Maximal Expiratory Flow-volume Curves Research Articles

Tidal expiratory flow limitation during exercise is unrelated to peripheral hypercapnic chemosensitivity

We sought to determine if peripheral hypercapnic chemosensitivity is related to expiratory flow limitation (EFL) during exercise. Twenty participants completed one testing day which consisted of peripheral hypercapnic chemosensitivity testing and a maximal exercise test to exhaustion. The chemosensitivity testing consisting of two breaths of 10% CO2 (O2∼21%) repeated 5 times during seated rest and the first 2 exercise intensities during the maximal exercise test. Following chemosensitivity testing, participants continued cycling with the intensity increasing 20 W every 1.5 minutes till exhaustion. Maximal expiratory flow-volume curves were derived from forced expiratory capacity maneuvers performed before and after exercise at varying efforts. Inspiratory capacity maneuvers were performed during each exercise stage to determine EFL. There was no difference between the EFL and non-EFL hypercapnic chemoresponse (mean response during exercise 0.96 ± 0.46 and 0.91 ± 0.33 l min−1 mmHg−1, p=0.783). Peripheral hypercapnic chemosensitivity during mild exercise does not appear to be related to the development of EFL during exercise.

The initial angle of the maximum expiratory flow-volume curve: a novel start-of-test criteria of spirometry in children.

The aim of the present study was to define an initial angle called β and to assess its diagnostic value for identifying poor-quality maneuvers in spirometry testing in children. Furthermore, its predictive equation or normal value was explored. Children aged 4-14years with respiratory symptoms who underwent spirometry were enrolled. Based on the efforts labeled during maneuvering and the quality control criteria of the guidelines, children were categorized into good-quality and poor-quality groups. According to ventilatory impairment, children in the good-quality group were divided into three subgroups: normal, restricted, and obstructed. Angle β was the angle between the line from the expiratory apex to the origin of coordinates and the x-axis of the maximal expiratory flow-volume (MEFV) curve. Demographic characteristics, angle β, and other spirometric parameters were compared among groups. The diagnostic values of angle β, forced expiratory time (FET), and their combination were assessed using receiver operating characteristic curves. Data from 258 children in the good-quality group and 702 healthy children in our previous study were used to further explore the predictive equation or normal value of angle β. The poor-quality group exhibited a significantly smaller angle β (76.44° vs. 79.36°; P < 0.001), significantly lower peak expiratory flow (PEF), FET, and effective FET (ETe), and significantly higher expiratory volume at peak flow rate (FEV-PEF) and ratio of extrapolated volume and forced vital capacity (EV/FVC) than the good-quality group. There was no significant difference in angle β among the normal, restricted, and obstructed groups. Logistic regression analysis revealed that smaller angle β and FET values indicated poor-quality MEFV curves. The combination of angle β < 74.58° and FET < 4.91s had a significantly larger area under the curve than either one alone. The normal value of angle β of children aged 4-14years was 78.40 ± 0.12°. Conclusions: Angle β contributes to the quality control evaluation of spirometry in children. Both angle β < 74.58° and FET < 4.91s are predictors of poor-quality MEFV curves, while their combination offers the highest diagnostic value. What is Known: • A slow start is one of the leading causes of poor-quality maximal expiratory flow-volume (MEFV) curves, which is a particularly prominent issue among children due to limited cooperation, especially those younger than 6years old. • It is relatively difficult to differentiate between ventilatory dysfunction and poor cooperation when a slow start occurs in children; therefore, there is an urgent need for an objective indicator that is unaffected by ventilatory impairment to evaluate quality control of spirometry. What is New: • The initial angle β, which was introduced at the ascending limb of the MEFV curve in the present study, has a certain diagnostic value for poor-quality MEFV curves in children. • Angle β < 74.58° is a predictor of poor-quality MEFV curves, and its combination with FET < 4.91s offers a higher diagnostic value.

