Study to Investigate Safety, Tolerability, Pharmacokinetics & Pharmacodynamics of Single & Repeat Doses of GSK2269557

The study will comprise three Parts: Part A will consist of two cohorts of healthy male volunteers to assess the safety, tolerability and pharmacokinetics of ascending single doses of nebulised GSK2269557. Blinded safety and available PK data will be reviewed before each dose escalation. Part B will be one cohort to examine the safety, tolerability and pharmacokinetics of a repeated dose of GSK2269557 given by nebuliser for 7 days in healthy male volunteers. The total daily dose will be the same as, or lower than, doses that are well tolerated in Part A. Part C will consist of two cohorts of single nebulised doses in healthy male smokers, to assess pharmacodynamic endpoints in sputum and bronchoalveolar lavage.