Influence of acclimatization time on parameters of barometric whole-body plethysmography in healthy adult cats.

BACKGROUND: Pulmonary function testing by barometric whole-body plethysmography (BWBP) is a long-established and well-accepted, non-invasive investigative procedure in cats. HYPOTHESIS/OBJECTIVES: To evaluate, if different acclimatization times influence the measurement parameters of BWBP in healthy adult cats. ANIMALS: 48 healthy adult cats. METHODS: In the prospective observational study, healthy cats were placed in a measuring chamber and BWBP was performed over 30 minutes. Parameters obtained during the three measurement units of 10 minutes each (T1, T2 and T3) were compared. RESULTS: All measurement parameters except for tidal volume per body weight changed significantly (p<0.05) over the three time periods. From T1-T2, the parameters minute volume per body weight (p<0.001), peak inspiratory flow per body weight (p<0.001), peak expiratory flow per body weight (p = 0.002), pause (p = 0.03), enhanced pause (p = 0.03) and quotient of peak expiratory flow divided by expiratory flow at end expiratory volume plus 50% tidal volume (p = 0.03) changed significantly. From the time interval T2-T3, only respiratory rate (p = 0.02), inspiratory time (p = 0.02), expiratory time (p = 0.04), and relaxation time (p = 0.01) changed significantly. All measurement parameters except for tidal volume per body weight changed significantly (p<0.05) between T1 and T3. Age had a significant influence on all parameters except for peak expiratory flow per body weight and peak inspiratory flow per body weight. The parameters were not influenced by sex. CONCLUSION AND CLINICAL IMPORTANCE: All measurement parameters except tidal volume per body weight were significantly affected by acclimatization time. Controlling for age and sex, there was still a significant influence of acclimatization time on all parameters except for tidal volume per body weight. Standardization of the acclimatization time for future studies would be appropriate in order to maintain comparability.

Evaluation of barometric whole-body plethysmography for therapy monitoring in cats with feline lower airway disease.

OBJECTIVES: Feline lower airway disease (FLAD) is a common respiratory condition in cats. Traditionally, response to therapy is monitored only by evaluation of clinical signs and radiographic examination of the lungs. Barometric whole-body plethysmography (BWBP) is considered a non-invasive, well-tolerated form of measuring airway reactivity in cats. The aim of the study was to assess pulmonary function testing by BWBP for non-invasive evaluation of response to therapy in cats with FLAD and to investigate whether BWBP parameters correlate with clinical severity. MATERIAL AND METHODS: The prospective study included 25 client-owned cats, diagnosed with FLAD on the basis of their medical history, clinical signs, radiographic findings, and bronchoalveolar lavage fluid (BALF) examination. At three time points (day 0, 14, and 60), a standardised owner questionnaire, a clinical examination and BWBP measurements were carried out. Results of the questionnaire and the clinical examination were evaluated using a clinical 12-point score. Individual therapy was administered to all patients after diagnosis, based on the severity of disease and compliance of the cat. RESULTS: The total clinical score significantly improved over the entire study period (p<0.001). Significant improvement was detected for the frequency of coughing (p = 0.009), respiratory distress (p = 0.001), lung auscultation findings (p = 0.002), and general condition and appetite (p = 0.045). The BWBP parameter Penh, an indicator of bronchoconstriction, improved significantly under initial therapy between day 0 and 14 (p = 0.009). A significant correlation between Penh and the severity of auscultation findings was seen on day 0 (r = 0.40; p = 0.013). CONCLUSION: The study supports the role of Penh as a non-invasive parameter for monitoring initial treatment response in cats with FLAD. Further studies are needed to address whether other BWBP parameters might be suitable for non-invasive therapy monitoring of FLAD. Clinical evaluation is always essential in cats with FLAD to evaluate treatment response.

Normative reference equations of airway dynamics assessed by whole-body plethysmography during spontaneous breathing evaluated in infants, children, and adults.

