Pellegrino et al. in the interpretative strategies for lung function tests stated that special attention must be paid when FEV₁ and FVC are concomitantly decreased and the FEV₁/FVC ratio is normal or almost normal. Apart incomplete inhalation or exhalation, these authors stated that a “possible cause of this pattern is patchy collapse of small airways early in exhalation” [1]. This small airways obstructive pattern (SAOP) is not infrequent, represents ~ 7% to 10% of all pulmonary function tests in two large databases and is not specific of any disease in adults [2, 3]. It can also be encountered in asthmatic children [4]. Since this pattern is deemed to be the consequence of “patchy collapse of small airways early in exhalation” one may wonder whether bronchodilator response should be assessed on flow (increase in FEV₁), volume (FVC and/or inspiratory capacity [IC] [5]) or both flow and volume. Moreover, improvements in IC correlate with improvements in exercise tolerance and endurance, which are recognized as important goals of disease management. Consequently, the primary objective of our study was to assess whether bronchodilator response should be assessed conventionally using FEV₁ and FVC, or using IC.

SAOP has initially been defined as a pseudo-restrictive syndrome because of the reduction of FEV₁ and FVC with normal FEV₁/FVC ratio. If TLC measurement is made using dilution techniques, one may wrongly conclude that the defect is restrictive [3]. Since body plethysmography is not available in all pulmonary function testing laboratories, another method for SAOP detection is mandatory. Impulse oscillometry (IOS) has the advantage of being simple to use and is effort-independent [6]. The contribution of the distal airways could be determined by the fall in resistance from 5 Hz to 20 Hz (ΔRrs_5Hz-20Hz) [6] and could therefore be useful to detect SAOP. Our additional objective was to assess the usefulness of IOS to diagnose SAOP (sensitivity) and its reversibility.

Patients’ description and lung function tests results are listed in Table 1.

Based on FEV₁% predicted, a moderate to moderately severe defect was observed, associated with mild hyperinflation (increase in RV).

IOS measurements (Rrs_5Hz) were coherent with plethysmographic measurements of airway resistance (Raw), Rrs_5Hz being slightly higher. ΔRrs_5Hz-20Hz was increased in 28/50 patients (56%, 95%CI: 42-70, with a higher value than upper limit of normal) that suggested airway obstruction (SAOP diagnosis) before TLC measurement, while AX was elevated (above upper limit of normal) in 42/50 patients.

RV/TLC % predicted only correlated with FEV_1% predicted (rho= -0.528, p=0.0002) and FVC % predicted (rho= -0.531, p=0.0002), no significant correlation was evidenced with IOS parameters.

Fifteen patients (30%, 95%CI: 17-43) exhibited a significant FEV₁ reversibility Fig. (1). Twenty-six patients (52%, 95%CI: 38-66) exhibited a significant IC reversibility Fig. (1), while 13 patients (26%, 95%CI: 14-38) exhibited a significant FVC reversibility.

Fig. (1). Relationship between proximal (increase in FEV1) and distal (increase in IC) response to bronchodilator. Dotted lines are 12% increase in FEV1 or IC as compared to baseline value. There was a non significant relationship between the two responses (p=0.465). Three patients, two with flow-responder group and one with non responder group, depicted a significant FVC response without significant IC response.

Six patients were flow-responders (proximal response), 20 were volume-responders (increase in IC and/or FVC: distal response), 9 were flow and volume responders (overall response) and 15 patients were non responders. Overall, 35 / 50 (70%, 95%CI: 57-83) exhibited a significant bronchodilator response Fig. (1).

Table 2 describes the correlations between the different parameters assessing bronchodilator response. IOS parameters correlated to FEV₁ response only, further suggesting their proximal assessment.

Our descriptive prospective study demonstrates that the bronchodilator response of peripheral airways related to SAOP should be evaluated using the increase in IC rather than the conventional increase in FEV₁ that assesses more central airways or even the increase in FVC. The study also shows that impedance measurements using the IOS method was not sufficiently sensitive to detect SAOP.

