Tidal Flow Volume Research Articles

Assessing the repeatability of expiratory flow limitation during incremental exercise in healthy adults.

We sought to determine the repeatability of EFL in healthy adults during incremental cycle exercise. We hypothesized that the repeatability of EFL would be "strong" when assessed as a binary variable (i.e., absent or present) but "poor" when assessed as a continuous variable (i.e., % tidal volume overlap). Thirty-two healthy adults performed spirometry and an incremental cycle exercise test to exhaustion on two occasions. Standard cardiorespiratory variables were measured at rest and throughout exercise, and EFL was assessed by overlaying tidal expiratory flow-volume and maximal expiratory flow-volume curves. The repeatability of EFL was determined using Cohen's κ for binary assessments of EFL and intraclass correlation (ICC) for continuous measures of EFL. During exercise, n = 12 participants (38%) experienced EFL. At peak exercise, the repeatability of EFL was "minimal" (κ = 0.337, p = 0.145) when assessed as a binary variable and "poor" when measured as a continuous variable (ICC = 0.338, p = 0.025). At matched levels of minute ventilation during high-intensity exercise (i.e., >75% of peak oxygen uptake), the repeatability of EFL was "weak" when measured as a binary variable (κ = 0.474, p = 0.001) and "moderate" when measured as a continuous variable (ICC = 0.603, p < 0.001). Our results highlight the day-to-day variability associated with assessing EFL during exercise in healthy adults.

Averaging Tidal Flow-volume Loops: A tale of two methods

Introduction: A standard practice in cardiopulmonary exercise testing (CPET) is calculating the average flow and volume data across multiple breaths. Currently, many laboratories find average flow-volume loops by taking equal increments of the tidal volume and averaging the respective increments of flow for each breath. However, it has been proposed that using equal increments of total time to find an average flow-volume loop could more accurately capture the shape of the loop, which could be critical to determining expiratory flow limitation (EFL) when placed within a maximal flow-volume loop. Purpose: To compare the use of time vs. volume bins on producing averaged flow-volume loops and evaluate whether the results could affect the interpretation of EFL. Methods: Time, volume, and flow data of consecutive breaths at rest and during exercise were obtained for four individuals: one younger healthy man, one older healthy woman, one older man with heart failure, and one child with obesity. The data were separated into individual breaths using zero flow points, then total time and tidal volume were calculated for each full breath. For the time bin method as proposed by M. Younes, equal intervals of time were calculated for both the inspiratory and expiratory phases of each breath. Linear interpolation between surrounding data points was performed to obtain volume and flow values at these intervals. Volume data were then normalized to the tidal volume of the breath by taking the value as a percentage of the total tidal volume. From here, the volume and flow data at the corresponding intervals for each breath were averaged to create the final average flow-volume loop. For the volume bin method, equal intervals of volume were determined based on the tidal volume. Linear interpolation was then used to calculate the respective flow values at these intervals. The volume and flow data at the corresponding intervals for each breath were then averaged to generate the average flow-volume loop data. Standard deviation at each averaged point was also calculated for both methods. Results: Minimal difference was visible between the time bin and volume bin methods at 20 intervals. As the number of intervals used increased, the difference became less apparent. At 250 intervals, the volume bin method depicted the average flow-volume loop as effectively as the time bin method. Addition of standard deviations gave a better view of the variability of flow at any volume. Conclusion: Despite the inherent incrementation associated with the use of time bins vs. volume bins the average flow-volume loops looked very similar. However, the addition of the standard deviations of flow and volume at each data point could yield different results for determining EFL. Also, the time bin method may yield more resolution at rapid transition points at the beginning of inspiration and expiration. Overall, the observed similarities between time bin and volume bin methods are likely due to increased computer capabilities and the ability to create more intervals (i.e., 20 vs. 250), making a constant unit of measurement less necessary. Funding: NIH R01 HL136643, NIH R01 AG070262, NIH P01 HL137630, King Charitable Foundation Trust, Susan Lay Atwell Annuity Trust for Pulmonary Research, Cain Foundation, and Texas Health Presbyterian Hospital Dallas. Dr. Daniel Wilhite was funded by an NIH Administrative Supplement to Promote Diversity in Health-Related Research (HL136643-01S1). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Determinants of lung function development from birth to age 5 years: an interrupted time series analysis of a South African birth cohort

