In the absence of appropriate medical care, exposure to organophosphorus nerve agents, such as VX, can lead to respiratory failure, and potentially death by asphyxiation. Despite the critical role of respiratory disturbances in organophosphorus-induced toxicity, the nature and underlying mechanisms of respiratory failure remain poorly understood. This study aimed to characterize respiratory alterations by determining their type and duration in mice exposed to a subcutaneous sublethal dose of VX. Respiratory ventilation in Swiss mice was monitored using dual-chamber plethysmography for up to 7 days post-exposure. Cholinesterase activity was assessed via spectrophotometry, and levels of inflammatory biomarkers were quantified using Luminex technology in blood and tissues involved in respiration (diaphragm, lung, and medulla oblongata). Additionally, a histological study was conducted on these tissues to ensure their structural integrity. Ventilatory alterations appeared 20-25 minutes after the injection of 0.9 LD50 VX and increased until the end of the recording, i.e., 40 minutes after intoxication. Concurrent with the occurrence of apnea, increased inspiratory and expiratory times resulted in a significant decrease in respiratory rate in exposed mice compared to controls. Ventilatory amplitude and, consequently, minute volume were reduced, while specific airway resistance significantly increased, indicating bronchoconstriction. These ventilatory effects persisted up to 24 or even 72 hours post-intoxication, resolving on the 7th day. They were correlated with a decrease in acetylcholinesterase activity in the diaphragm, which persisted for up to 72 hours, and with the triggering of an inflammatory reaction in the same tissue. No significant histologic lesions were observed in the examined tissues. The ventilatory alterations observed up to 72 hours post-VX exposure appear to result from a functional failure of the respiratory system rather than tissue damage. This comprehensive characterization contributes to a better understanding of the respiratory effects induced by VX exposure, which is crucial for developing specific medical countermeasures.

UNASSIGNED: Cardiopulmonary exercise testing (CPET) is nowadays used to study the exercise response in healthy subjects and in disease. Ventilatory efficiency is one of the main determinants in exercise tolerance, and its main variables are a useful tool to guide pathophysiologists toward specific diagnostic pathways, providing prognostic information and improving disease management, treatment, and outcomes.
UNASSIGNED: This review will be based on today\'s available scientific evidence, describing the main physiological determinants of ventilatory efficiency at rest and during exercise, and focusing also on how CPET variables are modified in specific diseases, leading to the possibility of early diagnosis and management.
UNASSIGNED: Growing knowledge on CPET interpretation and a wider use of this clinical tool is expected in order to offer more precise diagnostic and prognostic information to patients and clinicians, helping in the management of therapeutic decisions. Future research could be able to identify new and more simple markers of ventilatory efficiency, and to individuate new interventions for the improvement of symptoms, such as exertional dyspnea.

Current methods to diagnose and monitor COPD employ spirometry as the gold standard to identify lung function reduction with reduced forced expiratory volume (FEV1)/vital capacity (VC) ratio. Current methods utilise linear assumptions regarding airway resistance, where nonlinear resistance modelling may provide rapid insight into patient specific condition and disease progression. This study examines model-based expiratory resistance in healthy lungs and those with progressively more severe COPD.
Healthy and COPD pressure (P)[cmH2O] and flow (Q)[L/s] data is obtained from the literature, and 5 intermediate levels of COPD and responses are created to simulate COPD progression and assess model-based metric resolution. Linear and nonlinear single compartment models are used to identify changes in inspiratory (R1,insp) and linear (R1,exp)/nonlinear (R2Φ) expiratory resistance with disease severity and over the course of expiration.
R1,insp increases from 2.1 to 7.3 cmH2O/L/s, R1,exp increases from 2.4 to 10.0 cmH2O/L/s with COPD severity. Nonlinear R2Φ increases (mean R2Φ: 2.5 cmH2O/L/s (healthy) to 24.4 cmH2O/L/s (COPD)), with increasing end-expiratory nonlinearity as COPD severity increases.
Expiratory resistance is increasingly highly nonlinear with COPD severity. These results show a simple, nonlinear model can capture fundamental COPD dynamics and progression from regular breathing data, and such an approach may be useful for patient-specific diagnosis and monitoring.

