Assessing breathing effort by barometric whole-body plethysmography and its relationship with prognosis in client-owned cats with respiratory distress.

BACKGROUND: Cats in respiratory distress have limited tolerance for manipulation, hindering clinical monitoring. Minute volume (MV) can be utilized to rate dyspnea in humans, but its relationship with respiratory distress in cats remains poorly investigated. HYPOTHESIS: Cats with respiratory distress will show higher MV per kg body weight (MV/BW) than normal cats, and the MV/BW increase will correlate with survival. ANIMALS: Fifty-two cats with respiratory distress from lung parenchymal disease, pleural space disease, lower airway obstruction (LAO), or upper airway obstruction were recruited since 2014. METHODS: This is a prospective observational study. Study cats were placed in a transparent chamber, allowing clinicians to easily observe their breathing status and record ventilation using barometric whole-body plethysmography (BWBP). Ventilatory variables of the 52 cats were compared with those of 14 historic control cats. Follow-up data, including disease category, clinical outcomes, and survival, were prospectively collected. RESULTS: Cats in respiratory distress demonstrated significantly higher MV/BW (397 mL/kg; range, 158-1240) than normal cats (269 mL/kg; range, 168-389; P < .001). Among the etiologies, cats with LAO, parenchymal, and pleural space disease exhibited higher-than-normal MV/BW trends. A cutoff value of 373 mL/kg (1.4-fold increase) indicated abnormally increased breathing efforts (sensitivity, 67%; specificity, 93%). MV/BW was independently associated with increased cardiorespiratory mortality in cats with respiratory distress (adjusted hazard ratio 1.17, 95% confidence interval [CI] 1.02-1.35; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Breathing efforts in cats can be noninvasively quantified using BWBP. Measurement of MV/BW could serve as a prognostic index for monitoring cats experiencing respiratory distress.

Updated reference values for static lung volumes from a healthy population in Austria.

BACKGROUND: Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed. METHODS: We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6-80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models. RESULTS: Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results. CONCLUSION: GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6-80 years of age).

Body plethysmography - additional information on exercise capacity in patients with congenital heart disease?

AIMS: In each cardiopulmonary exercise test (CPET), resting spirometry is performed in advance. In patients with a congenital heart defect (CHD), lung volumes are often impaired. This study investigates correlations between lung volumes and CPET parameters and determines, whether body plethysmography provides substantial additional information for these patients. METHODS: Data from 102 patients (23.8 ± 10.4 years of age, 39 female) with various forms of CHD were examined from April 2018 to October 2022. All patients underwent spirometry (measuring forced vital capacity, FVC and forced expiratory volume in 1 s, FEV1), body plethysmography (measuring total lung capacity, TLC) and an exhausting CPET. Data is presented as the median and interquartile range (z-scores) and correlated with Spearman's rho. RESULTS: Fifty-five% of all patients had normal results in lung function and 45% had normal peak oxygen uptake (≥ 80% predicted in peak VO2). Patients with impaired lung function were significantly more likely to have low exercise capacity (Fisher's exact test: p = 0.028). FVC z-values and %predicted peak VO2 (r = 0.365, p < 0.001) correlated significantly as well as FEV1_z and %predicted peak VO2 (r = 0.320, p = 0.001), and TLC z-values and %predicted peak VO2 (r = 0.249, p = 0.012). No correlation was found between FEV1/FVC z-values and %predicted peak VO2 (r = -0.043, p = 0.670). CONCLUSION: Spirometry and exercise capacity positively correlate, also in CHD patients. However, body plethysmography does not provide additional or improved prediction and is therefore only recommended in noteworthy results in spirometry to exclude further lung co-morbidities.

Impulse Oscillometry as an Alternative Lung Function Test for Hospitalized Adults.

