Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

Abstract

BackgroundWe investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD).MethodsWe studied 100 (20 female; mean age: 68±10 years) patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10%) by impulse oscillometry system. Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L−1) and the fall in resistance from 5 Hz to 20 Hz (R5 – R20) were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L−1) was also measured. Significant response to bronchodilator (salbutamol 400 μg) was expressed as absolute (≥0.2 L) and percentage (≥12%) change relative to the prebronchodilator value of FEV1 (flow responders, FRs) and FVC (volume responders, VRs).ResultsEighty out of 100 participants had R5 – R20 >0.03 kPa·s·L−1 (> upper normal limit) and, compared to patients with R5 – R20 ≤0.030 kPa·s·L−1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons). Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 – R20 values (P<0.05), lower X5 values (P<0.05), and greater airflow obstruction and lung hyperinflation.ConclusionThis study shows that peripheral airway resistance is increased in the vast majority of patients with COPD, who showed worse respiratory reactance, worse spirometry results, more severe lung hyperinflation, and poorer health status. Small airway dysfunction was also associated with the bronchodilator responsiveness in terms of FVC, but not in terms of FEV1.

Prevalence of Small-Airway Dysfunction among COPD Patients with Different GOLD Stages and Its Role in the Impact of Disease

“…Despite everything, the prevalence of COPD patients with SAD categorized with 0.03 kPa × s × L -1 was 83% in our sample, similar to that recorded previously [13] and the results on the distribution and the model of prediction were not different in comparison to a cutoff of 0.07 kPa × s × L -1 (data not reported). …”

“…A previous observational study [13] on moderate COPD patients recently demonstrated a higher prevalence (80%), but it was calculated with another cutoff (0.03) reported from the literature [21]. Our current choice for a higher cutoff (0.07 and not 0.03) takes into account 2 aspects: (1) to have a reasonable certainty of the presence of SAD, and 0.07, as previously reported [19], represents a conservative upper limit of normality for R5-R20; and (2) to have a model, similar to asthmatics [22,23], that identifies a portion of patients who have poor control of the disease and could require the use of as-needed medications, such as short-acting β-agonists.…”

“…Our current choice for a higher cutoff (0.07 and not 0.03) takes into account 2 aspects: (1) to have a reasonable certainty of the presence of SAD, and 0.07, as previously reported [19], represents a conservative upper limit of normality for R5-R20; and (2) to have a model, similar to asthmatics [22,23], that identifies a portion of patients who have poor control of the disease and could require the use of as-needed medications, such as short-acting β-agonists. In fact, although COPD is considered not entirely reversible to airflow obstruction disease [2] that may show significant bronchodilator responsiveness [24], the assessment of SAD may be considered a functional marker useful to evaluate improvements of treatment and to identify flow and volume responders [13], and this despite an absence of a change in FEV 1 [25]. However, while in patients with asthma the role of SAD as a therapeutic target for extra-fine formulations is consolidated by an increasing peripheral airways drug deposition [26], in COPD this role is not yet fully established, although improvements in air trapping and dyspnoea perception [27] and in other patient-related outcomes [28] have been demonstrated.…”

“…6). As described above, with regard to the possibility to identify in COPD patients a bronchodilator responsiveness phenotype [13,41] suitable for a personalized pharmacotherapy, we may speculate that in selected patients with SAD and with a higher impact of disease (CAT score >9.5 or simply ≥10 as reported from guidelines), may find use also for COPD patients similarly to asthma [42] an as-needed therapeutic approach with extra-fine formulations.…”

“…In fact, while FEV 1 is mainly able to measure expiratory flow at high and mid volume [10], IOS provides measures of both proximal and distal airway resistance [11]. In COPD patients, IOS is useful to detect early phases of disease [12] or bronchodilator responsiveness [13], to define different subgroups of patients according to airflow obstruction [14], and to examine the effect of bronchodilator drugs [15]. …”