Single Breath-Hold MR Elastography for Fast Biomechanical Probing of Pancreatic Stiffness.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal disposition is thought to influence chemotherapy efficacy and increase tissue stiffness, which could be quantified noninvasively via MR elastography (MRE). Current methods cause position-based errors in pancreas location over time, hampering accuracy. It would be beneficial to have a single breath-hold acquisition. PURPOSE: To develop and test a single breath-hold three-dimensional MRE technique utilizing prospective undersampling and a compressed sensing reconstruction (CS-MRE). STUDY TYPE: Prospective. POPULATION: A total of 30 healthy volunteers (HV) (31 ± 9 years; 33% male) and five patients with PDAC (69 ± 5 years; 80% male). FIELD STRENGTH/SEQUENCE: 3-T, GRE Ristretto MRE. ASSESSMENT: First, optimization of multi breath-hold MRE was done in 10 HV using four combinations of vibration frequency, number of measured wave-phase offsets, and TE and looking at MRE quality measures in the pancreas head. Second, viscoelastic parameters delineated in the pancreas head or tumor of CS-MRE were compared against (I) 2D and (II) 3D four breath-hold acquisitions in HV (N = 20) and PDAC patients. Intrasession repeatability was assessed for CS-MRE in a subgroup of healthy volunteers (N = 15). STATISTICAL TESTS: Tests include repeated measures analysis of variance (ANOVA), Bland-Altman analysis, and coefficients of variation (CoVs). A P-value <.05 was considered statistically significant. RESULTS: Optimization of the four breath-hold acquisitions resulted in 40 Hz vibration frequency, five wave-phases, and echo time (TE) = 6.9 msec as the preferred method (4BH-MRE). CS-MRE quantitative results did not differ from 4BH-MRE. Shear wave speed (SWS) and phase angle differed significantly between HV and PDAC patients using 4BH-MRE or CS-MRE. The limits of agreement for SWS were [-0.09, 0.10] m/second and the within-subject CoV was 4.8% for CS-MRE. DATA CONCLUSION: CS-MRE might allow a single breath-hold MRE acquisition with comparable SWS and phase angle as 4BH-MRE, and it may still enable to differentiate between HV and PDAC. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2.

Resting diffusing capacity and severity of radiographic disease predict gas exchange abnormalities with exercise in former US coal miners.

BACKGROUND: The US Department of Labor (DOL) does not fund diffusing capacity (DLCO) or metabolic measurements from cardiopulmonary exercise testing (CPET) for coal miners' disability evaluations. Although exercise arterial blood gas testing is covered, many miners are unable to perform maximal tests, and sampling at peak exercise can be challenging. We explored the relationship between resting DLCO, radiographic disease severity, and CPET abnormalities in former US coal miners. METHODS: We analyzed data from miners evaluated between 2005 and 2015. Multivariable linear and logistic regression analyses were used to examine relationships between percent predicted (pp) forced expiratory volume in 1 s (FEV1pp), DLCOpp, VO2maxpp, A-a oxygen gradient (A-a)pp, dead space fraction (Vd/Vt), disabling oxygen tension (PO2), and radiographic findings of pneumoconiosis. RESULTS: Data from 2015 male coal miners was analyzed. Mean tenure was 28 years (SD 8.6). Thirty-twopercent had an abnormal A-a gradient (>150 pp), 20% had elevated Vd/Vt (>0.33), and 34% a VO2max < 60 pp. DLCOpp strongly predicted a disabling PO2, with an odds ratio (OR) of 2.33 [2.09-2.60], compared to 1.18 [1.08-1.29] for FEV1. Each increase in subcategory of small opacity (simple) pneumoconiosis increased the odds of a disabling PO2 by 42% [1.29-1.57], controlling for age, body mass index, pack-years of tobacco smoke exposure, and years of coal mine employment. CONCLUSIONS: DLCO is the best resting pulmonary function test predictor of CPET abnormalities. Radiographic severity of pneumoconiosis was also associated with CPET abnormalities. These findings support funding DLCO testing for impairment and suggest the term "small opacity" should replace "simple" pneumoconiosis to reflect significant associations with impairment.

[Feasibility of Single-Breath-Hold Compressed Sensing Real-Time Cine Imaging for Assessment of Ventricular Function and Left Ventricular Strain in Cardiac Magnetic Resonance].