Artificial neural network identification of exercise expiratory flow-limitation in adults

Identification of ventilatory constraint is a key objective of clinical exercise testing. Expiratory flow-limitation (EFL) is a well-known type of ventilatory constraint. However, EFL is difficult to measure, and commercial metabolic carts do not readily identify or quantify EFL. Deep machine learning might provide a new approach for identifying EFL. The objective of this study was to determine if a convolutional neural network (CNN) could accurately identify EFL during exercise in adults in whom baseline airway function varied from normal to mildly obstructed. 2931 spontaneous exercise flow-volume loops (eFVL) were placed within the baseline maximal expiratory flow-volume curves (MEFV) from 22 adults (15 M, 7 F; age, 32 yrs) in whom lung function varied from normal to mildly obstructed. Each eFVL was coded as EFL or non-EFL, where EFL was defined by eFVLs with expired airflow meeting or exceeding the MEFV curve. A CNN with seven hidden layers and a 2-neuron softmax output layer was used to analyze the eFVLs. Three separate analyses were conducted: (1) all subjects (n = 2931 eFVLs, [GRALL]), (2) subjects with normal spirometry (n = 1921 eFVLs [GRNORM]), (3) subjects with mild airway obstruction (n = 1010 eFVLs, [GRLOW]). The final output of the CNN was the probability of EFL or non-EFL in each eFVL, which is considered EFL if the probability exceeds 0.5 or 50%. Baseline forced expiratory volume in 1 s/forced vital capacity was 0.77 (94% predicted) in GRALL, 0.83 (100% predicted) in GRNORM, and 0.69 (83% predicted) in GRLOW. CNN model accuracy was 90.6, 90.5, and 88.0% in GRALL, GRNORM and GRLOW, respectively. Negative predictive value (NPV) was higher than positive predictive value (PPV) in GRNORM (93.5 vs. 78.2% for NPV vs. PPV). In GRLOW, PPV was slightly higher than NPV (89.5 vs. 84.5% for PPV vs. NPV). A CNN performed very well at identifying eFVLs with EFL during exercise. These findings suggest that deep machine learning could become a viable tool for identifying ventilatory constraint during clinical exercise testing.

Isolated abnormal FEF75% detects unsuspected bronchiolar obstruction in CF children.

Physiologic detection of bronchiolar obstruction in children with cystic fibrosis (CF) may be clinically unsuspected because of normal routine spirometry despite bronchiectasis on lung CT. Children from two accredited CF facilities had spirometry obtained every 3 months when clinically stable. Pre-bronchodilator maximum expiratory flow volume curves were retrospectively analyzed over 16 years to detect an isolated abnormal FEF75%, despite normal routine spirometry. At Miller Children's and Women's Hospital (MCWH), an abnormal FEF75% was initially detected in 26 CF children at age 7.5 ± 4 (SD) years despite normal routine spirometry initially. FEF75% remained an isolated abnormality for 2.5 ± 1.5 years after it was initially detected in these 26 CF children. At Cohen Children's Medical Center (CCMC), despite normal routine spirometry initially, abnormal FEF75% occurred in 13 children at age 11.7 ± 4.5 years, and abnormal FEF25-75% in 10 children at age 11.8 ± 5.3 years. FEF75% was most sensitive spirometric test for diagnosing both early and isolated progressive bronchiolar obstruction. Data from CCMC in older children demonstrated the simultaneous detection of abnormal FEF75% and FEF25-75% values consistent with greater bronchiolar obstruction when serial spirometry was initiated at an older age. There is very little published spirometric data regarding diagnosis of isolated small airways obstruction in CF children. FEF75% can easily detect unsuspected small airways obstruction in CF children with normal routine spirometry and bronchiectasis on lung CT and optimize targeted modulatory therapies.

Effect of exercise-induced bronchoconstriction on the configuration of the maximal expiratory flow-volume curve in adults with asthma.

We determined the effect of exercise-induced bronchoconstriction (EIB) on the shape of the maximal expiratory flow-volume (MEFV) curve in asthmatic adults. The slope-ratio index (SR) was used to quantitate the shape of the MEFV curve. We hypothesized that EIB would be accompanied by increases in SR and thus increased curvilinearity of the MEFV curve. Adult asthmatic ( n = 10) and non-asthmatic control subjects ( n = 9) cycled for 6-8 min at 85% of peak power. Following exercise, subjects remained on the ergometer and performed a maximal forced exhalation every 2 min for a total 20 min. In each MEFV curve, the slope-ratio index (SR) was calculated in 1% volume increments beginning at peak expiratory flow (PEF) and ending at 20% of forced vital capacity (FVC). Baseline spirometry was lower in asthmatics compared to control subjects (FEV1 % predicted, 89.1± 14.3 vs. 96.5± 12.2% [SD] in asthma vs. control; p < 0.05). In asthmatic subjects, post-exercise FEV1 decreased by 29.9± 13.2% from baseline (3.48 ± 0.74 and 2.24 ± 0.59 [SD] L for baseline and post-exercise nadir; p < 0.001). At baseline and at all timepoints after exercise, average SR between 80 and 20% of FVC was larger in asthmatic than control subjects (1.48 ± 0.02 vs. 1.23 ± 0.02 [SD] for asthma vs. control; p < 0.005). This averaged SR did not change after exercise in either subject group. In contrast, post-exercise SR between PEF and 75% of FVC was increased from baseline in subjects with asthma, suggesting that airway caliber heterogeneity increases with EIB. These findings suggest that the SR-index might provide useful information on the physiology of acute airway narrowing that complements traditional spirometric measures.

