The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study. Kraft M, Richardson M, Hallmark B, Billheimer D, Van den Berge M, Fabbri LM, Van der Molen T, Nicolini G, Papi A, Rabe KF, Singh D, Brightling C, Siddiqu S,  ATLANTIS study group. Lancet Respir Med. 2022 Mar 2;S2213-2600(21)00536-1.  doi: 10.1016/S2213-2600(21)00536-1. Online ahead of print.

Background: Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life.

Methods: In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed.

Findings: 773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0·20-0·25, p<0·0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life.

Interpretation: Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations.

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Interrelationships Among Small Airways Dysfunction, Neutrophilic Inflammation, and Exacerbation Frequency in COPD. Day K, etal. Chest 2021; 159(4):1391-1399.

BACKGROUND: Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline.

RESEARCH QUESTION: Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation?

STUDY DESIGN AND METHODS: Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n=17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n=22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (con[1]ducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of RV/TLC), single-breath transfer factor of the lung for CO, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions.

RESULTS: Sacin was significantly higher in the COPD FE group compared with the IFE group (P = .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, ρ = 0.560), residual volume to total lung capacity ratio (P = .004, r = 0.730), and the mean lung density of the paired CT scans (P = .018, r = 0.639).

INTERPRETATION: Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.

        The "Silent Zone" Screams Again: Identifying COPD Patients Most at Risk. Editorial.

        Lutchen KR.Chest. 2021 Apr; 159(4):1313-1314

 

Airway Oscillometry Detects Spirometric-Silent Episodes of Acute Cellular Rejection. Cho E, et al. Am J Respir Crit Care Med. 2020 Jun 15;201(12):1536-44.

Rationale: Acute cellular rejection (ACR) is common during the initial 3 months after lung transplant. Patients are monitored with spirometry and routine surveillance transbronchial biopsies. However, many centers monitor patients with spirometry only because of the risks and insensitivity of transbronchial biopsy for detecting ACR. Airway oscillometry is a lung function test that detects peripheral airway inhomogeneity with greater sensitivity than spirometry. Little is known about the role of oscillometry in patient monitoring after a transplant.   Objectives: To characterize oscillometry measurements in biopsy-proven clinically significant (grade ≥2 ACR) in the first 3 months after a transplant.

Methods: We enrolled 156 of the 209 double lung transplant recipients between December 2017 and March 2019. Weekly outpatient oscillometry and spirometry and surveillance biopsies at Weeks 6 and 12 were conducted at our center.  

Measurements and Main Results: Of the 138 patients followed for 3 or more months, 15 patients had 16 episodes of grade 2 ACR (AR2) and 44 patients had 64 episodes of grade 0 ACR (AR0) rejection associated with stable and/or improving spirometry. In 15/16 episodes of AR2, spirometry was stable or improving in the weeks leading to transbronchial biopsy. However, oscillometry was markedly abnormal and significantly different from AR0 (P < 0.05), particularly in integrated area of reactance and the resistance between 5 and 19 Hz, the indices of peripheral airway obstruction. By 2 weeks after biopsy, after treatment for AR2, oscillometry in the AR2 group improved and was similar to the AR0 group.  

Conclusions: Oscillometry identified physiological changes associated with AR2 that were not discernible by spirometry and is useful for graft monitoring after a lung transplant.

        Calling Time on Spirometry: Unlocking the Silent Zone in Acute Rejection after Lung Transplantation. Editorial.              Usmani OS. Am J Respir Crit Care Med. 2020 Jun 15; 201(12):1468-70.

 

Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study. Postma DS, et al; ATLANTIS study group. Lancet Respir Med. 2019 May; 7(5):402-416.

Background: Small airways dysfunction (SAD) is well recognised in asthma, yet its role in the severity and control of asthma is unclear. This study aimed to assess which combination of biomarkers, physiological tests, and imaging markers best measure the presence and extent of SAD in patients with asthma.