Objective: To explore the feasibility of single-breath-hold compressed sensing real-time cine imaging (CS-cine) in the assessment of ventricular function and left ventricular (LV) strain. Methods: A total of 70 subjects were enrolled prospectively, and all subjects underwent cardiac magnetic resonance imaging (cardiac MRI) using both the standard steady-state free procession cine (sta-cine) acquisition and a prototype CS-cine sequence. For both CS-cine and sta-cine imaging, continuous short-axis cine images were acquired from the base to the apex to cover the entire left ventricle, and long-axis cine images including two-, three-, and four-chamber views were also acquired. The scanning range, number of slices, slice thickness and intervals were kept identical for the two cine images of the same participant. Subjective evaluation of the image quality was performed on all cine images. For both sequences, the conventional function parameters of the left and the right ventricles and LV strain values were assessed with post-processing software analysis. The cine image quality, conventional ventricular function parameters, and LV strain values were compared between the two cine groups and the differences were examined. Inter- and intraobserver agreements for CS-cine images were measured using intraclass correlation coefficient ( ICC). Bland-Altman analysis was performed to assess reproducibility between the two cine methods. Results: The median scanning time of CS-cine was 21 s versus 272 s for sta-cine ( P<0.001). The median image quality scores of two groups were significantly different, 4 points for sta-cine and 2 points for CS-cine ( P<0.001). Bi-ventricular end-diastolic volumes (EDV), stroke volume (SV) and ejection fraction (EF) were significantly smaller in CS-cine ( P<0.001). Nevertheless, no significant differences between the two groups in bi-ventricular ESV or LV mass were observed ( P>0.05). LV strain parameters, including the peak radial strain, peak circumferential strain and peak longitudinal strain derived from LV mid-ventricular slice, were significantly different in the two sequences ( P<0.001). Moreover, CS-cine-derived functional parameters and strain measurements have a good correlation with those of sta-cine (for RV function parameters, and left ventricular PLS, PCS values, more than 95% points fell within the limits of agreement [ LoA]; meanwhile, more than 91% points fell within the LoA for other parameters) and inter- and intraobserver agreements were strong ( ICC=0.88 to 0.99) for CS-cine. Conclusion: CS-cine can well realize the rapid acquisition of cine images for quantitative analysis of cardiac function, and the conventional ventricular function parameters and LV globalized strain values obtained from CS-cine imaging have good reproducibility.

Magnetic resonance elastography for estimating in vivo stiffness of the abdominal aorta using cardiac-gated spin-echo echo-planar imaging: a feasibility study.

INTRODUCTION: Magnetic resonance elastography (MRE)-derived aortic stiffness is a potential biomarker for multiple cardiovascular diseases. Currently, gradient-recalled echo (GRE) MRE is a widely accepted technique to estimate aortic stiffness. However, multi-slice GRE MRE requires multiple breath-holds (BHs), which can be challenging for patients who cannot consistently hold their breath. The aim of this study was to investigate the feasibility of a multi-slice spin-echo echo-planar imaging (SE-EPI) MRE sequence for quantifying in vivo aortic stiffness using a free-breathing (FB) protocol and a single-BH protocol. METHOD: On Scanner 1, 25 healthy subjects participated in the validation of FB SE-EPI against FB GRE. On Scanner 2, another 15 healthy subjects were recruited to compare FB SE-EPI with single-BH SE-EPI. Among all volunteers, five participants were studied on both scanners to investigate the inter-scanner reproducibility of FB SE-EPI aortic MRE. Bland-Altman analysis, Lin's concordance correlation coefficient (LCCC) and coefficient of variation (COV) were evaluated. The phase-difference signal-to-noise ratios (PD SNR) were compared. RESULTS: Aortic MRE using FB SE-EPI and FB GRE yielded similar stiffnesses (paired t-test, P = 0.19), with LCCC = 0.97. The FB SE-EPI measurements were reproducible (intra-scanner LCCC = 0.96) and highly repeatable (LCCC = 0.99). The FB SE-EPI MRE was also reproducible across different scanners (inter-scanner LCCC = 0.96). Single-BH SE-EPI scans yielded similar stiffness to FB SE-EPI scans (LCCC = 0.99) and demonstrated a low COV of 2.67% across five repeated measurements. CONCLUSION: Multi-slice SE-EPI aortic MRE using an FB protocol or a single-BH protocol is reproducible and repeatable with advantage over multi-slice FB GRE in reducing acquisition time. Additionally, FB SE-EPI MRE provides a potential alternative to BH scans for patients who have challenges in holding their breath.

Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test.

Single- and multiple-breath washout tests (SBW and MBW) measure ventilation inhomogeneity, but the relationship between them is unclear. Forty-three subjects with cystic fibrosis (CF) and healthy controls (HC) 8-21 years of age were recruited (CF = 30 and HC = 13) and performed nitrogen MBW, vital capacity SBW, spirometry, and plethysmography. Mean phase III slope from SBW (SIII) and lung clearance index (LCI) were significantly different between CF and HC (p = 0.017 and p < 0.0001, respectively). Based on Pearson correlation, SIII and LCI showed strong correlation (ρ = 0.81, p < 0.0001). Both SIII and LCI significantly correlated with spirometry (all p < 0.05). Among CF subjects with normal FEV1 (≥ 80%; n = 17), 76% (n = 13) had normal SIII but abnormal LCI. We conclude that LCI can be abnormal despite normal SIII and FEV1 in CF children. Although LCI and SIII showed strong correlation, our results suggest that LCI is a better test to detect ventilation inhomogeneity in CF children with normal FEV1.

Autocalibrated cardiac tissue phase mapping with multiband imaging and k-t acceleration.

PURPOSE: To develop an autocalibrated multiband (MB) CAIPIRINHA acquisition scheme with in-plane k-t acceleration enabling multislice three-directional tissue phase mapping in one breath-hold. METHODS: A k-t undersampling scheme was integrated into a time-resolved electrocardiographic-triggered autocalibrated MB gradient-echo sequence. The sequence was used to acquire data on 4 healthy volunteers with MB factors of two (MB2) and three (MB3), which were reconstructed using a joint reconstruction algorithm that tackles both k-t and MB acceleration. Forward simulations of the imaging process were used to tune the reconstruction model hyperparameters. Direct comparisons between MB and single-band tissue phase-mapping measurements were performed. RESULTS: Simulations showed that the velocities could be accurately reproduced with MB2 k-t (average ± twice the SD of the RMS error of 0.08 ± 0.22 cm/s and velocity peak reduction of 1.03% ± 6.47% compared with fully sampled velocities), whereas acceptable results were obtained with MB3 k-t (RMS error of 0.13 ± 0.58 cm/s and peak reduction of 2.21% ± 13.45%). When applied to tissue phase-mapping data, the proposed technique allowed three-directional velocity encoding to be simultaneously acquired at two/three slices in a single breath-hold of 18 heartbeats. No statistically significant differences were detected between MB2/MB3 k-t and single-band k-t motion traces averaged over the myocardium. Regional differences were found, however, when using the American Heart Association model for segmentation. CONCLUSION: An autocalibrated MB k-t acquisition/reconstruction framework is presented that allows three-directional velocity encoding of the myocardial velocities at multiple slices in one breath-hold.

Single breath-hold saturation recovery 3D cardiac T1 mapping via compressed SENSE at 3T.

OBJECTIVES: To propose and validate a novel imaging sequence that uses a single breath-hold whole-heart 3D T1 saturation recovery compressed SENSE rapid acquisition (SACORA) at 3T. METHODS: The proposed sequence combines flexible saturation time sampling, compressed SENSE, and sharing of saturation pulses between two readouts acquired at different RR intervals. The sequence was compared with a 3D saturation recovery single-shot acquisition (SASHA) implementation with phantom and in vivo experiments (pre and post contrast; 7 pigs) and was validated against the reference inversion recovery spin echo (IR-SE) sequence in phantom experiments. RESULTS: Phantom experiments showed that the T1 maps acquired by 3D SACORA and 3D SASHA agree well with IR-SE. In vivo experiments showed that the pre-contrast and post-contrast T1 maps acquired by 3D SACORA are comparable to the corresponding 3D SASHA maps, despite the shorter acquisition time (15s vs. 188s, for a heart rate of 60 bpm). Mean septal pre-contrast T1 was 1453 ± 44 ms with 3D SACORA and 1460 ± 60 ms with 3D SASHA. Mean septal post-contrast T1 was 824 ± 66 ms and 824 ± 60 ms. CONCLUSION: 3D SACORA acquires 3D T1 maps in 15 heart beats (heart rate, 60 bpm) at 3T. In addition to its short acquisition time, the sequence achieves good T1 estimation precision and accuracy.