BACKGROUND: Impulse oscillometry (IOS) is a noninvasive technique that measures lung physiology independently of patient effort. In the present study, we aimed to investigate the utility of IOS parameters in comparison with pulmonary function testing (PFT) among hospitalized subjects, with emphasis on obstructive and small airway diseases. METHODS: Sixty-one subjects hospitalized either with unexplained dyspnea or for pre-surgery evaluation were included in the study. All subjects underwent PFTs and IOS test. The correlation between IOS results and PFTs was examined in different subgroups. The ability of IOS parameters to predict abnormal PFTs was evaluated using the area under the receiver operating characteristic (ROC) curve, and optimal cutoff values were calculated. RESULTS: IOS results were found to correlate with PFT values. Subgroup analysis revealed that these correlations were higher in younger (age < 70) and non-obese (body mass index < 25kg/m2) subjects. The resonant frequency was an independent predictor and had the best predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.732 [95% CI 0.57-0.90], optimal cutoff 17 Hz, 87% sensitivity, 62% specificity) and abnormal forced expiratory flow during the middle half of the FVC maneuver (area under the ROC curve 0.667 [95% CI 0.53-0.81], optimal cutoff 15 Hz, 77% sensitivity, 54% specificity). Area of reactance and the difference in respiratory resistance at 5 Hz and 20 Hz also showed a good predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.716 and 0.730, respectively). CONCLUSIONS: We found that the IOS performed well in diagnosing small airway and obstructive diseases among hospitalized subjects. IOS might serve as an alternative to standard PFTs in non-cooperative or dyspneic hospitalized patients.

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma.

BACKGROUND AND OBJECTIVES: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. METHODS: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. RESULTS: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. CONCLUSIONS: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma

Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. Methods: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. Results: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤−0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. Conclusion: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH. (AU)

Antecedentes: En el asma bronquial, la hiperinsuflación pulmonar estática (SLH) medida mediante pletismografía corporal (Pleth) se asocia a un peor pronóstico. La gravedad de la SLH podría estar asociada con la disfunción de las vías respiratorias pequeñas (SAD), que puede medirse mediante la oscilometría de impulsos (IOS). Objetivo: Este estudio pretende determinar la correlación entre el SLH y la SAD en pacientes con asma grave, y la mejora de ambos parámetros en respuesta al tratamiento. Métodos: Se analizaron los datos de los pacientes que se inscribieron en el Registro de Asma Grave de Taiwán, una cohorte observacional prospectiva. Se realizaron periódicamente mediciones de Pleth e IOS. Se determinó la relación entre los parámetros espirométricos e IOS. Se analizaron los cambios en los parámetros clínicos y funcionales en respuesta al tratamiento. Resultados: De una muestra de 107 pacientes con asma grave, 83 (77,6%) presentaban SLH, definida mediante una relación volumen residual/capacidad pulmonar total (VR/CTP) aumentada. La mayoría de los pacientes eran mujeres de edad avanzada con peor función pulmonar y SAD, en comparación con los que no tenían SLH. El SAD por aumento de la resistencia/reactancia de las vías respiratorias se correlacionó significativamente con el SLH. La reactancia de las vías respiratorias a 5 Hz (X5) ≤-0,21 [kPa/(L/s)] detectó el SLH con un área bajo la curva ROC de 0,84 (p < 0,0001, sensibilidad = 85,2% y especificidad = 83,3%). Después de 12 meses, los pacientes que recibieron tratamiento biológico adicional presentaron una reducción significativa de las exacerbaciones, del nivel de óxido nítrico exhalado, del recuento de eosinófilos en sangre, una mejora del volumen espiratorio forzado en el primer segundo, de la X5, y una tendencia a la reducción del cociente RV/TLC en comparación con los que no recibieron tratamiento biológico... (AU)

