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Aim: To determine if children with neonatal cholestatic liver disease had concurrent and later findings on brain imaging studies that could be attributed and the cholestasis to contribute to the understanding of the impaired neuropsychological development. Methods: Ovid MEDLINE and EMBASE were searched on July 21, 2022, and updated on March 26, 2023. Studies with children under 18 years of age with neonatal cholestasis and a brain scan at the time of diagnosis or later in life were included. Excluded studies were non-English, non-human, reviews or conference abstracts. Data were extracted on demographics, brain imaging findings, treatment and outcome. The results were summarised by disease categories. Risk of bias was assessed using JBI critical appraisal tools. Results: The search yielded 12 011 reports, of which 1261 underwent full text review and 89 were eligible for inclusion. Haemorrhage was the most common finding, especially in children with bile duct obstruction, including biliary atresia. Some findings were resolved after liver transplantation. Conclusion: Children with neonatal cholestasis had changes in brain imaging, which might play a role in impaired neuropsychological development, but longitudinal clinical research with structured assessment is needed to better qualify the aetiology of the impairment. [ABSTRACT FROM AUTHOR]

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if patients with COPD have reduced pulmonary blood volume (PBV) evaluated by 82Rb-positron emission tomography (PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6,301 82Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-yr period. We compared 77 patients with COPD with 44 healthy kidney donors (controls). Cardiac output ( Q ˙ ) and mean 82Rb bolus transit time (MBTT) were used to calculate PBV. Q ˙ was similar at rest (COPD: 3,649 ± 120 mL vs. control: 3,891 ± 160 mL, P = 0.368) but lower in patients with COPD compared with controls during adenosine infusion (COPD: 5,432 ± 124 mL vs. control: 6,185 ± 161 mL, P < 0.050). MBTT was shorter in patients with COPD compared with controls at rest (COPD: 8.7 ± 0.28 s vs. control: 11.4 ± 0.37 s, P < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 s vs. control: 10.2 ± 0.37 s, P < 0.014). PBV was lower in patients with COPD, even after adjustment for body surface area, sex, and age at rest [COPD: 530 (29) mL vs. 708 (38) mL, P < 0.001] and during adenosine infusion [COPD: 826 (29) mL vs. 1,044 (38) mL, P < 0.001]. In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact. NEW & NOTEWORTHY: The present study demonstrated that patients with chronic obstructive pulmonary disease (COPD) exhibit central hypovolemia compared with healthy controls. Pulmonary blood volume may thus be a relevant physiological and/or clinical outcome measure in future COPD studies. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of the study was to assess the validity of the hematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) and of pulmonary comorbidity prior to HCT in terms of predicting non‐relapse mortality (NRM) and overall survival (OS). Methods: In this retrospective single‐center study of 663 consecutive adult recipients of HCT, we stratified patients into groups by pulmonary comorbidity: low‐risk, intermediate‐risk, and high‐risk. The predictive value of this pulmonary comorbidity score (PCS) was compared to HCT‐CI. Results: In univariate analysis, the HCT‐CI and the PCS were associated with OS after transplantation when comparing patients in high‐risk groups with patients in low‐risk groups. Using the PCS, the hazard ratios (HRs) of the 2‐year OS in the entire population and in the myeloablative conditioning (MAC) group were 1.98 (p <.001) and 3.27 (p <.001), respectively, whereas the HRs using the HCT‐CI were 1.83 (p <.001) and 2.57 (p =.002). The 2‐year NRM incidence in the three risk‐groups in the entire population was significant using both indexes. In the MAC group, the 2‐year NRM was significant using the PCS (p =.003), but not using the HCT‐CI (p =.23). Conclusions: Our study suggest that pulmonary function alone is a strong predictor of 2‐year OS and NRM after HCT. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?The use of proning for improving pulmonary gas exchange in critically ill patients.What advances does it highlight?Proning places the lung in its 'natural' posture, and thus optimises the ventilation‐perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life‐threatening hypoxaemia in COVID‐19 and other types of critical illness with respiratory failure. The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID‐19‐associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation‐perfusion (V̇A--Q̇${\dot V_{\rm{A}}}\hbox{--}\dot Q$) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral‐to‐dorsal) V̇A/Q̇${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical V̇A/Q̇${\dot V_{\rm{A}}}/\dot Q$ ratio gradient is present in both postures, but with better V̇A--Q̇${\dot V_{\rm{A}}}\hbox{--}\dot Q$ matching in the prone position. In ARDS and CARDS, the vertical V̇A/Q̇${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life‐threatening hypoxaemia in patients with ARDS and CARDS. [ABSTRACT FROM AUTHOR]

Background: Impaired lung function is a well‐known risk factor in cardiac surgery patients and reduced forced expiratory volume in 1 second (FEV1) is associated with increased mortality. However, there is limited knowledge regarding the influence of impaired diffusing capacity of the lungs for carbon monoxide (DLCO) in unselected cardiac surgery patients. The aim of this study was to investigate the association of impaired DLCO and/or reduced FEV1 on post‐operative mortality and morbidity in cardiac surgery patients. Methods: In a prospective cohort study, 390 patients scheduled for elective cardiac surgery underwent preoperative lung function test including spirometry and DLCO measurements. We defined reduced FEV1 as FEV1 below lower limit of normal (LLN) and impaired DLCO as DLCO <60% of predicted. Results: Mortality within 1 year (90‐570 days) was significantly higher in patients with impaired DLCO (12% vs 3%, P =.010) and with reduced FEV1 (9% vs 3%, P =.028). Mortality was higher in patients with impaired DLCO both in the presence and absence of FEV1 < LLN. In multivariate analysis, only impaired DLCO [OR: 3.3, 95% confidence interval (CI) 1.4‐7.5; P =.005] and age (OR: 1.1 per year, 95% CI 1.0‐1.2; P =.001) were independent predictors of the combined outcome of mortality and prolonged intensive care unit (ICU) stay. Impaired DLCO was also associated with post‐operative respiratory complications. Conclusion: In patients undergoing elective cardiac surgery, preoperative impaired FEV1 and DLCO were associated with increased mortality and morbidity. In multivariate analysis, only DLCO and age were independent predictors of a combined outcome of mortality and prolonged ICU stay. [ABSTRACT FROM AUTHOR]

Introduction: Whole-body plethysmography is the preferred method for measuring the static lung volumes: total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV), as it also incorporates trapped gas - a common finding in chronic obstructive pulmonary disease (COPD). Quantitative computed tomography (CT) is a promising alternative to plethysmography, which can be challenging to perform for patients with severely impaired lung function. The present systematic review explores the agreement between lung volumes measured by plethysmography and CT, as well as the attempts being made to optimize alignment between these two methods., Methods: A literature search was performed on the PubMed database using the block search strategy. Articles were included if they provided both CT based and plethysmography based TLC. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) checklist., Results: 22 articles were included. On average, CT-derived TLC (CT-TLC) was 709 mL lower compared to plethysmography TLC (p-TLC) with a 12.1% deviation from the reference standard, p-TLC. This discrepancy (ΔTLC) appeared slightly larger in obstructive patients (obstructive: 781 mL, non-obstructive: 609 mL), whereas percent deviation was slightly smaller (obstructive: 11.4%, non-obstructive: 13.5%). CT-based RV analyses primarily based on COPD patients measured 603 mL higher than plethysmography (p-RV) with 17.8% deviation from p-RV. Studies utilizing spirometry-gating for CT acquisition reported good agreement between modalities (ΔTLC: 70-280 mL), and one study demonstrated noticeable improvements compared to conventional breath-hold instructions in an otherwise identical study setting., Conclusion: CT quantifications routinely underestimate TLC and overestimate RV in comparison to plethysmography. Spirometry gating reduces the level of disagreement and can be of assistance when patients are already undergoing CT. However, further studies are needed to confirm these results., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Primary ciliary dyskinesia (PCD) is a genetic disorder caused by aberrant motile cilia function that results in defective ciliary airway clearance and