Methods: In this baseline assessment of a multinational prospective cohort study (the Assessment of Small Airways Involvement in Asthma [ATLANTIS] study), we recruited participants with and without asthma (defined as Global Initiative for Asthma severity stages 1-5) from general practices, the databases of chest physicians, and advertisements at 29 centres across nine countries (Brazil, China, Germany, Italy, Spain, the Netherlands, the UK, the USA, and Canada). All participants were aged 18-65 years, and participants with asthma had received a clinical diagnosis of asthma more than 6 months ago that had been confirmed by a chest physician. This diagnosis required support by objective evidence at baseline or during the past 5 years, which could be: positive airway hyperresponsiveness to methacholine, positive reversibility (a change in FEV1 ≥12% and ≥200 mL within 30 min) after treatment with 400 μg of salbutamol in a metered-dose inhaler with or without a spacer, variability in peak expiratory flow of more than 20% (measured over 7 days), or documented reversibility after a cycle (eg, 4 weeks) of maintenance anti-asthma treatment. The inclusion criteria also required that patients had stable asthma on any previous regular asthma treatment (including so-called rescue β2-agonists alone) at a stable dose for more than 8 weeks before baseline and had smoked for a maximum of 10 pack-years in their lifetime. Control group participants were recruited by advertisements; these participants were aged 18-65 years, had no respiratory symptoms compatible with asthma or chronic obstructive pulmonary disease, normal spirometry, and normal airways responsiveness, and had smoked for a maximum of 10 pack-years. We assessed all participants with spirometry, body plethysmography, impulse oscillometry, multiple breath nitrogen washout, CT (in selected participants), and questionnaires about asthma control, asthma-related quality of life (both in participants with asthma only), and health status. We applied structural equation modelling in participants with asthma to assess the contribution of all physiological and CT variables to SAD, from which we defined clinical SAD and CT SAD scores. We then classified patients with asthma into SAD groups with model-based clustering, and we compared asthma severity, control, and health-care use during the past year by SAD score and by SAD group. This trial is registered with ClinicalTrials.gov, number NCT02123667.

Findings: Between June 30, 2014, and March 3, 2017, we recruited and evaluated 773 participants with asthma and 99 control participants. All physiological measures contributed to the clinical SAD model with the structural equation modelling analysis. The prevalence of SAD in asthma was dependent on the measure used; we found the lowest prevalence of SAD associated with acinar airway ventilation heterogeneity (Sacin), an outcome determined by multiple breath nitrogen washout that reflects ventilation heterogeneity in the most peripheral, pre-acinar or acinar airways. Impulse oscillometry and spirometry results, which were used to assess dysfunction of small-sized to mid-sized airways, contributed most to the clinical SAD score and differed between the two SAD groups. Participants in clinical SAD group 1 (n=452) had milder SAD than group 2 and comparable multiple breath nitrogen washout Sacin to control participants. Participants in clinical SAD group 2 (n=312) had abnormal physiological SAD results relative to group 1, particularly their impulse oscillometry and spirometry measurements, and group 2 participants also had more severe asthma (with regard to asthma control, treatments, exacerbations, and quality of life) than group 1. Clinical SAD scores were higher (indicating more severe SAD) in group 2 than group 1, and we found that these scores were related to asthma control, severity, and exacerbations. We found no correlation between clinical SAD and CT SAD scores.

Interpretation: SAD is a complex and silent signature of asthma that is likely to be directly or indirectly captured by combinations of physiological tests, such as spirometry, body plethysmography, impulse oscillometry, and multiple breath nitrogen washout. SAD is present across patients with all severities of asthma, but it is particularly prevalent in severe disease. The clinical classification of SAD into two groups (a milder and a more severe group) by use of impulse oscillometry and spirometry, which are easy to use, is meaningful given its association with GINA severity stages, asthma control, quality of life, and exacerbations.

         Listening in the quiet zone: will evaluation of small airways pay off? Editorial.

        Aaron CP. Lancet Respir Med. 2019 May;7(5):368-369.

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Seven Pillars of Small Airways Disease in Asthma and COPD: Supporting Opportunities for Novel Therapies. Review. Usmani OS, …, Kaminsky DA, Hogg J, ... Brown MN. 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.

 

Interrelationships Among Small Airways Dysfunction, Neutrophilic Inflammation, and Exacerbation Frequency in COPD. Day K, et al. Chest 2021; 159(4):1391-99.

Background: Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline.

Research Question: Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation?  Study Design And Methods: Thirty-nine COPD patients defined as either frequent exacerbator (FE) group ($ 2 exacerbations/y; n = 17) and infrequent exacerbator (IFE) group (# 1 exacerbation/y; n = 22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions.

Results: Sacin was significantly higher in the COPD FE group compared with the IFE group (p=p.027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (p=.001, r= 0.795), AX (p= .049, r = 0.560), residual volume to total lung capacity ratio (p= .004, r = 0.730), and the mean lung density of the paired CT scans (P =.018, r = 0.639).

Interpretation: Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.

The “Silent Zone” Screams Again Identifying COPD Patients Most at Risk. Editorial. Lutchen KR. . Chest 2021; 159(4):313-14.

 

The Relevance of Small Airway Dysfunction in Asthma with Nocturnal Symptoms. Abdo M, etal; the ALLIANCE study group. J Asthma Allergy  2021 Jul 13;14:897-905.