The first issue is whether the abnormal pattern of SAOP is always obstructive. From a physiological point of view (one compartment model for instance) [13] there are only three mechanisms explaining a decrease in FEV₁, obstructive, restrictive and mixed defects. Since the pattern is not restrictive (normal TLC), the defect is obstructive. The associated hyperinflation (increase in RV and sometimes FRC) further suggests peripheral obstruction. Logically, the ATS/ERS consensus on clinical pulmonary function testing stated that this pattern would be related to patchy collapse of small airways early in exhalation after exclusion of technical problems. The discussion comes from the clinical conditions associated with SAOP such as restricted thoracic expansion (obesity, thoracic deformation without restrictive defect), justifying the label of “non-specific pattern” for some investigators [2, 14], which is indefensible from a physiological basis. Nevertheless, the SAOP is a syndrome related to non-specific conditions leading to peripheral obstruction. The present study shows that a significant proximal and/or distal reversibility was found in 70% of the patients that clearly demonstrates the obstructive nature of the defect.

The causes of SAOP were those previously described, COPD and asthma being the more prevalent [3]. The prevalence of 30% FEV₁ reversibility is higher than that observed by Iyer et al. (13%, 95%CI: 11.2 to 14.8) [14], which may be related to recruitment bias. The more frequent reversibility, assessed on IC rather than FEV₁, in peripheral airway diseases (volume response) has previously been reported in COPD [15].

One may wonder why a more prevalent IC response than FVC response was evidenced. Our hypothesis is that patients exhibiting SAOP are characterized by a specific tendency to collapse their small airways in exhalation (often remaining after bronchodilator assessment), even from FRC to RV explaining that slow inspiratory vital capacity is similarly reduced than expiratory FVC. Consequently, significant bronchodilation is more often obtained on FRC (and IC) than on RV (and FVC). Moreover, the measurement of FVC is obtained after deep inspiration that may reduce FVC due to its bronchoconstrictor effect [16]. Along this line, the recent study of Jarenback and colleagues, in COPD and control patients, showed that a significant correlation between Δ FVC% predicted and Δ RV% predicted after bronchodilation was only evidenced in the subgroup of patients with FEV₁ < 65% predicted [17]. This result highlights that a reduction of hyperinflation is probably not necessarily associated with an increase in FVC.

Whether IOS parameters can assess peripheral airways obstruction remains debated because this statement mainly relies on modelling approaches [6, 18]. Based on simplistic physical grounds from healthy lungs, airway resistance measurement is deemed to assess proximal airways [1]. From previous studies, we suggested that 1) peripheral airways can significantly contribute to airway resistance in COPD patients based on a modelling approach [19], 2) airway resistance and specific airway resistance are often increased (~50%) in SAOP [3] and 3) some respiratory system resistance parameters could assess peripheral airways in COPD patients based on a statistical approach [20].

Despite this background, several arguments suggest that IOS parameters were not sensitive to detect small airways disease. Firstly, the IOS parameter ΔRrs_5Hz-20Hz, deemed to assess peripheral obstruction, was inconsistently increased (56%) and its change after bronchodilator was associated with FEV₁ change only. AX was more frequently elevated, but its increase does not necessarily traduce an obstructive defect, as demonstrated in interstitial lung diseases [21]. Since IOS does not rely on forced manoeuvres, it may reduce the effects of premature airway closure seen during forced spirometry manoeuvres, which could impede its ability to detect SAOP. Secondly, a significant increase in IC reflecting the decrease in dynamic hyperinflation, related to peripheral airways dilation, was not associated with any significant improvement in IOS parameters.

In conclusion, a significant reversibility is frequent (70%) in patients depicting a Small Airways Obstructive Pattern, mainly assessed by inspiratory capacity increase. Impulse oscillometry is of limited value in this context since only half of the patients were detected as obstructive using this method.