Impulse oscillometry defined small airway dysfunction in asthmatic patients with normal spirometry: Prevalence, clinical associations, and impact on asthma control.

BACKGROUND: The small-airway dysfunction (SAD), detected with impulse oscillometry (IOS) methods, has been recently better characterized in patients with asthma. However, little is known about SAD in asthmatic patients with normal spirometry (NS). OBJECTIVE: In this study, we aimed to investigate, in an unselected sample of 321 patients with physician-diagnosed asthma and NS, prevalence, clinical characterization, and impact on asthma control of IOS-defined SAD. As a secondary objective of the study, we focused on comparing the difference between IOS- and spirometry-defined SAD. METHODS: Consecutive patients with a previous diagnosis of asthma but normal spirometry at the moment of the enrollment were stratified by the presence of IOS-defined SAD (difference in resistance at 5 Hz and at 20 Hz [R5-R20] greater than 0.07 kPa x s x L-1). We have also assessed the presence of SAD defined by spirometry, according to FEF 25-75 < 65% of the predicted. Clinical and laboratory features were collected, and univariable and multivariable analyses were used to analyze cross-sectional associations between clinical variables and outcomes (SAD). RESULTS: IOS-defined SAD was present in 54.1% of the cohort. In contrast, spirometry-defined SAD was present in only 10% of patients. Subjects with IOS-defined SAD showed less well-controlled asthma and a higher mean inhaled corticosteroid dosage use compared with subjects without SAD (both P < .001). Overweight (odds ratio [OR], 1.14; 95% CI, 1.05-1.23), exacerbation history (OR, 3.06; 95% CI, 1.34-6.97), asthma-related night awakenings (OR, 6.88; 95% CI, 2.13-22.23), exercise-induced asthma symptoms (OR, 33.5; 95% CI, 9.51-117.8), and controlled asthma (OR, 0.22; 95% CI, 0.06-0.84) were independently associated with SAD. CONCLUSIONS: Asthmatic patients with IOS-defined SAD showed less well-controlled asthma, more severe exacerbations and higher mean inhaled corticosteroid dosage. We confirmed exercise-induced asthma, asthma-related night awakenings, exacerbation history, and overweight as independently associated with SAD, while showing well-controlled asthma as inversely associated. SAD may be overlooked by standard spirometry.

Small airway dysfunction and poor asthma control: a dangerous liaison.

Asthma is a common chronic condition, affecting approximately 339 million people worldwide. The main goal of the current asthma treatment guidelines is to achieve clinical control, encompassing both the patient symptoms and limitations and the future risk of adverse asthma outcomes. Despite randomized controlled trials showing that asthma control is an achievable target, a substantial proportion of asthmatics remain poorly controlled in real life. The involvement of peripheral small airways has recently gained greater recognition in asthma, and many studies suggest that the persistent inflammation at these sites leads to small airway dysfunction (SAD), strongly contributing to a worse asthma control. Overall, the impulse oscillometry (IOS), introduced in the recent years, seems to be able to sensitively assess small airways, while conventional spirometry does not. Therefore, IOS may be of great help in characterizing SAD and guiding therapy choice. The aim of this article is to review the literature on SAD and its influence on asthma control, emphasizing the most recent evidence.

Prevalence and features of IOS-defined small airway disease across asthma severities.

BACKGROUND: Impulse oscillometry (IOS) is a noninvasive method based on the forced oscillation technique able to detect small airway dysfunction (SAD) in asthma. We aimed to analyze the prevalence and the functional features of IOS-defined SAD across the different Global Initiative for Asthma (GINA) steps. METHODS: A cross-sectional, single-center study in which 400 consecutive adult patients with physician-diagnosed, community-managed asthma underwent standard spirometry and IOS, and were stratified by stepwise GINA classification. SAD was defined by IOS as a fall in resistance from 5 to 20 Hz [R5-R20]>0.07kPa × s × L-1. RESULTS: The prevalence of IOS-defined SAD ranged between 58.3% (GINA step 2) and 78.6% (GINA step 5), without statistically significant difference within GINA steps (p > 0.05 in all comparisons). Isolated SAD (i.e. without proximal airways involvement) was similarly represented across GINA steps 2-4. Peripheral airways resistance (R5-R20) tended to a progressive increase with the worsening of GINA steps, and was significantly higher in steps 4-5 compared to the other steps (p < 0.05). The proportion of patients with FEF25-75%-defined SAD (<60%) was lower than the IOS-defined one in GINA steps 2-4 (p < 0.05). Only non-significant or weak inverse correlations between R5-R20 and FEF25-75% were observed within each GINA step, with the exception of GINA step 5, which showed a strong, inverse correlation (r = -0.80, p = 0.0005). CONCLUSIONS: This study shows that first, IOS-defined SAD is overwhelmingly present across asthma severities; second, airways resistance increases with the worsening of GINA steps; and third, SAD may be overlooked by standard spirometry, especially in milder asthma.

Clinical Characterization and Predictors of IOS-Defined Small-Airway Dysfunction in Asthma.

BACKGROUND: The involvement of small airways has recently gained greater recognition in asthma. Impulse oscillometry (IOS) is a simple and noninvasive method based on the forced oscillation technique, for the detection of small-airway dysfunction (SAD). OBJECTIVE: To identify the predictors of SAD in an unselected sample of 400 patients with physician-diagnosed asthma. METHODS: All patients underwent standard spirometry and IOS at the first visit, and were stratified by the presence of SAD defined by IOS (fall in resistance from 5 to 20 Hz [R5-R20] > 0.07 kPa × s × L-1). Univariable and multivariable analyses and classification tree method were used to analyze cross-sectional relationships between clinical variables and outcome (SAD). RESULTS: SAD was present in 62% of the cohort. Subjects with SAD showed a less well-controlled asthma, according to the Global Initiative for Asthma definition, and a higher mean inhaled corticosteroid dosage use compared with subjects without SAD (both P < .001). Increased fractional exhaled nitric oxide (odds ratio [OR], 2.05; 95% CI, 1.14-3.70), female sex (OR, 2.27; 95% CI, 1.29-4.06), smoking (OR, 3.06; 95% CI, 1.60-6.05), older age (OR, 3.08; 95% CI, 1.77-5.49), asthma-related night awakenings (OR, 3.34; 95% CI, 1.85-6.17), overweight (OR, 3.64; 95% CI, 1.99-6.85), and exercise-induced asthma symptoms (OR, 6.39; 95% CI 3.65-11.45) were independent predictors of SAD. Classification tree analysis confirmed that exercise-induced asthma, overweight, asthma-related night awakenings, smoking, and older age have potential for clinical use in distinguishing patients with SAD from those without it. CONCLUSIONS: We identified predictors of SAD and showed that especially exercise-induced asthma, overweight, asthma-related night awakenings, smoking, and older age were strongly associated with SAD.