pathogens, treatment response and functional trajectory at routine and acute reviews.
- Interpretation and limitations
- Use CF-specific laboratory processing and infection controls. A fall in FEV1 is important even within the population range; compare with the individual's best recent value and symptoms.
- 04
Nutritional and pancreatic review - Why
- Detect inadequate energy absorption, enzyme mismatch and vitamin deficiency.
- Interpretation and limitations
- Trend height in adolescents, adult weight and BMI, bowel symptoms and fat-soluble vitamins. Faecal elastase supports pancreatic insufficiency but does not titrate replacement enzymes by itself.
- 05
Diabetes surveillance - Why
- Identify CF-related dysglycaemia before catabolism and lung decline become established.
- Interpretation and limitations
- Use the CF-centre schedule, commonly annual oral glucose tolerance testing from later childhood and additional testing during symptoms, enteral feeding, pregnancy, corticosteroids or exacerbation.
- 06
Liver, renal and bone assessment - Why
- Find chronic complications and treatment toxicity early enough to intervene.
- Interpretation and limitations
- Review LFT and imaging risk, creatinine and cumulative nephrotoxic antibiotics, vitamin D and fracture risk. Bone-density timing is personalised; normal enzymes do not exclude CF-related liver disease.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Primary ciliary dyskinesia
Neonatal respiratory distress, chronic ear disease and laterality defects support ciliary dysfunction; specialist multi-test assessment separates it from CF.
Non-CF bronchiectasis
Acquired infection, immune deficiency or ABPA can produce similar CT change but lack confirmatory CFTR dysfunction and multisystem phenotype.
CFTR-related disorder
Single-organ disease such as congenital bilateral absence of the vas deferens may reflect partial CFTR dysfunction without meeting full cystic-fibrosis criteria.
Immunodeficiency
Recurrent sinopulmonary infection with abnormal immunoglobulins or vaccine responses suggests impaired humoral defence rather than primary mucus-channel disease.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01TransitionMove to adult-centred care deliberatelyFirst stepAn adolescent is developing the capacity to manage treatment and prepare for adult services.+
- 1Begin planning over several years, assess understanding and practical skills, include private consultation time, and agree how parents or carers remain supportive without displacing the young person's voice.
- 2Transfer a complete summary of genotype, best lung function, microbiology, allergies, venous access, complications, modulator history, fertility discussion, mental health and emergency plans to the adult centre.
- 3Address school or university, employment, benefits, relationships, contraception, pregnancy and adherence openly; confirm the first adult appointment before paediatric follow-up closes.
02ExacerbationRespond to respiratory declineSymptoms, weight, oxygenation or spirometry deteriorate from the person's established baseline.+
- 1Contact the CF service early, obtain CF-processed sputum and assess oxygenation, imaging need, haemoptysis, pneumothorax and ability to maintain nutrition and airway clearance.
- 2Select oral or intravenous antibiotics from current and historical isolates, prior response and allergy, with centre-specific dosing and drug-level monitoring for nephrotoxic agents; avoid generic community regimens.
- 3Intensify physiotherapy safely, protect calorie and enzyme intake, monitor glucose and renal function, and compare post-treatment spirometry and symptoms with the pre-attack baseline.
03Precision therapyStart or continue a CFTR modulatorGenotype, age, marketing authorisation and NICE criteria indicate an available modulator regimen.+
- 1Confirm the validated genotype and current eligibility through the specialist centre, reconcile interacting medicines and establish liver tests, adherence priorities and reproductive counselling before prescribing.
- 2Teach the exact morning and evening products, fat-containing-food requirement, missed-dose rules and CYP3A interaction precautions from the current SmPC rather than relying on colour or brand memory.
- 3Monitor efficacy, transaminases and bilirubin and review rash, mood, weight, glucose and treatment burden; a clinical improvement does not justify unplanned withdrawal of other essential care.
04Whole personComplete the annual multisystem reviewScheduled comprehensive assessment or a new complication signal.+
- 1Review respiratory trajectory, cultures, imaging indication, technique and adherence alongside nutrition, enzymes, vitamins, glucose, liver, kidney and bone health.
- 2Discuss sinus, gastrointestinal and continence symptoms, fertility and pregnancy goals, contraception, sexual health, sleep, exercise, education or work and psychological wellbeing.