Hyperinflation and reduced diffusing capacity predict prognosis in SCLC: value of extended pre-therapeutic lung function testing.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by aggressive growth and poor prognosis. Although SCLC affects nearly exclusively heavy smokers and leads to frequent respiratory symptoms, the impact of pre-therapeutic lung function testing in SCLC is sparely investigated until now. Therefore, we sought to examine whether we could find prognostic markers in pre-therapeutic lung function testing of SCLC patients. PATIENTS AND METHODS: We retrospectively analysed a cohort of 205 patients with the diagnosis of SCLC between 2010 and 2018. Pre-therapeutic values of spirometry, body plethysmography and measurement of diffusing capacity was extracted from patients' charts. Comparisons between groups were performed using the Mann-Whitney U-test or by chi-square tests as appropriate. Kaplan-Meier analyses and COX-regression models were performed to correlate lung function parameters with patients' outcome. RESULTS: Airway obstruction itself, or the diagnosis chronic obstructive pulmonary disease (COPD) based on GOLD definitions did not correlate with survival in SCLC patients. Hyperinflation measured by increased residual volume and residual volume to total lung capacity ratio (log-rank p < 0.001) and reduced diffusing capacity (log-rank p = 0.007) were associated with reduced survival. Furthermore, patients with hyperinflation as well as impairments in gas exchange representing an emphysematic phenotype had the worst outcome (log-rank p < 0.001). CONCLUSION: We recommend including body plethysmography and measurement of diffusing capacity in the pre-therapeutic assessment of SCLC patients. Our findings suggest that reduction of hyperinflation may lead to better outcome in SCLC patients. Thus, in addition to effective tumour therapy, adequate therapy of the comorbidity of COPD should also be provided. In particular, measures to reduce hyperinflation by means of dual bronchodilation as well as respiratory physiotherapy should be further assessed in this setting.

An automated respiratory data pipeline for waveform characteristic analysis.

Comprehensive and accurate analysis of respiratory and metabolic data is crucial to modelling congenital, pathogenic and degenerative diseases converging on autonomic control failure. A lack of tools for high-throughput analysis of respiratory datasets remains a major challenge. We present Breathe Easy, a novel open-source pipeline for processing raw recordings and associated metadata into operative outcomes, publication-worthy graphs and robust statistical analyses including QQ and residual plots for assumption queries and data transformations. This pipeline uses a facile graphical user interface for uploading data files, setting waveform feature thresholds and defining experimental variables. Breathe Easy was validated against manual selection by experts, which represents the current standard in the field. We demonstrate Breathe Easy's utility by examining a 2-year longitudinal study of an Alzheimer's disease mouse model to assess contributions of forebrain pathology in disordered breathing. Whole body plethysmography has become an important experimental outcome measure for a variety of diseases with primary and secondary respiratory indications. Respiratory dysfunction, while not an initial symptom in many of these disorders, often drives disability or death in patient outcomes. Breathe Easy provides an open-source respiratory analysis tool for all respiratory datasets and represents a necessary improvement upon current analytical methods in the field. KEY POINTS: Respiratory dysfunction is a common endpoint for disability and mortality in many disorders throughout life. Whole body plethysmography in rodents represents a high face-value method for measuring respiratory outcomes in rodent models of these diseases and disorders. Analysis of key respiratory variables remains hindered by manual annotation and analysis that leads to low throughput results that often exclude a majority of the recorded data. Here we present a software suite, Breathe Easy, that automates the process of data selection from raw recordings derived from plethysmography experiments and the analysis of these data into operative outcomes and publication-worthy graphs with statistics. We validate Breathe Easy with a terabyte-scale Alzheimer's dataset that examines the effects of forebrain pathology on respiratory function over 2 years of degeneration.

Intermittent Hypoxia and Weight Loss: Insights into the Etiology of the Sleep Apnea Phenotype.

Sleep apnea (SA) is a major respiratory disorder with increased risk for hypertension and obesity; however, our understanding of the origins of this complex disorder remains limited. Because apneas lead to recurrent drops in O2 during sleep, intermittent hypoxia (IH) is the main animal model to explore the pathophysiology of SA. Here, we assessed the impacts of IH on metabolic function and related signals. Adult male rats were exposed to 1 week of moderate IH (FiO2 = 0.10-30 s, ten cycles/hour, 8 h/day). Using whole-body plethysmography, we measured respiratory variability and apnea index during sleep. Blood pressure and heart rate were measured by the tail-cuff method; blood samples were taken for multiplex assay. At rest, IH augmented arterial blood pressure, respiratory instability, but not apnea index. IH induced weight, fat, and fluid loss. IH also reduced food intake and plasma leptin, adrenocorticotropic hormone (ACTH), and testosterone levels but increased inflammatory cytokines. We conclude that IH does not replicate the metabolic clinical features of SA patient, thus raising our awareness of the limitations of the IH model. The fact that the risk for hypertension occurs before the appearance of apneas provides new insights into the progression of the disease.

