Oscillometric Markers of Knee-Shaped Expiratory Loops in Children with Recurrent Respiratory Symptoms

Mario Barreto^1*, Martina Piersanti², Giorgia Raponi², Melania Evangelisti², Maurizio Mennini², Laura Tiberia², Francesco Guglielmi², Pasquale Parisi²

¹Fondazione Sapienza, “Sapienza” University, Rome, Italy
²Pediatric Unit Sant’Andrea Hospital, NESMOS Department, Faculty of Medicine and Psychology, “Sapienza” University, Rome, Italy

*Correspondence author: Prof. M. Barreto, Fondazione Sapienza, Pediatric Unit Sant’Andrea University Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy; Email: mario.barreto@fondazione.uniroma1.it

Citation: Barreto M, et al. Oscillometric Markers of Knee-Shaped Expiratory Loops in Children with Recurrent Respiratory Symptoms. Jour Clin Med Res. 2025;6(3):1-11.

Copyright^© 2025 by Barreto M, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Table 1: Subject characteristics by “knee pattern” in expiratory loops.

Table 2: Respiratory function by “knee pattern” in expiratory loops.

Table 3: Logistic regression predictors of “knee pattern”.

Figure 1: Examples of spirometry flow-volume loops. A: “Normal”; B: “Scooped” (or concave); C: “Knee” pattern without a pre-plateau scoop; D: “Knee” pattern with a pre-plateau scoop. Arrows indicate the “knee”.

Figure 2: Comparison of ΔsR values in subgroups of patients with “knee” pattern loops, stratified by the presence or absence of a scoop before the expiratory plateau (A) and by the angle of inflection of the “knee”: “wide” >150° and “sharp” ≤150° (B), compared to controls without a “knee”-shaped spirometry. ΔsR = sRe – sRi.

Figure 3: Receiver Operating Characteristic (ROC) curves for the within-breath difference in R (ΔR) and its standardized measure (Δz-sR) in identifying the knee-pattern spirometry. AUCs: 0.69 (p = 0.004) and 0.73 (p < 0.001), respectively. ΔR = Re − Ri ; ΔsR = sRe – sRi.

Discussion

This study identifies the within-breath oscillometric parameter ΔsR as a promising marker for distinguishing pediatric patients with knee-pattern spirometry. Beyond its statistical association, ΔsR emerged as an independent predictor of this morphology, with ROC analysis demonstrating acceptable discriminative performance (AUC = 0.73). Although sensitivity was modest, the high specificity (96.8%) suggests that a ΔsR value ≥ 0.69 strongly supports the presence of a knee-shaped expiratory loop, offering a useful rule-in tool for bronchoscopy referral when supported by clinical context.

The use of z-scores helped mitigate age-related confounders, enhancing the interpretability of impedance values in pediatric populations. Collectively, these findings support the utility of within-breath oscillometry specifically standardized resistance shifts-in quantifying a traditionally visual spirometric phenotype. Separate measurements of inspiratory and expiratory resistance (Ri, Re) and reactance (Xi, Xe) at 8 Hz did not distinguish between patients with and without the knee pattern. By contrast, within-breath variations in resistance-particularly when expressed as z-score deltas-proved more sensitive to changes in upper intrathoracic airway mechanics.

Resistance (R), the impedance component in-phase with flow, reflects frictional losses along the airways and is influenced by airway diameter, tissue collapsibility and endoluminal secretions [13,18]. Typically, R increases during expiration and decreases during inspiration [19,20], generating a ΔR. In conditions such as floppy central airways, expiratory resistance may be accentuated, resulting in elevated ΔR values.

Reactance (X), the impedance component that is out-of-phase with flow and in-phase with volume, primarily reflects elastance-a measure of the combined stiffness of lung and chest wall tissues-since inertance at 8 Hz is negligible. X is sensitive to the volume of communicating lung units [21], making it a useful marker of airway closure [22]. ΔX tends to widen during peripheral airway closure at low lung volumes and is altered in conditions with expiratory flow limitation, such as COPD or exercise-induced airway hyperresponsiveness [17,23]. The absence of significant differences in ΔX within our cohort supports the hypothesis that the knee pattern originates from central rather than peripheral airway dynamics.

These physiological insights are consistent with previous clinical observations by Shin et al., who reported higher FEV₁/FVC ratios and mid-expiratory flow rates in patients with knee-pattern spirometry, along with a lower prevalence of asthma diagnoses [7]. Similarly, our cohort demonstrated elevated FEV₁/FVC, borderline FEF₂₅-₇₅ values, reduced bronchodilator responsiveness and fewer asthma cases within the knee-pattern group. Taken together, spirometric and oscillometric findings in this subgroup diverge from the patterns typically associated with small airway obstruction [24,25]. Beyond these physiological distinctions, the presence of knee-shaped expiratory loops was also associated with higher rates of respiratory exacerbations and increased use of oral corticosteroids and antibiotics in the preceding year. Clinical history-when interpreted alongside abnormal spirometry loops and elevated ΔsR values-may assist clinicians in determining whether further diagnostic interventions, such as bronchoscopy, are warranted. Although the knee pattern appears less frequent in asthmatic children, it may coexist with asthma, suggesting that floppy central airways could represent a comorbidity rather than an alternative diagnosis. Given the absence of a universally accepted definition of the knee pattern, we selected loops based on abnormally angled contours and previously published pediatric criteria [8]. To ensure consistency, we required repeatable measures and excluded ambiguous or intermediate tracings. This approach strengthens the validity of our comparisons and may provide a functional framework for future studies evaluating oscillometry in patients whose spirometry and clinical presentation suggest central airway involvement.