Early life is a key period that determines long-term health. Lung development in childhood predicts lung function attained in adulthood and morbidity and mortality across the life course. We aimed to assess the effect of early-life lower respiratory tract infection (LRTI) and associated risk factors on lung development from birth to school age in a South African birth cohort. We prospectively followed children enrolled in a population-based cohort from birth (between March 5, 2012 and March 31, 2015) to age 5 years with annual lung function assessment. Data on multiple early-life exposures, including LRTI, were collected. The effect of early-life risk factors on lung function development from birth to age 5 years was assessed using the Generalised Additive Models for Location, Scale and Shape and Interrupted Time Series approach. 966 children (475 [49·2%] female, 491 [50·8%] male) had lung function measured with oscillometry, tidal flow volume loops, and multiple breath washout. LRTI occurred in 484 (50·1%) children, with a median of 2·0 LRTI episodes (IQR 1·0-3·0) per child. LRTI was independently associated with altered lung function, as evidenced by lower compliance (0·959 [95% CI 0·941-0·978]), higher resistance (1·028 [1·016-1·041]), and higher respiratory rate (1·018 [1·063-1·029]) over 5 years. Additional impact on lung function parameters occurred with each subsequent LRTI. Respiratory syncytial virus (RSV) LRTI was associated with lower expiratory flow ratio (0·97 [0·95-0·99]) compared with non-RSV LRTI. Maternal factors including allergy, smoking, and HIV infection were also associated with altered lung development, as was preterm birth, low birthweight, female sex, and coming from a less wealthy household. Public health interventions targeting LRTI prevention, with RSV a priority, are vital, particularly in low-income and middle-income settings. UK Medical Research Council Grant, The Wellcome Trust, The Bill & Melinda Gates Foundation, US National Institutes of Health Human Heredity and Health in Africa, South African Medical Research Council, Hungarian Scientific Research Fund, and European Respiratory Society.

Maternal use of snus as smokeless tobacco in pregnancy and infant lung function.

Smoking in pregnancy has detrimental effects on infant respiratory health, while the effects of other nicotine-containing products on infant lung function are unclear. We aimed to explore if smokeless tobacco such as snus used in pregnancy increased the risk of lower lung function in infancy and if the associations differed by sex. From the Scandinavian population-based Preventing Atopic Dermatitis and ALLergies in Children birth cohort, we included 1163 infants with available tidal flow-volume measurements at 3 months of age and maternal self-reported use of nicotine-containing products in pregnancy. The risk of a ratio of time to peak tidal expiratory flow to total expiratory time <25th percentile by any nicotine exposure, snus exclusively and cigarette smoking with or without other nicotine-containing products was explored by regression analyses adjusting for maternal age, education and asthma. Overall 120 out of 1163 (10.3%) infants were exposed to any nicotine in utero, 71 out of 120 by snus exclusively and 49 out of 120 by smoking, with six also exposed to snus. By pregnancy week 6, 85.8% of mothers reported stopping nicotine use. The risk of lower lung function was higher in children exposed in utero to nicotine-containing products with an odds ratio (OR) of 1.63 (95% confidence interval (CI) 1.02-2.59) with a similar tendency for snus exclusively (OR 1.55, 95% CI 0.88-2.71) and smoking (OR 1.79, 0.84-3.84). Effect estimates were similar after adjusting for covariates. No differences of the effect by sex were observed. Our study suggests that in utero exposure to not only cigarettes, but also snus, may negatively affect infant lung function.

