Seven Pillars of Small Airways Disease in Asthma and COPD: Supporting Opportunities for Novel Therapies. Review. Usmani, Han, Kaminsky, Hogg, ... Brown. Chest 2021; 160(1): 114-34.

      Identification of pathologic changes in early and mild obstructive lung disease has shown the importance of the small airways and their contribution to symptoms. Indeed, significant small airways dysfunction has been found prior to any overt airway obstruction being detectable by conventional spirometry techniques. However, most therapies for the treatment of obstructive lung disease target the physiological changes and associated symptoms that result from chronic lung disease, rather than directly targeting the specific underlying causes of airflow disruption or the drivers of disease progression. In addition, although spirometry is the current standard for diagnosis and monitoring of response to therapy, the most widely used measure, FEV1, does not align with the pathologic changes in early or mild disease and may not align with symptoms or exacerbation frequency in the individual patient. Newer functional and imaging techniques allow more effective assessment of small airways dysfunction; however, significant gaps in our understanding remain. Improving our knowledge of the role of small airways dysfunction in early disease in the airways, along with the identification of novel end points to measure subclinical changes in this region (ie, those not captured as symptoms or identified through standard FEV1), may lead to the development of novel therapies that directly combat early airways disease processes with a view to slowing disease progression and reversing damage. This expert opinion paper discusses small airways disease in the context of asthma and COPD and highlights gaps in current knowledge that impede earlier identification of obstructive lung disease and the development and standardization of novel small airways-specific end points for use in clinical trials.

 

Small airway dysfunction and poor asthma control: a dangerous liaison. Cottini M, etal. Clin Mol Allergy. 2021 May 29;19(1):7.

       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.

 

The predictive value of impulse oscillometry for asthma exacerbations in childhood: A systematic review and meta-analyses. Ling Y, etal. Pediatr Pulmonol. 2021 Jul;56(7):1850-1856.

      Objective: Several studies have explored the predictive value of impulse oscillometry (IOS) for asthma exacerbations in childhood, but its specific parameters are still unclear. Therefore, we designed this meta-analysis to determine the related indicators of acute asthma attacks.

     Methods: A comprehensive literature search was performed on July 9, 2020 based on PubMed, Embase, and Web of Science database. Weighted mean differences (WMDs) were calculated using fixed- or random-effects models.

     Results: A total of 615 patients from six trials were included in this analysis. IOS may be a useful tool to predict asthma exacerbations. And the results showed that R5 (WMD = -1.21, 95% CI: -1.55 to -0.87, p < .001), Fres (WMD = -1.34, 95% CI: -2.03 to -0.65, p = .018), and AX (WMD = -7.35, 95% CI: -9.94 to -4.76, p < .001) had significant correlation with asthma exacerbations. In addition, X5 may also predict the acute attack of asthma (WMD = 0.81, 95% CI: 0.56 to 1.01, p < .001).

     Conclusions: R5, AX, Fres, and X5 may be able to identify the risk of an acute attack of asthma. Besides, our research further demonstrated that peripheral airway injury may play an important role in the acute attack of asthma.

 

Lung function testing and inflammation markers for wheezing preschool children: A systematic review for the EAACI Clinical Practice Recommendations on Diagnostics of Preschool Wheeze. Elenius V, etal; EAACI Preschool Wheeze Task Force for Diagnostics of Preschool Wheeze. Pediatr Allergy Immunol. 2021 Apr;32(3):501-513.          Background: Preschool wheeze is highly prevalent; 30%-50% of children have wheezed at least once before age six. Wheezing is not a disorder; it is a symptom of obstruction in the airways, and it is essential to identify the correct diagnosis behind this symptom. An increasing number of studies provide evidence for novel diagnostic tools for monitoring and predicting asthma in the pediatric population. Several techniques are available to measure airway obstruction and airway inflammation, including spirometry, impulse oscillometry, whole-body plethysmography, bronchial hyperresponsiveness test, multiple breath washout test, measurements of exhaled NO, and analyses of various other biomarkers.

     Methods: We systematically reviewed all the existing techniques available for measuring lung function and airway inflammation in preschool children to assess their potential and clinical value in the routine diagnostics and monitoring of airway obstruction.

     Results: If applicable, measuring FEV1 using spirometry is considered useful. For those unable to perform spirometry, whole-body plethysmography and IOS may be useful. Bronchial reversibility to beta2-agonist and hyperresponsiveness test with running exercise challenge may improve the sensitivity of these tests.

     Conclusions: The difficulty of measuring lung function and the lack of large randomized controlled trials makes it difficult to establish guidelines for monitoring asthma in preschool children.

 

Bronchodilator Response Assessed by the Forced Oscillation Technique Identifies Poor Asthma Control With Greater Sensitivity Than Spirometry. Cottee AM, etal. Chest 2021; 157(6):1435-41.

      Background: Persistent bronchodilator response (BDR) following diagnosis of asthma is an under-recognized treatable trait, associated with worse lung function and asthma control. The forced oscillation technique (FOT) measures respiratory system impedance, and BDR cutoffs have been proposed for healthy adults; however, the relevance in asthma is unknown. We compared BDR cutoffs, using FOT and spirometry, in asthma and the relationship with asthma control.

     Methods: Data from patients with asthma who withheld bronchodilator medication for at least 8 h before a tertiary airway clinic visit were reviewed. All subjects performed FOT and spirometry before and after salbutamol administration, and completed the Asthma Control Test. FOT parameters examined included respiratory system resistance (R5) and reactance (X5) at 5 Hz, and area under the reactance curve (AX). BDR was defined by standard recommendations for spirometry and based on the 95th percentile of BDR in healthy adults for FOT.             Results: Fifty-two subjects (18 men; mean age, 53 ± 18 years) were included. BDR was identified more frequently by FOT than spirometry (54% vs 27% of subjects). BDR assessed by X5 and AX, but not R5, was associated with spirometric BDR (χ2, P < .01) and correlated with asthma control (X5: rs = –0.36, P < .01; AX: rs = 0.34, P = .01). BDR measured by reactance parameters identified more subjects with poor asthma control than did spirometry (AX, 69% vs spirometry, 41%).

    Conclusions: BDR assessed by FOT can identify poor asthma control. Reactance parameters were more sensitive in identifying poor asthma control than spirometry, supporting the use of FOT to complement spirometry in the clinical management of asthma.

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