subsequently to recurrent airway infections and bronchiectasis., Question: How many functional multiciliated airway cells are sufficient to maintain ciliary airway clearance?, Methods: To answer this question we exploited the molecular defects of the X-linked recessive PCD variant caused by pathogenic variants in DNAAF6 ( PIH1D3 ), characterized by immotile cilia in the affected males. We carefully analyzed the clinical phenotype, molecular defect (immunofluorescence and transmission-electron microscopy) and performed in vitro (particle tracking in air-liquid interface cultures) and in vivo (radiolabeled tracer studies) studies to assess ciliary clearance of respiratory cells from females with heterozygous and males with hemizygous pathogenic DNAAF6 variants., Results: PCD males with hemizygous pathogenic DNAAF6 variants displayed exclusively immotile cilia, absence of ciliary clearance and severe PCD symptoms. Due to random or skewed X-chromosome inactivation in six females with heterozygous pathogenic DNAAF6 variants, 54.3%±10 (range 38%-70%) of multiciliated cells were defective. Nevertheless, in vitro and in vivo assessment of the ciliary airway clearance was normal or slightly abnormal. Consistently, heterozygous female individuals showed no or only mild respiratory symptoms., Conclusions: Our findings indicate that 30%-62% of functioning multiciliated respiratory cells are able to generate either normal or slightly reduced ciliary clearance. Because heterozygous females displayed either no or subtle respiratory symptoms, complete correction of 30% of cells by precision medicine might be able to improve ciliary airway clearance in PCD individuals as well as clinical symptoms., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Aim: To determine if children with neonatal cholestatic liver disease had concurrent and later findings on brain imaging studies that could be attributed and the cholestasis to contribute to the understanding of the impaired neuropsychological development., Methods: Ovid MEDLINE and EMBASE were searched on July 21, 2022, and updated on March 26, 2023. Studies with children under 18 years of age with neonatal cholestasis and a brain scan at the time of diagnosis or later in life were included. Excluded studies were non-English, non-human, reviews or conference abstracts. Data were extracted on demographics, brain imaging findings, treatment and outcome. The results were summarised by disease categories. Risk of bias was assessed using JBI critical appraisal tools., Results: The search yielded 12 011 reports, of which 1261 underwent full text review and 89 were eligible for inclusion. Haemorrhage was the most common finding, especially in children with bile duct obstruction, including biliary atresia. Some findings were resolved after liver transplantation., Conclusion: Children with neonatal cholestasis had changes in brain imaging, which might play a role in impaired neuropsychological development, but longitudinal clinical research with structured assessment is needed to better qualify the aetiology of the impairment., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if patients with COPD have reduced pulmonary blood volume (PBV) evaluated by 82 Rb-positron emission tomography (PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6,301 82 Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-yr period. We compared 77 patients with COPD with 44 healthy kidney donors (controls). Cardiac output ([Formula: see text]) and mean 82 Rb bolus transit time (MBTT) were used to calculate PBV. [Formula: see text] was similar at rest (COPD: 3,649 ± 120 mL vs. control: 3,891 ± 160 mL, P = 0.368) but lower in patients with COPD compared with controls during adenosine infusion (COPD: 5,432 ± 124 mL vs. control: 6,185 ± 161 mL, P < 0.050). MBTT was shorter in patients with COPD compared with controls at rest (COPD: 8.7 ± 0.28 s vs. control: 11.4 ± 0.37 s, P < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 s vs. control: 10.2 ± 0.37 s, P < 0.014). PBV was lower in patients with COPD, even after adjustment for body surface area, sex, and age at rest [COPD: 530 (29) mL vs. 708 (38) mL, P < 0.001] and during adenosine infusion [COPD: 826 (29) mL vs. 1,044 (38) mL, P < 0.001]. In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact. NEW & NOTEWORTHY The present study demonstrated that patients with chronic obstructive pulmonary disease (COPD) exhibit central hypovolemia compared with healthy controls. Pulmonary blood volume may thus be a relevant physiological and/or clinical outcome measure in future COPD studies.

