Ligustrazine Inhibits Lung Phosphodiesterase Activity in a Rat Model of Allergic Asthma

Objectives. This study sought to examine whether ligustrazine was capable of inhibiting phosphodiesterase (PDE) activity and improving lung function in a rat model of asthma. Methods. Rats were initially sensitized using ovalbumin (OVA) and then were challenged daily with aerosolized OVA beginning 14 days later (30 min/day) to generate a rat model of asthma. Changes in airway function following methacholine (MCh) injection were evaluated by monitoring lung resistance ( R L ) and dynamic lung compliance ( C dyn ) values using an AniRes2005 analytic system. In addition, serum IgE was measured via ELISA, while PDE expression was evaluated via qPCR and western blotting. Key Findings. Ligustrazine significantly impaired allergen-induced lung hyperresponsivity and inflammation in this asthma model system. Ligustrazine treatment was also associated with reduced expression of PDEs including PDE4 in the lungs of these rats. Conclusions. Ligustrazine suppresses airway inflammation and bronchial hyperresponsivity in this rat model system, and these changes are associated with decreased PDE expression at the protein and mRNA levels.

A new noninvasive method for measurement of dynamic lung compliance from fluctuations on photoplethysmography in respiration.

Lung compliance is important in interstitial lung disease (ILD) as a marker of lung sclerosis. However, the measurement requires placement of an esophageal pressure probe, and is therefore not done routinely in clinic. This study was performed to develop and verify a new noninvasive method for estimation of dynamic lung compliance (Cdyn) using a photoplethysmograph (PPG), and to examine its usefulness. A system for measuring Cdyn in combination with changes in estimated pleural pressure (Ppl) from the fluctuations on PPG with respiration and lung volume measured simultaneously by spirometry was developed, and verified to show correspondence with the estimated Ppl and the esophageal pressure (Pes) (healthy adult volunteers (HS); n = 3), and estimated Cdyn and Cdyn measured using an esophageal balloon (HS; n = 28, COPD; n = 14, ILD; n = 10). Further, the estimated Cdyn was compared among HS (n = 33), COPD (n = 31), and ILD (n = 30). Both the estimated Ppl and Cdyn were significantly correlated with the Pes (r = 0.89) and measured Cdyn (r = 0.63), respectively. The estimated Cdyn in ILD showed significant lower values than those in HS and COPD. The estimated Cdyn was significantly related to %VC (r = 0.56, P < 0.01) and %DLCO (r = 0.52, P < 0.01) in patients with ILD. These findings suggested that the newly developed noninvasive and convenient method for estimation of Cdyn using a combination of PPG and spirometry may be useful for the assessment of lung sclerosis in ILD.

Mechanisms of Orthopnoea in Patients with Advanced COPD

Many patients with severe chronic obstructive pulmonary disease (COPD) report unpleasant respiratory sensation at rest, further amplified by adoption of supine position (orthopnoea). The mechanisms of this acute symptomatic deterioration are poorly understood.16 patients with advanced COPD and history of orthopnoea and 16 age- and sex-matched healthy controls (CTRL) underwent pulmonary function tests and detailed sensory-mechanical measurements including inspiratory neural drive (IND, diaphragm electromyography), oesophageal and gastric pressures in sitting and supine positions.Patients had severe airflow obstruction (FEV1: 40±18%predicted) and lung hyperinflation. Regardless of the position, patients had lower inspiratory capacity (IC) and higher IND for a given tidal volume (i.e. greater neuromechanical dissociation (NMD)), higher intensity of breathing discomfort, minute ventilation (⩒E) and breathing frequency (Fb) compared with CTRL (all p<0.05). In supine position in CTRL (versus sitting erect): IC increased (by 0.48L) with a small drop in ⩒E mainly due to reduced Fb (all p<0.05). By contrast, patients’ IC remained unaltered, but dynamic lung compliance decreased (p<0.05) in the supine position. Breathing discomfort, inspiratory work of breathing, inspiratory effort, IND, NMD and neuro-ventilatory uncoupling all increased in COPD in the supine position (p<0.05), but not in CTRL. Orthopnoea was associated with acute changes in IND (r=0.65, p=0.01), neuro-ventilatory uncoupling (r=0.76, p=0.001) and NMD (r=0.73, p=0.002).In COPD, onset of orthopnoea coincided with an abrupt increase in elastic loading of the inspiratory muscles in recumbency in association with increased IND and greater neuromechanical dissociation of the respiratory system.

