Therapy With Macrolides in Patients With Cystic Fibrosis

Allyson S. Gaylor, Pharm.D., Joan C. Reilly, Pharm.D.

Pharmacotherapy. 2002;22(2) 

In This Article

Cystic Fibrosis and Diffuse Panbronchiolitis

Macrolide antibiotics have been suspected of having beneficial antiinflammatory effects on asthma since the 1950s. The theory for this beneficial action was presumed to be a steroid-sparing effect.[31,32,33] This theory was dismissed when troleandomycin was found to inhibit the clearance of methylprednisolone and theophylline, standard treatments at the time.[34,35]

One disorder in which macrolide antibiotics are most beneficial is DBP. Research on this condition provided much of the background data on therapy with macrolides for purposes other than their antibacterial properties.

Cystic fibrosis is the most common lethal autosomal recessive disease in people of northern European descent, with an incidence of 1/2500.[36] It is caused by a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, of which there are more than 600 different mutations.[36] Such mutations lead to chloride transport abnormalities. Dehydration of luminal secretions in lungs, pancreas, and liver are due to atypical chloride efflux and sodium influx into epithelial cells.[36] Cystic fibrosis is characterized by respiratory, gastrointestinal, pancreatic, and hepatic abnormalities. Ninety-five percent of its morbidity and mortality is associated with chronic obstructive lung disease.[37]

Respiratory function is compromised by copious thick, tenacious secretions, mucus plugging, inflammatory response, and recurrent infectious bronchitis. Patients typically become colonized with Staphylococcus aureus initially but are colonized with mucoid species of Pseudomonas aeruginosa as the disease progresses. Progression varies markedly among patients. Life expectancy nearly doubled from 18 to 32 years in the past 2 decades.[38] Much of this improvement is likely due to increased understanding of the disease as well as improved antibiotic and nutrition therapies. New research has focused on the inflammatory component of the disease, but despite these improvements some patients die at a young age due to a fulminant pulmonary process.

There are remarkable parallels between DPB and cystic fibrosis. First reported in Japan in 1969, DPB is characterized by chronic inflammation and inflammatory cell infiltration in the respiratory bronchioles.[39] Chronic cough and profuse amounts of sputum are frequent symptoms. Respiratory bronchioles become obstructed and dilated. Patients often are infected with Haemophilus influenzae early in the disease, followed by mucoid strains of P. aeruginosa as the disease progresses.[40,41] Colonization with P. aeruginosa leads to bronchiectasis and cystic changes. Left untreated, 5-year survival is 42%.[41]

Administration of macrolide antibiotics improves clinical symptoms and prognosis of patients with DPB who have chronic P. aeruginosa infections.[2,33,39,42] Long-term, low-dosage erythromycin improves symptoms and increases 10-year survival from 12.4% to greater than 90% in patients with DPB, even those colonized with mucoid strains of P. aeruginosa.[43] Similarities between the disease states led some to question if the pathophysiology is related.[40,44] This begs the question whether macrolide antibiotics would be beneficial in patients with cystic fibrosis and, if so, how they work.


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