Quality control in respiratory oscillometry: reproducibility measures ignoring reactance?

This study demonstrates the inadequacy of the current technical standards of oscillometry that are based on the within-trial reproducibility of the lowest-frequency Rrs, and suggests the use of a simple variability measure encompassing both Rrs and Xrs https://bit.ly/3AYRid6.

Specific Ventilation in Severe Asthma Evaluated with Noncontrast Tidal Breathing 1H MRI.

Purpose To determine if proton (1H) MRI-derived specific ventilation is responsive to bronchodilator (BD) therapy and associated with clinical biomarkers of type 2 airway inflammation and airways dysfunction in severe asthma. Materials and Methods In this prospective study, 27 participants with severe asthma (mean age, 52 years ± 9 [SD]; 17 female, 10 male) and seven healthy controls (mean age, 47 years ± 16; five female, two male), recruited between 2018 and 2021, underwent same-day spirometry, respiratory oscillometry, and tidal breathing 1H MRI. Participants with severe asthma underwent all assessments before and after BD therapy, and type 2 airway inflammatory biomarkers were determined (blood eosinophil count, sputum eosinophil percentage, sputum eosinophil-free granules, and fraction of exhaled nitric oxide) to generate a cumulative type 2 biomarker score. Specific ventilation was derived from tidal breathing 1H MRI and its response to BD therapy, and relationships with biomarkers of type 2 airway inflammation and airway dysfunction were evaluated. Results Mean MRI specific ventilation improved with BD inhalation (from 0.07 ± 0.04 to 0.11 ± 0.04, P < .001). Post-BD MRI specific ventilation (P = .046) and post-BD change in MRI specific ventilation (P = .006) were greater in participants with asthma with type 2 low biomarkers compared with participants with type 2 high biomarkers of airway inflammation. Post-BD change in MRI specific ventilation was correlated with change in forced expiratory volume in 1 second (r = 0.40, P = .04), resistance at 5 Hz (r = -0.50, P = .01), resistance at 19 Hz (r = -0.42, P = .01), reactance area (r = -0.54, P < .01), and reactance at 5 Hz (r = 0.48, P = .01). Conclusion Specific ventilation evaluated with tidal breathing 1H MRI was responsive to BD therapy and was associated with clinical biomarkers of airways disease in participants with severe asthma. Keywords: MRI, Severe Asthma, Ventilation, Type 2 Inflammation Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Moore and Chandarana in this issue.

Intra-breath changes in respiratory mechanics assessed from multi-frequency oscillometry measurements.

Objective. Recent studies in respiratory system impedance (Zrs) with single-frequency oscillometry have demonstrated the utility of novel intra-breath measures of Zrs in the detection of pathological alterations in respiratory mechanics. In the present work, we addressed the feasibility of extracting intra-breath information from Zrs data sets obtained with conventional oscillometry.Approach. Multi-frequency recordings obtained in a pulmonology practice were re-analysed to track the 11 Hz component of Zrs during normal breathing and compare the intra-breath measures to that obtained with a single 10 Hz signal in the same subjects. A nonlinear model was employed to simulate changes in Zrs in the breathing cycle. The values of resistance (R) and reactance (X) at end expiration and end inspiration and their corresponding differences (ΔRand ΔX) were compared.Main results. All intra-breath measures exhibited similar mean values at 10 and 11 Hz in each subject; however, the variabilities were higher at 11 Hz, especially for ΔRand ΔX. The poorer quality of the 11 Hz data was primarily caused by the overlapping of modulation side lobes of adjacent oscillation frequencies. This cross-talk was enhanced by double breathing frequency components due to flow nonlinearities.Significance. Retrospective intra-breath assessment of large or special data bases of conventional oscillometry can be performed to better characterise respiratory mechanics in different populations and disease groups. The results also have implications in the optimum design of multiple-frequency oscillometry (avoidance of densely spaced frequencies) and the use of filtering procedures that preserve the intra-breath modulation information.

Improved Detection of Chronic Obstructive Pulmonary Disease at Chest CT Using the Mean Curvature of Isophotes.

