You’re a few months into your first paediatrics rotation, and you’re finally finding your rhythm. Nebs? Charted. Sats probes? Miraculously working. Sticky toddlers in A&E with viral-induced wheeze? Bring them on.
So, when you’re called to review a 3-year-old with a persistent cough, poor weight gain, and yet another course of antibiotics, you stroll over with a mental list of differentials: post-viral wheeze, asthma, maybe even primary ciliary dyskinesia if you’re feeling clever.
But something doesn’t sit quite right. The child has a barrel-shaped chest, finger clubbing, nasal polyps, and their mum casually mentions, “He tastes salty when I kiss him.”
Wait—what?
You check the growth chart again. Below the 2nd centile. You call for a sweat test, and before you know it, the CF nurse specialist is on the ward, and you’re sitting in on the MDT.
What is cystic fibrosis?
CF is an autosomal recessive, multisystem disorder caused by pathogenic mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, which encodes a chloride channel found on epithelial surfaces.
It primarily affects the respiratory, gastrointestinal, hepatobiliary, and reproductive systems. The median life expectancy in the UK is now approaching 50 years, thanks to advances in early diagnosis, nutrition, physiotherapy, and CFTR modulators.
In paediatrics, you are likely to be involved in care from diagnosis to transitional planning into adult services, making longitudinal understanding essential.
The annual incidence of CF is 1 in 2,500 live births, with 1 in 25 people being carriers in white populations. In the UK, about 11,148 people were diagnosed as of December 2022; 63% of these are more than 16 years old.
What causes cystic fibrosis?
Think of CF as a plumbing problem at the microscopic level: the pipes (airways, pancreatic ducts, intestines) get clogged, not with limescale, but with thick, sticky secretions. This all starts with a single faulty protein: CFTR.
Step 1: The CFTR protein – the faulty gate
In healthy cells, the CFTR protein can open to allow chloride ions to flow out. Water follows these chloride ions, and this keeps the mucus thin and slippery.
In CF, a genetic mutation in the CFTR gene on chromosome 7 means that the CFTR protein is absent, misfolded, stuck inside the cell or works poorly. There are over 2000 mutations that can cause this, with the most common being Phe508del (catchy, right?).
Step 2: Without functional CFTR
Without correctly functioning CFTR proteins, fewer chloride ions move out of cells, and excessive sodium is reabsorbed. Water follows this sodium into cells, leading to epithelial surfaces becoming dehydrated. This causes thick, sticky mucus to coat epithelial surfaces.
Step 3: Why does this cause disease?
In the lungs:
In the lungs, the mucus becomes abnormally thick, making it difficult for the cilia to clear it effectively. As a result, inhaled bacteria are not swept out of the airways. This allows infections to develop, with Staphylococcus aureus being common in the early stages and Pseudomonas aeruginosa often appearing later on.
Persistent infection provokes chronic inflammation, and over the years, this cycle of damage leads to bronchiectasis, declining lung function and ultimately hypoxia.
In the pancreas:
In the pancreas, thick mucus obstructs the pancreatic ducts, preventing digestive enzymes from reaching the intestine. Without these enzymes, fats and proteins cannot be properly broken down, leading to steatorrhea—bulky, oily stools—along with malnutrition and deficiencies of the fat-soluble vitamins. Over time, the persistent blockage also damages the pancreas itself, destroying insulin-producing cells and can eventually cause cystic fibrosis–related diabetes. Mucus blocks pancreatic ducts.
In the intestines:
In newborns, the meconium becomes abnormally thick and sticky, sometimes leading to meconium ileus. In older children and adults, similar blockages can result in distal intestinal obstruction syndrome (DIOS).
In the sweat glands:
Normally, the CFTR protein reabsorbs chloride and sodium from sweat before it reaches the skin’s surface. In cystic fibrosis, this reabsorption does not occur, producing abnormally salty sweat—a feature that forms the basis of the diagnostic sweat test.
In the reproductive tract:
In males, the vas deferens may be blocked or absent, leading to obstructive azoospermia and infertility. In females, the thickened cervical mucus can reduce fertility, though many remain capable of conceiving.
Step 4: How this explains the clinical picture
Taken together, these abnormalities explain the typical clinical picture of cystic fibrosis.
The chronic cough and recurrent lung infections arise from mucus stasis and airway colonisation. Poor growth and nutritional difficulties result from pancreatic enzyme loss and malabsorption. The characteristic salty skin is due to the failure of sodium and chloride reabsorption in the sweat ducts. Finally, the long-standing lung damage and oxygen deprivation cause digital clubbing, a classic sign of chronic hypoxia.
Diagnosis
When a child presents with concerning features, be it poor growth, a persistent cough, or recurrent infections, digging into the history can be revealing.