Ventilatory Effects of Acute Intermittent Hypoxia in Conscious Dystrophic Mice.

Exposure to acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). Interest has grown in developing AIH interventions to treat ventilatory insufficiency, with promising results in spinal cord injury and amyotrophic lateral sclerosis. Therapeutic AIH may have application in neuromuscular disorders including muscular dystrophies. We sought to establish hypoxic ventilatory responsiveness and the expression of ventilatory LTF in X-linked muscular dystrophy (mdx) mice.Experiments were performed in 15 male wild-type (BL10) and 15 male mdx mice at 4 months of age. Ventilation was assessed using whole-body plethysmography. Baseline measures of ventilation and metabolism were established. Mice were exposed to 10 successive bouts of hypoxia, each lasting 5 min, interspersed with 5-min bouts of normoxia. Measurements were taken for 60 min following termination of AIH.In mdx mice, ventilation was significantly increased 60 min post-AIH compared to baseline. However, metabolic CO2 production was also increased. Therefore, ventilatory equivalent was unaffected by AIH exposure, i.e., no ventilatory LTF manifestation. In wild-type mice, ventilation and metabolism were not affected by AIH.Eliciting ventilatory LTF is dependent on many factors and may require concomitant isocapnia or hypercapnia during AIH exposures and/or repeated daily AIH exposures, which is worthy of further pursuit.

Fenofibrate attenuates asthma features in an ovalbumin-induced mouse model via suppressing NF-κB binding activity.

BACKGROUND/AIM: Asthma is a chronic inflammatory disease of the airways with a high prevalence. Asthma has a complex pathophysiology and about 5-10% of patients are not fully responsive to the currently available treatments. The aim of this study is to investigate the involvement of NF-κB in the effects of fenofibrate on a mouse model of allergic asthma. MATERIALS AND METHODS: A total of 49 BALB/c mice were randomly distributed into 7 groups (n = 7). Allergic asthma model was created by administering i.p. injections of ovalbumin on days 0, 14 and 21, followed by provocation with inhaled ovalbumin on days 28, 29 and 30. Fenofibrate was orally given in 3 different doses; 1, 10 and 30 mg/kg through days 21-30 of the experiment. On day 31, pulmonary function test using whole body plethysmography was performed. The mice were sacrificed 24 h later. Blood samples were obtained, and serum of each sample was separated for IgE determination. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to measure IL-5 and IL-13 levels. Nuclear extracts of lung tissues were employed to assess nuclear factor kappa B (NF-κB) p65 binding activity. RESULTS: Enhanced Pause (Penh) values were significantly increased in ovalbumin-sensitized and challenged mice (p < 0.01). Administration of fenofibrate (10 and 30 mg/kg) resulted in improved pulmonary function as shown by significantly lower Penh values (p < 0.01). Interleukin (IL) - 5 and IL-13 levels in BALF and lung tissues and immunoglobulin E (IgE) levels in serum were significantly elevated in the allergic mice. IL-5 levels in the lung tissues of mice treated with 1 mg/kg fenofibrate (FEN1) group were significantly reduced (p < 0.01). BALF and lung tissue IL-5 and IL-13 levels in mice treated with 10 and 30 mg/kg fenofibrate, FEN10 and FEN30, respectively, were significantly diminished when compared to the ovalbumin-treated (OVA) group, whereas treatment with 1 mg/kg fenofibrate resulted in insignificant changes. IgE levels in the serum of FEN30 group mice have shown a prominent reduction (p < 0.01). NF-κB p65 binding activity was higher in mice sensitized and challenged with ovalbumin (p < 0.01). NF-κB p65 binding activity was significantly reduced in allergic mice treated with 30 mg/kg (p < 0.01) fenofibrate. CONCLUSIONS: In this study, we showed that administration of 10 and 30 mg/kg fenofibrate effectively attenuated airway hyperresponsiveness and inflammation in a mouse model of allergic asthma, possibly through inhibition of NF-κB binding activity.