PURPOSE: To determine if the mean curvature of isophotes (MCI), a standard computer vision technique, can be used to improve detection of chronic obstructive pulmonary disease (COPD) at chest CT. MATERIALS AND METHODS: In this retrospective study, chest CT scans were obtained in 243 patients with COPD and 31 controls (among all 274: 151 women [mean age, 70 years; range, 44-90 years] and 123 men [mean age, 71 years; range, 29-90 years]) from two community practices between 2006 and 2019. A convolutional neural network (CNN) architecture was trained on either CT images or CT images transformed through the MCI algorithm. Separately, a linear classification based on a single feature derived from the MCI computation (called hMCI1) was also evaluated. All three models were evaluated with cross-validation, using precision-macro and recall-macro metrics, that is, the mean of per-class precision and recall values, respectively (the latter being equivalent to balanced accuracy). RESULTS: Linear classification based on hMCI1 resulted in a higher recall-macro relative to the CNN trained and applied on CT images (0.85 [95% CI: 0.84, 0.86] vs 0.77 [95% CI: 0.75, 0.79]) but with a similar reduction in precision-macro (0.66 [95% CI: 0.65, 0.67] vs 0.77 [95% CI: 0.75, 0.79]). The CNN model trained and applied on MCI-transformed images had a higher recall-macro (0.85 [95% CI: 0.83, 0.87] vs 0.77 [95% CI: 0.75, 0.79]) and precision-macro (0.85 [95% CI: 0.83, 0.87] vs 0.77 [95% CI: 0.75, 0.79]) relative to the CNN trained and applied on CT images. CONCLUSION: The MCI algorithm may be valuable toward the automated detection and diagnosis of COPD on chest CT scans as part of a CNN-based pipeline or with stand-alone features.Keywords: Chronic Obstructive Pulmonary Disease, Quantification, Lung, CT Supplemental material is available for this article. See also the invited commentary by Vannier in this issue.© RSNA, 2021.

Exploring the 175-year history of spirometry and the vital lessons it can teach us today.

175 years have elapsed since John Hutchinson introduced the world to his version of an apparatus that had been in development for nearly two centuries, the spirometer. Though he was not the first to build a device that sought to measure breathing and quantify the impact of disease and occupation on lung function, Hutchison coined the terms spirometer and vital capacity that are still in use today, securing his place in medical history. As Hutchinson envisioned, spirometry would become crucial to our growing knowledge of respiratory pathophysiology, from Tiffeneau and Pinelli's work on forced expiratory volumes, to Fry and Hyatt's description of the flow-volume curve. In the 20th century, standardization of spirometry further broadened its reach and prognostic potential. Today, spirometry is recognized as essential to respiratory disease diagnosis, management and research. However, controversy exists in some of its applications, uptake in primary care remains sub-optimal and there are concerns related to the way in which race is factored into interpretation. Moving forward, these failings must be addressed, and innovations like Internet-enabled portable spirometers may present novel opportunities. We must also consider the physiologic and practical limitations inherent to spirometry and further investigate complementary technologies such as respiratory oscillometry and other emerging technologies that assess lung function. Through an exploration of the storied history of spirometry, we can better contextualize its current landscape and appreciate the trends that have repeatedly arisen over time. This may help to improve our current use of spirometry and may allow us to anticipate the obstacles confronting emerging pulmonary function technologies.

IntraIndividual Variability in Serum Alpha-1 Antitrypsin Levels.

