Ventilatory Impairment Research Articles

Prediction of respiratory impairment in myotonic dystrophies using the ‘Respiratory involvement symptom checklist’ (Respicheck)

Chronic hypoventilation due to involvement of respiratory muscles is a frequent symptom in autosomal dominant inherited myotonic dystrophies, especially in type 1 (DM1), leading to a severely reduced quality of life, an early need for ventilatory support, or premature death. Thus, early knowledge of respiratory muscle weakness is essential to initiate further diagnostic and therapeutic measures.To get early, simple, and reliable information about respiratory impairment in DM patients, we performed a prospective controlled cohort study with DM1 and DM2 patients analysing the suitability of ‘Respiratory involvement symptom checklist (Respicheck) as a clinically meaningful screening questionnaire for ventilatory impairment in patients with DM1 or DM2. Clinical assessments included a one-time pulmonary function test (spirometry and manometry) and the completion of the Respicheck.172 participants were enrolled in this study (74 DM1, 72 DM2, 26 healthy controls). With a cut-off RespicheckCAT score of 4, the Respicheck can distinguish between patients with and without respiratory impairment with higher sensitivity and positive predictive value for DM1 than DM2 patients (DM1: sensitivity 77–87; positive predictive value 50–94%; DM2: sensitivity 67–80%; positive predictive value 14–38).In summary, our results confirm a clinically meaningful use of the Respicheck to detect respiratory impairments predominantly in DM1 patients.

The effectiveness of the respiratory muscles in children with oncohematological diseases after hematopoietic stem cell transplantation

The article analyzes the effectiveness of the respiratory muscles by measuring inspiratory mouth occlusion pressure at 0.1 seconds during quiet breathing (P0.1) and maximum voluntary ventilation maneuver (P0.1 max ) in children with acute leukemia and acquired idiopathic aplastic anemia after allogeneic hematopoietic stem cell transplantation (HSCT). We carried out a comparative analysis of the Р0.1 and Р0.1 max values measured before HSCТ and on days +30, +90, +180 and +360. In a group of patients with acquired idiopathic aplastic anemia, we revealed a significant decrease in these values starting from day +30, followed by a recovery to baseline values by one year of follow-up. In children with acute leukemia, effectiveness of the respiratory muscles was increased after 360 days of transplantation as a result of the aggravation of impaired ventilation. This method for measuring airway occlusion pressure can be used in a comprehensive assessment of the functional state of the respiratory system for the timely diagnosis of pulmonary complications after HSCT. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation.

Associations between the muscle quality index and adult lung functions from NHANES 2011-2012.

The muscle quality index (MQI), as an important component of sarcopenia, is defined as the ratio of muscle strength to muscle mass. Lung function, is a clinical indicator to assess ventilation and air exchange function. This study investigated the relationship between lung function indices and MQI in the NHANES database from 2011 to 2012. This study included 1,558 adults from the National Health and Nutrition Examination Survey from 2011 to 2012. Muscle mass and muscle strength were assessed using DXA and handgrip strength, and all participants underwent pulmonary function measurements. Multiple linear regression and multivariable logistic regression were used to assess the correlation between the MQI and lung function indices. In the adjusted model, MQI was significantly correlated with FVC% and PEF%. And, after quartiles of MQI in Q3, where FEV1%, FVC%, and PEF% were all associated with MQI, in Q4, a lower relative risk of a restrictive spirometry pattern was linked to increased MQI. Compared to the lower age group, the relationship between the MQI and lung function indices was more significant in the higher age group. There was an association between the MQI and lung function indices. Furthermore, in the middle-aged and older adult populations, lung function indicators and restrictive ventilation impairment were significantly associated with MQI. This implies that improving lung function through muscle training may be beneficial to this group.

Seizures Cause Prolonged Impairment of Ventilation, CO2 Chemoreception and Thermoregulation.