Prevalence of restrictive lung function in children and adults in the general population.

BACKGROUND: Restrictive lung function (RLF) is characterized by a reduced lung expansion and size. In the absence of lung volume measurements, restriction can be indirectly assessed with restrictive spirometric patterns (RSP) by spirometry. Prevalence data on RLF by the golden standard body plethysmography in the general population are scarce. Therefore, we aimed to evaluate the prevalence of RLF and RSP in the general population by body plethysmography and to determine factors influencing RLF and RSP. METHODS: Pre-bronchodilation lung function data of 8891 subjects (48.0% male, age 6-82 years) have been collected in the LEAD Study, a single-centered, longitudinal, population-based study from Vienna, Austria. The cohort was categorized in the following groups based on the Global Lung Initiative reference equations: normal subjects, RLF (TLC < lower limit of normal (LLN)), RSP (FEV1/FVC ≥ LLN and a FVC < LLN), RSP only (RSP with TLC ≥ LLN). Normal subjects were considered those with FEV1, FVC, FEV1/FVC and TLC between LLN and ULN (upper limit of normal). RESULTS: The prevalence of RLF and RSP in the Austrian general population is 1.1% and 4.4%. Spirometry has a positive and negative predictive value of 18.0% and 99.6% to predict a restrictive lung function. Central obesity was associated with RLF. RSP was related to smoking and underweight. CONCLUSIONS: The prevalence of true restrictive lung function and RSP in the Austrian general population is lower than previously estimated. Our data confirm the need for direct lung volume measurement to diagnose true restrictive lung function.

Changes in Pulmonary Functions of Adolescents with Pectus Excavatum Throughout the Nuss Procedure.

BACKGROUND: We aimed to determine the longitudinal changes in pulmonary functions of adolescents with Pectus Excavatum who underwent the Nuss procedure, the minimally invasive repair of pectus excavatum (MIRPE). METHODS: Lung function measurements were performed before bar implantation (T0), at least six weeks to ten months after implantation (T1a), at least eleven months to sixty-one months after bar implantation (T1b) and at least two weeks after bar explantation (T2). RESULTS: Data of 114 patients (83.3% male) whose median age at implantation was 15.6 years and at explantation 18.7 years were analyzed. Shortly after implantation at T1a a significant decline of vital capacity (VC; n = 82), forced vital capacity (FVC; n = 78) and forced expiratory volume in 1 second (FEV1; n = 80) compared to T0 was seen. At T1b a significant decline for the residual volume (RV; n = 83), the residual volume/total lung capacity ratio (RV/TLC; n = 81), the total specific airway resistance (sRaw; n = 80) and the total airway resistance (Raw; n = 84) also compared to T0 was measured. In the comparison of T1b to T2 a significant increase of VC, FVC (n = 67), FEV1 (n = 69), TLC (n = 67) and a significant decrease of Raw (n = 66), sRaw, RV (n = 65) and the RV/TLC (n = 64) ratio could be observed. In the direct analysis between T0 and T2, after the explantation of the bar a significant increase in VC (n = 54), FVC (n = 52), and TLC (n = 55) and a significant decrease of RV (n = 51) and the RV/TLC index (n = 50), and in airway resistance parameters like Raw (n = 52) and sRaw (n = 51) could be detected. CONCLUSIONS: Lung function values along with markers of airway resistance improve in patients after the complete procedure of MIRPE. LEVEL OF EVIDENCE: Level II.

Impulse Oscillometry as a Diagnostic Test for Pulmonary Emphysema in a Clinical Setting.

