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]

SAQ 2 (10 marks)

A 12-year-old boy with cystic fibrosis and chronic Pseudomonas infection presents with two weeks of increased cough, more purulent sputum, breathlessness, reduced appetite and a 2 kg weight loss. His FEV1 has fallen from a personal best of 85 percent predicted to 68 percent predicted. [8] [7]

1. What is your diagnosis and how did you reach it? (3) [8]
2. Outline your management of this episode. (4) [7] [8]
3. He later develops new wheeze, a rising IgE and new infiltrates that do not respond to antibiotics. What complication do you suspect and how would you treat it? (3) [8]

Model answer — SAQ 2

(1) Diagnosis (3). This is a pulmonary exacerbation, diagnosed from the change from his personal best rather than from any single sign. He has increased cough, more purulent sputum, new breathlessness, reduced appetite and weight loss, and, objectively, a fall in FEV1 from 85 to 68 percent predicted. In cystic fibrosis the exacerbation is defined by this deterioration from the child's usual state, and it matters because each severe exacerbation can cause a step-down in long-term lung function. [8] [7]

(2) Management (4). I would treat promptly and aggressively. I would intensify airway clearance physiotherapy and continue his mucoactive nebulisers, send sputum for culture and sensitivities, and start intravenous anti-pseudomonal antibiotics — typically two agents such as tobramycin with an anti-pseudomonal beta-lactam like ceftazidime — for about 14 days, using two drugs to limit resistance and guided by his prior isolates. I would optimise nutrition and calories during the illness, monitor his response with spirometry, and involve the multidisciplinary team. [7] [8]

(3) ABPA (3). New wheeze with a rising total IgE and new infiltrates that do not respond to antibacterial treatment suggests allergic bronchopulmonary aspergillosis, an allergic reaction to Aspergillus rather than a bacterial infection. I would confirm it with total and Aspergillus-specific IgE and imaging, and treat it with oral corticosteroids and an antifungal such as itraconazole, rather than simply escalating antibiotics, because untreated allergic bronchopulmonary aspergillosis causes further lung damage. [8] [1]