Cystic fibrosis: pulmonary and multidisciplinary management — formative SAQs

SAQ 1 (10 marks)

An 8-year-old girl with cystic fibrosis attends her routine clinic review. She is well and at her personal best spirometry, but her cough swab, which has never previously grown Pseudomonas, has now grown Pseudomonas aeruginosa. Her genotype is homozygous Phe508del. ^{[11] [1]}

1. Outline the four pillars of her ongoing pulmonary management. (4) ^[8]
2. What is your immediate response to the new Pseudomonas isolate, and why? (3) ^[11]
3. What disease-modifying therapy is she likely to be eligible for, and what does it do? (3) ^[1]

Model answer — SAQ 1

(1) Four pillars (4). Her pulmonary care rests on four pillars delivered daily and together. First, airway clearance physiotherapy and exercise to clear retained mucus. Second, mucoactive nebulisers — dornase alfa at 2.5 mg once daily to thin the DNA-rich sputum and hypertonic saline to rehydrate the airway surface. Third, an anti-infective strategy that eradicates new infection, suppresses chronic infection and treats exacerbations. Fourth, CFTR modulator therapy for eligible genotypes, all coordinated by the multidisciplinary team alongside high-calorie nutrition with pancreatic enzymes. ^{[8] [4]}

(2) First Pseudomonas isolate (3). This is a first isolate of Pseudomonas from a previously negative child, so I would attempt eradication immediately rather than observe. I would start an eradication regimen, typically inhaled tobramycin with or without oral ciprofloxacin, because prompt treatment of early Pseudomonas clears the organism in most children and delays the transition to chronic infection, which is a key driver of accelerated lung decline. I would repeat cultures to confirm clearance. ^{[11] [7]}

(3) Disease-modifying therapy (3). As a Phe508del homozygote she carries two copies of the commonest mutation, so she is eligible for the triple CFTR modulator elexacaftor-tezacaftor-ivacaftor, which combines two correctors and a potentiator to restore function of the defective CFTR protein. It improves lung function, reduces pulmonary exacerbations and improves weight and quality of life, and it is added to, not a replacement for, her airway clearance, mucoactive therapy, infection management and nutrition. ^{[1] [8]}