Principal component analysis of flow-volume curves in COPDGene to link spirometry with phenotypes of COPD

BackgroundParameters from maximal expiratory flow-volume curves (MEFVC) have been linked to CT-based parameters of COPD. However, the association between MEFVC shape and phenotypes like emphysema, small airways disease (SAD) and bronchial wall thickening (BWT) has not been investigated.Research questionWe analyzed if the shape of MEFVC can be linked to CT-determined emphysema, SAD and BWT in a large cohort of COPDGene participants.Study design and methodsIn the COPDGene cohort, we used principal component analysis (PCA) to extract patterns from MEFVC shape and performed multiple linear regression to assess the association of these patterns with CT parameters over the COPD spectrum, in mild and moderate-severe COPD.ResultsOver the entire spectrum, in mild and moderate-severe COPD, principal components of MEFVC were important predictors for the continuous CT parameters. Their contribution to the prediction of emphysema diminished when classical pulmonary function test parameters were added. For SAD, the components remained very strong predictors. The adjusted R2 was higher in moderate-severe COPD, while in mild COPD, the adjusted R2 for all CT outcomes was low; 0.28 for emphysema, 0.21 for SAD and 0.19 for BWT.InterpretationThe shape of the maximal expiratory flow-volume curve as analyzed with PCA is not an appropriate screening tool for early disease phenotypes identified by CT scan. However, it contributes to assessing emphysema and SAD in moderate-severe COPD.

Exercise‐induced Bronchoconstriction does not Change the Configuration of the Maximal Expiratory Flow‐Volume Curve in Adults with Asthma

BackgroundSeveral indices of airflow and volume derived from the maximal expiratory flow volume (MEFV) curve are used to identify and diagnose the severity of respiratory disease. In addition to the objective measures of expiratory airflow and volume, the shape of the MEFV curve is thought to provide information on pulmonary (patho)physiology. In the asthmatic, the MEFV curve is often convex relative to the volume axis (“scooped”). This “scooped” curve is thought to indicate heterogeneous airway emptying during the forced exhalation. The effect of exercise‐induced airway narrowing on the shape of the MEFV curve is not known. The purpose of this study was to determine the effect of exercise‐induced bronchoconstriction (EIB) on the shape of the MEFV curve in asthmatic adults. We hypothesized that the slope‐ratio (SR) index, and thus the overall shape of the MEFV curve would not be affected by EIB.MethodsAdult male and female asthmatics (n=9; age, 26.8 ± 8.4 yrs; BMI, 27.4 ± 4.3 kg/m2) and non‐asthmatics (n=9; age, 25.4 ± 7.8 yrs; BMI, 21.9 ± 2.0 kg/m2) completed a high‐intensity cycle ergometry bout for six minutes at 85% of peak power. Maximal forced exhalations (MFE) were performed before exercise. Following exercise cessation, subjects remained on the ergometer and performed a MFE every two‐minutes for a total 20 minutes. In each MEFV curve, the SR index was calculated in 1% volume increments between 20% and 80% of the vital capacity. To calculate SR, the tangent and chord slope were generated at each point of interest, and the tangent slope was divided by the chord slope.ResultsPulmonary function at baseline was lower in asthmatics compared to the control group (FEV1% predicted, 84.9 ± 11.0 vs. 96.5 ± 12.2% in asthmatics vs. control, respectively; P&lt;0.05). In asthmatic subjects, post‐exercise nadir FEV1 decreased by 29.1 ± 13.7% from baseline (3.40 ± 0.74 to 2.47 ± 0.7 L for baseline and nadir, respectively; P&lt;0.001), whereas FEV1 did not change after exercise in control subjects (3.84 ± 0.9 to 3.70 ± 0.8 L for baseline and nadir, respectively). At all time points, the average SR between 20 and 80% of vital capacity was significantly larger in asthmatic than control subjects (1.49 ± 0.02 vs. 1.23 ± 0.02 [SD] for asthma vs. control; P&lt;0.005). However, in both control and asthmatic subjects, post‐exercise SR was not different from baseline at any time point. In asthmatic subjects, average SR between 20 and 80% of vital capacity was 1.49 ± 0.13 at baseline and averaged 1.49 ± 0.02 across all post‐exercise time points (range = 1.48 to 1.53).ConclusionIn this group of adults with asthma, EIB did not influence the SR index, indicating no change to the overall shape of the MEFV curve. Thus, these findings suggest that inhomogeneities in airway caliber and lung emptying are not magnified during an episode of EIB.