Pseudomonas aeruginosa induced acute emphysema through bacterial secretion in mice

Pulmonary emphysema is the major pathological feature of chronic obstructive pulmonary disease (COPD). Although the pathogenesis of emphysema is still not completely understood, but until now a bacterial cause has not really been considered. Recently, we found that the secretion from Pseudomonas aeruginosa could cause severe lung emphysema in mice rapidly. Since the bacterium is ubiquitous and secrets proteases, we hypothesized that direct P. aeruginosa airway infection would have a similar effect. To address this issue, we applied a unilateral lung injury model. First, we observed the dynamic pathophysiology change of acute emphysema. P. aeruginosa secretion was extracted and instilled intratracheally into the left lungs of C57BL/6 and C3H/HeJ mice, while the right lungs were saved as self-control. Alveolar diameter and lung compliance were measured. Later, we tested the effect of P. aeruginosa inoculation in normal C57BL/6 mice, immunosuppressed C57BL/6 mice, and C3H/HeJ (TLR4 deficient) mice. P. aeruginosa secretion extract caused acute panacinar emphysema and decreased dynamic lung compliance. Different types of emphysema are transformable. However, the P. aeruginosa infection could only elicit emphysema in immunosuppressed C57BL/6 mice and C3H/HeJ mice, indicating that normal immunity is essential to protect the hosts from emphysema. Emphysema induced by P. aeruginosa in mice recapitulates all the main features of human emphysema and COPD. Our finding filled a major gap in COPD pathogenesis. We believe P. aeruginosa is the underlying cause of COPD.

Lung ultrasound score as an indicator of dynamic lung compliance during veno-venous extra-corporeal membrane oxygenation

Decisions on weaning from veno-venous extra-corporeal membrane oxygenation (VV-ECMO) requires the ability to maintain adequate gas exchange and work of breathing with reductions in ECMO pump flow and fresh gas flow. Testing of the readiness to wean the patient from ECMO however may vary dependent upon local protocols and clinical judgment. This study sought to validate the use of the LUS-score during VV-ECMO against the changes in chest x-ray infiltrates, dynamic lung compliance (CLdyn) and VV-ECMO settings (as standard measures of native lung function and the level of ECMO support) during the ECMO cycle. This prospective cohort study of 10 patients on VV-ECMO compared the LUS score (range 0–36) within 48-h, day 5 and day 10 of commencement of ECMO (or on the day of ECMO decannulation) to dynamic lung compliance, Murray Lung Injury Score and ECMO settings. Seven Male and three Female patients were included (average age 37 years (SD 14.8) and weight 71 Kg (SD 16.9). Median (IQR) duration of ECMO, ICU and hospital length of stay was 7.5 days (5.2–19.0), 12.5 days (8.5–22.7), 19.0 days (12.1– 36.1), respectively. There was a strong negative association between LUS-score and dynamic lung compliance (rs(33) = –0.66, p < .001) providing some validation on the use of the LUS score as a potential surrogate measure of lung aeration and lung mechanics during VV-ECMO weaning.

Volume of Tidal Gas Movement in the Nonventilated Lung during One-lung Ventilation and its Relevant Factors

Background: The passive ventilation of nonventilated lung results in tidal gas movement (TGM) and thus affects lung collapse. The present study aimed to measure the volume of TGM and to analyse the relevant factors of the TGM index (TGM/body surface area).Methods: One hundred eight patients scheduled for elective thoracoscopic surgeries were enrolled. Lung isolation was achieved with a double-lumen endobronchial tube (DLT). The paediatric spirometry sensor was connected to the double-lumen connector of the nonventilated lung to measure the volume of TGM during one-lung ventilation (OLV) in the lateral position. The TGM index was calculated. The multiple linear regression was analysed using the TGM index as the dependent variables. Independent variables were also recorded: 1) age, sex, body mass index (BMI); 2) forced vital capacity (FVC), FEV1/FVC, minute ventilation volume (MVV); 3) dynamic lung compliance (Cdyn) and peak inspiratory pressure (PIP) during dual lung ventilation; 4) the side of OLV; and 5) whether lung puncture for localization of the pulmonary nodule was performed on the day of surgery. The oxygen concentration in the nonventilated lung was measured at 5 min after OLV, and its correlation with the TGM index was analysed.Results: The volume of TGM in the nonventilated lung during OLV was 78 [37] mL. The TGM index was 45 [20] mL/m2 and was negatively correlated with the oxygen concentration in the nonventilated lung at 5 min after OLV. The multiple linear regression model for the TGM index was deduced as follows: TGM index (mL/m2)=C+12.770×a-3.987×b-1.237×c-2.664×d, where C is a constant 95.621 mL/m2, a is 1 for males and 0 for females, b is 1 for right OLV and 0 for left OLV, c is BMI (kg/m2), and d is PIP (cmH2O).Conclusions: The TGM index is negatively correlated with the oxygen concentration of the nonventilated lung at 5 min after OLV. Sex, side of OLV, BMI and PIP are independently correlated with the TGM index.Trial registration: This study was registered at ChiCTR (www.chictr.org.cn, ChiCTR1900024220) on July 1, 2019.Key Words: tidal gas movement, TGM index, one-lung ventilation, lung collapse, double-lumen endobronchial tube, dynamic lung compliance, thoracoscopy

