Circulating markers of extracellular matrix remodelling in severe COVID-19 patients

Background Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 patients. Methods Serial blood samples were obtained from two cohorts of hospitalised COVID-19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3-month follow-up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60-day total mortality and pulmonary pathology after 3-months. We also evaluated the direct effect of inactivated SARS-CoV-2 on the release of the different ECM mediators in relevant cell lines. Results Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium-binding protein A12 and YKL-40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3-months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS-CoV-2 suggesting a direct link between these mediators and the causal agent of COVID-19. Conclusion Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL-40 in the pathogenesis of severe COVID-19

Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal (GI) tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. Methods: Plasma was collected during hospital admission and after three months from the NOR-Solidarity trial (n = 181) and analysed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analysed by sequencing the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal three months after hospitalisation. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalisation, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 -(P/F ratio)Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterationsacceptedVersio

Cardiorespiratory fitness on a treadmill in an adult cystic fibrosis population

Objectives: (1) To describe the cardiorespiratory fitness (CRF) in an adult cystic fibrosis population related to sex and age, (2) to evaluate the cause of low CRF and (3) to study the association between peak oxygen uptake (VO2peak) and forced expiratory volume in 1 s (FEV1). Methods: A total of 204 cardiopulmonary treadmill exercise tests (CPETs) performed by 116 patients were included. VO2peak, gas exchange, heart rate, oxygen saturation and ventilatory variables were measured. A low CRF was defined as a VO2peak <80% of predicted, ventilatory limitation was defined as a breathing reserve <15%, exercise hypoxaemia was defined as an oxygen saturation <88% and ventilation-perfusion mismatch was defined as a minute ventilation/ventilatory equivalent for carbon dioxide slope ≥34. In patients who had performed three or more CPETs, the annual change in FEV1 and VO2peak were calculated using linear regression. Results: The VO2peak was 40.6±11.5 and 35.2±8.9 mL kg−1 min−1, which was 87±23 and 93±20 in percentage of predicted for men and women, respectively. VO2peak was moderately affected by age, for men (r=−0.36, p<0.001) and women (r=−0.53, p<0.001), respectively. In 45 of 101 tests where CRF was low, no cardiorespiratory limiting factors were identified. The correlation coefficient between VO2peak and FEV1 was r=0.64 (p<0.001). In participants with a low CRF, FEV1 ranged from 20% to 112% of predicted. Conclusions: The correlation between VO2peak and FEV1 was moderate. The majority of the tests resulted in a VO2peak within normal limits. Interestingly, 44% of the tests with a low VO2peak could be explained by deconditioning. Thus, exercise therapy may be beneficial for these patients

Cardiorespiratory fitness on a treadmill in an adult cystic fibrosis population

Objectives (1) To describe the cardiorespiratory fitness (CRF) in an adult cystic fibrosis population related to sex and age, (2) to evaluate the cause of low CRF and (3) to study the association between peak oxygen uptake (VO 2 peak) and forced expiratory volume in 1 s (FEV 1 ). Methods A total of 204 cardiopulmonary treadmill exercise tests (CPETs) performed by 116 patients were included. VO 2 peak, gas exchange, heart rate, oxygen saturation and ventilatory variables were measured. A low CRF was defined as a VO 2 peak &lt;80% of predicted, ventilatory limitation was defined as a breathing reserve &lt;15%, exercise hypoxaemia was defined as an oxygen saturation &lt;88% and ventilation-perfusion mismatch was defined as a minute ventilation/ventilatory equivalent for carbon dioxide slope ≥34. In patients who had performed three or more CPETs, the annual change in FEV 1 and VO 2 peak were calculated using linear regression. Results The VO 2 peak was 40.6±11.5 and 35.2±8.9 mL kg −1 min −1 , which was 87±23 and 93±20 in percentage of predicted for men and women, respectively. VO 2 peak was moderately affected by age, for men (r=−0.36, p&lt;0.001) and women (r=−0.53, p&lt;0.001), respectively. In 45 of 101 tests where CRF was low, no cardiorespiratory limiting factors were identified. The correlation coefficient between VO 2 peak and FEV 1 was r=0.64 (p&lt;0.001). In participants with a low CRF, FEV 1 ranged from 20% to 112% of predicted. Conclusions The correlation between VO 2 peak and FEV 1 was moderate. The majority of the tests resulted in a VO 2 peak within normal limits. Interestingly, 44% of the tests with a low VO 2 peak could be explained by deconditioning. Thus, exercise therapy may be beneficial for these patients