Ultrafast 3D Bloch-Siegert B 1 + -mapping using variational modeling.

PURPOSE: Highly accelerated B 1 + -mapping based on the Bloch-Siegert shift to allow 3D acquisitions even within a brief period of a single breath-hold. THEORY AND METHODS: The B 1 + dependent Bloch-Siegert phase shift is measured within a highly subsampled 3D-volume and reconstructed using a two-step variational approach, exploiting the different spatial distribution of morphology and B 1 + -field. By appropriate variable substitution the basic non-convex optimization problem is transformed in a sequential solution of two convex optimization problems with a total generalized variation (TGV) regularization for the morphology part and a smoothness constraint for the B 1 + -field. The method is evaluated on 3D in vivo data with retro- and prospective subsampling. The reconstructed B 1 + -maps are compared to a zero-padded low resolution reconstruction and a fully sampled reference. RESULTS: The reconstructed B 1 + -field maps are in high accordance to the reference for all measurements with a mean error below 1% and a maximum of about 4% for acceleration factors up to 100. The minimal error for different sampling patterns was achieved by sampling a dense region in k-space center with acquisition times of around 10-12 s for 3D-acquistions. CONCLUSIONS: The proposed variational approach enables highly accelerated 3D acquisitions of Bloch-Siegert data and thus full liver coverage in a single breath hold.

Correlation of single-breath count test and neck flexor muscle strength with spirometry in myasthenia gravis.

INTRODUCTION: Although formal spirometry is the gold standard for monitoring respiratory function in patients with myasthenia gravis (MG), such testing is often delayed or unavailable. There is a need for a simple bedside test that can accurately measure respiratory function. METHODS: We conducted a prospective, cross-sectional, single-blind study in adults with acetylcholine receptor antibody positive MG. Participants performed the single breath count test (SBCT) and underwent manual muscle strength testing, and a respiratory therapist performed spirometry blinded to SBCT and strength results. RESULTS: Thirty-one patients, aged 57 ± 19 years participated. SBCT showed significant correlations with forced vital capacity (FVC), negative inspiratory force, and neck flexor strength (P < 0.01). FVC showed significant correlation with neck flexor strength (P = 0.02) but no correlation with shoulder abductor strength. CONCLUSIONS: These data suggest that the SBCT and neck flexor strength testing are valuable tools for bedside assessment of respiratory function in MG patients.

Single-breath analysis using a novel simple sampler and capillary electrophoresis with contactless conductometric detection.

The analysis of ionic content of exhaled breath condensate (EBC) from one single breath by CE with C(4) D is demonstrated for the first time. A miniature sampler made from a 2-mL syringe and an aluminum cooling cylinder for collection of EBC was developed. Various parameters of the sampler that influence its collection efficiency, repeatability, and effect of respiratory patterns were studied in detail. Efficient procedures for the cleanup of the miniature sampler were also developed and resulted in significant improvement of sampling repeatability. Analysis of EBC was performed by CE-C(4) D in a 60 mM MES/l-histidine BGE with 30 µM CTAB and 2 mM 18-crown-6 at pH 6 and excellent repeatability of migration times (RSD < 1.3% (n = 7)) and peak areas (RSD < 7% (n = 7)) of 12 inorganic anions, cations, and organic acids was obtained. It has been shown that the breathing pattern has a significant impact on the concentration of the analytes in the collected EBC. As the ventilatory pattern can be easily controlled during single exhalation, the developed collection system and method provides a highly reproducible and fast way of collecting EBC with applicability in point-of-care diagnostics.

Single breath count test and its applications in clinical practice: a systematic review.

Background: Single breath count test (SBCT) may be a reproducible, rapid, easy to perform and easy to interpret substitute to spirometry especially in low resource settings for certain conditions. Its interest has been rekindled with the recent COVID-19 pandemic and it can be done as a part of tele-medicine as well. Objectives: The objective of this review was to summarize the evidence of SBCT in clinical practice. Methods: The authors searched EMBASE, PubMed and Google Scholar for all the relevant articles as per exclusion and inclusion criteria. Two authors independently screened all the studies. Newcastle Ottawa Scale was used to assess the quality of the studies. The systematic review was carried following the PRISMA guidelines. Results: After the rigorous process of screening, a total of 13 articles qualified for the systematic review. SBCT greater than 25 had sensitivity of greater than 80% in diagnosing myasthenia gravis exacerbation and SBCT less than or equal to 5 predicted the need for mechanical ventilation in Guillain-Barre syndrome (GBS) patients with 95.2% specificity. Also, Single breath count correlated significantly with forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) in children with pulmonary pathology and in patients with COVID-19 it was used to rule out the need for noninvasive respiratory support. Conclusion: SBCT will undoubtedly be an asset in low resource settings and in tele-medicine to assess the prognosis and guide management of different respiratory and neuromuscular diseases.