Start at the beginning: Was there a delay in passing meconium? That first poo tells you more than you think. In fact, around 10–20% of babies with CF present with meconium ileus. And, of course, a family history, even if vague, can raise your index of suspicion significantly.
Respiratory red flags
ask about the breathing pattern; has the family noticed a fast respiratory rate, noisy breathing, or tugging at the ribs? A persistent or wet-sounding cough, particularly if it’s been going on for weeks (or months!), is worth digging into. Hard coughing spells and sputum production are clues, especially if the child is too young to expectorate and just ends up vomiting mucus.
Recurrent chest infections are classic, those “bronchitis” or “pneumonia” episodes that keep returning and need yet another round of antibiotics. In older children, you might even hear about blood-streaked sputum. Rarely, massive haemoptysis (think >300 ml in 24 hours) can occur, which is alarming for everyone involved.
Tummy trouble
Then, shift gears to ask about the gut. Appetite? Great. But are they actually absorbing anything? Kids with CF can have an insatiable appetite but still fall off their centile lines. Frequent, bulky, greasy poos are classic—think fat malabsorption and pancreatic insufficiency.
Watch for signs of bowel obstruction, especially in those with fewer stools than usual, abdominal bloating, or vomiting. It’s far more common in CF than in your average child. Recurrent pancreatitis or episodes of severe abdominal pain? That’s another red flag—especially in those with particular CFTR mutations (like the bicarbonate transport defects, which can increase pancreatitis risk several-fold).
In short, ask broadly but listen closely. CF doesn’t always shout; sometimes, it whispers through recurrent infections, failure to thrive, or stools that are just a bit… off.
Examination
In the early stages, the examination may be completely normal, particularly if the child has been diagnosed through newborn screening and started on treatment promptly. However, certain patterns and signs can develop over time that give important clues.
General appearance and growth
Nutritional status: Look for reduced subcutaneous fat, muscle wasting, or a protuberant abdomen.
Growth parameters: Plot weight, height, and BMI on growth charts. Faltering growth despite a good appetite is a red flag.
Posture and energy: Children with advanced lung disease may appear fatigued, sit forward to ease breathing, or avoid physical play.
Face and upper airway
Nasal polyps: Common in older children; can be small and easily missed unless you look with a light source.
Sinus tenderness or swelling: Suggests chronic sinusitis.
Clubbing of the fingers: Usually appears with more advanced lung disease; indicates chronic hypoxia and inflammation.
Respiratory system
Inspection
Increased anteroposterior chest diameter (“barrel chest”).
Use of accessory muscles or intercostal recession during breathing.
Fast breathing rate or pursed-lip breathing in older children.
Palpation:
Reduced chest expansion in advanced disease.
Percussion:
May be hyper-resonant in hyperinflation or dull over areas of consolidation.
Auscultation:
Coarse crackles (often in the upper lobes).
Wheeze in acute exacerbations.
Reduced air entry in bronchiectasis areas.
Abdomen
Protuberant abdomen from poor muscle tone and bloating.
Palpable stool masses from constipation or distal intestinal obstruction syndrome.
Hepatomegaly or splenomegaly from chronic liver involvement or portal hypertension.
Musculoskeletal and other systems
Joint swelling or tenderness — rare but may be seen in CF-related arthritis.
Signs of osteoporosis in older patients (kyphosis, fractures).
Skin: Salt crystals on the skin after sweating may be noted in hot weather.
The gold standard test to confirm a clinical diagnosis of CF is a positive sweat test. Genetic investigations can be used to gain a deeper understanding of the exact genetic mechanisms involved.
Management
Cystic fibrosis is a complex, multisystem disorder requiring proactive, lifelong management.
Given the variability in presentation and progression, care should be coordinated by a specialist Cystic Fibrosis multidisciplinary team (MDT) in line with national standards such as those set out by the UK Cystic Fibrosis Trust and international consensus guidelines.
The management of cystic fibrosis is guided by several overarching priorities.
Preserving lung function and limiting long-term airway damage remain central aims, while equal importance is placed on supporting nutrition and growth through careful dietary and enzyme management.
At the same time, clinicians remain vigilant for complications, working to identify and address them promptly. Alongside these medical aspects, effective care also recognises the psychological and social impact of the disease, ensuring that patients and their families receive the support needed to manage its daily challenges.
The Cystic Fibrosis MDT
The management of cystic fibrosis requires an MDT with each member playing a vital role in supporting patients and their families. Specialist physicians, including paediatric and adult CF consultants, oversee clinical care and coordinate long-term treatment plans. CF nurse specialists provide continuity of care, home support, and education, acting as key points of contact for families.
