Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Cystic fibrosis in adolescents and adults
Respiratory · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Time-critical presentation
Severe pulmonary exacerbation with hypoxaemia or exhaustion, major haemoptysis, pneumothorax, suspected distal intestinal obstruction with vomiting, sepsis related to a vascular device, or acute hepatic decompensation needs urgent hospital and CF-centre involvement. Infection-control arrangements and the patient's usual antimicrobial history should travel with them, but specialist contact must not delay ABCDE stabilisation, oxygen or treatment of sepsis.
Overview
Coordinate specialist multisystem care through transition and adulthood, recognise pulmonary and gastrointestinal emergencies, individualise airway and nutritional treatment, and use CFTR modulators safely by genotype.
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
Aetiology
01
CFTR variants
Biallelic pathogenic CFTR variants impair epithelial chloride and bicarbonate transport, with genotype influencing residual protein function and treatment eligibility.
02
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.
03
Modifier influences
Other genes, airway infections, treatment access, nutrition and environmental exposures shape severity beyond the CFTR genotype alone.
Pathophysiology
1
Dehydrated secretions
Defective ion transport reduces airway-surface hydration and alters mucus properties across respiratory, pancreatic, biliary and reproductive epithelia.
2
Impaired 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.
3
Progressive bronchiectasis
Repeated infection and protease-rich inflammation damage bronchial walls, producing dilatation, mucus plugging and worsening airflow obstruction.
4
Duct obstruction
Thick secretions block pancreatic and biliary ducts, causing maldigestion, nutritional deficiency, diabetes and liver complications in susceptible people.
Clinical features and red flags
Pulmonary exacerbation
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.
Major haemoptysis or pneumothoraxRed flag
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.
Distal intestinal obstruction syndromeRed flag
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.
CF-related diabetes
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.
Late or atypical diagnosis
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.
Treatment-burden distress
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.
Investigations
01Sweat 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.
02CFTR 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.
03Respiratory 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.
04Nutritional 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.
Differential diagnosis
01
Primary ciliary dyskinesia
Neonatal respiratory distress, chronic ear disease and laterality defects support ciliary dysfunction; specialist multi-test assessment separates it from CF.
02
Non-CF bronchiectasis
Acquired infection, immune deficiency or ABPA can produce similar CT change but lack confirmatory CFTR dysfunction and multisystem phenotype.
03
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.
04
Immunodeficiency
Recurrent sinopulmonary infection with abnormal immunoglobulins or vaccine responses suggests impaired humoral defence rather than primary mucus-channel disease.
Management
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.+
Complications
01
Pulmonary exacerbation
Increased infection and inflammation acutely worsen sputum, breathlessness, weight and lung function, with incomplete recovery contributing to long-term decline.
02
Respiratory failure
Advanced bronchiectasis and airflow obstruction cause hypoxaemia, hypercapnia, pulmonary hypertension and eventual need for transplant assessment.
03
Massive haemoptysis or pneumothorax
Hypertrophied bronchial vessels may bleed and damaged subpleural lung may rupture, each creating a potentially life-threatening respiratory emergency.
04
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.
05
Malnutrition and hepatobiliary disease
Pancreatic insufficiency and chronic inflammation cause undernutrition, while focal biliary obstruction can progress to portal hypertension and liver disease.
Monitoring and follow-up
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.
Special situations
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.
Common pitfalls
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.
Practice
Two practice questions
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Question 1 of 2
0 correct
RespiratoryOriginal SBA
Possible adult CF diagnosis
A 28-year-old man has diffuse bronchiectasis, chronic sinus symptoms, recurrent pancreatitis and obstructive azoospermia. A childhood record says a small CF mutation panel was negative. What is the best next step?
Sources and review status5 sources · checked 27 Aug 2026 · clinical review pending+
Sources
Sources and review status
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
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.
05Diabetes 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.
06Liver, 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.
1
Contact 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+
CFTR-modulator treatment for specialist-confirmed CF with at least one F508del mutation under NICE TA988 and the current marketing authorisation.
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.
Replaces pancreatic lipase in exocrine insufficiency to support absorption, growth, weight and fat-soluble-vitamin status.
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.