Comparison of Forced Oscillation Technique, Lung Volumes by Body Plethysmography, and Spirometry in Moderate Persistent Adult Asthma.

BACKGROUND: Spirometry is used extensively, but airway oscillometry is gaining acceptance for evaluating obstructive airway disorders. Moderate persistent asthma requires daily treatment with inhaled corticosteroids (ICS). MATERIALS AND METHODS: We aimed to examine the relationship between airway oscillometry and lung volumes, which are the markers of lung physiology in obstructive airway disease and spirometry in the real-world clinical setting. A total of 72 adults with moderate persistent asthma followed up in our outpatient department from November 2021 to August 2022, and their clinical details and tests of spirometry, forced oscillation technique (FOT), and lung volumes by body plethysmography (BP) performed before and after bronchodilator administration were analyzed. RESULTS: The mean age of the study population was 40 years, and the majority (57%) were females. FOT detected airflow limitation in 12 of the 31 patients with normal spirometry. BP detected abnormalities in more patients than both spirometry and FOT (91.6 vs 73.6%, p < 0.001). Respiratory resistance 5 (R5) had a negative correlation with functional residual capacity (FRC) and total lung capacity (TLC). Reactance 5 (X5) correlated positively with inspiratory capacity (IC) and TLC and negatively with reserve volume (RV)/TLC ratio. A positive correlation was found between IC/TLC% and postbronchodilator X5 and between R5 and 19 and RV/TLC. R5 had a negative and X5 had a positive correlation with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, and maximal mid expiratory flow rates (MMEF). ∇X5 had a negative correlation with FEV1, MMEF, and FEV1/FVC. Spirometry detected postbronchodilator responsiveness in more patients than FOT when only the R5 criterion was used and in a comparable number when the X5 criterion was added. ∇X5 and R5-R19/R5 declined significantly after bronchodilators. CONCLUSION: We concluded that there is a moderate correlation between FOT and spirometry and lung volumes by BP. FOT and spirometry should be used together to identify airflow obstruction and postbronchodilator responsiveness in asthma. Lung volumes by BP identify more abnormalities in adults with asthma than both spirometry and FOT. Thresholds to define postbronchodilator responsiveness (PBDR) for ∇X5 and R5-R19 need to be defined.

Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome.

STUDY OBJECTIVES: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. METHODS: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. RESULTS: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. CONCLUSIONS: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies.

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.

Validity of the 6-Minute Walk Test in Patients with End-Stage Lung Diseases Wearing an Oronasal Surgical Mask in Times of the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: The 6-minute walk test (6MWT), as a clinical assessment tool for functional exercise capacity, is an integral component of lung allocation scores (LASs). In times of the coronavirus disease (COVID-19) pandemic, patients underwent 6MWTs wearing a surgical mask in ambulatory care. We investigated the impact of wearing a mask on 6-minute walk distances (6MWDs). METHOD: 6MWDs of 64 patients with end-stage lung diseases wearing an oronasal surgical mask were retrospectively compared to previously investigated 6MWDs of the same cohort, in a pre-COVID-19 pandemic era, without wearing a mask. Four patients were excluded due to a primary vascular disease, 29 patients due to clinically unstable pulmonary functions, and 1 patient due to a psychiatric disorder. RESULTS: The median age of the patients included was 55 (46-58) years; 15 (48%) were male. Ten (32.2%) were on the Eurotransplant lung transplant waiting list with a median LAS of 34.3 (31.9-36.2). Twenty (64.5%) patients had chronic obstructive pulmonary diseases, 7 (22.6%) had interstitial lung diseases, and 4 (12.9%) had other end-stage lung diseases. The mean 6MWD without versus with wearing a mask was 306.9 (101.9) versus 305.7 (103.8) m, with a mean difference of -1.19 m (95% confidence interval -13.4 to 11.03). The observed difference is statistically equivalent to zero (p < 0.001). No significant differences in 6MWDs were observed between the clinical groups. CONCLUSION: Wearing an oronasal surgical mask did not affect the 6MWDs of patients with advanced lung diseases. Therefore, a masked 6MWT appears to provide a reliable examination of functional exercise capacity in this cohort.

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.

Nebulization of epinephrine to reduce the severity of brachycephalic obstructive airway syndrome in dogs.