Body plethysmography (BP) is the standard pulmonary function test (PFT) in pulmonary emphysema diagnosis, but not all patients can cooperate to this procedure. An alternative PFT, impulse oscillometry (IOS), has not been investigated in emphysema diagnosis. We investigated the diagnostic accuracy of IOS in the diagnosis of emphysema. Eighty-eight patients from the pulmonary outpatient clinic at Lillebaelt Hospital, Vejle, Denmark, were included in this cross-sectional study. A BP and an IOS were performed in all patients. Computed tomography scan verified presence of emphysema in 20 patients. The diagnostic accuracy of BP and IOS for emphysema was evaluated with two multivariable logistic regression models: Model 1 (BP variables) and Model 2 (IOS variables). Model 1 had a cross-validated area under the ROC curve (CV-AUC) = 0.892 (95% CI: 0.654-0.943), a positive predictive value (PPV) = 59.3%, and a negative predictive value (NPV) = 95.0%. Model 2 had a CV-AUC = 0.839 (95% CI: 0.688-0.931), a PPV = 55.2%, and an NPV = 93.7%. We found no statistically significant difference between the AUC of the two models. IOS is quick and easy to perform, and it can be used as a reliable rule-out method for emphysema.

Understanding the Impact of Pulmonary Rehabilitation on Airway Resistance in Patients with Severe COPD: A Single-Center Retrospective Study.

Purpose: We investigated the effect of pulmonary rehabilitation (PR) on airway resistance in chronic obstructive pulmonary disease (COPD) patients with severe airway obstruction and hyperinflation. Patients and Methods: This retrospective cohort study was conducted with data from severe COPD cases with those who underwent an 8-week PR program. Main inclusion criteria were having severe airflow obstruction (defined as a forced expiratory volume in one second (FEV1) <50%) and plethysmographic evaluation findings being compatible with hyperinflation supporting the diagnosis of emphysema (presence of hyperinflation defined as functional residual capacity ratio of residual volume to total lung capacity (RV/TLC) >120%). Primary outcomes were airway resistance (Raw) and airway conductance (Gaw) which were measured by body plethysmography, and other measurements were performed, including 6-minute walk test (6-MWT), modified Medical Research Council dyspnea scale (mMRC) and COPD assessment test (CAT). Results: Twenty-six severe and very severe COPD patients (FEV1, 35.0 ± 13.1%; RV/TLC, 163.5 ± 29.4) were included in the analyses, mean age 62.6 ± 5.8 years and 88.5% males. Following rehabilitation, significant improvements in total specific airway resistance percentage (sRawtot%, p = 0.040) and total specific airway conductance percentage (sGawtot%; p = 0.010) were observed. The post-rehabilitation mMRC scores and CAT values were significantly decreased compared to baseline results (p < 0.001 and p < 0.001, respectively). Although there were significant improvements in 6-MWT value (p < 0.001), exercise desaturation (ΔSaO2, p = 0.026), the changes in measured lung capacity and volume values were not significant. Conclusion: We concluded that PR may have a positive effect on airway resistance and airway conductance in COPD patients with severe airflow obstruction.

CYX-5, a G-protein biassed MOP receptor agonist, DOP receptor antagonist and KOP receptor agonist, evokes constipation but not respiratory depression relative to morphine in rats.

BACKGROUND: Strong opioid analgesics such as morphine alleviate moderate to severe acute nociceptive pain (e.g. post-surgical or post-trauma pain) as well as chronic cancer pain. However, they evoke many adverse effects and so there is an unmet need for opioid analgesics with improved tolerability. Recently, a prominent hypothesis has been that opioid-related adverse effects are mediated by ß-arrestin2 recruitment at the µ-opioid (MOP) receptor and this stimulated research on discovery of G-protein biassed opioid analgesics. In other efforts, opioids with MOP agonist and δ-opioid (DOP) receptor antagonist profiles are promising for reducing side effects c.f. morphine. Herein, we report on the in vivo pharmacology of a novel opioid peptide (CYX-5) that is a G-protein biassed MOP receptor agonist, DOP receptor antagonist and kappa opioid (KOP) receptor agonist. METHODS: Male Sprague-Dawley received intracerebroventricular bolus doses of CYX-5 (3, 10, 20 nmol), morphine (100 nmol) or vehicle, and antinociception (tail flick) was assessed relative to constipation (charcoal meal and castor oil-induced diarrhoea tests) and respiratory depression (whole body plethysmography). RESULTS: CYX-5 evoked naloxone-sensitive, moderate antinociception, at the highest dose tested. Although CYX-5 did not inhibit gastrointestinal motility, it reduced stool output markedly in the castor oil-induced diarrhoea test. In contrast to morphine that evoked respiratory depression, CYX-5 increased tidal volume, thereby stimulating respiration. CONCLUSION: Despite its lack of recruitment of ß-arrestin2 at MOP, DOP and KOP receptors, CYX-5 evoked constipation, implicating a mechanism other than ß-arrestin2 recruitment at MOP, DOP and KOP receptors, mediating constipation evoked by CYX-5 and potentially other opioid ligands.

