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Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE).Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls.Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO2 and plasma NE occurred in the late exercise phase after the ‘break point’. Compared with controls, patients with IPF had significantly higher HCO3- levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (ΔBorg scale/Δminute ventilation) correlated with the pH slope (ΔpH/Δoxygen uptake) (before the break point: r = −0.537, P = 0.0022; r = −0.886, P < 0.0001, after the break point) and the NE slope (ΔNE/Δoxygen uptake) (before the break point: r = 0.481, P = 0.0075; R = 0.784, P < 0.0001, after the break point).In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.