Background: Primary ciliary dyskinesia (PCD) is an inherited disorder in which dyskinetic cilia cause impaired mucociliary clearance of upper and lower airways. Airway ciliary movement can be indirectly tested in vivo after administration of a radiolabelled tracer to the lower airways for assessment of pulmonary mucociliary clearance or to the nose for assessing nasal mucociliary clearance (NMC). With this study, we investigated NMC as a quantifiable study outcome parameter in patients with PCD., Material and Methods: This single centre proof-of-concept study on NMC velocity investigated patients with PCD across different genotypes and nasal nitric oxide (nasal NO) levels. Healthy controls were used for comparison. NMC was determined as velocity in mm·min -1 of a nasally applied 99m Tc-albumin colloid tracer. Using a gamma camera, repeated dynamic series of images each lasting 30 s were acquired during a 10-minute period and digitally stored., Results: NMC velocity was investigated in seven patients with PCD (aged 9-31 years) and five adult healthy controls. Mean NMC velocity in healthy controls (8.5 mm·min -1 ) was significantly higher compared with people with PCD (0.00 mm·min -1 , p<0.0001). NMC was completely absent in all included patients with PCD across different PCD genotypes and regardless of nasal NO values. The success rate of the test was 100% in both groups., Conclusion: NMC velocity discriminated highly significantly between patients with PCD and healthy controls. We suggest here a fast and feasible set up for NMC measurements that is easily applicable for any clinical trial involving PCD medication aimed for the nasal compartment, a step before or parallel to conducting clinical trials investigating whole-lung ciliary function in PCD., Competing Interests: Conflict of interest: The authors J.K. Marthin, K.G. Nielsen and J. Mortensen have no conflicts of interests to disclose., (Copyright ©The authors 2023.)

Background: Impaired lung function is a well-known risk factor in cardiac surgery patients and reduced forced expiratory volume in 1 second (FEV 1 ) is associated with increased mortality. However, there is limited knowledge regarding the influence of impaired diffusing capacity of the lungs for carbon monoxide (DLCO) in unselected cardiac surgery patients. The aim of this study was to investigate the association of impaired DLCO and/or reduced FEV 1 on post-operative mortality and morbidity in cardiac surgery patients., Methods: In a prospective cohort study, 390 patients scheduled for elective cardiac surgery underwent preoperative lung function test including spirometry and DLCO measurements. We defined reduced FEV 1 as FEV 1 below lower limit of normal (LLN) and impaired DLCO as DLCO <60% of predicted., Results: Mortality within 1 year (90-570 days) was significantly higher in patients with impaired DLCO (12% vs 3%, P = .010) and with reduced FEV 1 (9% vs 3%, P = .028). Mortality was higher in patients with impaired DLCO both in the presence and absence of FEV 1  < LLN. In multivariate analysis, only impaired DLCO [OR: 3.3, 95% confidence interval (CI) 1.4-7.5; P = .005] and age (OR: 1.1 per year, 95% CI 1.0-1.2; P = .001) were independent predictors of the combined outcome of mortality and prolonged intensive care unit (ICU) stay. Impaired DLCO was also associated with post-operative respiratory complications., Conclusion: In patients undergoing elective cardiac surgery, preoperative impaired FEV 1 and DLCO were associated with increased mortality and morbidity. In multivariate analysis, only DLCO and age were independent predictors of a combined outcome of mortality and prolonged ICU stay., (© 2021 Acta Anaesthesiologica Scandinavica Foundation.)