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In the aforementioned Equation?1, �� is an estimate, and the value of DM is determined over two separate periods at different inspired oxygen fraction values during which several factors may influence the measurement.25 Different techniques, including steady-state, intrabreath and rebreathing techniques, may be used to estimate DLCO.26�C28 The single-breath technique is the method of choice, as it does not require arterial blood sampling or meticulous [http://www.selleckchem.com/products/Tenofovir.html Tenofovir cell line] timing of alveolar samples. The measurement is usually performed according to the joint ATS/ERS statement.29 Reference values for DLCO are determined in relation to gender, age, height, weight and haemoglobin concentration.29 The reference values of Miller and associates30 were developed in Michigan, and another set of reference equations for non-smoking Chinese subjects was developed in Hong Kong.31 A decrease in the gas exchange area of the lungs or the volume of blood in the pulmonary capillaries, an increase in the alveolocapillary membrane thickness, and ventilation-perfusion mismatching will lead to a reduction in DLCO.32 Low DLCO has been generally described in interstitial lung diseases and sarcoidosis.24 Small airway disease, [https://en.wikipedia.org/wiki/Sitaxentan Sitaxentan] chronic airway inflammation and involvement of the lung parenchyma may also manifest as a reduction in DLCO.33 Chronic pulmonary embolism, primary pulmonary hypertension (PPH) and other pulmonary vascular diseases may also result in a decline in DLCO.34 There are known associations between reduced DLCO and clinical conditions such as mixed connective tissue disease,35 gastro-oesophageal reflux,36 diabetes mellitus37 and liver cirrhosis.38 It is therefore crucial for clinicians to have a clear understanding of how [http://www.selleckchem.com/products/nutlin-3a.html Mdm2 inhibitor] lung function, and in particular DLCO, is affected by these extrapulmonary diseases. The decrease in DLCO can be classified into different degrees of severity, with a % predicted DLCO of 60% to the lower limits of normal indicating mild impairment, 40�C60% moderate impairment and