Effective specific airway resistance (sReff ), its reciprocal the effective specific airway conductance (sGeff ) are computed as ratios between the integral of the resistive aerodynamic work of breathing (sWOB) and the integral of the tidal flow/volume loop, the reciprocal, respectively. Unfortunately, reference equations to obtain normative values for sReff , sGeff , and sWOB are not yet available. To assess reference equations for sWOB, sReff , and sGeff during tidal breathing at resting level in healthy infants, children, and adults by a multidimensional model. Retrospectively exported data were collected from databases of five Swiss lung function centers, in which plethysmography (Jaeger Würzburg, Germany) was performed for the assessment of airway dynamics, static lung volumes, and forced breathing flow-volume loops, in a collective of 28 healthy infants, 47 children, and 273 adults. From this cohort, reference equations were computed based on anthropometric measures, lung volumes, indices of the breathing pattern, and timing of breathing. By multi-linear modeling reference equations of sReff , sGeff , and sWOB could be defined taking as independent parameters apart from anthropometric parameters, also parameters given by the ratio between the tidal volume and functional residual capacity (FRCpleth /VT ), and the ratio between VT and inspiratory time (VT /TI ). An alternative statistical approach to define reference equations of airway dynamics reveals that apart from the subject's anthropometric measurements, parameters of the magnitude of static lung volumes, the breathing pattern, and the timing of breathing are co-variants of reference equations of airway dynamics over a large age range.

Comportamiento de volúmenes pulmonares estáticos por pletismografía en enfermedad pulmonar obstructiva crónica con disociación clínico-espirométrica / Behavior of static lung volumes due to plethysmography in chronic obstructive pulmonary disease with clinical-spirometric dissociation

Introducción: La enfermedad pulmonar obstructiva crónica es un problema sanitario mundial por su elevada prevalencia, morbilidad y cuantioso costo económico. Objetivo: Caracterizar mediante la pletismografía a los pacientes con diagnóstico de enfermedad pulmonar obstructiva crónica que presentaron una discrepancia clínica espirométrica. Métodos: Se realizó un estudio descriptivo y transversal en 33 pacientes con diagnóstico de enfermedad pulmonar obstructiva crónica que acudieron a consulta externa del Hospital Neumológico Benéfico Jurídico y el Centro de Investigaciones Clínicas. Se les realizaron volúmenes pulmonares por pletismografía corporal y espirometría en el período comprendido de noviembre 2016 a marzo 2018. Resultados: El sexo masculino (69,7 por ciento) resultó el más frecuente y el grupo de edad predominante fue mayor de 65 años (60,6 por ciento). El 41,2 por ciento de los pacientes presentaron grado de obstrucción moderadamente severo. La capacidad pulmonar total y el volumen residual fueron normales (72,7 por ciento y 42,5 por ciento) respectivamente. El 43,8 por ciento de los pacientes presentaron hiperinsuflación leve. El grado 3 de disnea fue el que predominó en los pacientes. El 12,1 por ciento de los pacientes presentaron aumento del volumen residual dado por atrapamiento aéreo grave con la disminución del volumen espiratorio forzado en el primer segundo. Conclusiones: El comportamiento de los volúmenes pulmonares por pletismografía corporal en la enfermedad pulmonar obstructiva crónica con disociación clínico-espirométrica, evidenció la disminución del volumen espiratorio forzado en el primer segundo y el aumento del volumen residual relacionándose con el grado de disnea(AU)

Introduction: Chronic obstructive pulmonary disease is a global health problem due to its high prevalence, morbidity and high economic cost. Objective: By using plethysmography, to describe patients with diagnosis of chronic obstructive pulmonary disease that had spirometric clinical discrepancy. Methods: A descriptive and cross-sectional study was carried out in 33 patients with diagnosis of chronic obstructive pulmonary disease who attended the outpatient clinic at Benéfico Jurídico Pneumologic Hospital and the Clinical Research Centre. Lung volumes were performed by body plethysmography and spirometry from November 2016 to March 2018. Results: The male sex (69.7 percent) was the most frequent and the predominant age group was older than 65 years (60.6 percent). 41.2 percent of the patients had moderately severe degree of obstruction. Total lung capacity and residual volume were normal, 72.7 percent and 42.5 percent, respectively. 43.8 percent of the patients had mild hyperinflation. Grade 3 dyspnea was the one that predominated in the patients. 12.1 percent of the patients showed increased residual volume due to severe air trapping with decreased forced expiratory volume in the first second. Conclusions: The behavior of lung volumes by body plethysmography in chronic obstructive pulmonary disease with clinical-spirometric dissociation, evidenced decrease in forced expiratory volume in the first second and increased in residual volume related to the degree of dyspnea(AU)

Noninvasive Measurement of Pulmonary Function in Experimental Mouse Models of Airway Disease.

