Pharmacy Times offers relevant, clinical information for pharmacists that they can use in their daily practice. These include OTC and Rx product news, disease conditions, patient education guides, drug diversion and abuse, and more.
Issue link: http://pharmacytimes.epubxp.com/i/614520
December 2015 PharmacyTimes.org 101 Treatment of CF Traditionally, CF management has focused on treating the symptoms rath- er than the underlying disease process, centering on relieving airway obstruc- tion, improving ventilation, increasing expectoration of retained sputum, and treating respiratory infections. 14 As such, CF therapy is centered on treating acute pulmonary exacerbations with systemic antibiotic therapy for a period of 10 to 14 days. In addition, chronic suppressive therapy has been directed at prolonging the time to another exacerbation and possible delay in chronic colonization of pathogens in the CF lung. However, since the discovery of the CFTR gene, extensive research has gone into under- standing the functional consequences of the mutations and development of strate- gies that can be used to alter proteomics or modify the mutations. Treatment of Respiratory Symptoms Inflammation indisputably plays a cen- tral role in lung destruction in patients with CF, and symptomatic therapy is directed at preventing the infection and alleviating the inflammation. 6 Doing this in a timely manner is key to improving the quality of life of these patients. 15,16 Obstruction can be alleviated with phys- iotherapy, bronchodilators, dornase alfa, and hypertonic saline solution, whereas prevention of inflammation requires using anti-inflammatory agents, such as macrolide antibiotics with anti-inflam- matory actions (azithromycin) and high- dose ibuprofen. Prevention of infection requires initiating infection-control strat- egies as well as acute and chronic antibi- otic therapy. 14 Physiotherapy Techniques Physiotherapy techniques aim to relieve airway obstruction, improve ventilation, and increase expectoration of retained sputum. Chest physiotherapy is time- consuming, however, making adherence a serious issue. 17 There are various methods to deliv- er this chest percussion and drainage, with several devices available to help maximize efforts of this therapy. Recent evidence suggests that exercise can be an alternative to chest physiotherapy given its benefit and the improvement in adherence. The most common rea- sons cited by patients for nonadher- ence to physiotherapy include a sense of well-being, time, and interruption of life activities. 14,18 During an acute pulmonary exacerbation, patients are instructed to increase the frequency of this therapy to help facilitate mucociliary clearance. Pharmacists and other health care pro- fessionals need to be supportive of these efforts since they consume up to 2 hours per day. A careful review of their medi- cation therapies can help streamline the time patients may need, as well as a strategy to make sure medications are available for the patient. An encouraging reminder by telephone or e-mail, along with an in-person discussion asking if they are having any problems, may be helpful and reinforce adherence. Bronchodilators Bronchodilators are a standard compo- nent of the CF treatment regimen, with aerosolized, short-acting, b 2 -adrenergic receptor agonists being the most com- monly prescribed. 5 They provide symp- tomatic relief, facilitate expectoration, and are often prescribed on an as-needed basis. 5 Traditional doses of albuterol 2.5 mg either by nebulizations or by metered dose inhalers are often used prior to some other respiratory treatment (ie, dornase alfa, hypertonic saline, or antibiotics) to allow for better deposition into the airway. Mucolytic agents, such as recombi- nant human DNase I or dornase alfa 2.5 mg daily, cleave extracellular DNA and decrease purulent sputum viscosity; they have demonstrated modest increases in forced expiratory volume in the first sec- ond of expiration (FEV 1 ) (3%-16%) in patients with chronic productive cough and moderate to severe obstructive air- way disease. 5,10,19-22 The adverse effect (AE) profile of this drug is quite benign and is often one of the first aerosol- ized drug therapies instituted in young patients with CF. This therapy is given on a daily basis by aerosol administra- tion. Since it is an enzyme, it cannot be mixed with other aerosol prepara- tions for fear that it might denature the protein. Dornase alfa has been used in patients of all ages to help maintain or improve mucociliary clearance. Restoring the pericellular fluid level with 7% sodium chloride for inhalation has demonstrated a reduction in the pro- gressive loss of lung function in patients with CF and a decreased incidence of acute pulmonary exacerbations over time. 23 Studies from Australia demon- strate a 56% reduction in the incidence of pulmonary exacerbation in patients using this therapy 2 times a day. 23 Anti-Inflammatory Agents Anti-inflammatory agents, such as ibu- profen, may help inhibit migration, adher- ence, and aggregation of neutrophils and slow down the annual rate of decline in lung function in patients with CF. 24 Konstan et al demonstrated a sig- nificant reduction in the decline of lung function with children taking high-dose ibuprofen (20-30 mg/kg twice daily) over a 4-year period. 25 This approach required dosing to specific peak serum concentrations (50-100 mcg/mL) and careful monitoring of patients for possi- ble GI toxicity given its chronic adminis- tration. 25,26 Follow-up analysis of nearly 1400 patients in the CF Foundation patient registry demonstrated a 29% reduction in the loss of lung function per year, with only a very small increase in GI bleeding requiring hospitalization. A more widely used approach has been with the use of macrolide antibiot- ics. Azithromycin has also been shown to decrease production of cytokines and proinflammatory mediators and interfere with biofilm formation in the airways of patients with CF. 27 Saiman et al demon- strated a 50% decrease in the frequency of acute exacerbation in a large cohort of patients assigned to azithromycin therapy during their study. 27 Doses of either 250 mg or 500 mg 3 times a week were used over a 6-month period. Macrolides also have antibacterial properties against gram-positive and atypical infectious organisms. 24,28 Acute Antibiotic Therapy Antibiotic therapy is the mainstay of current CF therapy, unquestionably con- tributing to the improved survival of patients with CF. 14 Bacterial pathogens remain one of the biggest challenges fac- ing patients with CF, and treatment with chronic suppressive therapy with inhaled antibiotics, in conjunction with intrave- nous antibiotics for acute episodes, may help to initially improve then stabilize and maintain or slow the decline of pul- monary function. 14 Upon presentation for an acute pulmo-