Predictors of Expiratory Flow Limitation during Exercise in Healthy Males and Females

It is unclear whether the frequency and mechanisms of expiratory flow limitation (EFL) during exercise differ between males and females. This study aimed to determine which factors predispose individuals to EFL during exercise and whether these factors differ based on sex. We hypothesized that i) EFL frequency would be similar in males and females and ii) in females, EFL would be associated with indices of low ventilatory capacity, whereas in males, EFL would be associated with indices of high ventilatory demand. Data from n = 126 healthy adults (20-45 y, n = 60 males, n = 66 females) with a wide range of cardiorespiratory fitness (81%-182% predicted maximal oxygen uptake) were included in the study. Participants performed spirometry and an incremental cycle exercise test to exhaustion. Standard cardiorespiratory variables were assessed throughout exercise. The tidal flow-volume overlap method was used to assess EFL based on a minimum threshold of 5% overlap between the tidal and the maximum expiratory flow-volume curves. Predictors of EFL during exercise were determined via multiple logistical regression using anthropometric, pulmonary function, and peak exercise data. During exercise, EFL occurred in 49% of participants and was similar between the sexes (females = 45%, males = 53%; P = 0.48). In males, low forced expired flow between 25% and 75% of forced vital capacity and high slope ratio as well as low end-expiratory lung volume, high breathing frequency, and high relative tidal volume at peak exercise were associated with EFL ( P < 0.001; Nagelkerke R2 = 0.73). In females, high slope ratio, high breathing frequency, and tidal volume at peak exercise were associated with EFL ( P < 0.001; Nagelkerke R2 = 0.61). Despite sex differences in respiratory system morphology, the frequency and the predictors of EFL during exercise do not substantially differ between the sexes.

Examination Of The Maximum Expiratory Flow-Volume Curve In Young Adults Following SARS-CoV-2 Infection

Examination Of The Maximum Expiratory Flow-Volume Curve In Young Adults Following SARS-CoV-2 Infection

Baseline spirometry parameters as predictors of airway hyperreactivity in adults with suspected asthma

BackgroundMethacholine challenge tests (MCTs) are used to diagnose airway hyperresponsiveness (AHR) in patients with suspected asthma where previous diagnostic testing has been inconclusive. The test is time consuming and usually requires referral to specialized centers. Simple methods to predict AHR could help determine which patients should be referred to MCTs, thus avoiding unnecessary testing. Here we investigated the potential use of baseline spirometry variables as surrogate markers for AHR in adults with suspected asthma.MethodsBaseline spirometry and MCTs performed between 2013 and 2019 in a large tertiary center were retrospectively evaluated. Receiver-operating characteristic curves for the maximal expiratory flow-volume curve indices (angle β, FEV1, FVC, FEV1/FVC, FEF50%, FEF25–75%) were constructed to assess their overall accuracy in predicting AHR and optimal cutoff values were identified.ResultsA total of 2983 tests were analyzed in adults aged 18–40 years. In total, 14% of all MCTs were positive (PC20 ≤ 16 mg/ml). All baseline spirometry parameters were significantly lower in the positive group (p < 0.001). FEF50% showed the best overall accuracy (AUC = 0.688) and proved to be useful as a negative predictor when applying FEF50% ≥ 110% as a cutoff level.ConclusionsThis study highlights the role of FEF50% in predicting AHR in patients with suspected asthma. A value of ≥ 110% for baseline FEF50% could be used to exclude AHR and would lead to a substantial decrease in MCT referrals.