Neither the presence of a pre-plateau scoop nor the degree of inflection in flow-volume curves significantly affected oscillometry outcomes within knee-pattern subgroups. All patients reported mild to moderate respiratory symptoms and none had underlying chronic disease. Although the scoop has been associated with tracheomalacia, we lacked bronchoscopic data to confirm anatomical differences. Importantly, both the scoop and knee angle are features observed during forced expiratory maneuvers, whereas oscillometry measurements are obtained during quiet breathing. Forced vital capacity maneuvers may better reveal the mechanical consequences of variable central airway obstruction as choke points migrate peripherally [4]. In contrast, within-breath FOT parameters such as ΔsR may complement spirometry by assessing central airway dynamics without requiring forced maneuvers-a particularly advantageous approach in pediatric populations.

Despite growing interest, pediatric data on impedance in variable central airway obstruction remain sparse. Hamlington, et al., studied 50 patients with Down syndrome, 72% of whom had co-occurring conditions such as congenital heart disease, dysphagia with aspiration, obstructive sleep apnea and tracheomalacia. Among the subgroup who underwent bronchoscopy, six patients with tracheomalacia showed no significant differences in R and X z-scores compared to 18 patients without tracheomalacia [26]. The heterogeneity of clinical characteristics and small sample size complicate the physiological interpretation of oscillometry results in this population.

Studies in adults have explored oscillometry in central airway obstruction due to neoplastic, inflammatory and other etiologies [27-29]. One study reported elevated Ri and Re and reduced Xi in CAO patients but found no significant differences in within-breath parameters such as ΔR or ΔX compared to patients with COPD. Additionally, CAO patients exhibited less pronounced within-breath changes in resonance frequency (ΔFres) than those with COPD characterized by airway wall thickening [27]. Verbanck, et al., proposed a regression-based index, ΔR/ΔV, for assessing tracheal stenosis, but its reliance on multiple maneuvers-including repeated quiet and rapid breaths at similar tidal volumes-may limit feasibility in pediatric populations [28]. Handa, et al., compared variable and fixed CAO, reporting elevated R and X during both respiratory phases in patients with variable CAO, although within-breath differences were not evaluated [29]. These adult studies underscore the novelty of our findings and highlight the need for pediatric-specific methodologies.

This study is the first to evaluate within-breath oscillometry parameters in children with knee-pattern spirometry, offering a novel approach to characterizing central airway dynamics. Our results suggest that ΔsR is a feasible and informative metric that complements spirometry in evaluating suspected central variable obstruction, particularly when traditional measures are inconclusive.

Limitations

This study presents several limitations. Its exploratory and retrospective design restricts anatomical interpretation and may introduce bias, particularly in symptom reporting-whether from children, caregivers or through variable physician documentation, which may be incomplete or inconsistently classified. Additionally, retrospective spirometry assessments may lack contextual alignment with clinical records, potentially affecting patient classification and therapeutic decisions. Visual evaluation of angled spirometry loops remains inherently subjective. Although ambiguous tracings were excluded to enhance diagnostic clarity, this may have introduced selection bias. Furthermore, ΔR was calculated from mean inspiratory and expiratory values, which are susceptible to flow dependence. Intra-breath assessments of Ri and Re at zero flow currently unavailable on our device-would offer greater precision and mitigate this limitation [30]. Despite these constraints, our primary aim was to assess the feasibility of within-breath oscillometry measurements in children presenting with atypically angled flow-volume loops. These findings lay the groundwork for future prospective studies in pediatric populations who may benefit from endoscopic evaluation. Incorporating imaging or bronchoscopic data in future research could help validate the anatomical correlates of ΔsR and refine its diagnostic utility.

Conclusion

In children with recurrent respiratory symptoms, elevated ΔsR may help identify those with knee-pattern spirometry suggestive of central airway collapse. This non-invasive metric offers a practical adjunct to clinical evaluation when spirometry is inconclusive, supporting decisions about further investigation or bronchoscopy referral. By quantifying a visual spirometric phenotype, ΔsR enhances diagnostic precision and expands the utility of oscillometry in pediatric respiratory care.

Conflict of Interest

The authors declare no conflicts of interest that may have influenced the research, authorship or publication of the article.

Financial Disclosure

This research did not receive any grant from funding agencies in the public, commercial or not-for-profit sectors.

Ethical Statement

This project was exempt from IRB review as it did not qualify as human subject research under federal regulations.

Acknowledgment

We thank nurse Anna Calavita, for her assistance in the pulmonary function laboratory.

Consent To Participate

Informed consent was obtained from the participant involved in this study.

Data Availability and Consent of Patient

Informed consent was obtained from the participant involved in this study.

Author’s Contribution

Informed consent was obtained from the participant involved in this study.

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