Rationale: 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. 87 patients (52%) reported to have nocturnal symptoms at least once in the last 4 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.

Small airway dysfunction and poor asthma control: a dangerous liaison. Cottini M, et al. 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.

 

Small Airways Disease, Biomarkers and COPD: Where are We? Chukowry PS, et al. Int J Chron Obstruct Pulmon Dis. 2021 Feb 18; 16:351-365.

The response to treatment and progression of Chronic Obstructive Pulmonary Disease (COPD) varies significantly. Small airways disease (SAD) is being increasingly recognized as a key pathological feature of COPD. Studies have brought forward pathological evidence of small airway damage preceding the development of emphysema and the detection of obstruction using traditional spirometry. In recent years, there has been a renewed interest in the early detection of SAD and this has brought along an increased demand for physiological tests able to identify and quantify SAD. Early detection of SAD allows early targeted therapy and this suggests the potential for altering the course of disease. The aim of this article is to review the evidence available on the physiological testing of small airways. The first half will focus on the role of lung function tests such as maximum mid-expiratory flow, impulse oscillometry and lung clearance index in detecting and quantifying SAD. The role of Computed Tomography (CT) as a radiological biomarker will be discussed as well as the potential of recent CT analysis software to differentiate normal aging of the lungs to pathology. The evidence behind SAD biomarkers sourced from blood as well as biomarkers sourced from sputum and broncho-alveolar lavage (BAL) will be reviewed. This paper focuses on CC-16, sRAGE, PAI-1, MMP-9 and MMP-12.

 

Pulmonary function testing in COPD: looking beyond the curtain of FEV1. Kakavas S, et al. NPJ Prim Care Respir Med. 2021 May 7;31(1):23.

COPD management remains challenging due to the high heterogeneity of clinical symptoms and the complex pathophysiological basis of the disease. Airflow limitation, diagnosed by spirometry, remains the cornerstone of the diagnosis. However, the calculation of FEV1 alone, has limitations in uncovering the underlying complexity of the disease. Incorporating additional pulmonary function tests (PFTs) in the everyday clinical evaluation of COPD patients, like resting volume, capacity and airway resistance measurements, diffusion capacity measurements, forced oscillation technique, field and cardiopulmonary exercise testing and muscle strength evaluation, may prove essential in tailoring medical management to meet the needs of such a heterogeneous patient population. We aimed to provide a comprehensive overview of the available PFTs, which can be incorporated into the primary care physician's practice to enhance the efficiency of COPD management.

 

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

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, et al. 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.

Computer-aided classification of small airways dysfunction using impulse scillometric features: a children-focused review. Avila N, etal. Biomed Tech (Berl). 2020 Apr 28;65(2):121-131.

      Background and objective Spirometry, which is the most commonly used technique for asthma  diagnosis, is often unsuitable for small children as it requires them to follow exact instructions and  perform extreme inspiration and expiration maneuvers. In contrast, impulse oscillometry (IOS) is a  child-friendly technique that could serve as an alternative pulmonary function test (PFT) for asthma  diagnosis and control in children as it offers several advantages over spirometry. However, the  complex test results of IOS may be difficult to be understood by practitioners due to its reliance on  mechanical and electrical models of the human pulmonary system. Recognizing this reality, computer aided decision systems could help to improve the utility of IOS. The main objective of this paper is to  understand the current computer-aided classification research works on this topic. Methods This  paper presents a methodological review of research works related to the computer-aided classification  of peripheral airway obstruction using the IOS technique, which is focused on, but not limited to,  asthmatic children. Publications that focused on computer-aided classification of asthma, peripheral  dysfunction and/or small airway impairment (SAI) based on impulse oscillometric features were  selected for this review. Results Out of the 34 articles that were identified using the selected  scientific web databases and topic-related parameters, only eight met the eligibility criteria. The most  relevant results of the articles reviewed are related to the performance of the different classifiers using  static features which are solely based on the first pulmonary function testing measurements (IOS and  spirometry). These results included an overall classifiers' accuracy performance ranging from 42.24%  to 98.61%. Conclusion There is still a great opportunity to improve the utility of IOS by developing  more computer-aided robust classifiers, specifically for the asthmatic children population as the  classification studies performed to date (1) are limited in number, (2) include features derived from  tests that are not optimally suitable for children, (3) are solely bi-class (mostly asthma and non asthma) and therefore fail to include different degrees of peripheral obstruction for disease prevention  and control and (4) lack of validation in cases that focus on multi-class classification of the different  degrees of peripheral airway obstruction.

 

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