Longitudinal Examination of the Shape of the Maximum Expiratory Flow‐Volume Curve in Young Adults Following SARS‐CoV‐2 Infection

Examination of the shape of the maximum expiratory flow‐volume curve represents a method to noninvasively describe lung and airway function in health and disease. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection can result in pulmonary dysfunction and may result in changes to the shape of the maximum expiratory flow‐volume curve during the recovery period following SARS‐CoV‐2 infection.PurposeThe purpose of this study was to quantitatively examine the shape and the area of the maximum expiratory flow volume curve in otherwise healthy, young adults during the three months following SARS‐CoV‐2 infection.MethodsOtherwise healthy, young adults (4M/3F, age: 21 ± 1 y, height: 174.9 ± 11.2 cm, body mass index: 23.6 ± 1.6 kgᐧm‐2) who tested positive for SARS‐CoV‐2 completed spirometry testing on three occasions. The first visit (BL) took place three‐to‐four weeks after positive test confirmation. Approximately four weeks separated each subsequent visit (1M and 2M, respectively). Following each spirometry test, the flow‐volume loop with the greatest sum of forced vital capacity (FVC) and forced expiratory volume in one second was chosen for analysis. The angle beta (β°) and flow ratio were calculated using standard pulmonary function parameters. Slope ratios at increments of 5% of FVC were determined from 80% to 20% FVC. Additionally, the area under the maximum expiratory flow‐volume curve was calculated. Data were compared using repeated measures analysis of variance. Statistical significance was set at p = 0.05.ResultsFVC remained similar over the study period (p > 0.05). The β° was significantly reduced at 2M compared with BL (BL: 188.8 ± 15.7°, 1M: 180.9 ± 6.9°; 2M: 176.8 ± 5.0°, p = 0.012). Flow ratios were similar between visits (BL: 20.3 ± 11.7%, 1M: 13.0 ± 6.4%, 2M: 18.1 ± 5.9%; p = 0.53). Additionally, the slope ratios at each lung volume were similar between visits. However, while not statistically different, the slope ratio at 80% FVC approached significance (BL: 1.22 ± 0.98, 1M: 2.37 ± 1.00, 2M: 2.13 ± 0.86; p = 0.07). The total area under the maximum flow‐volume curve was not different between visits (BL: 21.0 ± 5.1 L2∙s‐1, 1M: 21.5 ± 4.5 L2∙s‐1; 2M: 21.9 ± 4.7 L2∙s‐1; p = 0.49). The percentages of the total area under the curve that were contained between peak expiratory flow (PEF) and 75% FVC and between 50% FVC and 25% FVC were altered at 1M and 2M compared with BL (p < 0.05). PEF tended to be greater during 2M compared with BL (BL: 8.49 ± 1.34 L2∙s‐1, 1M: 9.34 ± 1.92 L2∙s‐1, 2M: 9.44 ± 1.53 L2∙s‐1; p = 0.056) and the changes in PEF from BL to 2M were significantly correlated with the changes in β° and area under the curve subdivisions over the same time period (p < 0.05).ConclusionThese data demonstrate that the shape of the maximum expiratory flow‐volume curve changes marginally during the initial three months following SARS‐CoV‐2 infection. Yet, the changes appear to be largely driven by increases in peak expiratory flow and suggests that SARS‐CoV‐2 infection is acutely involved in large airway dysfunction.

Use of Area under the Expiratory Flow-volume Curve and Rectangular Area Ratio in Detecting Ventilatory Impairments in Spirometry: A Pilot Study

Purpose: This study aimed at demonstrating the reliability of surface area under the maximum expiratory flow volume curve (Aex) and rectangular area ratio (RAR) to define the type of ventilatory impairment and assessing potential clinical value of Aex ratio (measured / predicted Aex) to indicate the severity of ventilatory obstruction. Methods: Spirometric data of 75 subjects were analyzed by qualified pulmonologists to distinguish between different spirometric patterns representing expert decision. Computerized graphic analysis methodology was used, Aex was used to calculate other parameters (area of concavity and RAR) and an algorithm for diagnosis was proposed. For validation of the proposed grading and cutoff values, we compared them with expert decision using classification and regression trees (CART). Results: According to calculated parameters, obstructive pattern is realized if area of concavity (Au) has positive value and RAR is less than 0.5. While convexity/linearity is indicated if RAR ≥ 0.5 and Au has negative value or equal zero, indicating normal or restrictive pattern. Aex ratio was selected as second-best predictor of restriction at a cut-off value of 49%. Furthermore, the diagnostic performance of Aex ratio in predicting moderate-to-severe obstructive lung disease was excellent. Conclusion: The proposed computerized technique succeeded using RAR and Aex in differentiating between restriction, obstruction and normal patterns. Additionally, Aex ratio may be a valid parameter to grade the severity of obstruction.

Factors for the Variability of Three Acceptable Maximal Expiratory Flow-Volume Curves in Chronic Obstructive Pulmonary Disease.

