Cystic fibrosis lung transplantation

Dosanjh AK, Elashoff D, Robbins RC. The bronchoalveolar lavage fluid of cystic fibrosis lung transplant recipients demonstrates increased interleukin-8 and elastase and decreased IL-10. J Interferon Cytokine Res 1998 18 851. 

Nunley DR, Ohori P, Grgurich WF, lacono AT, Williams PA, Keenan RJ, Dauber JH (1998) Pulmonary aspergillosis in cystic fibrosis lung transplant recipients. Chest 114 1321-1329... 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

The first combined heart-lung transplant was performed in 1981 at Stanford University. Combined heart-lung donors need to satisfy both the requirements already described separately. Combined heart-lung transplant is recommended in patients with congenital problems affecting these organs, pulmonary hypertension and/or cystic fibrosis. The recipients for the combined transplant are recommended to be less than 55 years old. Survival rates are 79, 66, and 54% at 1 month, 1 year and 3 years, respectively, after transplantation. 

Ierano, T., Siiipo, A., Sturiale, L., Garozzo, D., Corns, P., Perry, J., Lanzetta, R., Parrilli, M., De Soyza, A., Molinaro, A. Structural elucidation of a novel B. cenocepacia ET-12 lipooligosac-charide isolated from a cystic fibrosis patient after lung transplantation. Eur J Org Chem 7 (2010a) 1299-1306. 

Couetil, J.R, Houssin, D.R, Donsset, B.E., Chevalier, P.G., Gulnvarch, A., Loumet, D., Achkar, A., Carpentier, A.F. Combined heart-lung-liver, double lung-hver, and isolated hver transplantation for cystic fibrosis in children. Transpl. Int. 1997 19 33-39... 

A 29-year-old man received a double lung transplantation for end-stage cystic fibrosis. After uneventful surgery, he was accidentally given ten times the intended dose of ciclosporin (30 instead of 3 mg/kg) and 18 hours later became anuric. His blood ciclosporin concentration was 4100 ng/ml. Hemodialysis was required for 6 weeks. A renal biopsy 7 weeks later showed typical features of acute tubular necrosis and lesions that resembled chronic nephrotoxicity. Renal function was stiU abnormal when he died from another cause 14 weeks after the accidental overdose. 

A 17-year-old man with cystic fibrosis who took itraconazole after a lung-Uver transplant had high trough concentrations of tacrolimus, despite the relatively low dosage (0.1-0.3 mg/kg/day) (113). 

The pharmacokinetics of tobramycin in patients with cystic fibrosis is significantly altered after lung transplantation, and early and close drug monitoring is recommended (43). 

Bauldoff GS, Nunley DR, Manzetti JD. Use of aerosolized colistin sodium in cystic fibrosis awaiting lung transplantation. Transplantation 64 748-752, 1997. 

Yankaskas JR, Westerman JH, Thompson JT, et al. Improved results of lung transplantation for patients with cystic fibrosis. J Thorac Cardiovasc Surg 1995 109 224-234. 

Tsang VT, Johnston A, Heritier F, Leaver N, HodsonME, YacoubM Cyclosporin pharmacokinetics in heart-lung transplant recipients with cystic fibrosis. Fur J CUn Pharmacol (1994) 46, 261-5. 

A study in heart-lung transplant patients with cystic fibrosis found that they needed almost five times the oral dose of ciclosporin of other patients, confirming other studies in these patients that had shown a very much reduced bioavailability of oral ciclosporin. This is probably a reflection of the generally poor digestion and absorption in cystic fibrosis patients. The addition of pancreatic enzymes (Creori) was not found to improve this poor ciclosporin bioavailability. No adverse effects were reported. ... 

The exact mechanisms of voriconazole-associated photosensitivity are unknown, but inhibition of retinoid metabolism or a direct phototoxic effect of voriconazole or its N-oxide main metabolite, formed by the action of CYP2C19, has been implicated. There was no significant correlation between the incidence of photosensitivity and voriconazole serum concentrations in six children with allergic bronchopulmonary aspergillosis [3T]. In a retrospective study of 24 lung transplant recipients with cystic fibrosis who took voriconazole, heterozygous carriers of the CYP2C19 2 allele required lower maintenance doses than... 

Tacrolimus The co-prescription of posaconazole with tacrolimus has been evaluated in 14 lung transplant recipients with cystic fibrosis. Posaconazole inhibited CYP3A4-mediated tacrolimus metabolism, resulting in a threefold reduction in tacrolimus dosage requirements f4T]. 

Berge M, Chevalier P, Benammar M, Guillemain R, Amrein C, Lefeuvre S, Boussaud V, Billaud EM. Safe management of tacrolimus together with posaconazole in lung transplant patients with cystic fibrosis. Ther Drug Monit 2009 31 396-9. 

Liver Hepatotoxicity was retrospectively evaluated in a cohort study in 105 lung transplant recipients taking voriconazole [25 ]. Age less than 40 years, cystic fibrosis, use of azathioprine, history of liver disease and early initiation of voriconazole were associated with hepatotoxicity and in multivariable logistic regression analysis, perioperative initiation of voriconazole was independently associated with hepatotoxicity. 

Caronia CG, Silver P, Nimkoff L, et al. Use of bilevel positive airway pressure (BIPAP) in end-stage patients with cystic fibrosis awaiting lung transplantation. Clin Pediatr (Phila) 1998 37(9) 555-559. 

Marom E, McAdams H, Palmer S et al (1999) Cystic fibrosis usefulness of thoracic CT in the examination of patients before lung transplantation. Radiology 213(l) 283-288 Matas A, Schnitzler M (2004) Payment for living donor (vendor) kidneys a cost-effectiveness analysis. Am J Transplant 4(2) 216-221... 

In 1983 the Toronto Lung Transplant Group (1986) performed the first single-lung transplantations for patients with end-stage chronic obstructive pulmonary disease and advanced pulmonary fibrosis. Their technique was later expanded to bilateral sequential single-lung transplantation for patients with bronchiectasis and cystic fibrosis. 

Since the early experimental success with gene therapy in the 1990s, the clinical use of gene therapy has been proven to be difficult. Phase I clinical trials for pulmonary diseases have focused primarily on cystic fibrosis and more recently on lung cancer (109,110). Although gene therapy for lung transplantation has seen increased experimental success, no clinical trials have been conducted. 

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