BACKGROUND: Measuring alpha-1 antitrypsin (AAT) serum levels is often the first step when investigating for alpha-1 antitrypsin deficiency (AATD). The purpose of this study was to determine the test-retest reproducibility of AAT serum levels and to determine if between-measurements variability was associated with acute phase markers of inflammation. METHODS: We retrospectively analyzed a sample of 255 patients from a community respirology practice with chronic obstructive pulmonary disease (COPD) in whom AAT serum levels were measured twice, on separate visits. White blood cell count and fibrinogen were also measured at the time of the second blood sampling as markers of acute phase inflammation. Intraclass correlation coefficient (ICC), Pearson correlation coefficient, and Bland-Altman analysis were used to document test-retest reproducibility. Regression analyses were used to identify potential correlates of test-retest AAT level differences. RESULTS: Although the 2 AAT serum levels were significantly correlated, the between-measurement agreement was weak (ICC of 0.38 [95% confidence interval (CI), 0.27 to 0.48]; Pearson correlation coefficient of 0.34 [95% CI, 0.23 to 0.44]) and Bland-Altman analysis revealed wide 95% limits of agreement. Considering that an AAT serum level below 1.13g/L should trigger further investigations to confirm the AAT status, discrepancies between the test-retest AAT levels resulted in reconsidering requirement for further investigation in 22% of patients. A significant correlation between the fibrinogen value and the second AAT level was found (r=0.21, p=0.004 [n=173]). CONCLUSIONS: Serum AAT levels showed weak intra-individual reproducibility which could lead to AATD status misclassification and potentially a missed diagnosis of AATD.

Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study.

BACKGROUND: Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed. ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated. METHOD: Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care. Data were obtained from the Optimum Patient Care Research Database (OPCRD) in the UK. RESULTS: A total of 1046 patients who withdrew ICS were matched 1:4 by time on TT to 4184 patients who continued with TT. Up to 76.1% of the total population had 0 or 1 exacerbation the previous year. After controlling for confounders, patients who discontinued ICS did not have an increased risk of moderate or severe exacerbations (adjusted HR: 1.04, 95% confidence interval (CI) 0.94-1.15; p = 0.441). However, rates of exacerbations managed in primary care (incidence rate ratio (IRR) 1.33, 95% CI 1.10-1.60; p = 0.003) or in hospital (IRR 1.72, 95% CI 1.03-2.86; p = 0.036) were higher in the cessation group. Unsuccessful ICS withdrawal was significantly and independently associated with more frequent courses of oral corticosteroids the previous year and with a blood eosinophil count ≥ 300 cells/µL. CONCLUSIONS: In this primary care population of patients with COPD, composed mostly of infrequent exacerbators, discontinuation of ICS from TT was not associated with an increased risk of exacerbation; however, the subgroup of patients with more frequent courses of oral corticosteroids and high blood eosinophil counts should not be withdrawn from ICS. Trial registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS30851).

Description of Participation in Daily and Social Activities for Individuals with COPD.

This study described the participation in daily and social activities and the perceived barriers and facilitators to participation of individuals with chronic obstructive pulmonary disease (COPD). Individuals, recruited from outpatient clinics, responded to a survey on their participation in, and barriers and facilitators towards, 26 daily and social activities, divided into 3 categories: (1) physical activity and movement (PAM); (2) self-care; and (3) social engagement. For each activity, chi-square analyses were used to examine participation differences by individuals': quartiles of airflow obstruction [percent predicted forced expiratory volume in 1 second (FEV1%predicted)] and breathlessness burden and exacerbation risk. Of the 200 participants (47% women; mean ± standard deviation age = 68 ± 9 years), most wanted to increase their participation in PAM activities (range 21-75%) and significant differences were found in 5/10 PAM activities for individuals' breathlessness burden and exacerbation risk (e.g., more individuals than expected in group A (modified Medical Research Council breathlessness score <2 and 0-1 exacerbations in past 12 months) participated in regular exercise as much as they wanted (χ(9)2=20.43, Cramer's V=.23)). Regardless of the degree of airflow obstruction or breathlessness burden and exacerbation risk, the most common barrier to participation was breathlessness (p<.001, η2p=.86) and the most common facilitator was engaging as part of their routine (p<.001, η2p=.75). Individuals with COPD want to increase their participation in daily and social activities but are limited by breathlessness. Strategies to alleviate breathlessness should be identified/prioritized and incorporated into individuals' daily routines to meet their self-reported participation objectives in daily and social activities.

Development of Quality Assurance and Quality Control Guidelines for Respiratory Oscillometry in Clinic Studies.

