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The aim of this study was to evaluate the effect of negative mood states at the moment of questionnaire, and other patient and disease characteristics on quality of life (QoL) in patients with asthma. The study groups were composed of 116 stable adult asthmatic patients and 116 age and sex matched healthy subjects. We used Short-Form Health Survey-36 (SF-36) for the assessment of general QoL in all participants, and the Asthma Quality of Life Questionnaire (AQLQ) for the assessment of disease specific QoL in patients with asthma. We evaluated negative mood in all subjects with a questionnaire including six mood subscales in three categories (nervous-anxious, hostile-angry and fearful-panicky). Negative mood scores were not different between asthmatic and comparison groups (p=0.4), but both SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were significantly lower in asthmatic group (p=0.003 and p=0.001, respectively). Multiple linear regression analysis in all study population indicated that both reduced PCS and MCS scores of SF-36 were associated with negative mood score (beta=-0.28, p<0.001 and beta=-0.37, p<0.001, respectively) and with FEV(1)% (beta=0.19, p=0.001 and beta=0.25, p<0.001, respectively) after adjusting for age, female sex, and the presence of asthma. On the other hand, multiple linear regression analysis in patients with asthma revealed that negative mood score and disease severity score were significant predictors for overall score of AQLQ after adjusting for other patient and disease characteristics (beta=-0.17, p=0.008 and beta=-0.64, p<0.001, respectively). The level of negative mood and disease severity in asthmatics significantly impair QoL. Thus, considering that one of the main objectives of health care should be preserving a satisfactory QoL in asthmatics, the presence and seriousness of negative mood and their effects on QoL should be taken into account as part of the clinical evaluation in asthmatics.