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A minimal clinically important difference (MCID) is important in evaluating clinical measures such as health-related quality of life (HRQOL) instruments. The purpose of this analysis is to evaluate MCID for the UCSD Shortness of Breath Questionnaire (SOBQ).We examined measures of disease-specific and generic HRQOL in 164 subjects with chronic lung disease before and after pulmonary rehabilitation. Subjects completed 2 disease-specific [SOBQ, Chronic Respiratory Questionnaire (CRQ)], and 2 generic HRQOL measures [RAND-36 and Quality of Well-Being Scale (QWB)]. The MCID was calculated using 3 methods: effect size, standard error of the measurement (SEM), and comparison between the SOBQ and CRQ Dyspnea scores.HRQOL measures correlated moderately with measures of maximum exercise tolerance but not with lung function (FEV1, FVC). HRQOL and exercise capacity improved significantly after pulmonary rehabilitation. A change of 5 units for the SOBQ appears to be a reasonable MCID for this instrument. The calculated MCIDs for the CRQ (0.47/item) and QWB (0.031) were consistent with established change scores.The MCID calculated using an SEM approach for the SOBQ, CRQ, and QWB meets clinical expectations for these instruments. HRQOL measures provide information that is complementary and distinct from physiological measures.