Small Airway Dysfunction Links Asthma Severity with Physical Activity and Symptom Control

Abdo, Mustafa; Kirsten, Anne-Marie; Pedersen, Frauke; Herzmann, Christian; Kopp, Matthias; Hansen, Gesine; Waschki, Benjamin; Rabe, Klaus F.; Watz, Henrik; Bahmer, Thomas

doi:10.1016/j.jaip.2021.04.035

Cited by 48 publications

(47 citation statements)

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“…In the ATLANTIS study, the largest multinational study showing the contribution of SAD to asthma severity, 91% of asthmatics was found to have SAD, defined as any abnormal physiological variable, and SAD was strongly present across all GINA severity stages ( 18 ). Several other cohort studies showed the prevalence of SAD as defined by impulse oscillometry (IOS) ( 19 , 20 , 22 , 23 ). We found ( 19 , 22 ) in a cohort of 400 community-managed patients with physician-diagnosed asthma an overall prevalence of SAD of 62% in all the GINA step classes (step 2 58.3%; step 3 60.9%; step 4 63.3%; step 5 78.6%).…”

Section: Prevalence Of Sad In Asthmatic Patientsmentioning

confidence: 99%

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

Cottini¹,

Lombardi

Passalacqua

et al. 2022

Front. Med.

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Asthma is a chronic disease, affecting approximately 350 million people worldwide. Inflammation and remodeling in asthma involve the large airways, and it is now widely accepted that the small airways (those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and are the major determinant of airflow obstruction in this disease. From a clinical perspective, small airways dysfunction (SAD) is associated with more severe bronchial hyperresponsiveness, worse asthma control and more exacerbations. Unlike the GOLD guidelines which, in their definition, identify COPD as a disease of the small airways, the Global Initiative for Asthma (GINA) guidelines do not refer to the prevalence and role of SAD in asthmatic patients. This decision seems surprising, given the growing body of compelling evidence accumulating pointing out the high prevalence of SAD in asthmatic patients and the importance of SAD in poor asthma control. Furthermore, and remarkably, SAD appears to possess the characteristics of a treatable pulmonary trait, making it certainly appealing for asthma control optimization and exacerbation rate reduction. In this mini-review article, we address the most recent evidence on the role of SAD on asthma control and critically review the possible inclusion of SAD among treatable pulmonary traits in international guidelines on asthma.

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Section: Prevalence Of Sad In Asthmatic Patientsmentioning

confidence: 99%

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

Cottini¹,

Lombardi

Passalacqua

et al. 2022

Front. Med.

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“…While the reason behind this is not fully clear, this might be reflecting that SAD is rather a spectrum of diverse lung function impairments that correlate differently with the various clinical manifestations of asthma. 10 An alternative explanation is that the LCI is a universal measure of SAD that indicates the subsequent ventilation heterogeneity caused by multiple lung function impairments, particularly, air trapping. 10 Mechanistically, the nighttime enhancement of inflammation in the airway has been incriminated in the nocturnal worsening of asthma symptoms and lung function.…”

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confidence: 99%

“…10 An alternative explanation is that the LCI is a universal measure of SAD that indicates the subsequent ventilation heterogeneity caused by multiple lung function impairments, particularly, air trapping. 10 Mechanistically, the nighttime enhancement of inflammation in the airway has been incriminated in the nocturnal worsening of asthma symptoms and lung function. [28][29][30] In a previous study, Kraft and colleagues performed lung biopsies and bronchoalveolar lavage in patients with nocturnal asthma and described an augmented eosinophilic influx in the distal airways compared to proximal airways that were also increased at nighttime compared to daytime.…”

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confidence: 99%

The Relevance of Small Airway Dysfunction in Asthma with Nocturnal Symptoms

Abdo¹,

Kirsten²,

Biller³

et al. 2021

JAA

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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.

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“…The compartmental models have been shown to work reasonably well for healthy lungs. However, it does not describe well the impedance vs. frequency in disease, since the resistance can be frequency-dependent due to disease-induced flow heterogeneity [10][11][12][13][14]. Moreover, lung diseases can occur in different regions with varying severities and phenotypes, so it is challenging to study how regional airway remodeling contribute differently to the overall impedance [15,16].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Impulse Oscillometry in Respiratory Airway Casts with Varying Obstruction Phenotypes, Locations, and Complexities

Talaat

et al. 2022

JoR

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The use of impulse oscillometry (IOS) for lung function testing does not need patient cooperation and has gained increasing popularity among both young and senior populations, as well as in patients with breathing difficulties. However, studies of the IOS sensitivity to regional lung obstructions are limited and have shown mixed results. The objective of this study was to evaluate the performance of an IOS system in 3D-printed lung models with structural abnormalities at different locations and with different severities. Lung trees of two complexity levels were tested, with one extending to the sixth generation (G6) and the other to G12. The IOS responses to varying glottal apertures, carina ridge tumors, and segmental bronchial constrictions were quantified in the G6 lung geometry. Both the G6 and G12 lung casts were prepared using high-resolution 3D printers. Overall, IOS detected the progressive airway obstructions considered in this study. The resonant frequency dropped with increasing obstructions for all three disease phenotypes in the G6 lung models. R20Hz increased with the increase in airway obstructions. Specifically, R20Hz in the airway model with varying glottal apertures agreed reasonably well with complementary measurements using TSI VelociCalc. In contrast to the high-resistance (R) sensitivity to the frequency in G6 lung models, R was nearly independent of frequency in G12 lung models. IOS R20Hz demonstrated adequate sensitivity to the structural remodeling in the central airways. However, the changes of R5Hz and X5Hz vs. airway obstructions were inconclusive in this study, possibly due to the rigid lung casts and the difference of a container–syringe system from human lungs.

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Small Airway Dysfunction Links Asthma Severity with Physical Activity and Symptom Control

Cited by 48 publications

References 50 publications

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

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

The Relevance of Small Airway Dysfunction in Asthma with Nocturnal Symptoms

Evaluation of Impulse Oscillometry in Respiratory Airway Casts with Varying Obstruction Phenotypes, Locations, and Complexities

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