Single-Breath Simultaneous Measurement of DLNO and DLCO as Predictor of the Emphysema Component in COPD - A Retrospective Observational Study.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost. Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO). Methods: COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC). Results: Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema. Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.

Single breath counting technique to assess pulmonary function: a systematic review and meta-analysis.

Pulmonary function is usually assessed by measuring Vital Capacity (VC) using equipment such as a spirometer or ventilometer, but these are not always available to the population, as they are relatively expensive tests, difficult to transport and require trained professionals. However, the single breath counting technique (SBCT) appears as a possible alternative to respiratory function tests, to help in the pathophysiological understanding of lung diseases. The objective is to verify the applicability of the SBCT as a parameter for evaluating VC. This is a systematic review registered in the International Prospective Register of Systematic Reviews (CRD42023383706) and used for PubMed®, Scientific Electronic Library Online, LILACS, EMBASE, and Web of Science databases of articles published until January 2023. Methodological quality regarding the risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and National Institutes of Health tools. Eleven of a total of 574 studies were included, of these, nine showed a correlation between VC and SBCT (weak in healthy, moderate in neuromuscular and strong in hospitalized patients). One study of hospitalized patients accurately identified a count value of 21 for a VC of 20 ml kg-1(Sensitivity = 94% and Specificity = 77%), and another estimated a count lower than 41 for a VC below 80% of predicted in patients with neuromuscular dystrophy (Sensitivity = 89% and Specificity = 62%), and another showed good intra and inter-examiner reproducibility in young, adult, and elderly populations. A meta-analysis of three studies showed a moderate correlation in subjects with neuromuscular diseases (r= 0.62, 95% CI = 0.52-0.71,p< 0.01). A high risk of bias was identified regarding the justification of the sample size and blinding of the evaluators. SBCT has been presented as an alternative to assess VC in the absence of specific equipment. There is a clear relationship between SBCT and VC, especially in neuromuscular and hospitalized individuals. New validation studies conducted with greater control of potential bias risks are necessary.

Pulmonary Function Assessment in Myasthenia Gravis Patients in a National Referral Hospital in Indonesia.

Purpose: Myasthenia gravis (MG) can cause respiratory muscle weakness and the need of ventilator support. Spirometry as the gold standard for pulmonary function examination has limited availability, especially in our hospital which is only available in outpatient clinic during work hours (not in emergency room or patient room). Furthermore, all primary healthcare in Indonesia do not have spirometry equipment, thus other alternatives are required. This study aimed to analyze the relationship between a single breath counting test (SBCT), peak flow meter (PFM), and spirometry to assess pulmonary function in MG patients in a national referral hospital in Indonesia. Patients and Methods: A single-center, cross-sectional study was conducted and SBCT, PFM, and spirometry examination were performed in MG patients and healthy controls. Results: Seventy patients, aged 47.7 ± 13.4 years old, participated in this study. SBCT, forced vital capacity first second (FVC1), and forced expiratory volume first second (FEV1) value between MG patients and healthy controls showed a significant difference, in which healthy controls have higher SBCT, FVC1, and FEV1 values (p = 0.000, p = 0.000 and p = 0.001 respectively). There was a significant difference between PFM with SBCT and FVC1 value in MG patients. Strong correlation was found between SBCT and FVC1 in MG patients. Conclusion: MG patients had worse pulmonary function compared to healthy controls. SBCT and PFM examination have a significant correlation with FVC1 in MG patients. Therefore, SBCT and PFM can be used as a bedside tool to detect respiratory impairment in MG patients.

Validation of the Single Breath Count Test for Assessment of Inspiratory Muscle Strength in Healthy Subjects and People with Neuromuscular Disorders.