OBJECTIVE: To determine the preoperative and postoperative effect of nebulized epinephrine on brachycephalic obstructive airway syndrome (BOAS) severity in dogs. STUDY DESIGN: Prospective clinical study. SAMPLE POPULATION: Thirty-one client-owned pugs, French bulldogs, and English bulldogs with moderate to severe BOAS. METHODS: Whole body barometric plethysmography was used to determine BOAS severity (BOAS index; 0%-100%) prior to and after nebulization with 0.05 mg/kg epinephrine diluted in 0.9% saline preoperatively. The same protocol was repeated postoperatively (within 24 hours of surgery). RESULTS: Five dogs were excluded because they did not tolerate nebulization, and postoperative data were available for 13 dogs. Epinephrine nebulization resulted in a decreased BOAS index across all breeds of dog both before (9.6% [3.1% to -30.2%], n = 26) and after surgery (14.3% [0.9% to -24.3%], n = 13). The preoperative reduction in BOAS index was greater (17.3% [1.8% to -27.4%]) in dogs with a baseline BOAS index >70% (P = .006) and in pugs (16.9% [0.8% to -27.4%]) compared with French bulldogs (5.2% [3.1% to -30.2%], P = .03). Simple linear regression was used to identify a positive relationship between baseline BOAS index and reduction in BOAS index for pugs (n = 10, P = .001). Nausea was noted as a side effect in four dogs. CONCLUSION: Nebulized epinephrine reduced the BOAS index of dogs in this study. This effect was clinically significant in preoperative dogs with a BOAS index >70% and in dogs recovering from surgery. CLINICAL SIGNIFICANCE: This study provides evidence to support the use of nebulized epinephrine in the perioperative management of BOAS-affected dogs.

Cinnamon extract inhibits allergen-specific immune responses in human and murine allergy models.

BACKGROUND: Ceylon cinnamon has been shown to possess anti-inflammatory properties in many diseases including allergic inflammation. OBJECTIVE: The aim of this study was to analyse in more detail the effects of cinnamon extract (CE) and its major compounds p-cymene and trans-cinnamaldehyde (CA) on allergen-specific immune responses in vitro and in vivo. METHODS: Therefore, monocyte-derived mature dendritic cells (DC) from grass or birch pollen allergic donors were pulsed with the respective allergen in the presence or absence of CE, p-cymene, CA or the solvent ethanol and co-cultured with autologous CD4+ T cells. Furthermore, basophil activation test was performed with or without CE or ethanol treatment. For the in vivo experiments, BALB/c mice were immunized with ovalbumin (OVA) and orally treated with CE or ethanol. RESULTS: Addition of CE, p-cymene or CA, but not ethanol significantly inhibited DC maturation and subsequent allergen-specific T cell proliferation as well as Th1 and Th2 cytokine production. Sulphidoleukotriene release and CD63 expression by basophils were also significantly diminished after addition of CE. In vivo, treatment of OVA-sensitized mice with CE led to a significant shift from OVA-specific IgE towards IgG2a production and to a strong inhibition of OVA-specific proliferation. Moreover, airway inflammation as well as anaphylaxis after intranasal or systemic allergen challenge was significantly reduced in CE-treated mice. Furthermore, topical application of CE prevented calcipotriol-induced atopic dermatitis-like inflammation in these mice. CONCLUSIONS AND CLINICAL RELEVANCE: Taken together, our data indicate that the anti-inflammatory effect of cinnamon might be exploited for treatment of allergic inflammation, which needs to be further investigated.

Caffeine prevents prostaglandin E1-induced disturbances in respiratory control in neonatal rats: implications for infants with critical congenital heart disease.

Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-ß (PDGF-ß) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.

Progesterone decreases apnoea and reduces oxidative stress induced by chronic intermittent hypoxia in ovariectomized female rats.