On the relation between tidal and forced spirometry

Spirometry is a lung function test involving deep inhalation and forceful deep exhalation. It is widely used to obtain objective information about airflow limitation and to diagnose lung diseases. In contrast, tidal spirometry is based on normal breathing and therefore much more convenient, but it is hardly used in medical care and its relation with conventional (forced) spirometry is largely unknown. Therefore, the objective of this work is to reveal the relation between tidal and forced spirometry. Employing the strong correspondence between the forced flow-volume curves and the Tiffeneau-Pinelli (TP) index, we present a method to obtain (a) the expected tidal flow-volume curve for a given TP-index, and (b) the expected TP-index for a given tidal curve. For patients with similar values of the TP-index, the tidal curves show a larger spread than the forced curves, but their average shape varies in a characteristic way with varying index. Therefore, just as with forced curves, the TP-index provides a useful objective ranking of the average of tidal curves: upon decreasing TP-index the expiratory flow rate changes in that its peak shifts towards smaller expiratory volumes, and its post-peak part becomes dented.

Lung function in preterm infants at 3 months corrected age after neonatal LC-PUFA supplementation.

To test the hypothesis that long-chain polyunsaturated fatty acid (LC-PUFA) supplementation improves lung function at 3 months corrected age (CA) compared with standard treatment in very preterm infants. We also aimed to investigate the association between bronchopulmonary dysplasia (BPD), longitudinal growth, and lung function at 3 months CA. A secondary analysis from the ImNuT trial, in which 121 infants with gestational age <29 weeks were randomized to a daily supplement with arachidonic acid (ARA) and docosahexaenoic acid (DHA) (ARA:DHA group) or MCT-oil (control group) from birth up to 36 weeks postmenstrual age (PMA). Lung function was assessed at 3 months CA by tidal flow volume loops and the outcomes were the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) and tidal volume (VT ) per body weight (mL/kg). Thirty-nine infants in the ARA:DHA group versus 51 in the control group had a successful lung function test. There was no mean difference (MD) in tPTEF /tE ratio (MD: 0.01, 95% confidence interval [CI]: -0.04 to 0.05; p = .77) or VT (MD: 0.09 mL/kg, 95% CI: -0.79 to 0.62; p = .81) between the study groups. The multivariable regression model showed that BPD was associated with tPTEF /tE ratio ≤ 0.25 (p = .03) and that an increase in z score for length after 36 weeks PMA correlated positively with VT (mL/kg) (p = .03). Neonatal LC-PUFA supplementation did not improve lung function at 3 months CA in very preterm infants. BPD was independently associated with reduced lung function, while improved linear growth correlated with higher tidal volumes.

Fetal pulmonary artery Doppler blood flow velocity measures and early infant lung function. A prospective cohort study

Background Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function. Objective Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures. Methods In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (t PTEF/t E), t PTEF/t E <25th percentile, and tidal volume per kg body weight (V T/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions. Results The infants were born at median (min - max) 40.3 (35.6 − 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) t PTEF/t E was 0.39 (0.1) and the 25th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and t PTEF/t E, t PTEF/t E <25th percentile, or V T/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures. Conclusion In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.

Role of small airway dysfunction in unexplained exertional dyspnoea.

