All subjects performed oscillometry and flow-volume spirometry (Jaeger MasterScreen; Erich Jaeger GmbH, Würzburg, Germany) according to European Respiratory Society and American Thoracic Society (ERS/ATS) recommendations (Pellegrino et al. 2005). Spirometry included the following: FEV₁/FVC and FEV₃/FVC, the ratio of forced expiratory volume in 1 s and 3 s, respectively, to forced vital capacity; FEV₁%pred, the ratio of forced expiratory volume in 1 s to its predicted value; FVC %pred, the ratio of forced vital capacity to its predicted value; MEF₂₅, maximal expiratory flow measured in the terminal part of FVC; MEF₅₀, maximal expiratory flow measured in mid-FVC; MEF₇₅, maximal expiratory flow measured in the proximal part of FVC; and MMEF, maximal mid-expiratory flow. The criterion for the diagnosis of bronchial obstruction was a fixed ratio of FEV₁/FVC of less than the 5th percentile. The severity of airway obstruction in COPD patients was defined on the basis of FEV₁%pred value according to the GOLD recommendations (GOLD 2016). The following degrees of airway obstruction were defined: mild (FEV₁ ≥ 80%pred), moderate (50% < FEV₁ < 80%pred.), severe (30% < FEV₁ < 50%pred), and very severe (FEV₁ < 30%pred). The predicted values of FEV₃/FVC and the lower limit of normal (LLN) were determined using the data elaborated by Hansen et al. (2006), based on the Third National Health and Nutrition Examination Survey (NHANES III). These values were calculated according to the following formulas: 100.63 – (0.1692 * age) and 95.00 – (0.1692 * age) for males, and 102.41 – (0.1826 * age) and 96.56 – (0.1826 * age) for females, respectively. The IOS assessed R5 at 5 Hz, consisting of extra-thoracic, central and peripheral airways, R20 at 20 Hz, consisting of mainly extra-thoracic and central airways, and the distal capacitive reactance X5 at 5 Hz, consisting of elastic lung and thorax components. The R5–R20 difference, corresponding to small airway resistance, was calculated. In addition, neurological condition and disability were assessed using a modified Rankin scale (Wilson et al. 2002). Mini-mental scale examination (MMSE) was performed to assess possible mental and cognitive deficits.

Continuous variables were described as means ±SD and categorical variables as percentages. The Kruskal-Wallis and Chi-squared tests were used for comparison between groups as appropriate. Spearman’s correlation coefficient was used for the assessment of relationship between pulmonary variables. Sensitivity, specificity, and positive predictive (PPV) and negative predictive value (NPV) were evaluated. A p-value <0.05 defined statistically significant differences. All analyses were conducted using STATISTICA 12.0 for Windows (Statsoft; Tulsa, OK).

Spirometry confirmed mild airway obstruction in 16, moderate in 45, severe in 34, and very severe in 13 COPD patients. The mean FEV₃/FVC and MMEF values in COPD patients were lower than those in healthy subjects and were reduced with increasing bronchial obstruction. The mean R5-R20 difference was greater in COPD patients than that in controls and it increased with the severity of airway obstruction (Table 2). No appreciable neurological deficits were found in the patients; thus the Rankin score equaled zero. Nor were there any dementia symptoms substantiated (MMSE: 29 and 25–30 points; median and minimum-maximum, respectively).

We found a significant negative correlation between the R5-R20 difference and MMEF (r = −0.45; p < 0.0001) and between the FEV₃/FVC ratio and MMEF (r = −0.28; p < 0.0001) (Figs. 1 and 2; Table 3). Sensitivity and specificity of R5-R20 in reflecting the MMEF changes was 84.0% and 44.2%, respectively. On the other hand, FEV₃/FVC had a lower sensitivity of 52.1%, but 100% specificity with regard to MMEF, which translates into a high probability of identifying people without ventilatory disorders (Table 4). The evaluation of small airway obstruction in relation to COPD stage showed a good sensitivity of R5-R20 difference for detection of mild obstruction in COPD stage I as well as in more severe stages. The sensitivity of MMEF was low in mild obstruction and increased in moderate-to-severe stages and that of FEV₃/FVC ratio increased progressively with disease stage (Table 5).