Mouse models have become an indispensable tool in translational research of human airway disease and have provided much of our understanding of the pathogenesis of airway disease such as asthma. In these models the ability to assess pulmonary function and particularly airway responsiveness is critically important. Existing methods for testing pulmonary function in mice in vivo include noninvasive and invasive technologies. Noninvasive head-out body plethysmography is a well-established and widely accepted technique which has been proven as a reliable method to measure lung function on repeated occasions in intact, conscious mice. We have performed several validation studies in allergic mice to compare the parameter midexpiratory flow (EF50) as a noninvasive marker of airflow limitation with invasively measured gold standard parameters of lung mechanics. The results of these studies showed a good agreement of EF50 with the invasive assessment of lung resistance and dynamic compliance with a somewhat lower sensitivity of EF50. The measurement of EF50 together with basic respiratory parameters is particularly appropriate for simple and repeatable screening of pulmonary function in large numbers of mice or if noninvasive measurement without use of anesthesia is required. Beyond known applications, head-out body plethysmography also provides a much-needed high-throughput screening tool to gain insights into the impact and kinetics of respiratory infections such as SARS-COV-2 on lung physiology in laboratory mice.

Effect of Predicted Versus Measured Thoracic Gas Volume on Body Fat Percentage in Young Adults.

The BodPod® (COSMED, Concord, CA) uses predicted (pTGV) or measured thoracic gas volume (mTGV) during estimations of percentage body fat (%BF). In young adults, there is inconsistent evidence on the variation between pTGV and mTGV, and the effect of sex as a potential covariate on this relationship is unknown. This study examined the difference between TGV assessments and its effect on %BF and potential sex differences that may impact this relationship. A retrospective analysis of BodPod® pTGV and mTGV for 95 men and 86 women ages 18-30 years was performed. Predicted TGV was lower than mTGV for men (-0.49 ± 0.7 L; p < .0001). For men, %BF derived by pTGV was lower than that by mTGV (-1.3 ± 1.8%; p < .0001). For women, no differences were found between pTGV and mTGV (-0.08 ± 0.6 L; p > .05) or %BF (-0.03 ± 0.2%; p > .05). The two-predictor model of sex and height was able to account for 57.9% of the variance in mTGV, F(2, 178) = 122.5, p < .0001. Sex corrected for the effect of height was a significant predictor of mTGV (ß = 0.483 L, p < .0001). There is bias for pTGV to underestimate mTGV in individuals with a large mTGV, which can lead to significant underestimations of %BF in young adults; this was especially evident for men in this study. Sex is an important covariate that should be considered when deciding to use pTGV. The results indicate that TGV should be measured whenever possible for both men and women ages 18-30 years.

Simple low dose radiography allows precise lung volume assessment in mice.

X-ray based lung function (XLF) as a planar method uses dramatically less X-ray dose than computed tomography (CT) but so far lacked the ability to relate its parameters to pulmonary air volume. The purpose of this study was to calibrate the functional constituents of XLF that are biomedically decipherable and directly comparable to that of micro-CT and whole-body plethysmography (WBP). Here, we developed a unique set-up for simultaneous assessment of lung function and volume using XLF, micro-CT and WBP on healthy mice. Our results reveal a strong correlation of lung volumes obtained from radiographic XLF and micro-CT and demonstrate that XLF is superior to WBP in sensitivity and precision to assess lung volumes. Importantly, XLF measurement uses only a fraction of the radiation dose and acquisition time required for CT. Therefore, the redefined XLF approach is a promising tool for preclinical longitudinal studies with a substantial potential of clinical translation.

Functional role of carbon dioxide on intermittent hypoxia induced respiratory response following mid-cervical contusion in the rat.