Effect of Respiratory Events on Health-Related Quality of Life in Patients Treated with Long-Term Noninvasive Ventilation

Background: Long-term noninvasive ventilation (NIV) can increase or maintain health-related quality of life (HRQoL) for patients with chronic hypercapnic respiratory failure (CHRF). Evidence from studies systematically assessing how NIV-specific factors influence HRQoL is limited. Objectives: The objective of this study was to describe HRQoL measured by the Severe Respiratory Insufficiency Questionnaire (SRI) in patients with CHRF treated with long-term NIV and to analyze the associations between HRQoL and hypoxemia, hypercapnia, and respiratory events such as apneas, hypopneas (AHI), and patient ventilator asynchrony (PVA) occurring during long-term NIV. Methods: We included sixty-seven stable patients with established long-term NIV due to neuromuscular disease or thoracic cage disorders in a prospective cross-sectional study at Oslo University Hospital. Patients answered the SRI and underwent daytime arterial blood gases, nocturnal pulse oximetry, sleep polygraphy, and nocturnal transcutaneous CO2. Results: The mean global SRI for 62 patients was 64.8 ± 14.5, with the highest score in SRI Social Relationships (79.5 ± 15.6). There were no differences in HRQoL between the different patient groups. Compliant patients had a significantly higher score in SRI Attendant and Sleep. Residual nocturnal hypoxemia affected both the subscale SRI “Respiratory Complaints” and SRI “Attendant Symptoms and Sleep.” Persisting daytime hypercapnia, nocturnal hypoventilation, and high AHI affected the subscale SRI “Anxiety” negatively, while frequent PVA was associated with a lower score in SRI “Physical Function.” Conclusion: In a group of patients with long-term NIV, undesired respiratory events during NIV are associated with lower HRQoL in several of the SRI subscales. We suggest designing interventional studies to confirm the possible relationship between HRQoL and respiratory events during long-term NIV.</p

Measuring diaphragm movement and respiratory frequency using a novel ultrasound device in healthy volunteers

Purpose To evaluate the ability of a novel ultrasound (US) device, DiaMon, to monitor diaphragm movement via its proxy liver movement, and compare it with the respired flow measured with a flowmeter, in awake and healthy volunteers. We wanted to (1) establish the optimal anatomical position for attaching the DiaMon device to the abdominal wall, and (2) evaluate the accuracy of continuous monitoring of respiratory frequency. Methods Thirty healthy subjects were recruited. The DiaMon probe was applied subcostally in four different positions with the subjects in five different postures. The subjects breathed tidal volumes into a spirometer for 30–60 s with the DiaMon recording simultaneously. Results The device detected a readable signal in 83–100% of the position/posture-combinations. The technical correlation between the two signals was highest in the anterior axillary-supine position (mean ± SD: 0.95 ± 0.03), followed by paramidline-supine (0.90 ± 0.09) and midclavicular-supine (0.89 ± 0.12). The frequency measurements yielded a mean difference of 0.03 (95% limits of agreement − 0.11, 0.16) breaths per minute in the anterior axillary-supine position. Conclusion The DiaMon device is able to detect liver movement in most subjects, and it measures breathing frequency accurately

Validity of transcutaneous PCO2 in monitoring chronic hypoventilation treated with non-invasive ventilation

Non-invasive ventilation (NIV) is an efficient treatment for patients with chronic hypercapnic respiratory failure (CRF), but requires regular monitoring to detect both diurnal and nocturnal residual hypercapnia. The present study was designed to determine 1) whether transcutaneous PCO2 (PtcCO2) is a valid tool for monitoring PaCO2 in this group of patients, and 2) if overnight instrumental drift of the PtcCO2 sensor is clinically significant

Sleep related respiratory events during non-invasive ventilation of patients with chronic hypoventilation

Non-invasive ventilation (NIV) is increasingly used in the treatment of patients with chronic hypercapnic respiratory failure (CRF). Residual sleep related respiratory events under NIV such as obstructive or central apnea/hypopnea (AH), or patient-ventilator asynchrony (PVA), may compromise treatment efficacy and/or comfort

Diagnostic accuracy of simple tools in monitoring patients with chronic hypoventilation treated with non-invasive ventilation; a prospective cross-sectional study

To evaluate the sensitivity and specificity of a screening test panel for nocturnal hypoventilation (NH) and other sleep related respiratory events during monitoring of patients with chronic hypercapnic respiratory failure (CRF) treated with NIV