OBJECTIVE: This study aimed to validate the single breath count test (SBCT) against volitional measures of respiratory muscle function in healthy subjects and people with neuromuscular disorders (NMD; n = 100 per group). METHODS: Testing comprised upright and supine SBCT, forced vital capacity (FVC), maximum inspiratory pressure (MIP), and sniff nasal inspiratory pressure (SNIP). Predictability of FVC by SBCT was assessed using logarithmic regression analysis. Receiver operating characteristics curves were used to identify SBCT thresholds for lung restriction (FVC < 80% predicted), inspiratory muscle weakness (MIP < 60 cmH2O), and indication for non-invasive ventilation (NIV) in NMD patients. RESULTS: In both groups, SBCT showed moderate correlation with FVC. In patients, SBCT values were also correlated with MIP and SNIP. Strength of correlations was similar with supine and upright SBCT which accounted for 23.7% of FVC variance in healthy individuals (44.5% in patients). Predictive thresholds of upright SBCT were < 27 for MIP < 60 cmH2O (sensitivity 0.61/specificity 0.86), <39 for NIV indication (0.92/0.46), and <41 for FVC < 80% predicted (0.89/0.62). CONCLUSION: The SBCT is positively correlated with spirometry. It predicts both lung restriction and NIV indication in NMD patients. The SBCT allows for remote monitoring and may substitute for spirometry/manometry if appropriate devices are unavailable.

Peak expiratory flow and the single-breath count test as markers of respiratory function in patients with myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease characterised by fluctuating, fatigable muscle weakness, frequently involving bulbar and respiratory muscles. Considering the severity of respiratory involvement in MG, routine evaluation of respiratory function is essential. The aim of this study was to identify a useful clinical marker of respiratory involvement in patients with MG. METHODS: We performed an observational study of patients with MG. All cases were evaluated with the single-breath count test, peak expiratory flow (PEF), a modified Medical Research Council dyspnoea scale (mMRC), and a neck strength assessment. The results of these parameters were correlated with forced vital capacity (FVC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). RESULTS: The study included 45 patients with MG: 2 patients classified as grade I on the Myasthenia Gravis Foundation of America classification at the time of evaluation, 35 classified as grade II, 7 classified as grade III, and one classified as grade IV. Positive correlations were found between single-breath count test scores and FVC values (r = 0.57, P = .000), and between PEF and FVC values (r = 0.76, P = .000). Severity of dyspnoea according to the mMRC scale showed a negative correlation with FVC values (r = -0.31, P = .03). PEF also showed a significant correlation with MEP (r = 0.51, P = .002). CONCLUSIONS: PEF, the single-breath count test, and the mMRC scale are useful measures for evaluating respiratory function in patients with MG.

Test-retest reliability of lung diffusing capacity for nitric oxide during light to moderate intensity cycling exercise.

This study examined test-retest reliability of single-breath lung diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) during exercise. Sixteen healthy subjects (age 20-67 years) performed DLNO-DLCO tests during light and moderate intensity cycling exercise at 50% and 80% of individual anaerobic threshold (IAT). Primary endpoint was DLNO at 80% IAT. Precision of DLNO, DLCO, and alveolar volume was quantified by within-subject standard deviation (SDws, measurement error) and intraclass correlation coefficients (ICC). Reproducibility was determined by SDws* 2.77. Overall, reliability was excellent for all outcomes. SDws and reproducibility for DLNO at 80% IAT were 4.6 and 12.7 mL.min-1.mmHg-1, and the ICC was 0.99 (95% confidence interval 0.98-0.99). Median breathlessness at 80% IAT was 4 (interquartile range 3-6) on a 0-10 scale. Our data suggest excellent reliability of single-breath DLNO during moderate intensity exercise, but perceived levels of breathlessness may limit its usefulness, especially at exercise intensities beyond IAT.

Single breath nitrogen test as predictor of lung function decline and COPD over an 8-year follow-up.