Volume of Tidal Gas Movement in the Nonventilated Lung during One-lung Ventilation and its Relevant Factors

Background: The passive ventilation of nonventilated lung results in tidal gas movement (TGM) and thus affects lung collapse. The present study aimed to measure the volume of TGM and to analyse the relevant factors of the TGM index (TGM/body surface area).Methods: One hundred eight patients scheduled for elective thoracoscopic surgeries were enrolled. Lung isolation was achieved with a double-lumen endobronchial tube (DLT). The paediatric spirometry sensor was connected to the double-lumen connector of the nonventilated lung to measure the volume of TGM during one-lung ventilation (OLV) in the lateral position. The TGM index was calculated. The multiple linear regression was analysed using the TGM index as the dependent variables. Independent variables were also recorded: 1) age, sex, body mass index (BMI); 2) forced vital capacity (FVC), FEV1/FVC, minute ventilation volume (MVV); 3) dynamic lung compliance (Cdyn) and peak inspiratory pressure (PIP) during dual lung ventilation; 4) the side of OLV; and 5) whether lung puncture for localization of the pulmonary nodule was performed on the day of surgery. The oxygen concentration in the nonventilated lung was measured at 5 min after OLV, and its correlation with the TGM index was analysed.Results: The volume of TGM in the nonventilated lung during OLV was 78 [37] mL. The TGM index was 45 [20] mL/m2 and was negatively correlated with the oxygen concentration in the nonventilated lung at 5 min after OLV. The multiple linear regression model for the TGM index was deduced as follows: TGM index (mL/m2)=C+12.770×a-3.987×b-1.237×c-2.664×d, where C is a constant 95.621 mL/m2, a is 1 for males and 0 for females, b is 1 for right OLV and 0 for left OLV, c is BMI (kg/m2), and d is PIP (cmH2O).Conclusions: The TGM index is negatively correlated with the oxygen concentration of the nonventilated lung at 5 min after OLV. Sex, side of OLV, BMI and PIP are independently correlated with the TGM index.Trial registration: This study was registered at ChiCTR (www.chictr.org.cn, ChiCTR1900024220) on July 1, 2019.Key Words: tidal gas movement, TGM index, one-lung ventilation, lung collapse, double-lumen endobronchial tube, dynamic lung compliance, thoracoscopy

Volume of Tidal Gas Movement in the Nonventilated Lung during One-lung Ventilation and its Relevant Factors

Background: The passive ventilation of nonventilated lung results in tidal gas movement (TGM) and thus affects lung collapse. The present study aimed to measure the volume of TGM and to analyse the relevant factors of the TGM index (TGM/body surface area).Methods: One hundred eight patients scheduled for elective thoracoscopic surgeries were enrolled. Lung isolation was achieved with a double-lumen endobronchial tube (DLT). The paediatric spirometry sensor was connected to the double-lumen connector of the nonventilated lung to measure the volume of TGM during one-lung ventilation (OLV) in the lateral position. The TGM index was calculated. The multiple linear regression was analysed using the TGM index as the dependent variables. Independent variables were also recorded: 1) age, sex, body mass index (BMI); 2) forced vital capacity (FVC), FEV1/FVC, minute ventilation volume (MVV); 3) dynamic lung compliance (Cdyn) and peak inspiratory pressure (PIP) during dual lung ventilation; 4) the side of OLV; and 5) whether lung puncture for localization of the pulmonary nodule was performed on the day of surgery. The oxygen concentration in the nonventilated lung was measured at 5 min after OLV, and its correlation with the TGM index was analysed.Results: The volume of TGM in the nonventilated lung during OLV was 78 [37] mL. The TGM index was 45 [20] mL/m2 and was negatively correlated with the oxygen concentration in the nonventilated lung at 5 min after OLV. The multiple linear regression model for the TGM index was deduced as follows: TGM index (mL/m2)=C+12.770×a-3.987×b-1.237×c-2.664×d, where C is a constant 95.621 mL/m2, a is 1 for males and 0 for females, b is 1 for right OLV and 0 for left OLV, c is BMI (kg/m2), and d is PIP (cmH2O).Conclusions: The TGM index is negatively correlated with the oxygen concentration of the nonventilated lung at 5 min after OLV. Sex, side of OLV, BMI and PIP are independently correlated with the TGM index.Trial registration: This study was registered at ChiCTR (www.chictr.org.cn, ChiCTR1900024220) on July 1, 2019.Key Words: tidal gas movement, TGM index, one-lung ventilation, lung collapse, double-lumen endobronchial tube, dynamic lung compliance, thoracoscopy