Intermittent hypoxia induces respiratory neuroplasticity to enhance respiratory motor outputs and is a potential rehabilitative strategy to improve respiratory function following cervical spinal injury. The present study was designed to evaluate the functional role of intermittent and sustained carbon dioxide (CO2) on intermittent hypoxia-induced ventilatory responses in rats with mid-cervical spinal contusion. The breathing pattern of unanesthetized rats at the subchronic and chronic injured stages was measured in response to one of the following treatments: (1) Intermittent hypercapnic-hypoxia (10 × 5 min 10%O2 + 4%CO2 with 5 min normoxia interval); (2) Intermittent hypoxia with sustained hypercapnia (10 × 5 min 10%O2 + 4%CO2 with 5 min 21%O2 + 4%CO2 interval); (3) Intermittent hypoxia (10 × 5 min 10%O2 with 5 min normoxia interval); (4) Intermittent hypercapnia (10 × 5 min 21%O2 + 4%CO2 with 5 min normoxia interval); (5) Sustained hypercapnia (100 min, 21% O2 + 4% CO2); (6) Sustained normoxia (100 min, 21% O2). The results demonstrated that intermittent hypoxia associated with intermittent hypercapnia or sustained hypercapnia induced a greater ventilatory response than sustained hypercapnia during stimulus exposure. The tidal volume was significantly enhanced to a similar magnitude following intermittent hypercapnic-hypoxia, intermittent hypoxia with sustained hypercapnia, and intermittent hypoxia in subchronically injured animals; however, only intermittent hypercapnic-hypoxia and intermittent hypoxia were able to evoke long-term facilitation of the tidal volume at the chronic injured stage. These results suggest that mild intermittent hypercapnia did not further enhance the therapeutic effectiveness of intermittent hypoxia-induced respiratory recovery in mid-cervical contused animals. However, sustained hypercapnia associated with intermittent hypoxia may blunt ventilatory responses following intermittent hypoxia at the chronic injured stage.

The sensitivity and specificity of the forced oscillation technique in the diagnosis of bronchoconstriction in children.

OBJECTIVE: The forced oscillation technique (FOT) is a useful diagnostic respiratory system for children. However, the final value of the FOT in the diagnosis of bronchoconstriction is still open. The aim of the study was to evaluate the sensitivity and specificity of the FOT vs. body plethysmography tests in the measure of bronchoconstriction in asthmatic children. MATERIALS AND METHODS: A total of 102 children aged 2 to 6 years diagnosed with early-onset asthma and 52 healthy controls were included in this prospective, randomized study. All asthmatic patients and healthy controls underwent a basic FOT as one measurement, according to the recommendation of the Resmon Pro FOT. Then, the reversibility test was performed 20 min after the administration of 200 mg salbutamol using the FOT and body plethysmography in all patients. RESULTS: The mean basic Rrs, Xrs and sRaw in asthmatic patients were, respectively, 11.13 ± 1.28 kPa sL-1, -4.6 ± 1.18 kPa sL-1 and 1.72 ± 0.58 kPa s. Similar parameters were significantly better in the control group (p < 0.05). A total of 73 (71.6%) asthmatic patients had a positive test using the FOT according to Calogero. In 4 (7.7%) patients in the control group, a positive test was obtained. In body plethysmography, similar results were reached, with a positive test in 76 (74.5%) study patients and 5 (9.6%) control patients. CONCLUSIONS: A bronchial reversibility test with the use of the FOT is useful for the diagnosis of bronchial asthma, especially with the use of an Rrs parameter, such as the body plethysmography test.

Diagnostic accuracy of FeNO [fractional exhaled nitric oxide] and asthma symptoms increased when evaluated with a superior reference standard.

OBJECTIVES: The objective of the study is to determine the impact of changing reference standards (RS), namely spirometry vs. whole-body plethysmography (WBP), on estimation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and clinical signs and symptoms (CSS) as index tests regarding asthma diagnosis. STUDY DESIGN AND SETTING: This was a diagnostic study conducted in 393 patients attending a private practice of pneumologists with complaints suspicious of asthma. First, the index tests were compared with the diagnostic results of spirometry in terms of forced expiratory volume in the first second (FEV1) responsiveness. Second, the index tests were compared with the results of WBP in terms of specific airway resistance and FEV1 responsiveness. Areas under the curve (AUC) were compared with a generalized estimating equation approach based on binary logistic regression. RESULTS: FeNO values and CSS 'wheezing' and 'allergic rhinitis' showed higher specificities (P < 0.001) and sensitivities (not significant) when evaluated with WBP; also, Youden indices increased in these CSS (P < 0.05). AUC of FeNO in combination with 'wheezing' and 'allergic rhinitis' when WBP was used as RS (AUC = 0.724; 95% confidence interval 0.672 to 0.776) was higher compared with spirometry as RS (AUC = 0.654; 95% confidence interval 0.585 to 0.722) (P < 0.001). CONCLUSION: In case of asthma, superior RS led to more favorable assessment of index tests. FeNO measurement might have been underestimated in some previous studies.

Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae.