BackgroundGenerally, the maximal expiratory flow–volume (MEFV) curve must be measured for the diagnosis and staging of chronic obstructive pulmonary disease (COPD). As this test is effort dependent, international guidelines recommend that three acceptable trials are required for each test. However, no study has examined the magnitude and factors for the variability in parameters among three acceptable trials.MethodsWe evaluated the intra-individual variations in several parameters among three acceptable MEFV curves obtained at one-time point in patients with COPD (n = 28, stage 1; n = 36, stage 2; n = 21, stages 3–4). Next, the factors for such variations were examined using forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).ResultsThe averages of coefficient of variation (CV) for FEV1 and FVC were 2.0% (range: 1.0–3.0%) and 1.6% (0.9–2.2%), respectively. Both parameters were significantly better than peak expiratory flow rate, forced expiratory flow at 50% of expired FVC, and forced expiratory flow at 75% of expired FVC (CVs: 5.0–6.9%). A higher spirometric stage was significantly associated with higher CVs for FVC and FEV1, and older age was significantly correlated with a higher variation in FEV1 alone. Furthermore, a significantly inverse association was observed between emphysema severity, and the CVs for FEV1, but not that for FVC, regardless of spirometric stage.ConclusionBoth FVC and FEV1 are highly reproducible; nevertheless, older age, lower FEV1 at baseline, and non-emphysema phenotype are factors for a higher variability in FEV1 in patients with COPD.

Ventilatory responses to constant load exercise following the inhalation of a short-acting ß2-agonist in a laboratory-controlled diesel exhaust exposure study in individuals with exercise-induced bronchoconstriction

ObjectiveIndividuals with exercise-induced bronchoconstriction (EIB) use ß2-agonists to reduce respiratory symptoms during acute exercise. The resultingbronchodilation could increase the dose of inhaled pollutants and impair respiratory function when exercise is performedin air pollution. We aimed to assess respiratory responses in individuals with EIB when completing a cycling bout while being exposed to diesel exhaust (DE) or filtered air (FA) with and without the inhalation of salbutamol (SAL), a short-acting ß2-agonist. MethodsIn a double-blind, repeated-measures design, 19 participants with EIB (22-33 years of age) completed four visits: FA-placebo (FA-PLA), FA-SAL, DE-PLA, DE-SAL. After the inhalation of either 400 µg of SAL or PLA, participants sat in the exposure chamber for 60 min, breathing either FA or DE (PM2.5 = 300 μg/m3). Participants then cycled for 30 min at 50 % of peak work rate while breathing FA or DE. Respiratory responses were assessed via spirometry, work of breathing (WOB), fractional use of ventilatory capacity (V̇E/V̇E,CAP), area under the maximal expiratory flow-volume curve (MEFVAUC), and dyspnea during and following cycling. ResultsBronchodilation in response to SAL and acute cycling was observed, independent of FA/DE exposure. Specifically, FEV1 was increased by 7.7 % (confidence interval (CI): 7.2–8.2 %; p < 0.01) in response to SAL, and MEFVAUC was increased after cycling by 1.1 % (0.9–1.3 %; p = 0.03). Despite a significant decrease in total WOB by 6.2 J/min (4.7–7.5 J/min; p = 0.049) and a reduction in V̇E/V̇E,CAP by 5.8 % (5–6 %, p < 0.01) in the SAL exposures, no changes were observed in dyspnea. The DE exposure significantly increased V̇E/V̇E,CAP by 2.4 % (0.9–3.9 %; p < 0.01), but this did not affect dyspnea. DiscussionOur findings suggest that the use of SAL prior to moderate-intensity exercise when breathing high levels of DE, does not reduce respiratory function or exercise ventilatory responses for up to 60 min following exercise.

Deep-learning algorithm helps to standardise ATS/ERS spirometric acceptability and usability criteria.

