As a result of the complex and multisystemic involvement of cystic fibrosis (CF) and the need for care by specialists, treatment and follow-up care at specialty centers with multidisciplinary care teams (ie, cystic fibrosis centers) is recommended.
At the time of initial confirmation of the diagnosis, the patient should undergo baseline assessment, investigations, and initiation of therapy. In addition, patient/parent education, including counseling and instructions regarding airway clearance techniques and the use of equipment (eg, nebulizer, spacer for metered-dose inhaler), is recommended.
When a patient presents with complications necessitating hospital admission, these objectives can be obtained during hospitalization. Follow-up outpatient visits are scheduled at 2-3 monthly intervals. Hospital admission is required for treatment of acute pulmonary exacerbation and severe complications.
The primary goals of CF treatment include the following:
Maintaining lung function as near to normal as possible by controlling respiratory infection and clearing airways of mucus
Administering nutritional therapy (ie, enzyme supplements, multivitamin and mineral supplements) to maintain adequate growth
Managing complications
Mild acute pulmonary exacerbations of cystic fibrosis can be treated successfully at home with the following measures:
Increasing the frequency of airway clearance
Inhaled bronchodilator treatment (especially if bronchial hyperresponsiveness is present or as part of airway clearance [inhaled bronchodilator followed by chest physical therapy and postural drainage])
Chest physical therapy and postural drainage
Increasing the dose of the mucolytic agent dornase alfa (Pulmozyme)
Use of oral antibiotics (eg, oral fluoroquinolones)
Medications used to treat patients with cystic fibrosis may include the following:
Pancreatic enzyme supplements
Multivitamins (including fat-soluble vitamins)
Mucolytics
Nebulized, inhaled, oral, or intravenous antibiotics
Bronchodilators
Anti-inflammatory agents
Agents to treat associated conditions or complications (eg, insulin, bisphosphonates)
Agents devised to potentially reverse the abnormalities in chloride transport (eg, ivacaftor [2] , lumacaftor/ivacaftor [50] )
In addition to mucolytics such as dornase alfa, hypertonic saline inhalation has been proposed as a therapy to increase hydration of airway surface liquid in patients with CF.[51] Elkins et al reported that patients receiving 7% hypertonic saline (4 mL via nebulizer bid) had improved lung function and fewer pulmonary exacerbations, compared with patients receiving normal saline in a similar fashion.[52] Hypertonic saline was not associated with worsening bacterial infections or inflammation.
The Pulmonary Therapies Committee of Cystic Fibrosis Foundation recommends long-term use of hypertonic saline for patients with cystic fibrosis aged 6 years or older to improve lung function and to reduce the number of exacerbations.[53]
When meconium ileus is diagnosed prenatally, the authors recommend immediate referral to a tertiary care facility equipped to manage the needs of the mother, fetus, neonate, and family. A multidisciplinary team of perinatologists, neonatologists, obstetricians, pediatric surgeons, and CF specialists is prepared for the delivery of these high-risk neonates.
The team performs serial sonographic examinations on a monthly basis prior to delivery, a procedure that allows early detection of potential complications to prepare clinicians for special or urgent medical or surgical needs upon delivery.
The cystic fibrosis transmembrane conductance regulator (CFTR), ivacaftor (Kalydeco), was approved by the FDA in January 2012. A study by Ramsey et al observed lung function improvement at 2 weeks that was sustained through 48 weeks. The study also observed improvements in risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight gain, and concentration of sweat chloride.[2] Ivacaftor was initially approved for adults and children aged 6 years or older who have at least 1 copy of the G551D mutation in the CFTR gene. In February 2014, ivacaftor gained approval for an additional 8 CFTR gene mutations - G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R.[54] In December 2014, ivacaftor gained approval for the 10th CFTR gene mutation, R117H. The drug was approved by the FDA for children aged 2-5 years for all 10 CFTR mutations in March 2015.
Approval of lumacaftor/ivacaftor was based on data from 2 Phase III studies (TRAFFIC and TRANSPORT) that enrolled more than 1100 people with CF aged 12 years and older who had 2 copies of the F508del mutation. People with 2 copies of the F508del mutation represent the largest group of people with CF. Of the 30,000 people in the United States with CF, approximately 8,500 individuals aged 12 years or older have 2 copies of the F508del mutation. Patients treated with lumacaftor/ivacaftor experienced statistically significant improvements in lung function. Patients also experienced reductions in pulmonary exacerbations and improvements in body mass index (BMI).[50]
While corticosteroids have been shown to slow the progression of lung disease, they also had significant adverse effects, especially on growth.[55]
A 2012 study exploring new treatment strategies for CF assessed whether long-term treatment with inhaled mannitol improves lung function and morbidity. Results showed that adding inhaled dry powder mannitol to standard therapy for CF produced sustained improvement in lung function for up to 52 weeks.[56]
In March 2013, the FDA approved tobramycin inhalation powder for the treatment of CF patients with P aeruginosa.[57] The powder is inhaled twice daily for 28 days; treatment is then stopped for 28 days before resuming. In a study of 95 pediatric and adult CF patients infected with P aeruginosa, those treated with inhaled tobramycin powder experienced a significant increase in forced expiratory volume in 1 second (FEV1) compared with placebo-treated patients (12.5% vs 0.09%).
Bisphosphonate treatment initiated during childhood may help counter the bone mineral density (BMD) loss seen in patients with CF, according to the results of a 2013 prospective, open-label observational study of the effects of calcium and vitamin D on BMD in 171 young CF patients, which was followed by a randomized, placebo-controlled trial of the bisphosphonate alendronate.[58, 59]
In the first part of the study, calcium and vitamin D intake were monitored; patients whose BMD had not improved more than 5% within 1 year (75%) joined the second part of the study, in which 128 patients were randomly assigned to treatment with either daily oral alendronate or placebo for 1 year.[59] Among the 65 patients who received alendronate, BMD increased by 16.3%, compared with 3.1% among the 63 patients who received placebo. Among the treated patients, approximately one third attained a BMD that was normal for their ages.
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