BACKGROUND: Since December 2019 the novel coronavirus disease 2019 (COVID-19) has been burdening all health systems worldwide. However, pulmonary and extrapulmonary sequelae of COVID-19 after recovery from the acute disease are unknown. MATERIAL AND METHODS: Hospitalized COVID-19 patients not requiring mechanical ventilation were included and followed 6 weeks after discharge. Body plethysmography, lung diffusion capacity (DLco), blood gas analysis (ABG), 6-min walk test (6MWT), echocardiography, and laboratory tests were performed. Quality of life (QoL), depression, and anxiety were assessed using validated questionnaires. RESULTS: 33 patients with severe disease were included. Patients were discharged without prophylactic anticoagulation. At follow-up there were no thromboembolic complications in any patient. 11 patients (33%) had dyspnea, 11 (33%) had cough, and 15 (45%) suffered from symptoms of fatigue. Pulmonary function tests including ABG did not reveal any limitations (TLC: median=94% of predicted {IQR:85-105}; VC: 93% {78-101}; FEV1: 95% {72-103}; FEV1/FVC 79% {76-85}; PaO2: 72 mmHg {67-79}; PaCO2: 38 mmHg {35-38}), except for slightly reduced DLco (77% {69-95}). There were no echocardiographic impairments. 6MWT distance was reduced in most patients without oxygen desaturation. According to standardized questionnaires, patients suffered from reduced QoL, mainly due to decreased mobility (SGRQ activity score: 54 {19-78}). There were no indicators for depression or anxiety (PHQ-9: 7 {4-11}, GAD-7: 4 {1-9}, respectively). CONCLUSIONS: Hospitalized patients with severe COVID-19, who did not require mechanical ventilation, are unlikely to develop pulmonary long-term impairments, thromboembolic complications or cardiac impairments after discharge but frequently suffer from symptoms of fatigue.

Correspondence between Capnovolumetric and Conventional Lung Function Parameters in the Diagnosis of Obstructive Airway Diseases.

BACKGROUND: Capnovolumetry is of interest as a method for the diagnosis of obstructive airway diseases, requiring little cooperation from the patient. OBJECTIVE: To help in the interpretation of capnovolumetric parameters, we aimed to identify their correspondence to conventional lung function indices. METHODS: We studied 978 patients from a diagnostic study with complete functional data and the clinical diagnosis of asthma, chronic obstructive pulmonary disease (COPD), or no respiratory disease. Using path analysis, four capnovolumetric parameters (slope of expiratory phase 3, ratio of slopes of phases 3 and 2, volume of phase 2, and the ratio area/volume of phase 3) previously identified as predictors of airway obstruction in terms of spirometry and body ple-thysmography, were analyzed regarding their relationship to each other and the diagnostic categories of asthma or COPD versus control, or obstruction versus no obstruction. We then identified four lung function parameters showing relationships as much as possible isomorphic to those between capnovolumetric parameters. RESULTS: The four capnovolumetric parameters were related to COPD and obstruction via both direct and indirect influences, but only two of them to asthma. Regarding the correspondence to lung function parameters, the slope of expiratory phase 3 corresponded best to the ratio of residual volume to total lung capacity, the ratio of slopes of phases 3 and 2 to forced expiratory volume in 1 s, the volume of phase 2 to forced expired flow at 50% of vital capacity, and the ratio area/volume of phase 3 to forced vital capacity. CONCLUSIONS: Our results indicated an intricate relationship of capnovolumetric parameters to each other and to airway obstruction, asthma, or COPD. The correspondence to conventional lung function measures seemed to reflect the entities lung hyperinflation, overall ventilatory impairment, bronchoconstriction, and ventilated lung volume, in that order. These findings might be helpful for clinicians in the interpretation of capnovolumetry.

P2X3 receptor antagonism reduces the occurrence of apnoeas in newborn rats.

Hyperreflexia of the peripheral chemoreceptors is a potential contributor of apnoeas of prematurity (AoP). Recently, it was shown that elevated P2X3 receptor expression was associated with elevated carotid body afferent sensitivity. Therefore, we tested whether P2X3 receptor antagonism would reduce AoP known to occur in newborn rats. Unrestrained whole-body plethysmography was used to record breathing and from this the frequency of apnoeas at baseline and following administration of either a P2X3 receptor antagonist - AF-454 (5 mg/kg or 10 mg/kg s.c.) or vehicle was derived. In a separate group, we tested the effects of AF-454 (10 mg/kg) on the hypoxic ventilatory response (10 % FiO2). Ten but not 5 mg/kg AF-454 reduced the frequency of AoP and improved breathing regularity significantly compared to vehicle. Neither AF-454 (both 5 and 10 mg/kg) nor vehicle affected baseline respiration. However, P2X3 receptor antagonism (10 mg/kg) powerfully blunted hypoxic ventilatory response to 10 % FiO2. These data suggest that P2X3 receptors contribute to AoP and the hypoxic ventilatory response in newborn rats but play no role in the drive to breathe at rest.