Spinal cord injury (SCI) often results in impaired respiratory function. Paresis or paralysis of inspiratory and expiratory muscles can lead to respiratory dysfunction depending on the level and severity of the injury, which can affect the management and care of SCI patients. Respiratory dysfunction after SCI is more severe in high cervical injuries, with vital capacity (VC) being an essential indicator of overall respiratory health. Respiratory complications include hypoventilation, a reduction in surfactant production, mucus plugging, atelectasis, and pneumonia. Respiratory management includes mechanical ventilation and tracheostomy in high cervical SCI, while noninvasive ventilation is more common in patients with lower cervical and thoracic injuries. Mechanical ventilation can negatively impact the function of the diaphragm and weaning should start as soon as possible. Patients can sometimes be weaned from mechanical ventilation with assistance of electrical stimulation of the phrenic nerve or the diaphragm. Respiratory muscle training regimens may also improve patients\' inspiratory function following SCI. Despite the critical advances in preventing, diagnosing, and treating respiratory complications, they continue to significantly affect persons living with SCI. Additional studies of interventions to reduce respiratory complications are likely to further decrease the morbidity and mortality associated with these injuries.

Background and objectives Coronavirus disease 2019 (COVID-19) is mainly a disease of the respiratory system that can lead to acute respiratory distress syndrome (ARDS). The pathophysiology of COVID-19 ARDS and consequently its management is a disputable subject. Early COVID-19 investigators hypothesized that the pathogenesis of COVID-19 ARDS is different from the usual ARDS. The aim of this study was to describe the lung mechanics in mechanically ventilated COVID-19 patients with ARDS. Methodology An observational retrospective cohort study was conducted on adult COVID-19 patients with ARDS who needed mechanical ventilation in the ICU of Ohoud Hospital, Madinah, KSA, from June to September 2020. Data were collected from the patients\' medical charts and electronic medical records and analyzed using Statistical Package for the Social Sciences (SPSS) software package version 22 (IBM Corp., Armonk, NY) for descriptive statistical analysis. Measurements and main results A total of 52 patients were analyzed: on intubation, the median positive end-expiratory pressure (PEEP) was 10 cm H2O (IQR, 2.3-16), the median plateau pressure was 27 cm H2O (IQR, 12-40), and the median driving pressure was 17 cm H2O (IQR, 3-30). The median static compliance of the respiratory system was 24.7 mL/cm H2O (IQR, 12.8-153.3). 59.5% had severe ARDS (the PaO2/FiO2 ratio was less than 100 mmHg), and 33% had moderate ARDS (the PaO2/FiO2 ratio ranged from 100 to 200 mmHg). Conclusion Our results suggest that the lung mechanics in COVID-19 ARDS patients who need mechanical ventilation do not differ from non-COVID-19 patients.

Over the last decade interest has been shown in people with symptomatic lung disease who have features both of COPD and asthma. In this review we examine how COPD and asthma are defined and examine clinical characteristics of people defined by researchers as having asthma-COPD overlap (ACO). We look at pathological and physiological features along with symptoms and consider the impact of each diagnosis upon therapeutic management. We highlight challenges in the diagnosis and management of airway disease and the various phenotypes that could be part of ACO, in so doing suggesting ways for the clinician to manage patients with features of both asthma and COPD.

Plethysmographic alveolar pressure-flow (Palv-F) loops contain potentially relevant information about the pathophysiology of chronic obstructive pulmonary disease (COPD), but no quantitative analysis of these loops during spontaneous breathing has ever been performed. The area of the loop\'s inspiratory (Ains) and expiratory portion (Aexp), and the difference between the end-expiratory and end-inspiratory alveolar pressure (ΔPalv) were measured in 20 young, 20 elderly healthy subjects, and 130 stable COPD patients. Ains and ΔPalv increased by 55 and 78% from young to elderly subjects, and by 107 and 122% from elderly subjects to COPD patients, reflecting changes in mechanical heterogeneity, lung-units recruitment/derecruitment, and possibly air trapping occurring with aging and/or obstructive disease. Aexp increased by 38% from young to elderly subjects, and by 198% from elderly subjects to COPD patients, consistent with the additional contribution of tidal expiratory flow-limitation, which occurs only in COPD patients and affects Aexp only. In COPD patients, Aexp and ΔPalv showed a significant negative correlation with VC, FEV1, IC, and a significant positive correlation with RV/TLC. The results suggest that the analysis of plethysmographic Palv-F loops provides an insight of the pathophysiological factors, especially tidal expiratory flow-limitation, that affect lung function in COPD patients.