Isolated small airway abnormalities may be demonstrable at rest in patients with normal spirometry; however, the relationship of these abnormalities to exertional symptoms remains uncertain. This study uses an augmented cardiopulmonary exercise test (CPET) to include evaluation of small airway function during and following exercise to unmask abnormalities not evident with standard testing in individuals with dyspnoea and normal spirometry. Three groups of subjects were studied: 1) World Trade Center (WTC) dust exposure (n=20); 2) Clinical Referral (n=15); and Control (n=13). Baseline evaluation included respiratory oscillometry. Airway function during an incremental workload CPET was assessed by: 1) tidal flow versus volume curves during exercise to assess for dynamic hyperinflation and expiratory flow limitation; and 2) post-exercise spirometry and oscillometry to evaluate for airway hyperreactivity. All subjects demonstrated normal baseline forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). Dyspnoea was reproduced during CPET in WTC and Clinical Referral groups versus Control without abnormality in respiratory pattern and minute ventilation. Tidal flow-volume curves uncovered expiratory flow limitation and/or dynamic hyperinflation with increased prevalence in WTC and Clinical Referral versus Control (55%, 87% versus 15%; p<0.001). Post-exercise oscillometry uncovered small airway hyperreactivity with increased prevalence in WTC and Clinical Referral versus Control (40%, 47% versus 0%, p<0.05). We uncovered mechanisms for exertional dyspnoea in subject with normal spirometry that was attributable to either small airway dysfunction during exercise and/or small airway hyperreactivity following exercise. The similarity of findings in WTC environmentally exposed and clinically referred cohorts suggests broad relevance for these evaluations.

Skin Barrier Function and Infant Tidal Flow-Volume Loops-A Population-Based Observational Study.

The relationship between the skin barrier- and lung function in infancy is largely unexplored. We aimed to explore if reduced skin barrier function by high transepidermal water loss (TEWL), or manifestations of eczema or Filaggrin (FLG) mutations, were associated with lower lung function in three-month-old infants. From the population-based PreventADALL cohort, 899 infants with lung function measurements and information on either TEWL, eczema at three months of age and/or FLG mutations were included. Lower lung function by tidal flow-volume loops was defined as a ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE) &lt;0.25 and a tPTEF &lt;0.17 s (&lt;25th percentile). A high TEWL &gt;8.83 g/m2/h (&gt;75th percentile) denoted reduced skin barrier function, and DNA was genotyped for FLG mutations (R501X, 2282del4 and R2447X). Neither a high TEWL, nor eczema or FLG mutations, were associated with a lower tPTEF/tE. While a high TEWL was associated with a lower tPTEF; adjusted OR (95% CI) 1.61 (1.08, 2.42), the presence of eczema or FLG mutations were not. Overall, a high TEWL, eczema or FLG mutations were not associated with lower lung function in healthy three-month-old infants. However, an inverse association between high TEWL and tPTEF was observed, indicating a possible link between the skin barrier- and lung function in early infancy.

Infant lung function and maternal physical activity in the first half of pregnancy.

Physical activity (PA) in pregnancy is important for maternal and possibly offspring health. To study the early origins of lung function we aimed to determine whether PA in the first half of pregnancy is associated with lung function in healthy 3-month-old infants. From the general population-based Preventing Atopic Dermatitis and Allergies in Children birth cohort recruiting infants antenatally in Norway and Sweden, all 812 infants (48.8% girls) with available tidal flow-volume measures in the awake state at 3 months of age and mid-pregnancy data on PA were included. PA was self-reported by the mothers and, based on intensity, we categorised them as active or inactive during pregnancy. Furthermore, we defined active mothers as fairly or highly active. The main outcome was a ratio of time to peak tidal expiratory flow to expiratory time (t PTEF/t E) <0.25. Associations were analysed by logistic regression, adjusting for maternal age, education, parity, pre-pregnancy body mass index, in utero nicotine exposure and parental atopy. The mean±sd t PTEF/t E was 0.391±0.08 and did not differ significantly according to maternal PA level in pregnancy. The 290 infants of inactive mothers had higher odds of having t PTEF/t E <0.25 compared to infants of all active mothers (OR 2.07, 95% CI 1.13-3.82; p=0.019) and compared to infants (n=224) of fairly active (OR 2.83, 95% CI 1.26-7.24; p=0.018) but not highly active mothers (n=298). Based on self-reported maternal PA in the first half of pregnancy, 3-month-old infants of inactive compared to active mothers had higher odds of a low t PTEF/t E.