Physiotherapists design and monitor airway clearance and exercise regimens, while dietitians optimise nutrition and manage pancreatic insufficiency. Pharmacists contribute by tailoring medication regimens and supporting adherence. Clinical psychologists help patients and families cope with the psychological burden of treatment and chronic illness, while social workers assist with practical matters such as housing, benefits, and school liaison. In some cases, additional professionals such as youth workers, occupational therapists, and genetic counsellors may also be involved.
Respiratory Care
Respiratory care is central to the management of cystic fibrosis.
Chest physiotherapy is essential for preventing mucus plugging and infection, with techniques such as the active cycle of breathing, huffing, and positive expiratory pressure (PEP) devices. These interventions should be carried out at least twice daily in stable patients and increased in frequency during exacerbations (McIlwaine et al., 2015).
Alongside physiotherapy, inhaled therapies play a critical role. Hypertonic saline improves mucociliary clearance by rehydrating airway secretions, while dornase alfa (recombinant human DNase) reduces sputum viscosity by breaking down extracellular DNA released from neutrophils. Bronchodilators such as salbutamol are often given beforehand to enhance tolerance of these mucolytic therapies.
Antibiotics remain a cornerstone of treatment. Acute pulmonary exacerbations should be managed promptly with pathogen-directed antibiotics, often requiring a 14-day course of intravenous therapy in severe cases (Flume et al., 2009). For patients with chronic Pseudomonas aeruginosa colonisation, long-term suppression is typically achieved with inhaled antibiotics such as tobramycin or colistin.
CFTR modulators
What are they?
CFTR modulators are small-molecule drugs designed to improve the function of the defective cystic fibrosis transmembrane conductance regulator protein. Modulators target the basic defect, leading to measurable improvements in lung function, fewer exacerbations, better quality of life, lower sweat chloride, and gains in nutrition for eligible genotypes.
Two main mechanisms are used:
Potentiators, such as ivacaftor, act at the cell surface by helping the CFTR channel open and remain open, thereby improving chloride transport when the protein is present at the membrane but does not function correctly.
Correctors, such as lumacaftor, tezacaftor, and elexacaftor, address defective folding and trafficking of the protein, allowing more of it to reach the cell surface. Correctors are often used in combination with a potentiator to maximise channel activity.
Which medicine for which child?
The choice of medicine depends on the child’s genotype.
Ivacaftor is used for specific gating and conductance mutations, including G551D and R117H, with guidelines providing precise mutation lists and age bands; eligibility must always be checked against the latest licensing and formulary guidance.
Combinations of lumacaftor/ivacaftor or tezacaftor/ivacaftor are used primarily for children with two copies of the Phe508del mutation, with tezacaftor generally preferred because of its more favourable drug interaction profile.
The triple therapy elexacaftor/tezacaftor/ivacaftor—marketed as Kaftrio in the UK and Trikafta in the US—represents the most significant advance to date. It is indicated for most patients with at least one Phe508del allele, including those with Phe508del/minimal-function genotypes. In the UK and Europe, this regimen is now licensed from the age of two years, with weight-appropriate granules and tablets available.
Licensing is rapidly involving to include younger age groups, so it’s important to always conform current cut-offs and formulations locally.
Dosing and age bands:
Granule formulations allow weight-based dosing in younger children and should be taken with fat-containing food to optimise absorption. Labels continue to evolve as younger cohorts are studied, so prescribers must check the latest licensing information before initiating treatment.
Expected outcomes:
Triple therapy with elexacaftor/tezacaftor/ivacaftor produces the largest improvements in clinical trials for those with at least one Phe508del allele:
Clinical trial data show that triple therapy provides the greatest benefits for eligible patients. In those with at least one Phe508del allele, mean absolute improvements in per cent-predicted FEV₁ of around 14 percentage points are observed within 4–24 weeks, accompanied by a 63% reduction in pulmonary exacerbations. Patients also report substantial quality-of-life improvements, with CFQ-R respiratory scores rising by about 20 points—far exceeding the minimal clinically important difference of 4. Biochemically, sweat chloride falls by approximately 42 mmol/L, reflecting meaningful restoration of CFTR function.
Safety, monitoring, and interactions:
Safety monitoring is an essential component of modulator therapy. Baseline and follow-up liver function tests are required due to the risk of transaminase elevation. In preschool children, ophthalmology assessment is recommended because non-congenital cataracts have been reported with ivacaftor-containing regimens.
Lumacaftor/ivacaftor can sometimes cause transient reductions in spirometry, so blood pressure and lung function should be monitored closely, particularly in advanced disease.
Since all modulators are substrates of CYP3A, drug–drug interactions are common, and dose adjustments or avoidance may be required with strong or moderate inhibitors and inducers. Rashes, particularly in females taking triple therapy, should be anticipated and counselled for.