BACKGROUND: The guidelines to conduct and interpret conventional pulmonary function (PFT) tests are frequently reviewed and updated. However, the quality assurance and quality control (QA/QC) guidelines for respiratory oscillometry testing remain limited. QA/QC guidelines are essential for oscillometry to be used as a diagnostic pulmonary function test (PFT) in a clinical setting. METHODS: We developed a QA/QC protocol shortly after oscillometry was introduced in our laboratory as part of a clinical study. The first clinical study began after the research personnel completed 3 h of combined didactic and hands-on training and establishment of a standard operating protocol (SOP) for oscillometry testing. All oscillometry tests were conducted using the initial SOP protocol from October 17, 2017, to April 6, 2018. At this time, the first QA/QC audit took place, followed by revisions to the SOP, the addition of a QA/QC checklist, and the development of a 12-h training program. A second audit of oscillometry tests was conducted from April 9, 2018, to June 30, 2019. Both audits were completed by a registered cardiopulmonary technologist from the Toronto General Pulmonary Function Lab. RESULTS: The first audit evaluated 197 paired oscillometry-PFT tests and found 10 tests (5.08%) to be invalid, with a coefficient of variation > 15%. The second audit examined 1,930 paired oscillometry-PFT tests; only 3 tests (0.16%) were unacceptable, with a coefficient of variation > 15%. Improvement in QA/QC was significantly better compared to the first audit (P < .001). CONCLUSIONS: Although oscillometry requires minimal subject cooperation, application of the principles that govern the conduct and application of a PFT are important for ensuring that oscillometry testing is performed according to acceptability and reproducibility. Specifically, the inclusion of a SOP, a proper training program, a QA/QC checklist, and regular audits with feedback are vital to ensure that oscillometry is conducted accurately and precisely.

Comparison of oscillometry devices using active mechanical test loads.

Noninvasiveness, low cooperation demand and the potential for detailed physiological characterisation have promoted the use of oscillometry in the assessment of lung function. However, concerns have been raised about the comparability of measurement outcomes delivered by the different oscillometry devices. The present study compares the performances of oscillometers in the measurement of mechanical test loads with and without simulated breathing. Six devices (five were commercially available and one was custom made) were tested with mechanical test loads combining resistors (R), gas compliances (C) and a tube inertance (L), to mimic respiratory resistance (R rs) and reactance (X rs) spectra encountered in clinical practice. A ventilator was used to simulate breathing at tidal volumes of 300 and 700 mL at frequencies of 30 and 15 min-1, respectively. Measurements were evaluated in terms of R, C, L, resonance frequency (f res), reactance area (AX ) and resistance change between 5 and 20 or 19 Hz (R 5-20(19)). Increasing test loads caused progressive deviations in R rs and X rs from calculated values at various degrees in the different oscillometers. While mean values of R rs were recovered acceptably, some devices exhibited serious distortions in the frequency dependences of R rs and X rs, leading to large errors in C, L, f res, AX and R 5-20(19). The results were largely independent of the simulated breathing. Simplistic calibration procedures and mouthpiece corrections, in addition to unknown instrumental and signal processing factors, may be responsible for the large differences in oscillometry measures. Rigorous testing and ongoing harmonisation efforts are necessary to better exploit the diagnostic and scientific potential of oscillometry.

Prevalence and Characteristics of Asthma-Chronic Obstructive Pulmonary Disease Overlap in Routine Primary Care Practices.

