What maintenance therapy is recommended for a 14-year-old patient with a history of cystic fibrosis (CF), presenting with worsening chronic cough, increased sputum production, dyspnea, wheezing, digital clubbing, and apical crackles, due to a mutation affecting the cystic fibrosis transmembrane conductance regulator (CFTR) sodium chloride exchange channels?

From the Guidelines

The patient with cystic fibrosis should receive comprehensive maintenance therapy including airway clearance techniques, inhaled medications such as dornase alfa and hypertonic saline, CFTR modulators, chronic antibiotic therapy, and nutritional support to improve lung function, quality of life, and reduce exacerbations. The maintenance therapy for a 14-year-old patient with cystic fibrosis (CF) should prioritize treatments that improve lung function, quality of life, and reduce exacerbations, as recommended by the CF Foundation guidelines 1.

Key Components of Maintenance Therapy

• Airway clearance techniques (ACTs) such as chest physiotherapy, flutter devices, or high-frequency chest wall oscillation performed 2-4 times daily to improve mucus clearance.
• Inhaled medications:
  • Dornase alfa (Pulmozyme) 2.5mg once daily to break down DNA in sputum, as recommended for individuals with CF, 6 years of age and older, with moderate to severe lung disease 1.
  • Hypertonic saline 7% solution twice daily to improve mucus clearance, as recommended for individuals with CF, 6 years of age and older 1.
  • Bronchodilators like albuterol before airway clearance to help improve lung function.
• CFTR modulators:
  • Ivacaftor for individuals with at least one G551D CFTR mutation, as strongly recommended by the Pulmonary Clinical Practice Guidelines Committee 1.
  • Other CFTR modulators such as lumacaftor/ivacaftor, elexacaftor/tezacaftor/ivacaftor may be considered based on the patient's specific mutation.
• Chronic antibiotic therapy:
  • Inhaled tobramycin or aztreonam on alternating months for Pseudomonas infections, as recommended for individuals with CF, 6 years of age and older, with moderate to severe lung disease and Pseudomonas aeruginosa persistently present in cultures of the airways 1.
• Nutritional support:
  • Pancreatic enzyme replacement therapy (PERT) taken with meals and snacks to improve nutritional status.
  • Fat-soluble vitamin supplements (A, D, E, K) to prevent deficiencies.
  • A high-calorie, high-protein diet to support growth and development.

Additional Considerations

• Anti-inflammatory therapy with azithromycin three times weekly may help reduce pulmonary exacerbations, as recommended for individuals with CF, 6 years of age and older, with Pseudomonas aeruginosa persistently present in cultures of the airways 1.
• The patient's specific mutation and lung disease severity should be considered when selecting CFTR modulators and chronic antibiotic therapy.
• Regular monitoring of lung function, nutritional status, and adherence to treatment is essential to adjust the maintenance therapy as needed.

From the FDA Drug Label

PULMOZYME has been evaluated in a randomized, placebo-controlled trial of clinically stable cystic fibrosis patients, 5 years of age and older, with baseline forced vital capacity (FVC) greater than or equal to 40% of predicted and receiving standard therapies for cystic fibrosis. Patients were treated with placebo (325 patients), 2. 5 mg of PULMOZYME once a day (322 patients), or 2. 5 mg of PULMOZYME twice a day (321 patients) for six months administered via a Hudson T Up-draft II® nebulizer with a Pulmo-Aide® compressor. Both doses of PULMOZYME resulted in significant reductions in the number of patients experiencing respiratory tract infections requiring use of parenteral antibiotics compared with the placebo group

The recommended maintenance therapy for a 14-year-old patient with a history of cystic fibrosis (CF) is dornase alfa (PULMOZYME), administered at a dose of 2.5 mg once or twice daily via a nebulizer, as it has been shown to reduce the incidence of respiratory tract infections and improve lung function in patients with CF, including those with an FVC ≥40% of predicted 2.

• Key benefits of dornase alfa include:
  • Reduced risk of respiratory tract infections
  • Improved lung function (FEV1)
• Dosing considerations:
  • Patients with baseline FVC > 85% may benefit from twice daily dosing
  • Twice daily dosing may be required in older patients (> 21 years)

From the Research

Maintenance Therapy for Cystic Fibrosis

The patient's symptoms, such as worsening chronic cough, increased sputum production, dyspnea, wheezing, digital clubbing, and apical crackles, are consistent with cystic fibrosis (CF) exacerbation.

• Azithromycin maintenance therapy has been shown to improve respiratory function in patients with CF 3, 4.
• The recommended dose of azithromycin is 22-30 mg/kg/week, which can be divided into one to seven dosing moments depending on patient preference and gastrointestinal tolerance 3.
• However, concomitant use of azithromycin and intravenous tobramycin for pulmonary exacerbation treatment may be associated with poorer clinical outcomes 5.
• Other maintenance therapies for CF include mucolytics, such as dornase alfa, and CFTR modulators, such as ivacaftor and elexacaftor-tezacaftor-ivacaftor, which have been shown to improve lung function and reduce pulmonary exacerbations 6.
• Inhaled antibiotics, such as colistin, tobramycin, aztreonam lysine, and levofloxacin, are also used as maintenance treatment for CF patients with chronic Pseudomonas aeruginosa infection 7.

Considerations for Treatment

• The choice of maintenance therapy should be individualized based on the patient's specific needs and medical history.
• The potential benefits and risks of concomitant therapy with azithromycin and other medications, such as intravenous tobramycin, should be carefully considered.
• Regular monitoring of lung function and adjustment of treatment as needed are crucial to managing CF effectively.