While American Thoracic Society (ATS)/European Respiratory Society (ERS) quality control criteria for spirometry include several quantitative limits, it also requires manual visual inspection. The current approach is time consuming and leads to high intertechnician variability. We propose a deep-learning approach called convolutional neural network (CNN), to standardise spirometric manoeuvre acceptability and usability. In 36 873 curves from the National Health and Nutritional Examination Survey USA 2011-2012, technicians labelled 54% of curves as meeting ATS/ERS 2005 acceptability criteria with satisfactory start and end of test, but identified 93% of curves with a usable forced expiratory volume in 1 s. We processed raw data into images of maximal expiratory flow-volume curve (MEFVC), calculated ATS/ERS quantifiable criteria and developed CNNs to determine manoeuvre acceptability and usability on 90% of the curves. The models were tested on the remaining 10% of curves. We calculated Shapley values to interpret the models. In the test set (n=3738), CNN showed an accuracy of 87% for acceptability and 92% for usability, with the latter demonstrating a high sensitivity (92%) and specificity (96%). They were significantly superior (p<0.0001) to ATS/ERS quantifiable rule-based models. Shapley interpretation revealed MEFVC<1 s (MEFVC pattern within first second of exhalation) and plateau in volume-time were most important in determining acceptability, while MEFVC<1 s entirely determined usability. The CNNs identified relevant attributes in spirometric curves to standardise ATS/ERS manoeuvre acceptability and usability recommendations, and further provides individual manoeuvre feedback. Our algorithm combines the visual experience of skilled technicians and ATS/ERS quantitative rules in automating the critical phase of spirometry quality control.

Validation of a method to assess emphysema severity by spirometry in the COPDGene study

BackgroundStandard spirometry cannot identify the predominant mechanism underlying airflow obstruction in COPD, namely emphysema or airway disease. We aimed at validating a previously developed methodology to detect emphysema by mathematical analysis of the maximal expiratory flow-volume (MEFV) curve in standard spirometry.MethodsFrom the COPDGene population we selected those 5930 subjects with MEFV curve and inspiratory-expiratory CT obtained on the same day. The MEFV curve descending limb was fit real-time using forced vital capacity (FVC), peak expiratory flow, and forced expiratory flows at 25, 50 and 75% of FVC to derive an emphysema severity index (ESI), expressed as a continuous positive numeric parameter ranging from 0 to 10. According to inspiratory CT percent lung attenuation area below − 950 HU we defined three emphysema severity subgroups (%LAA-950insp < 6, 6–14, ≥14). By co-registration of inspiratory-expiratory CT we quantified persistent (%pLDA) and functional (%fLDA) low-density areas as CT metrics of emphysema and airway disease, respectively.ResultsESI differentiated CT emphysema severity subgroups increasing in parallel with GOLD stages (p < .001), but with high variability within each stage. ESI had significantly higher correlations (p < .001) with emphysema than with airway disease CT metrics, explaining 67% of %pLDA variability. Conversely, standard spirometric variables (FEV1, FEV1/FVC) had significantly lower correlations than ESI with emphysema CT metrics and did not differentiate between emphysema and airways CT metrics.ConclusionsESI adds to standard spirometry the power to discriminate whether emphysema is the predominant mechanism of airway obstruction. ESI methodology has been validated in the large multiethnic population of smokers of the COPDGene study and therefore it could be applied for clinical and research purposes in the general population of smokers, using a readily available online website.

Airway function throughout the lifespan: Pediatric origins of adult respiratory disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death of adults in the USA and worldwide. While environmental factors such as smoking and air pollution are major contributors to COPD, pediatric respiratory disease and more specifically early childhood wheezing are frequent predisposing factors. It is therefore possible that aggressive prevention and treatment of childhood respiratory illness may modify adult COPD risk. This article reviews some of the physiological factors that may explain the pediatric origins of childhood lung disease. One such factor is the “tracking” of normal lung function which occurs with growth. The maximal expiratory flow volume (MEFV) curve is an ideally suited tool to monitor tracking of airway function over the lifespan, as its relative effort independence makes it highly reliable. Study of the MEFV curve has demonstrated that individuals with similar lung volumes can have large differences in maximal flows, reflecting a disconnection between airway and lung growth (“dysanapsis”). Less than average airway size due to dysanaptic airway growth or airway remodeling may be independent risk factors for the development of COPD and the asthma/COPD overlap syndrome in adult life. There are intriguing early data suggesting that perhaps at least some of this risk is modifiable by improving asthma control with inhaled corticosteroids and minimizing asthma exacerbations.

Curvilinearity of a Maximum Expiratory Flow-Volume Curve: A Useful Indicator for Assessing Airway Obstruction in Children With Asthma.