- 3Update vaccination, emergency antibiotics, vascular-access and treatment-ceiling plans where relevant, and consider timely lung, liver or other transplant referral before crisis dependence.
Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
Elexacaftor–tezacaftor–ivacaftor plus ivacaftor for eligible people aged at least 12 years
The current Kaftrio tablet SmPC uses two 75 mg/50 mg/100 mg combination tablets in the morning and one ivacaftor 150 mg tablet in the evening, about 12 hours apart with fat-containing food.Specialist initiation only. Check ALT, AST and bilirubin before treatment, every three months during year one and annually thereafter, more often with liver disease. Review strong or moderate CYP3A modifiers, grapefruit and Seville orange, hepatic impairment, rash, pregnancy and missed-dose instructions.
Pancreatic enzyme replacement therapy
Dose lipase units individually with every fat-containing meal, snack and supplement using the CF dietitian's plan; adjust to weight, stool and dietary response and remain within the current product and CF-centre safety ceiling.Swallow enteric-coated microspheres as instructed and do not crush them. Persistent symptoms require review of timing, adherence, acid suppression, diet, constipation and alternate diagnoses; very high cumulative doses are associated with fibrosing colonopathy.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Pulmonary exacerbation
Increased infection and inflammation acutely worsen sputum, breathlessness, weight and lung function, with incomplete recovery contributing to long-term decline.
Respiratory failure
Advanced bronchiectasis and airflow obstruction cause hypoxaemia, hypercapnia, pulmonary hypertension and eventual need for transplant assessment.
Massive haemoptysis or pneumothorax
Hypertrophied bronchial vessels may bleed and damaged subpleural lung may rupture, each creating a potentially life-threatening respiratory emergency.
CF-related diabetes
Progressive pancreatic endocrine dysfunction impairs glucose control, worsening nutrition and pulmonary outcomes if unrecognised, and increasing the burden of otherwise local respiratory disease.
Malnutrition and hepatobiliary disease
Pancreatic insufficiency and chronic inflammation cause undernutrition, while focal biliary obstruction can progress to portal hypertension and liver disease.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- At routine CF review, compare symptoms, weight, oxygen saturation, spirometry, microbiology, physiotherapy technique and treatment burden with the individual's recent best state.
- Complete the centre's annual multisystem assessment, including nutritional and vitamin status, glucose screening, liver and renal review, bone risk, fertility needs and psychological wellbeing.
- For elexacaftor–tezacaftor–ivacaftor, monitor liver biochemistry at the SmPC frequency and repeat sooner after symptoms, significant elevation, interacting treatment or known hepatic disease.
- During intravenous antibiotic courses, use drug-specific renal, auditory and serum-level monitoring and record cumulative aminoglycoside exposure where applicable.
- Maintain infection-prevention arrangements for visits, admissions, nebulisers and shared spaces, and investigate new NTM or transmissible organisms through the specialist centre.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Late diagnosis is still CF
Pancreatic sufficiency or mild childhood disease does not exclude CF. Adult bronchiectasis plus pancreatitis or male infertility merits a proper CFTR-function pathway.
Modulators change baselines
Rapid weight gain, fewer secretions and altered glucose or fertility may require diet, enzyme, contraception and airway-regimen review rather than simple celebration of a higher FEV1.
HbA1c can be late
Early CF-related diabetes often appears as post-prandial hyperglycaemia and catabolism, so dedicated glucose screening remains important even when HbA1c looks reassuring.
Cross-infection shapes service design
Separating people with CF is not social stigma: shared air and equipment can transmit difficult organisms, and remote or carefully scheduled contact protects access to specialist care.
11Common pitfallsFrequent interpretation and management errors.
- 01
Assuming an adult cannot have cystic fibrosis because newborn screening was unavailable, negative or used a limited mutation panel.
- 02
Prescribing a CFTR modulator from a remembered brand regimen without validated genotype, interaction review and liver monitoring.
- 03
Treating a pulmonary exacerbation with a generic non-CF antibiotic plan while ignoring the person's resistant-organism history and prior response.
- 04
Using HbA1c alone to exclude CF-related diabetes in someone losing weight or lung function.
- 05
Ending paediatric care before an adult centre has accepted the patient and a practical transition plan is functioning.
- 06
Relaxing cross-infection precautions because two patients carry the same broad organism name without strain-level or NTM considerations.