NEW FINDINGS: What is the central question of this study? Does progesterone reduce the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory control and oxidative stress in the central nervous system in ovariectomized rats? What is the main finding and its importance? Progesterone does not prevent the elevation of arterial blood pressure in rats exposed to CIH, but normalizes respiratory control, and reduces cerebral oxidative stress. This study draws focus to a potential role of progesterone and the consequences of sleep apnoea in menopausal women. ABSTRACT: We tested the hypothesis that progesterone (Prog) reduces the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory chemoreflexes and oxidative stress in the central nervous system. Ovariectomized female rats were implanted with osmotic pumps delivering vehicle (Veh) or Prog (4 mg kg-1  day-1 ). Two weeks following the surgery, rats were exposed to room air (Air) or CIH (7 days, 10% O2 , 10 cycles h-1 , 8 h day-1 ). We studied three groups: Veh-Air, Veh-CIH and Prog-CIH. After the CIH exposures, we measured the mean arterial pressure (MAP; tail cuff) and assessed the frequency of apnoeas at rest and ventilatory responses to hypoxia and hypercapnia (whole body plethysmography). The activities of the pro-oxidant enzyme NADPH oxidase (NOX) and antioxidant enzymes superoxide dismutase (SOD; in mitochondrial and cytosolic fractions) and glutathione peroxidase (GPx), as well as the concentration of malondialdehyde (MDA), a marker of lipid peroxidation, were measured in brain cortex and brainstem samples. CIH exposure increased the MAP, the frequency of apnoeas, and the respiratory frequency response to hypoxia and hypercapnia. Prog did not prevent the CIH-induced elevation in MAP, but it reduced the CIH-induced frequency of apnoeas and increased hypoxic and hypercapnic ventilatory responses. In the brain cortex, CIH increased NOX activity, and decreased the cytosolic and mitochondrial SOD activities. These effects were prevented by Prog. NOX activity was increased by CIH in the brainstem, and this was also blocked by Prog. The study draws focus to the links between ovarian hormones and the consequences of sleep apnoea in women.

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.

Determining Static Hyperinflation in Patients with Severe Emphysema: Relation Between Lung Function Parameters and Patient-Related Outcomes.

BACKGROUND: Bronchoscopic lung volume reduction techniques are minor invasive treatment modalities for severely hyperinflated emphysema patients. The severity of static lung hyperinflation determines eligibility and success rate for these treatments. However, it is not exactly known what parameter should be used to optimally reflect hyperinflation. Commonly used parameters are residual volume (RV) and the RV/Total lung capacity (TLC) ratio. Other parameters reflecting hyperinflation are Inspiratory Capacity/TLC and forced vital capacity. OBJECTIVES: To define which of these function parameters is the most optimal reflection of hyperinflationin in relation to patient-related outcomes. METHODS: In a retrospective cohort study, data from measurements during baseline visits of eight studies were pooled. Primary outcomes were RV/TLC ratio and RV as percentage of predicted (RV%pred), both measured by bodyplethysmography, compared to the patient-related outcome variables: 6-min walk distance (6MWD), the St. George's Respiratory Questionnaire (SGRQ), and the modified Medical Research Council (mMRC). RESULTS: Two hundred seventy-four COPD patients (mean age 59 years; 66% female), FEV1 0.74 ± 0.28 L, RV 4.94 ± 1.06 L, 6MWD of 339 ± 95 m, were included in the analysis. Significant correlations (all p < 0.01) were found between RV%pred and 6MWD (r = - 0.358), SGRQ (r = 0.184), and mMRC (r = 0.228). Also, there was a significant correlation between RV/TLC ratio and 6MWD (r = - 0.563), SGRQ (r = 0.289) and mMRC (r = 0.354). Linear regression analyses showed that RV/TLC ratio was a better predictor of patient outcomes than RV%pred. CONCLUSION: This study demonstrates that both RV/TLC ratio and RV%pred are relevant indicators of hyperinflation in patients with severe emphysema in relation to patient-related outcomes. RV/TLC ratio is more strongly related to the patient-related outcomes than RV%pred.

Alteration of Swallowing and Ventilation Coordination in Respiratory Diseases in Small Mammals.