The hypoxia tolerance of eight related African mole-rat species rivals that of naked mole-rats, despite divergent ventilatory and metabolic strategies in severe hypoxia.

AIMS: Burrowing mammals tend to be more hypoxia tolerant than non-burrowing mammals and rely less on increases in ventilation and more on decreases in metabolic rate to tolerate hypoxia. Naked mole-rats (Heterocephalus glaber, NMRs), eusocial mammals that live in large colonies, are among the most hypoxia-tolerant mammals, and rely almost solely on decreases in metabolism with little change in ventilation during hypoxia. We hypothesized that the remarkable hypoxia tolerance of NMRs is an evolutionarily conserved trait derived from repeated exposure to severe hypoxia owing to their burrow environment and eusocial colony organization. METHODS: We used whole-body plethysmography and indirect calorimetry to measure the hypoxic ventilatory and metabolic responses of eight mole-rat species closely related to the NMR. RESULTS: We found that all eight species examined had a strong tolerance to hypoxia, with most species tolerating 3 kPa O2 , Heliophobius emini tolerating 2 kPa O2 and Bathyergus suillus tolerating 5 kPa O2 . All species examined employed a combination of increases in ventilation and decreases in metabolism in hypoxia, a response midway between that of the NMR and that of other fossorial species (larger ventilatory responses, lesser reductions in metabolism). We found that eusociality is not fundamental to the physiological response to hypoxia of NMRs as Fukomys damarensis, another eusocial species, was among this group. CONCLUSIONS: Our data suggest that, while the NMR is unique in the pattern of their physiological response to hypoxia, eight closely related mole-rat species share the ability to tolerate hypoxia like the current "hypoxia-tolerant champion," the NMR.

Diagnostic accuracy of capnovolumetry for the identification of airway obstruction - results of a diagnostic study in ambulatory care.

BACKGROUND: One of the known weaknesses of spirometry is its dependence on patients' cooperation, which can only partially be alleviated by educational efforts. Therefore, procedures less dependent on cooperation might be of value in clinical practice. We investigated the diagnostic accuracy of ultrasound-based capnovolumetry for the identification of airway obstruction. METHODS: Consecutive patients from a pulmonary outpatient clinic were included in the diagnostic study. As reference standard, the presence of airway obstruction was evaluated via spirometry and bodyplethysmography. Capnovolumetry was performed as index test with an ultrasound spirometer providing a surrogate measure of exhaled carbon dioxide. Receiver operating characteristic (ROC) analysis was performed using the ratio of slopes of expiratory phases 3 and 2 (s3/s2) ≥ 0.10 as primary capnovolumetric parameter for the recognition of airway obstruction. Logistic regression was performed as secondary analysis to identify further useful capnovolumetric parameters. The diagnostic potential of capnovolumetry to identify more severe degrees of airway obstruction was evaluated additionally. RESULTS: Of 1400 patients recruited, 1287 patients were included into the analysis. Airway obstruction was present in 29% of patients. The area under the ROC-curve (AUC) of s3/s2 was 0.678 (95% CI 0.645, 0.710); sensitivity of s3/s2 ≥ 0.10 was 47.7 (95% CI 42.7, 52.8)%, specificity 79.0 (95% CI 76.3, 81.6)%. When combining this parameter with three other parameters derived from regression analysis (ratio area/volume phase 3, slope phase 3, volume phase 2), an AUC of 0.772 (95% CI 0.743, 0.801) was obtained. For severe airway obstruction (FEV1 ≤ 50% predicted) sensitivity of s3/s2 ≥ 0.10 was 75.9 (95% CI 67.1, 83.0)%, specificity 75.8 (95% CI 73.3, 78.1)%; for very severe airway obstruction (FEV1 ≤ 30% predicted) sensitivity was 86.7 (95% CI 70.3, 94.7)%, specificity 72.8 (95% CI 70.3, 75.2)%. Sensitivities increased and specificities decreased considerably when the combined capnovolumetric score was used as index test. CONCLUSIONS: Capnovolumetry by way of an ultrasound spirometer had a statistically significant albeit moderate potential for the recognition of airway obstruction in a heterogeneous population of patients typically found in clinical practice. Diagnostic accuracy of the capnovolumetric device increased with the severity of airway obstruction. TRIAL REGISTRATION: The study is registered under DRKS00013935 at German Clinical Trials Register (DRKS).