Infant lung function: criteria for selecting tidal flow-volume loops.

BackgroundTidal flow–volume (TFV) loops are commonly recorded in infants during sleep, due to the more regular breathing patterns compared to the awake state. Standardised deselection of loops outside pre-specified ranges are based on periods of regular breathing, while criteria and available software for visual evaluation of TFV loops are lacking. We aimed to determine the reliability of standardised criteria for manual selection of infant TFV loops.MethodsUsing a pre-defined set of criteria, three independent raters manually evaluated TFV loops among 57 randomly selected awake healthy 3-month-old infants with available TFV measurements in the Scandinavian Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) study. The TFV loops were sampled using the Eco Medics Exhalyzer D. Criteria for selecting TFV loops included reproducible shape and volume with only one peak in tidal expiratory flow (PTEF), excluding loops with no clear or uneven flow towards PTEF. By intraclass coefficient (ICC), the reliability of agreement between raters was determined for the time to PTEF (tPTEF) to expiratory time (tE) and other TFV loop parameters.ResultsFive infants had unsuccessful tests. Among the remaining 52 infants, the raters selected a median of 25, 26 and 15 loops per test. The ICCs (95% CI) were 0.97 (0.92–0.98) for tPTEF/tE, 0.99 (0.99–1.00) for respiratory rate, 0.98 (0.97–0.99) for tidal volume per kg and 0.98 (0.97–0.99) for expiratory volume, reflecting excellent agreement in all categories.ConclusionManual TFV loop selection using standardised criteria provides a reliable alternative for lung function measures in awake infants with interrupted breathing cycles in a real-life setting.

Evidence of ventilatory constraints during exercise in hypermobile Ehlers-Danlos syndrome.

Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder with many different symptoms such as pain, fatigue, dysautonomia, or respiratory symptoms. Among the respiratory manifestations described, the most frequent are exertional dyspnea and breathing difficulties. Mechanical ventilatory constraints during exercise could participate in these respiratory manifestations. The objective of this study was to explore the response of pulmonary flow-volume loops to exercise in patients with hEDS and to look for dynamic hyperinflation and expiratory flow limitation during exercise. For this purpose, breathing pattern and tidal exercise flow-volume loops were recorded at two workloads (30% and 80% of the peak power output) of a constant load exercise test. Twelve patients were included (11 women, mean age 41 ± 14years). The results showed a decrease (p = 0.028) in the inspiratory capacity (from 3.12 ± 0.49L to 2.97 ± 0.52L), an increase (p = 0.025) in the end-expiratory lung volume (from 0.73 ± 0.68L to 0.88 ± 0.66L, i.e., from EELV comprising 17 ± 12% to 21 ± 12% of forced vital capacity) between the two workloads in favor of dynamic hyperinflation, and half of the patients had expiratory flow limitations. This exploratory study provides evidence for mechanical ventilatory constraints during exercise in patients with hEDS, which may induce discomfort during exercise and could contribute to the respiratory symptomatology. This study is part of a larger clinical trial (ID: NCT04680793, December 2020).

Infant tidal flow-volume parameters and arousal state.

BackgroundInfant lung function can be assessed with tidal flow–volume (TFV) loops. While TFV loops can be measured in both awake and sleeping infants, the influence of arousal state in early infancy is not established. The aim of the present study was to determine whether TFV loop parameters in healthy infants differed while awake compared to the sleeping state at 3 months of age.MethodsFrom the population-based Scandinavian Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) birth cohort, 91 infants had reproducible TFV loops measured with Exhalyzer® D in both the awake and sleeping state at 3 months of age. The TFV loops were manually selected according to a standardised procedure. The ratio of time to peak tidal expiratory flow (tPTEF) to expiratory time (tE) and the corresponding volume ratio (VPTEF/VE), as well as tidal volume (VT) and respiratory rate were compared using nonparametric tests.ResultsThe mean (95% CI) tPTEF/tE was significantly higher while awake compared to the sleeping state: 0.39 (0.37–0.41) versus 0.28 (0.27–0.29); with the corresponding VPTEF/VE of 0.38 (0.36–0.40) versus 0.29 (0.28–0.30). The VT was similar, while the respiratory rate was higher while awake compared to the sleeping state: 53 (51–56) breaths·min−1 versus 38 (36–40) breaths·min−1.ConclusionHigher tPTEF/tE, VPTEF/VE and respiratory rate, but similar VT while awake compared to the sleeping state suggests that separate normative TFV loop values according to arousal state may be required in early infancy.