Lung function parameters are used as signs in the diagnosis and evaluation of asthma; however, their sensitivity and specificity are not ideal. We calculated and combined angle β with lung function parameters to identify the ideal indicator. We aimed to identify an ideal indicator for evaluating the severity of airway obstruction in children with asthma. In total, 151 school-age children diagnosed with asthma were selected as the asthma group, and 106 healthy children were selected as the control group. The subjects were divided into the exacerbation group, chronic persistent group, and clinical remission group. Furthermore, the subjects were classified into mild and moderate groups or severe and critical groups. Angle β was calculated in each group. A receiver operating characteristic curve analysis was performed to determine the cutoff values of angle β and lung function parameters that together provided high sensitivity and specificity for airway obstruction evaluation in children with asthma. The mean value of angle β in the asthma group was significantly smaller than that in the control group (178.18° and 196.72°, respectively, P < .001). More exacerbations or greater severity corresponded to smaller angle β values (P < .001). The best cutoff value of angle β was 189.43°, and the area under the receiver operating characteristic curve of angle β was 0.877, which is greater than the area under the receiver operating characteristic curve of FEV1, forced expiratory flow (FEF) at 75% vital capacity (FEF25%), and FEF at 50% vital capacity (FEF50%), but smaller than the area under the receiver operating characteristic curve of FEF75% and FEV1/FVC%. Interestingly, combining these measures can enhance the sensitivity and specificity in assessing airway obstruction. Angle β was a useful indicator for assessing airway obstruction. Furthermore, angle β combined with FEV1, FEV1/FVC%, FEF25%, FEF50%, and FEF75% can enhance the sensitivity and specificity of airway obstruction evaluations.

Reference value for expiratory time constant calculated from the maximal expiratory flow-volume curve

BackgroundThe expiratory time constant (RCEXP), which is defined as the product of airway resistance and lung compliance, enable us to assess the mechanical properties of the respiratory system in mechanically ventilated patients. Although RCEXP could also be applied to spontaneously breathing patients, little is known about RCEXP calculated from the maximal expiratory flow-volume (MEFV) curve. The aim of our study was to determine the reference value for RCEXP, as well as to investigate the association between RCEXP and other respiratory function parameters, including the forced expiratory volume in 1 s (FEV1)/ forced vital capacity (FVC) ratio, maximal mid-expiratory flow rate (MMF), maximal expiratory flow at 50 and 25% of FVC (MEF50 and MEF25, respectively), ratio of MEF50 to MEF25 (MEF50/MEF25).MethodsSpirometric parameters were extracted from the records of patients aged 15 years or older who underwent pulmonary function testing as a routine preoperative examination before non-cardiac surgery at the University of Tokyo Hospital. RCEXP was calculated in each patient from the slope of the descending limb of the MEFV curve using two points corresponding to MEF50 and MEF25. Airway obstruction was defined as an FEV1/FVC and FEV1 below the statistically lower limit of normal.ResultsWe retrospectively analyzed 777 spirometry records, and 62 patients were deemed to have airway obstruction according to Japanese spirometric reference values. The cut-off value for RCEXP was 0.601 s with an area under the receiver operating characteristic curve of 0.934 (95% confidence interval = 0.898–0.970). RCEXP was strongly associated with FEV1/FVC, and was moderately associated with MMF and MEF50. However, RCEXP was less associated with MEF25 and MEF50/MEF25.ConclusionsOur findings suggest that an RCEXP of longer than approximately 0.6 s can be linked to the presence of airway obstruction. Application of the concept of RCEXP to spontaneously breathing subjects was feasible, using our simple calculation method.

The Concavity of the Maximal Expiratory Flow\u2013Volume Curve Reflects the Extent of Emphysema in Obstructive Lung Diseases

A concave-shaped maximal expiratory flow-volume (MEFV) curve is a spirometric feature in chronic obstructive pulmonary disease (COPD). The MEFV curve is characterized by an increase in the Obstructive Index, which is defined as a ratio of forced vital capacity to the volume-difference between two points of half of the peak expiratory flow on the MEFV curve. We hypothesized that the Obstructive Index would reflect the severity of emphysema in patients with COPD and asthma-COPD overlap (ACO). Thus, the aim of this retrospective study was to evaluate whether the Obstructive Index on spirometry is associated with the extent of emphysema on computed tomography (CT) in patients with COPD, ACO, and asthma (N = 65, 15, and 53, respectively). The percentage of low-attenuation volume (LAV%) and wall area (WA%) were measured on CT. The Obstructive Index was higher in patients with COPD and ACO than in those with asthma. Spearman correlation showed that a greater Obstructive Index was associated with a higher LAV%, but not WA%. Multivariate analysis showed that Obstructive Index was associated with LAV% (standardized β = 0.43, P < 0.0001) independent of other spirometric indices. The Obstructive Index is a useful spirometric index that reflects the extent of emphysema.