Correlation of spirometry and body plethysmography during exercise-induced bronchial obstruction.

BACKGROUND: The exercise challenge is the gold standard for diagnosing exercise-induced bronchoconstriction (EIB). Airway obstructions appear up to 30 min after the challenge, with a maximum decrease in spirometry and a maximum increase in airway resistance. There is evidence that changes in body plethysmography parameters are more sensitive to the exercise challenge and precede those in spirometry. PURPOSE: To compare changes in body plethysmography and spirometry parameters after exercise challenges and to verify the cut-off values of sReff in EIB. PROCEDURES: In 82 subjects with suspected EIB, a total of 473 lung function tests were measured at baseline and at 5, 10, 15, and 30 min after exercise challenges at different stages of bronchial obstruction. FINDINGS: The maximum changes in the body plethysmography parameter sReff significantly preceded the maximum changes in the spirometry parameter FEV1 (sReff: 12.2 min ±8.8, FEV1: 15.2 min ±9.3, p < 0.005). The parameters of sReff and FEV1 had a strong negative correlation (r = -0.63, p < 0.0001) with a nonlinear, polynomial relationship. Furthermore, sReff and Reff had a strong linear correlation (r = 0.86, p < 0.001), and Reff and Rtot had a perfect linear correlation (r = 0.99, p < 0.001). Based on baseline values and on quantile regression, an increase of 0.25 kPa s in sReff was defined as significant. Using this cut-off value, FEV1 and sReff almost equally detected EIB. CONCLUSION: The changes in sReff were more sensitive and better indicated lung impairment than did the changes in FEV1, which underestimated the degree of hyperinflation.

Whole-Body Plethysmography and Blood Gas Analysis in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD) often occur together. However, COPD is underdiagnosed among CHD patients. OBJECTIVES: This study investigated the prevalence of COPD and relevant pulmonary function test (PFT) impairments in patients with acute myocardial infarction (AMI). METHODS: Patients undergoing coronary angiography for AMI were prospectively included. Body plethysmography, lung diffusing capacity, blood gas analysis, and echocardiography were performed. The following patient subgroups were compared: with versus without COPD, ST elevation myocardial infarction (STEMI) versus non-STEMI (NSTEMI). The prevalence of PFT impairments was also recorded. RESULTS: A total of 100 patients (51 with NSTEMI, 49 with STEMI) were included. Twenty patients had diagnosed COPD, of whom 15 were diagnosed for the first time; 80% of all COPD patients were not receiving COPD therapy. Patients with COPD had higher maximum creatine kinase (p = 0.008) and troponin T (p = 0.054) levels than those without COPD. Hypoxaemia was more common in COPD patients (lower oxygen saturation [p = 0.008] and partial pressure of oxygen [PaO2] [p = 0.005]). PaO2 was significantly lower in STEMI compared with NSTEMI (p = 0.017). Independent of a COPD diagnosis, 65 patients had relevant PFT impairments. CONCLUSIONS: The high prevalence of undiagnosed COPD and relevant pulmonary function impairments in this cohort of patients with AMI, and the fact that pulmonary disease was untreated in the majority of COPD patients, highlight the importance of a general pulmonary workup of patients with AMI. Furthermore, patients with CHD should undergo screening for COPD, given the fact that COPD patients had larger infarction size.