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.

The role of inspiratory capacity and tidal flow in diagnosing exercise ventilatory limitation in Cystic Fibrosis

BackgroundExercise ventilatory limitation conventionally defined by reduced breathing reserve (BR) may underestimate the effect of lung disease on exercise capacity in patients with mild to moderate obstructive lung diseases. ObjectiveTo investigate whether ventilatory limitation may be present despite a normal BR in Cystic Fibrosis (CF). MethodsTwenty adult CF patients (age 16-58y) with a wide range of pulmonary obstruction severity completed a symptom-limited incremental exercise test on a cycle ergometer. Operating lung volumes were derived from inspiratory capacity (IC) measurement during exercise and exercise tidal flow volume loop analysis.Results: six patients had a severe airway obstruction (FEV1<45% predicted) and conventional evidence of ventilatory limitation (low BR). Fourteen patients had mild to moderate-severe airway obstructive (FEV1 46–103% predicted), and a normal BR [12–62 L/min, BR% (17–40)]. However, dynamic respiratory mechanics demonstrated that even CF patients with mild to moderate-severe lung disease had clear evidence of ventilatory limitation during exercise. IC was decreased by (median) 580 ml (range 90–1180 ml) during exercise, indicating dynamic hyperinflation. Inspiratory reserve volume at peak exercise was 445 ml (241–1350 ml) indicating mechanical constraint on the respiratory system. The exercise tidal flow met or exceeded the expiratory boundary of the maximal flow volume loop over 72% of the expiratory volume (range 40–90%), indicating expiratory flow limitation. ConclusionReduced BR as a sole criterion underestimates ventilatory limitation during exercise in mild to moderate-severe CF patients. Assessment of dynamic respiratory mechanics during exercise revealed ventilatory limitation, present even in patients with mild obstruction.

Quantifying tidal expiratory flow limitation using a vector-based analysis technique

Objective. Tidal expiratory flow limitation (EFLT) is commonly identified by tidal breaths exceeding the forced vital capacity (FVC) loop. This technique, known as the Hyatt method, is limited by the difficulties in defining the FVC and tidal flow-volume (TV) loops. The vector-based analysis (VBA) technique described and piloted in this manuscript identifies and quantifies EFLT as tidal breaths that conform to the contour of the FVC loop. Approach. The FVC and TV loops are interpolated to generate uniformly spaced plots. VBA is performed to determine the smallest vector difference between each point on the FVC and TV curves, termed the flow reserve vector (FRV). From the FVC point yielding the lowest FRV, the tangential angles of the FVC and TV segments are recorded. If the TV and FVC loops become parallel, the difference between the tangential angles tends towards zero. We infer EFLT as parallel TV and FVC segments where the FRV is < 0.1 and the tangential angle is within ±18 degrees for ≥5% of TV. EFLT is quantified by the percent of TV loop fulfilling these criteria. We compared the presence and degree of EFLT at rest and during peak exercise using the Hyatt method and our VBA technique in 25 healthy subjects and 20 subjects with moderate-severe airflow obstruction. Main results. Compared to the Hyatt method, our VBA technique reported a significantly lower degree of EFLT in healthy subjects during peak exercise, and in obstructed subjects at rest and during peak exercise. In contrast to the Hyatt method, our VBA technique re-classified five subjects (one in the healthy group and four in the obstructed group) as demonstrating EFLT. Significance. Our VBA technique provides an alternative approach to determine and quantify EFLT which may reduce the overestimation of the degree EFLT and more accurately identify subjects experiencing EFLT.

