Patient description: A 39-year-old man came to the clinic with cough and shortness of breath that was not relieved by his inhaler. He had these symptoms for 5 days during the past 2 weeks. He doubled his oral corticosteroids in the past week. He is a chef with a history of asthma for 3 years, suffering from frequent cough, wheezing, and shortness of breath and chest tightness. The symptoms become more bothersome within 1-2 hours of starting work every day and worsen throughout the work week. His symptoms improve within 1-2 hours outside the workplace. Spirometry was performed revealing a forced expiratory volume in the first second (FEV1) of 63% of the predicted. His past medical history is significant for seasonal allergic rhinitis in the summer. He doesn't smoke or use illicit drugs. His family history is significant for asthma in his father and sister. He currently uses inhaled corticosteroid (ICS) and fluticasone 500 mcg/salmeterol 50 mcg, one puff twice daily.

Clinical trial eligibility criteria: eligible ages (years): 18.0-65.0,  Asthma A subject will be eligible for in this study only if all of the following apply ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) Single QTc, QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent A female subject is eligible to participate if she is of Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the protocol approved contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks should elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method Child-bearing potential and is abstinent or agrees to use one of the protocol approved contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit Capable of giving informed consent, which includes compliance with the study requirements and restrictions listed in the consent form BMI within the range 18 and 35 kg/m2 (inclusive)  A subject will not be eligible for in this study if any of the following apply: Medical Condition Exclusions Subjects who have a current diagnosis or a history of asthma, excluding childhood asthma which has been discharged by physician (e.g., for any FTIH where risk of bronchoconstriction is unknown, or compound specific where risk of bronchoconstriction). This must be documented in the subject's medical notes Subjects who have a current and previous diagnosis of COPD. This must be documented in the subject's medical notes Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening A positive test for HIV antibody Pregnant females as determined by positive serum hCG test at screening or prior to dosing Lactating females Subject is mentally or legally incapacitated Unwillingness or inability to follow the procedures outlined in the protocol. Medical Exclusions