Effect of Thoracic Epidural Anesthesia in a Rat Model of Phrenic Motor Inhibition after Upper Abdominal Surgery.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: One important example of impaired motor function after surgery is diaphragmatic dysfunction after upper abdominal surgery. In this study, the authors directly recorded efferent phrenic nerve activity and determined the effect of the upper abdominal incision. The authors hypothesized that phrenic motor output would be decreased after the upper abdominal incision; it was also hypothesized that blocking sensory input from the incision using thoracic epidural anesthesia would diminish this incision-induced change in phrenic motor activity. METHODS: Efferent phrenic activity was recorded 1 h to 10 days after upper abdominal incision in urethane-anesthetized rats. Ventilatory parameters were measured in unanesthetized rats using whole-body plethysmography at multiple time points after incision. The authors then determined the effect of thoracic epidural anesthesia on phrenic nerve activity and ventilatory parameters after incision. RESULTS: Phrenic motor output remained reduced by approximately 40% 1 h and 1 day after incision, but was not different from the sham group by postoperative day 10. One day after incision (n = 9), compared to sham-operated animals (n = 7), there was a significant decrease in spike frequency area-under-the-curve (median [interquartile range]: 54.0 [48.7 to 84.4] vs. 97.8 [88.7 to 130.3]; P = 0.0184), central respiratory rate (0.71 [0.63 to 0.79] vs. 0.86 [0.82 to 0.93]/s; P = 0.0460), and inspiratory-to-expiratory duration ratio (0.46 [0.44 to 0.55] vs. 0.78 [0.72 to 0.93]; P = 0.0023). Unlike humans, a decrease, not an increase, in breathing frequency has been observed after the abdominal incision in whole-body plethysmography. Thoracic epidural anesthesia attenuated the incision-induced changes in phrenic motor output and ventilatory parameters. CONCLUSIONS: Upper abdominal incision decreased phrenic motor output and ventilatory parameters, and this incision-induced impairment was attenuated by thoracic epidural anesthesia. The authors' results provide direct evidence that afferent inputs from the upper abdominal incision induce reflex inhibition of phrenic motor activity.

Respiratory-induced hemodynamic changes measured by whole-body multichannel impedance plethysmography.

The cardiovascular system is described by parameters including blood flow, blood distribution, blood pressure, heart rate and pulse wave velocity. Dynamic changes and mutual interactions of these parameters are important for understanding the physiological mechanisms in the cardiovascular system. The main objective of this study is to introduce a new technique based on parallel continuous bioimpedance measurements on different parts of the body along with continuous blood pressure, ECG and heart sound measurement during deep and spontaneous breathing to describe interactions of cardiovascular parameters. Our analysis of 30 healthy young adults shows surprisingly strong deep-breathing linkage of blood distribution in the legs, arms, neck and thorax. We also show that pulse wave velocity is affected by deep breathing differently in the abdominal aorta and extremities. Spontaneous breathing does not induce significant changes in cardiovascular parameters.

Skeletal, cardiac, and respiratory muscle function and histopathology in the P448Lneo- mouse model of FKRP-deficient muscular dystrophy.

BACKGROUND: Fukutin-related protein (FKRP) mutations are the most common cause of dystroglycanopathies known to cause both limb girdle and congenital muscular dystrophy. The P448Lneo- mouse model has a knock-in mutation in the FKRP gene and develops skeletal, respiratory, and cardiac muscle disease. METHODS: We studied the natural history of the P448Lneo- mouse model over 9 months and the effects of twice weekly treadmill running. Forelimb and hindlimb grip strength (Columbus Instruments) and overall activity (Omnitech Electronics) assessed skeletal muscle function. Echocardiography was performed using VisualSonics Vevo 770 (FujiFilm VisualSonics). Plethysmography was performed using whole body system (ADInstruments). Histological evaluations included quantification of inflammation, fibrosis, central nucleation, and fiber size variation. RESULTS: P448Lneo- mice had significantly increased normalized tissue weights compared to controls at 9 months of age for the heart, gastrocnemius, soleus, tibialis anterior, quadriceps, and triceps. There were no significant differences seen in forelimb or hindlimb grip strength or activity monitoring in P448Lneo- mice with or without exercise compared to controls. Skeletal muscles demonstrated increased inflammation, fibrosis, central nucleation, and variation in fiber size compared to controls (p < 0.05) and worsened with exercise. Plethysmography showed significant differences in respiratory rates and decreased tidal and minute volumes in P448Lneo- mice (p < 0.01). There was increased fibrosis in the diaphragm compared to controls (p < 0.01). Echocardiography demonstrated decreased systolic function in 9-month-old mutant mice (p < 0.01). There was increased myocardial wall thickness and mass (p < 0.001) with increased fibrosis in 9-month-old P448Lneo- mice compared to controls (p < 0.05). mRNA expression for natriuretic peptide type A (Nppa) was significantly increased in P448Lneo- mice compared to controls at 6 months (p < 0.05) and for natriuretic peptide type B (Nppb) at 6 and 9 months of age (p < 0.05). CONCLUSIONS: FKRP-deficient P448Lneo- mice demonstrate significant deficits in cardiac and respiratory functions compared to control mice, and this is associated with increased inflammation and fibrosis. This study provides new functional outcome measures for preclinical trials of FKRP-related muscular dystrophies.