In human and animal, swallowing and ventilation are coordinated to avoid laryngeal penetration or tracheal aspiration, and respiration is interrupted during swallowing and resumes in the expiratory phase. Some respiratory diseases may alter this coordination due to impaired lung function. The aim of this study was to evaluate swallowing-ventilation coordination in unrestrained rats with pulmonary emphysema or with pulmonary fibrosis. Two protocols were performed in 38 male Sprague-Dawley rats (2-3 months, 250-300 g): pulmonary emphysema and pulmonary fibrosis. Ventilation during swallowing and swallowing-ventilation coordination were recorded using a whole-body plethysmography and video recordings. The rats were free to take water after 24 h without drinking. Compared to control groups, swallowing frequency was significantly higher in rats with pulmonary emphysema and there was a decrease of swallows during expiration in rats with pulmonary emphysema and in rats with pulmonary fibrosis. In this study, we show that respiratory diseases are associated with changes in swallowing-ventilation coordination and hypothesize that they increase the risk of aspiration.

Advanced Lung Disease in Patients with Cystic Fibrosis Is Associated with Low Diffusion capacity.

BACKGROUND: The single-breath diffusing capacity of the lungs (DLCOSB) test measures the extent to which carbon monoxide (CO) passes from the lung air sacs into the blood. The accessible alveolar volume (VASB) is measured by inert gas during a 10-second period. The single-breath transfer coefficient of the lung for carbon monoxide (KCOSB) is the DLCOSB divided by VASB. Cystic fibrosis (CF) disease comprises progressive airway obstruction with bronchiectasis and parenchyma fibrosis. Yet, the KCOSB appears insignificant in the assessment of pulmonary function in CF. OBJECTIVES: To challenge the precision of normal KCOSB in CF. METHODS: The authors collected pulmonary function tests (PFT) data from 74 confirmed CF patients (mean age 26 ± 10 years) with various levels of pulmonary disease severity. Tests included spirometry, DLCOBP, and body plethysmography (BP). Anatomical dead space was calculated by deducting anatomical dead space from total lung capacity TLC(BP) to establish alveolar volume (VABP) and to determine KCOBP. We also included individual data of arterial pCO2 blood-gas level. RESULTS: KCOSB values were normal or higher in most patients, regardless of patient FEV1 value (R2 = 0.2204; P < 0.02). In contrast, the measurements of KCOBP were low corresponding with low FEV1 values, and negatively correlated with the elevation of trapped air and pCO2 levels (R2 = 0.1383; P = 0.0133, P > 0.05, respectively). CONCLUSIONS: The 10- second perfusion time of the inert gas during DLCOSB represent the communicative alveolar volume in CF patients with advanced pulmonary disease. The findings justify the use of DLCOSB with the deterioration of FEV1 and elevation of pCO2 levels.

Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models.

The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channel expressed on capsaicin-sensitive afferents, immune and endothelial cells is activated by inflammatory mediators and exogenous irritants, e.g., endotoxins, nicotine, crotonaldehyde and acrolein. We investigated its involvement in acute and chronic pulmonary inflammation using Trpa1 gene-deleted (Trpa1-/-) mice. Acute pneumonitis was evoked by intranasal Escherichia coli endotoxin (lipopolysaccharide: LPS) administration, chronic bronchitis by daily cigarette smoke exposure (CSE) for 4 months. Frequency, peak inspiratory/expiratory flows, minute ventilation determined by unrestrained whole-body plethysmography were significantly greater, while tidal volume, inspiratory/expiratory/relaxation times were smaller in Trpa1-/- mice. LPS-induced bronchial hyperreactivity, myeloperoxidase activity, frequency-decrease were significantly greater in Trpa1-/- mice. CSE significantly decreased tidal volume, minute ventilation, peak inspiratory/expiratory flows in wildtypes, but not in Trpa1-/- mice. CSE remarkably increased the mean linear intercept (histopathology), as an emphysema indicator after 2 months in wildtypes, but only after 4 months in Trpa1-/- mice. Semiquantitative histopathological scores were not different between strains in either models. TRPA1 has a complex role in basal airway function regulation and inflammatory mechanisms. It protects against LPS-induced acute pneumonitis and hyperresponsiveness, but is required for CSE-evoked emphysema and respiratory deterioration. Further research is needed to determine TRPA1 as a potential pharmacological target in the lung.

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).

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.

Cardiopulmonary Exercise Testing Allows Discrimination Between Idiopathic Non-specific Interstitial Pneumonia and Idiopathic Pulmonary Fibrosis in Mild to Moderate Stages of the Disease.

