These associations further justify investigation of MMP-9 and TIMP-1 as biomarkers for short- to medium-term FEV1 decline and mortality in patients with CF.

Background and ObjectiveCysteamine is licensed for use in nephropathic cystinosis but preclinical data suggest a role in managing cystic fibrosis (CF). This study aimed to determine whether oral cysteamine is absorbed in adult CF patients and enters the bronchial secretions. Tolerability outcomes were also explored.MethodsPatients ≥18 years of age, weighing >50 kg with stable CF lung disease were commenced on oral cysteamine bitartrate (Cystagon®) 450 mg once daily, increased weekly to 450 mg four times daily. Serial plasma cysteamine concentrations were measured for 24 h after the first dose. Participants were reviewed every week for 6 weeks, except at 4 weeks. Plasma cysteamine concentrations were measured 8 h after dosing when reviewed at 1, 2 and 3 weeks and 6 h after dosing when reviewed at 5 weeks. Sputum cysteamine concentration was also quantified at the 5-week assessment.ResultsSeven of the ten participants reported adverse reactions typical of cysteamine, two participants discontinued intervention. Following the first 450-mg dose, mean (SD) maximum concentration (Cmax) was 2.86 (1.96) mg/l, the time corresponding to Cmax (Tmax) was 1.2 (0.7) h, the half-life (t½) was 3.7 (1.7) h, clearance (CL/F) 89.9 (30.5) L/h and volume of distribution (Vd/F) 427 (129) L. Cysteamine appeared to accumulate in sputum with a median (interquartile range) sputum:plasma cysteamine concentration ratio of 4.2 (0.98–8.84).ConclusionOral cysteamine is absorbed and enters the bronchial secretions in patients with CF. Although adverse reactions were common, the majority of patients continued with cysteamine. Further trials are required to establish the risk benefit ratio of cysteamine therapy in CF.

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