Tidal spirometric curves obtained from a nasal cannula

Spirometry is a gold standard to assess lung function, and to identify respiratory impairments seen in obstructive lung diseases. The method is used for periodic monitoring, but it only provides snapshot information, and it requires forceful exhalation which is associated with limited reliability and repeatability. Several studies indicate that tidal flow-volume curves measured by pneumotachography or plethysmography can also be used to assess lung function. These methods avoid the forced manoeuvre, but are complex to set up or sensitive to movement. In the present work we address the long-standing problem of the unavailability of an easy-to-use and accurate method for monitoring tidal breathing frequently or even continuously. We show that pressure recordings from a nasal cannula can be accurately converted into scaled flow-volume curves by means of an algorithm that continuously calibrates itself. The method has been validated by feeding realistic healthy and unhealthy breathing patterns to anatomically correct 3D-printed upper airways of an infant and an adult, and by comparing the imposed flow-volume curves to the pressure-derived flow-volume curves. The observed very high level of accuracy opens the route towards remotely monitoring patients with chronic lung diseases.

Pitfalls in Expiratory Flow Limitation Assessment at Peak Exercise in Children: Role of Thoracic Gas Compression.

Thoracic gas compression and exercise-induced bronchodilation can influence the assessment of expiratory flow limitation (EFL) during cardiopulmonary exercise tests. The purpose of this study was to examine the effect of thoracic gas compression and exercise-induced bronchodilation on the assessment of EFL in children with and without obesity. Forty children (10.7 ± 1.0 yr; 27 obese; 15 with EFL) completed pulmonary function tests and incremental exercise tests. Inspiratory capacity maneuvers were performed during the incremental exercise test for the placement of tidal flow volume loops within the maximal expiratory flow volume (MEFV) loops, and EFL was calculated as the overlap between the tidal and the MEFV loops. MEFV loops were plotted with volume measured at the lung using plethysmography (MEFVp), with volume measured at the mouth using spirometry concurrent with measurements in the plethysmograph (MEFVm), and from spirometry before (MEFVpre) and after (MEFVpost) the incremental exercise test. Only the MEFVp loops were corrected for thoracic gas compression. Not correcting for thoracic gas compression resulted in incorrect diagnosis of EFL in 23% of children at peak exercise. EFL was 26% ± 15% VT higher for MEFVm compared with MEFVp (P < 0.001), with no differences between children with and without obesity (P = 0.833). The difference in EFL estimation using MEFVpre (37% ± 30% VT) and MEFVpost (31% ± 26% VT) did not reach statistical significance (P = 0.346). Not correcting the MEFV loops for thoracic gas compression leads to the overdiagnosis and overestimation of EFL. Because most commercially available metabolic measurement systems do not correct for thoracic gas compression during spirometry, there may be a significant overdiagnosis of EFL in cardiopulmonary exercise testing. Therefore, clinicians must exercise caution while interpreting EFL when the MEFV loop is derived through spirometry.

Predicting the outcome of respiratory disease in wheezing infants using tidal flow-volume loop shape

Introduction and objectivesWheezing (RW) infants with a positive asthma predictive index (API+) have a lower lung function as measured by forced expiratory techniques. Tidal flow-volume loops (TFVL) are easy to perform in infants, and sedation is not necessary. Materials and methodsA total of 216 wheezing infants were successfully measured, and 183 of them were followed for over a year. TFVL loops were classified into one of three categories depending of their geometric shape (symmetric, convex, and concave). Respiratory rate (Rr), presence of API+, and the number of exacerbations during the following year were also recorded. ResultsChildren with concave loops had more exacerbations in the following year (OR = 6.8 [IC95% 3.33;13.91]). Infants API + were also significantly more related to concave loops (OR = 10.02 [IC 95% 4.53; 22.15]). Rr was higher in infants with concave loops (44+/−15.5 vs. 36.6 +/−12.6; p < 0.01). ConclusionInfants with a concave TFVL have a higher probability of experiencing exacerbations in the following year, and are at a higher risk of suffering asthma.