Vaccinations
Annual influenza vaccination and pneumococcal immunisation are recommended for all patients with cystic fibrosis, and varicella vaccination should be considered in those who are non-immune.
Nutrition and Endocrine Care
Most patients require pancreatic enzyme replacement therapy (PERT), with lipase, protease, and amylase supplements taken with all meals and snacks.
Supplementation with fat-soluble vitamins (A, D, E, and K) is also essential. Caloric intake should exceed standard age-specific recommendations, often ranging from 110% to 200%, with increased protein and fat intake. Oral nutritional supplements or enteral feeding may be required in severe cases.
Cystic fibrosis–related diabetes (CFRD) should be screened for annually from the age of ten using an oral glucose tolerance test, and insulin therapy is preferred over oral hypoglycaemics because CFRD is associated with worse lung outcomes (Moran et al., 2010).
Bone health must also be safeguarded, as reduced bone mineral density is common; DXA scans are advised from adolescence, with vitamin D, calcium, or bisphosphonates prescribed where indicated.
Advanced and Specialist Care
For those with advanced disease, lung transplantation remains an important option. Referral should be considered when lung function falls below 30% of predicted, or earlier in cases of rapid decline despite optimal therapy.
Outcomes are better with timely referral rather than late consideration. Looking to the future, new therapeutic approaches are being actively investigated, including gene therapy, novel CFTR correctors, and biologics targeting airway inflammation.
Psychological and Social Support
Finally, psychological and social support are integral to care. Cystic fibrosis is associated with a high treatment burden, an increased risk of depression and anxiety, and the potential for social isolation, particularly during adolescence. Early and routine psychological input for patients and their families can improve adherence, resilience and overall quality of life.
Take-home messages
History-taking is key – ask about cough, poor weight gain and stool pattern.
CF management is multidisciplinary, individualised, and lifelong.
Airway clearance and targeted infection control remain the foundation of care.
CFTR modulators are a major therapeutic breakthrough but require mutation-specific prescribing.
Nutrition and endocrine management are critical for growth and survival.
Psychosocial support is not optional—it is integral to care.
References
Castellani, C., et al., 2018. ECFS best practice guidelines: the 2018 revision. Journal of Cystic Fibrosis, 17(2), pp.153-178.
National Institute for Health and Care Excellence (NICE), 2017. Overview | Cystic fibrosis: diagnosis and management | Guidance | NICE.
Wilson, L.M., Morrison, L. and Robinson, K.A., 2019. Airway clearance techniques for cystic fibrosis: an overview of Cochrane systematic reviews. Cochrane Database of Systematic Reviews, 1(1).
Flume, P.A., et al., 2009. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. American Journal of Respiratory and Critical Care Medicine, 180(9), pp. 802-808.
Middleton, P.G., et al., 2019. Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single Phe508del allele. New England Journal of Medicine, 381(19), pp. 1809-1819.
Moran, A., et al., 2010. Diagnosis, screening, and management of cystic fibrosis-related diabetes mellitus: a consensus report. Diabetes Care, 33(12), pp. 2697-2708.
Benden, C., et al., 2019. Lung transplantation for cystic fibrosis. Lancet Respiratory Medicine, 7(3), pp. 272-284.
Quittner, A.L., et al., 2014. Prevalence and impact of depression in cystic fibrosis. Current Opinion in Pulmonary Medicine, 20(6), pp. 632-639.
Middleton, P.G., Mall, M.A., Dřevínek, P., et al., 2019. Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single Phe508del allele. New England Journal of Medicine, 381(19), pp. 1809–1819.
Heijerman, H.G.M., McKone, E.F., Downey, D.G., et al., 2019. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for Phe508del: a double-blind, randomised, phase 3 trial. Lancet, 394(10212), pp. 1940–1948.
National Institute for Health and Care Excellence (NICE), 2024. Ivacaftor, lumacaftor–ivacaftor, tezacaftor–ivacaftor, and elexacaftor–tezacaftor–ivacaftor for treating cystic fibrosis. Technology appraisal guidance [TA988]. London: NICE.
European Medicines Agency (EMA), 2024. Kaftrio: EPAR – Product Information. European Medicines Agency.
European Medicines Agency (EMA), 2024. Kalydeco, Orkambi, Symkevi: EPAR – Product Information. European Medicines Agency.
US Food and Drug Administration (FDA), 2024. Ivacaftor and combination products – prescribing information. US Food and Drug Administration.
Davies, J.C., Moskowitz, S.M., Brown, C., et al., 2012. VX-770 in subjects with cystic fibrosis who carry a G551D-CFTR mutation: a randomised, double-blind, placebo-controlled trial. New England Journal of Medicine, 366, pp. 1991–2002.