Validation of the clinical utility of sGaw as a response variable in methacholine challenge testing.

BACKGROUND AND OBJECTIVE: Airway hyperresponsiveness (AHR) is commonly assessed by a methacholine challenge test (MCT), during which a provocative concentration causing a 20% reduction in forced expiratory volume in 1 second (FEV1 ) (PC20 ) < 8 mg/ml is considered a positive response. However, a fall in specific airway conductance (sGaw) may also have clinical significance. The purpose of this study was to assess whether AHR determined by a provocative concentration causing a 40% reduction in sGaw (PC40 ) < 8 mg/ml corresponds to a clinical diagnosis of asthma. METHODS: We analysed the changes in spirometry, lung volumes and sGaw during MCT in 211 randomly selected patients being evaluated for AHR to support a clinical diagnosis of asthma. RESULTS: The mean (SD) age of the group was 53 (15) years, with 141 women (67%). Overall lung function was normal, with FEV1  = 92 (15) % predicted, total lung capacity = 97 (13) % predicted and sGaw = 0.19 (0.15-0.23) L/s/cm H2 O/L, (median, 25-75 IQR). There were many more patients who responded by PC40 only (n = 120) than who responded by PC20 (n = 52). There was no significant difference in asthma diagnosis between the PC20 (98%) and PC40 (93%) groups, and we estimate 34% of patients with a diagnosis of asthma would have been classified as having no AHR if only the FEV1 criterion was used. CONCLUSION: Changes in sGaw during MCT indicate clinically significant AHR in support of a clinical diagnosis of asthma among patients being evaluated for asthma.

Diagnostic accuracy of peripheral lung function measurements in paediatric asthma control assessment: a pilot study.

Introduction: Recent studies have indicated the significance of the peripheral airways in asthma control. Methods estimating airway resistance, air trapping, and ventilation inhomogeneity are useful for assessing this area of the lung and have proven utility in the evaluation of asthma; however, it is unclear which method is most effective at characterising uncontrolled asthma. Aim: To evaluate the diagnostic accuracy of various peripheral airway function measurements in the assessment of asthma control in children. Material and methods: Children with controlled (n = 35) and uncontrolled (n = 29) asthma performed a sequence of pulmonary function tests (i.e. spirometry, body plethysmography, oscillometry, nitrogen washout test, and exhaled nitric oxide). The diagnostic accuracy of each peripheral airway measure was evaluated by an area under the receiver operating characteristic curve (AUC). Results: Most peripheral airway parameters were significantly increased in children with uncontrolled asthma compared with children with controlled asthma. The measures with the highest diagnostic accuracy for asthma control were lung clearance index (LCI) (AUC = 0.76), with high specificity (0.97) and modest sensitivity (0.46), acinar ventilation heterogeneity (Sacin) (AUC = 0.73), with high sensitivity (0.85) and modest specificity (0.54), and resonance frequency (Fres) (AUC= 0.74), with perfect specificity (1.0) but low sensitivity (0.38). Conclusions: LCI, Sacin and Fres had the highest discriminative capacity for distinguishing children with controlled and uncontrolled asthma among all evaluated peripheral airways measures. Discrepancies in the performance (i.e. sensitivity and specificity) of each parameter suggest that a combination may be most effective in determining asthma control status.