STATIN-INDUCED DIAPHRAGMATIC MUSCLE WEAKNESS CAUSING HYPERCAPNIA AND SHORTNESS OF BREATH

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Statins are commonly used medications in medicine. One of their side effects is muscle injury. We present a case of a patient (PT) who presented with chronic shortness of breath (SOB) and hypercapnia secondary to statin therapy. CASE PRESENTATION: A 77 y/o male with history of DM, HTN, HLD and Asthma; no smoking or toxic exposures presented to the hospital due to SOB on exertion for the last 5-6 months. His SOB was relieved by rest, but noted hoarseness and weakness with discomfort of his legs. Upon admission PT had stable VS, physical exam was unremarkable with no muscle tenderness and clear lungs. Chest X-ray and CT scan (Fig. 1) showed only bibasilar atelectasis and small lung volumes. Cardiovascular work up was negative. Laboratory evaluation was significant for an elevated Creatinine Kinase of 470 U/L. He had been on Atorvastatin with increased dosage by his PCP a few months prior. Serum HCO3 level was elevated at 35 mmol/L without diuretic use. An arterial blood gas confirmed hypercapnia(pH 7.37, PCO2 58, PO2 67, O2 saturation at 92% at room air). Thyroid function test were normal and myositis work up was sent for ESR, Anti-Jo, Anti-Ro, Anti-La antibody, Lactate levels, ANA and were found to negative. BMI was calculated to 28. Aldolase was elevated at 21 U/L. Pulmonary Function testing (PFT) were performed showing a restrictive lung pattern with FEV1/FVC ratio of 89% with FVC 41% predicted, TLC was 3.39 L (68% predicted) (Fig.2), DLCO was 49% predicted with a normal DLCO/VA. Tidal-flow volume loop was almost completely shifted to the left suggesting that the PT couldn’t take a deeper breath as there was no airway obstructive pattern. After workup was completed, the statin was discontinued and the PT's SOB slowly improved over the course of a few days. He was successfully discharged without additional intervention. DISCUSSION: Statin induced myopathy is the most common side effect associated to statin therapy(1). Hypercapnia secondary to statin therapy causing diaphragmatic muscle weakness is uncommon in the literature.(2) Most people associate statin myopathies with skeletal muscle and diaphragmatic involvement is not routinely considered. In our PT any underlying lung pathology was ruled out by imaging studies along with central causes for hypoventilation. Autoimmune myositis work up was negative, thyroid function was normal and PFT were consistent with a restrictive lung defect suggesting muscle weakness given negative CT findings for interstitial lung disease or other extra-thoracic causes of restriction. Cognitive biases can frequently limit consideration of rarer causes of dyspnea. CONCLUSIONS: Hypercapnia in the hospital setting is mistakenly attributed to COPD without other causes being considered. We suggest statin induced myopathy causing diaphragmatic weakness to be considered as a differential on PTs on statin and unexplained SOB especially due to the frequency of their use. Reference #1: Upreti, Sunita, Beenish Fayyaz, and Ramchandran P. Bongu. "Anti-HMG-CoA reductase myopathy, an undesirable evolution of statin induced myopathy: a case report.” Journal of Community Hospital Internal Medicine Perspectives 9.1 (2019): 33-35 Reference #2: Biagioni, Bradly, et al. "Diaphragmatic Weakness Due to Statin Myopathy.” Chest 150.4 (2016): 1085A. DISCLOSURES: No relevant relationships by Walter Chua, source=Web Response No relevant relationships by Christian Lopez-Padilla, source=Web Response