BACKGROUND: The single breath nitrogen (SBN2) test was proposed for early detection of "small airways disease" in the seventies. Few longitudinal studies have subsequently evaluated the relationships between SBN2 test measurements and lung function decline or COPD incidence. AIM: This study evaluates whether SBN2 test abnormalities may be significant predictors of lung function decline and COPD incidence over an 8-year follow-up. STUDY DESIGN AND METHODS: In this longitudinal study, 907 adults (20+ years old; 56% males) from the prospective Po River Delta epidemiological study underwent SBN2 test at baseline and spirometry testing at both baseline and follow-up 8-year apart. Multinomial and multiple regression models were used to assess associations of SBN2 indexes and rates of FEV1 decline or risk of COPD incidence over time, after adjusting for sex, height and baseline age, FEV1 and smoking status. COPD was defined according to either GOLD or ATS-ERS criteria. RESULTS: Among SBN2 indexes, only the slope of alveolar plateau (N2-slope) was significantly associated with rates of FEV1 decline (7.93 mL/year for a one-unit change in N2-slope, p<0.0001), and with an increased risk of developing COPD as defined by GOLD (RR 1.81, 95%CI 1.29-2.52, mild; RR 2.78, 95%CI 1.70-4.53, moderate or severe obstruction) and ATS-ERS criteria (RR 1.62, 95%CI 1.14-2.29, mild; RR 3.40, 95%CI 1.72-6.73, moderate or severe obstruction). CONCLUSION: In this population-based study, N2-slope from SBN2 test is a significant predictor of lung function decline and COPD incidence over an 8-year follow-up, confirming the role of the "small airways disease" in the natural history of COPD.

Single breath counting is an effective screening tool for forced vital capacity in ALS.

Objective: To measure the correlation between single breath counting (SBC) and forced vital capacity (liters, FVCL) in amyotrophic lateral sclerosis (ALS) patients and to define the utility of SBC for determining when patients meet the threshold for initiation of noninvasive positive pressure ventilation (FVC < 50% predicted [FVCpred]). Methods: Both patient paced (SBCpp) or externally paced (SBCep) counting along with FVCL+pred and standard clinical data were collected. Linear regression was used to examine SBCpp and SBCep as a predictor of FVCL. Receiver operating characteristic curve analysis evaluated the sensitivity and specificity of SBC categorically predicting FVCpred of ≤50%. Results: In 30 ALS patients, SBC explained a moderate proportion of the variance in FVCL (SBCpp: R2= 0.431, p < 0.001; SBCep: R2 = 0.511, p < 0.01); this proportion improved when including covariates (SBCpp: R2= 0.635, p < 0.01; SBCep: R2= 0.657, p < 0.01). Patients with minimal speech involvement performed similarly in unadjusted (SBCpp: R2 = 0.511, p < 0.01; SBCep: R2= 0.595, p < 0.01) and adjusted (SBCpp: R2 = 0.634, p < 0.01; SBCep: R2= 0.650, p < 0.01) models. SBCpp had 100% sensitivity and 60% specificity (area under curve (AUC) = 0.696) for predicting FVCpred <50%. SBCep had 100% sensitivity and 56% specificity (AUC = 0.696). With minimal speech involvement SBCpp and SBCep both had 100% sensitivity and 76.1% specificity (SPCpp: AUC = 0.845; SBCep: AUC = 0.857). Conclusions: SBC explains a moderate proportion of variance in FVC and is an extremely sensitive marker of poor FVC. When FVC cannot be obtained, such as during the current COVID-19 pandemic, SBC is helpful in directing patient care.

Single-breath oxygen dilution for the measurement of total lung capacity: technical description and preliminary results in healthy subjects.

Objective. Total lung capacity (TLC) assessment outside of a research laboratory is challenging. We describe a novel method for measuring TLC that is both simple and based only on portable equipment, and report preliminary data in healthy subjects.Approach. We developed an open circuit system to administer a known amount of oxygen to a subject in a single maximal inspiratory maneuver. Oxygen fraction, expired and inspired flows were continuously monitored to allow a precise computation of the mass balance. Values of TLC and functional residual capacity (FRC) were compared with standard methods (body plethysmography and multiple-breath helium dilution). Twenty healthy subjects participated to the study, eleven of which performed the maneuver twice to assess test-retest reliability.Main results.There was high agreement in TLC between the proposed method and the two standard methods (R2 > 0.98, bias not different from 0, and 95% limits of agreements <± 0.4 l for both). Test-retest reliability was high (intraclass correlation coefficient >0.99 and no bias). Results were similar for FRC, with a slightly higher variability due its sensitivity to changes in posture or breathing pattern.Significance.Single-breath oxygen dilution is accurate and reliable in assessing TLC and FRC in healthy subjects. The technique is appealing for time- or resource-limited settings, such as field physiological research expeditions or mass screenings.