Rationale: Adults may exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD), a situation recently described as asthma-COPD overlap (ACO). There is a paucity of information about ACO in primary care.Objectives: To estimate the prevalence and describe characteristics of individuals with ACO in primary care practices among patients currently diagnosed with asthma, COPD, or both; and to compare the prevalence and characteristics of ACO among the three source populations.Methods: The Respiratory Effectiveness Group conducted a cross-sectional study of individuals ≥40 years old and with ≥2 outpatient primary care visits over a 2-year period in the UK Optimum Patient Care Research Database. Patients were classified into one of three source populations based on diagnostic codes: 1) COPD only, 2) both asthma and COPD, or 3) asthma only. ACO was defined as the presence of all of the following 1) age ≥40 years, 2) current or former smoking, 3) post-bronchodilator airflow limitation (forced expiratory volume in 1 second/forced vital capacity <0.7), and 4) ≥12% and ≥200 ml reversibility in post-bronchodilator forced expiratory volume in 1 second.Results: Among 2,165 individuals (1,015 COPD only, 395 with both asthma and COPD, and 755 asthma only), the overall prevalence of ACO was 20% (95% confidence interval, 18-23%). Patients with ACO had a mean age of 70 years (standard deviation, 11 yr), 60% were men, 73% were former smokers (the rest were current smokers), and 66% were overweight or obese. Comorbid conditions were common in patients with ACO, including diabetes (53%), cardiovascular disease (36%), hypertension (30%), eczema (23%), and rhinitis (21%). The prevalence of ACO was higher in patients with a diagnosis of both asthma and COPD (32%) compared with a diagnosis of COPD only (20%; P < 0.001) or asthma only (14%; P < 0.001). Demographic and clinical characteristics of ACO varied across these three source populations.Conclusions: One in five individuals with a diagnosis of COPD, asthma, or both asthma and COPD in primary care settings have ACO based on the Respiratory Effectiveness Group ACO Working group criteria. The prevalence and characteristics of patients with ACO varies across the three source populations.

Oscillometry and pulmonary magnetic resonance imaging in asthma and COPD.

Developed over six decades ago, pulmonary oscillometry has re-emerged as a noninvasive and effort-independent method for evaluating respiratory-system impedance in patients with obstructive lung disease. Here, we evaluated the relationships between hyperpolarized 3 He ventilation-defect-percent (VDP) and respiratory-system resistance, reactance and reactance area (AX ) measurements in 175 participants including 42 never-smokers without respiratory disease, 56 ex-smokers with chronic-obstructive-pulmonary-disease (COPD), 28 ex-smokers without COPD and 49 asthmatic never-smokers. COPD participants were dichotomized based on x-ray computed-tomography (CT) evidence of emphysema (relative-area CT-density-histogram ≤ 950HU (RA950 ) ≥ 6.8%). In asthma and COPD subgroups, MRI VDP was significantly related to the frequency-dependence of resistance (R5-19 ; asthma: ρ = 0.48, P = 0.0005; COPD: ρ = 0.45, P = 0.0004), reactance at 5 Hz (X5 : asthma, ρ = -0.41, P = 0.004; COPD: ρ = -0.38, P = 0.004) and AX (asthma: ρ = 0.47, P = 0.0007; COPD: ρ = 0.43, P = 0.0009). MRI VDP was also significantly related to R5-19 in COPD participants without emphysema (ρ = 0.54, P = 0.008), and to X5 in COPD participants with emphysema (ρ = -0.36, P = 0.04). AX was weakly related to VDP in asthma (ρ = 0.47, P = 0.0007) and COPD participants with (ρ = 0.39, P = 0.02) and without (ρ = 0.43, P = 0.04) emphysema. AX is sensitive to obstruction but not specific to the type of obstruction, whereas the different relationships for MRI VDP with R5-19 and X5 may reflect the different airway and parenchymal disease-specific biomechanical abnormalities that lead to ventilation defects.

Extrafine Versus Fine Inhaled Corticosteroids in Relation to Asthma Control: A Systematic Review and Meta-Analysis of Observational Real-Life Studies.

BACKGROUND: The particle size of inhaled corticosteroids (ICSs) may affect airway drug deposition and effectiveness. OBJECTIVE: To compare the effectiveness of extrafine ICSs (mass median aerodynamic diameter, <2 µm) versus fine-particle ICSs administered as ICS monotherapy or ICS-long-acting ß-agonist combination therapy by conducting a meta-analysis of observational real-life asthma studies to estimate the treatment effect of extrafine ICSs. METHODS: MEDLINE and EMBASE databases were reviewed for asthma observational comparative effectiveness studies from January 2004 to June 2016. Studies were included if they reported odds and relative risk ratios and met all inclusion criteria (Respiratory Effectiveness Group/European Academy of Allergy and Clinical Immunology quality standards, comparison of extrafine ICSs with same or different ICS molecule, ≥12-month follow-up). End-point data (asthma control, exacerbations, prescribed ICS dose) were pooled. Random-effects meta-analysis modeling was used. The study protocol is published in the PROSPERO register CRD42016039137. RESULTS: Seven studies with 33,453 subjects aged 5 to 80 years met eligibility criteria for inclusion. Six studies used extrafine beclometasone propionate and 1 study used both extrafine beclometasone propionate and extrafine ciclesonide as comparators with fine-particle ICSs. The overall odds of achieving asthma control were significantly higher for extrafine ICSs compared with fine-particle ICSs (odds ratio, 1.34; 95% CI, 1.22-1.46). Overall exacerbation rate ratios (0.84; 95% CI, 0.73-0.97) and ICS dose (weighted mean difference, -170 µg; 95% CI, -222 to -118 µg) were significantly lower for extrafine ICSs compared with fine-particle ICSs. CONCLUSIONS: This meta-analysis demonstrates that extrafine ICSs have significantly higher odds of achieving asthma control with lower exacerbation rates at significantly lower prescribed doses than fine-particle ICSs.

