The Relevance of Small Airway Dysfunction in Asthma with Nocturnal Symptoms

Abstract

Small airway dysfunction (SAD) is a frequent feature of asthma that has been linked to disease severity and poor symptom control. However, little is known about the role of SAD in nocturnal asthma. Objective: To study the association between the severity of SAD and frequency of nocturnal symptoms compared to conventional lung function testing. Methods: We assessed the frequency of self-reported nocturnal symptoms through the asthma control test. We studied the impact of nocturnal asthma using the Asthma Quality of Life Questionnaire (AQLQ) and the Multidimensional Fatigue Inventory (MFI-20). We assessed the lung function using spirometry, body plethysmography, impulse oscillometry, single and multiple inert gas washout and measured markers of T2-inflammation (blood and sputum eosinophils; fractional exhaled nitric oxide (FeNo)). We stratified the patients according to the presence and frequency of nocturnal asthma. Results: A total of 166 asthma patients were enrolled in the analysis. Eighty-seven patients (52%) reported to have nocturnal symptoms at least once in the last four weeks. The odds ratio of nocturnal asthma correlated with the severity of all non-spirometric measures of SAD, yet neither with airflow obstruction (FEV1 and FEV/FVC) nor with large airway resistance (R20). Patients with frequent nocturnal asthma (n = 29) had a numerical increase of T2 markers and more severe SAD, as indicated by all non-spirometric measures of SAD (all p-values < 0.05), worse overall asthma control, increased fatigue and reduced quality of life (all p-values < 0.01) compared to patients with infrequent nocturnal asthma (n = 58) or patients without nocturnal asthma (n = 79). We identified 63 patients without airflow obstruction, nearly 43% of them (n = 27) had nocturnal asthma. In this subgroup, only markers of air trapping and ventilation heterogeneity were significantly elevated and correlated with the frequency of nocturnal symptoms: LCI (Spearman's coefficient = −0.42, p < 0.001), RV% (−0.32, p = 0.02). Conclusion: SAD is closely associated to asthma with nocturnal symptoms. Spirometry might underestimate the broad spectrum of distal lung function impairments in this population of patients.

Longitudinal Impact of Sputum Inflammatory Phenotypes on Small Airway Dysfunction and Disease Outcomes in Asthma

“…SAD is a highly prevalent feature of asthma that has been linked to disease severity, poor symptom control, frequent exacerbation, and physical inactivity. [10][11][12] SAD entails a spectrum of inter-related distal lung function impairments including increased small airway resistance, decreased lung elastance, the subsequent limitation of airflow in the peripheral airways, air trapping, and ventilation inhomogeneity. 12 In light of the increasing recognition of the significant role of SAD in asthma, it is important to investigate whether different asthma phenotypes confer different associations with markers of SAD.…”

Small Airways: The “Silent Zone” of 2021 GINA Report?

“…The limit of most of the available studies is that they analyze the association of single features with SAD, instead ofcomprehensively address multiple asthma features associated with SAD. In more recent studies, multivariable analyses, classification tree analysis and structural equation modeling indicated that exercise-induced symptoms, overweight/obesity, asthma-related nocturnal symptoms, older age, smoking, and T2 inflammation are strong independent predictors of SAD in patients with community-managed asthma ( 19 , 20 , 27 ). Furthermore, emerging evidence shows that small conducting airways are an important site of disease also in pediatric asthma and are affected from an early stage of the disease ( 28 ).…”

BMAL1/FOXA2-induced rhythmic fluctuations in IL-6 contribute to nocturnal asthma attacks

“…On the day of the experiments, the culture media were replaced with RPMI 1640 medium containing 50% horse serum (Yuanye, Shanghai, China) for 2 h. The media were then replaced with serum-free RPMI 1640. The cells were harvested and assayed at different time points (0, 4,8,12,16,20,24,28,32,36,40, and 44 h) following serum shock and labelled as ZT0-ZT44, respectively.…”

“…Nocturnal asthma also appears to be associated with an increased risk of mortality as 50-68% of asthma-related deaths and respiratory arrest occurred at night (4,5). Previous studies have demonstrated a circadian variation in the fractional exhaled nitric oxide (FeNO) and lung function in nocturnal asthma (6)(7)(8), which may be triggered by inflammations in the airways at night. FeNO has emerged as an important biomarker of T helper 2 (Th2)-mediated airway inflammation in asthma (9).…”