It is unclear whether there are cardiopulmonary exercise testing (CPET) parameters which may indicate poor prognosis in the early course of fibrosing interstitial lung disease. 27 untreated consecutive subjects (13 idiopathic non-specific interstitial pneumonia (iNSIP), 14 idiopathic pulmonary fibrosis (IPF); 19 male; age 69 ± 10 years) were enrolled in this observational pilot study. Subjects underwent routine pulmonary function testing and CPET. Statistically, the t test and the Mann-Whitney-U test were applied in the presence of normal and non-normal distribution (according to Shapiro-Wilk), respectively. Analyzing the whole cohort, only mild functional impairments were determined. Comparison of iNSIP and IPF groups detected significant differences for the CPET parameters V'O2Peak[%pred] (p = 0.011), V'O2/kgPeak (p = 0.033), Watt[%pred] (p = 0.048), V'E/V'CO2 (Rest: p = 0.016; AT: p = 0.011; Peak: p = 0.019; Slope: p = 0.040), V'E/V'O2 (Rest: p = 0.033 AT: p = 0.014; Peak: p = 0.035). CPET parameters may indicate IPF-specific impairments even in mild disease. It may be hypothesized that these parameters are early biomarkers of poor prognosis.

Significant Differences in Body Plethysmography Measurements Between Hospitals in Patients Referred for Bronchoscopic Lung Volume Reduction.

During the evaluation of potential bronchoscopic lung volume reduction (BLVR) candidates in our hospital, we frequently observe patients with a lower residual volume (RV) value compared to the value measured in their referring hospital, although both measured by body plethysmography. We explored to what degree RV and other pulmonary function measurements match between referring hospitals and our hospital. We retrospectively analyzed a total of 300 patients with severe emphysema [38% male, median age 62 years (range 38-81), median forced expiratory volume in 1 s 29% (range 14-65) of predicted, and a median of 40 packyears (range 2-125)]. We measured a median RV of 4.47 l (range 1.70-7.57), which was a median 310 ml lower than in the referring hospitals (range - 3.04 to + 1.94), P < 0.001). In conclusion, this retrospective analysis demonstrated differences in RV measurements between different hospitals in patients with severe emphysema. Overestimation of RV can lead to unnecessary referrals for BLVR and potential treatment failures. To avoid disappointment and unnecessary hospital visits, it is important that body plethysmography measurements are accurately performed by applying preferably the unlinked method in these patients.

Validation of exercise testing and laryngeal auscultation for grading brachycephalic obstructive airway syndrome in pugs, French bulldogs, and English bulldogs by using whole-body barometric plethysmography.

OBJECTIVE: To determine whether the sensitivity of clinical examination for assessing upper airway disease severity in 3 breeds of brachycephalic dogs can be improved by incorporating an exercise test (ET) or by auscultation of a laryngeal stridor to predict laryngeal collapse. STUDY DESIGN: Prospective clinical study. ANIMALS: Client-owned brachycephalic dogs (n = 44 ET; n = 57 laryngeal stridor assessment). METHODS: In the first part of the study, clinical examinations were performed at rest and after 5-minute walk and 3-minute trot tests, and a grade reflective of brachycephalic obstructive airway syndrome (BOAS) severity was assigned. Whole-body barometric plethysmography was used as a comparative, objective measure of disease severity. In the second part of the study, the degree of laryngeal collapse present in dogs undergoing BOAS surgery was compared to pre-exercise and postexercise laryngeal stridor detected during functional testing. RESULTS: The sensitivity of clinical examination for BOAS diagnosis was 56.7% pre-ET, 70% after a 5-minute walk test, and 93.3% after a 3-minute trot test. The sensitivity of laryngeal stridor as a predictor of laryngeal collapse was improved after exercise (70%) compared with before exercise (60%). Specificity of laryngeal stridor for laryngeal collapse was 100% (pre-exercise and postexercise). CONCLUSION: The sensitivity of clinical examination for BOAS diagnosis was improved by inclusion of an ET, particularly the 3-minute trot test. Audible laryngeal stridor was highly specific but only moderately sensitive for laryngeal collapse. CLINICAL SIGNIFICANCE: Inclusion of a 3-minute trot test and careful auscultation for laryngeal stridor are recommended during BOAS assessment of brachycephalic dogs.