Assessment of Airway Distensibility by the Forced Oscillation Technique: Reproducible and Potentially Simplifiable.

A non-invasive index of airway distensibility is required to track airway remodeling over time. The forced oscillation technique (FOT) provides such an index by measuring the change in respiratory system conductance at 5 Hz over the corresponding change in lung volume (ΔGrs5/ΔVL). To become useful clinically, this method has to be reproducible and easy to perform. The series of breathing maneuvers required to measure distensibility would be greatly facilitated if the difficulty of breathing below functional residual capacity (FRC) could be precluded and the number of maneuvers could be reduced. The distensibility at lung volumes below FRC is also reduced by several confounders, suggesting that excluding data points below FRC should provide a better surrogate for airway remodeling. The objectives of this study were to investigate the reproducibility of airway distensibility measured by FOT and to assess whether the method could be simplified to increase feasibility. Distensibility was measured at three separate occasions in 13 healthy volunteers. At each visit, three deflationary maneuvers were performed, each consisting of tidal breathing from total lung capacity (TLC) to residual volume by slowly decreasing the end-expiratory volume on each subsequent breath. Distensibility was calculated by using either all data points from TLC to residual volume (RV) or only data points from TLC to FRC for either all three or only the first two deflationary maneuvers. Intra-class correlation coefficients (ICC) were used to assess reproducibility and Bland-Altman analyses were used to assess the level of agreement between the differently calculated values of distensibility. The results indicate that distensibility calculated using all data points is reproducible (ICC = 0.64). Using data points from TLC to FRC slightly improved reproducibility (ICC = 0.68) and increased distensibility by 19.4%, which was expected as distensibility above FRC should not be affected by confounders. Using only data points within the first two maneuvers did not affect reproducibility when tested between TLC and FRC (ICC = 0.66). We conclude that a valuable measure of airway distensibility could potentially be obtained with only two deflationary maneuvers that do not require breathing below FRC. This simplified method would increase feasibility without compromising reproducibility.

"Trying, But Failing" - The Role of Inhaler Technique and Mode of Delivery in Respiratory Medication Adherence.

Inhaled therapies are the backbone of asthma and chronic obstructive pulmonary disease management, helping to target therapy at the airways. Adherence to prescribed treatment is necessary to ensure achievement of the clinician's desired therapeutic effect. In the case of inhaled therapies, this requires patients' acceptance of their need for inhaled therapy together with successful mastery of the inhaler technique specific to their device(s). This article reviews a number of challenges and barriers that inhaled mode of delivery can pose to optimum adherence-to therapy initiation and, thereafter, to successful implementation and persistence. The potential effects on adherence of different categories of devices, their use in multiplicity, and the mixing of device categories are discussed. Common inhaler errors identified by the international Implementing Helping Asthma in Real People (iHARP) study are summarized, and adherence intervention opportunities for health care professionals are offered. Better knowledge of common errors can help practicing clinicians identify their occurrence among patients and prompt remedial actions, such as tailored education, inhaler technique retraining, and/or shared decision making with patients regarding suitable alternatives. Optimizing existing therapy delivery, or switching to a suitable alternative, can help avoid unnecessary escalation of treatment and health care resources.