Sudden unexpected death in epilepsy (SUDEP) has been linked to respiratory dysfunction, but the mechanisms underlying this association remain unclear. Here we found that both focal and generalized convulsive seizures (GCSs) in epilepsy patients caused a prolonged decrease in the hypercapnic ventilatory response (HCVR; a measure of respiratory CO2 chemoreception). We then studied Scn1a R1407X/+ (Dravet syndrome; DS) and Scn8a N1768D/+ (D/+) mice of both sexes, two models of SUDEP, and found that convulsive seizures caused a postictal decrease in ventilation and severely depressed the HCVR in a subset of animals. Those mice with severe postictal depression of the HCVR also exhibited transient postictal hypothermia. A combination of blunted HCVR and abnormal thermoregulation is known to occur with dysfunction of the serotonin (5-hydroxytryptamine; 5-HT) system in mice. Depleting 5-HT with para-chlorophenylalanine (PCPA) mimicked seizure-induced hypoventilation, partially occluded the postictal decrease in the HCVR, exacerbated hypothermia, and increased postictal mortality in DS mice. Conversely, pretreatment with the 5-HT agonist fenfluramine reduced postictal inhibition of the HCVR and hypothermia. These results are consistent with the previous observation that seizures cause transient impairment of serotonergic neuron function, which would be expected to inhibit the many aspects of respiratory control dependent on 5-HT, including baseline ventilation and the HCVR. These results provide a scientific rationale to investigate the interictal and/or postictal HCVR as noninvasive biomarkers for those at high risk of seizure-induced death, and to prevent SUDEP by enhancing postictal 5-HT tone.SIGNIFICANCE STATEMENT There is increasing evidence that seizure-induced respiratory dysfunction contributes to the pathophysiology of sudden unexpected death in epilepsy (SUDEP). However, the cellular basis of this dysfunction has not been defined. Here, we show that seizures impair CO2 chemoreception in some epilepsy patients. In two mouse models of SUDEP we found that generalized convulsive seizures impaired CO2 chemoreception, and induced hypothermia, two effects reported with serotonergic neuron dysfunction. The defects in chemoreception and thermoregulation were exacerbated by chemical depletion of serotonin and reduced with fenfluramine, suggesting that seizure-induced respiratory dysfunction may be due to impairment of serotonin neuron function. These findings suggest that impaired chemoreception because of transient inhibition of serotonergic neurons may contribute to the pathophysiology of SUDEP.

L-DOPA Improves Ventilation but Not the Ventilatory Response to Hypercapnia in a Reserpine Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurological disorder characterized by progressive degeneration of the substantia nigra that affects mainly movement control. However, pathological changes associated with the development of PD may also alter respiration and can lead to chronic episodes of hypoxia and hypercapnia. The mechanism behind impaired ventilation in PD is unclear. Therefore, in this study, we explore the hypercapnic ventilatory response in a reproducible reserpine-induced (RES) model of PD and parkinsonism. We also investigated how dopamine supplementation with L-DOPA, a classic drug used to treat PD, would affect the breathing and respiratory response to hypercapnia. Reserpine treatment resulted in decreased normocapnic ventilation and behavioral changes manifested as low physical activity and exploratory behavior. The respiratory rate and the minute ventilation response to hypercapnia were significantly higher in sham rats compared to the RES group, while the tidal volume response was lower. All of this appears to be due to reduced baseline ventilation values produced by reserpine. L-DOPA reversed reduced ventilation, indicating a stimulatory effect of DA on breathing, and showed the potency of DA supplementation in restoring normal respiratory activity.

Combined Radiological and Endoscopic Evaluation of Sino Nasal Anatomical Variations in Patients of Chronic Rhinosinusitis: A North Indian Study.

To determine the prevalence of anatomical variations of nasal cavity and paranasal sinuses of patients with chronic rhinosinusitis (CRS) on CT scan imaging. To correlate the Anatomical variations with the extent of CRS. 100 patients attending the ENT outpatient department with clinically diagnosed CRS were selected for study based on inclusion and exclusion criteria. Patients were subjected to CT scan and diagnostic nasal endoscopy. The correlation of anatomical variation with severity of CRS based on radiological score and endoscopic score was observed. Deviated nasal septum was the most common anatomical variation observed in 71% cases. Followed by Agger nasi (68%), concha bullosa (55%), Onodi cell (25%), Haller cell (14%), frontal sinus hypoplasia (2%) and uncinate bulla (1%) respectively. Statistically significant relationship of radiological score with left side Bullous Concha Bullosa and highly statistically significant relationship with Haller Cell was observed. While statistically significant relationship between Deviated Nasal Septum on left side with endoscopic score was also observed. Correlation of anatomical variation with CRS concludes on the notethat some variations cause impaired sinus drainage and ventilation leading to recurrent sinusitis. Also, incidence of these variations was comparable to other studies done in asymptomatic population therefore, simply detection of a solitary anatomical variant itself does not determine predisposition to disease or the pathogenesis of the CRS and that we should have a critical look out for these anatomical variations from point of view of surgical management.

Considerations for perioperative opioid analgesic stewardship in Australia: a focus on tapentadol.

Opioid-related harm remains a serious public health issue in Australia, where there is a strong focus on judicious use of opioids to optimize postoperative patient outcomes. The risks associated with preoperative opioid use (worsened postoperative pain, surgical outcomes, increased length of stay and financial costs) must be balanced with the risks of sub-optimal post-surgical pain management (development of chronic pain, persistent postsurgical opioid use and opioid dependence). In addition to significantly lower rates of gastrointestinal adverse effects (nausea, vomiting, constipation), tapendatol (vs oxycodone) is less likely to cause excessive sedation and opioid-induced ventilatory impairment, may be associated with less withdrawal symptoms of mild to moderate intensity and significantly lower odds of 3-month persistent postoperative opioid use in certain patient populations. Studies included in this review were phase III/meta-analyses, referenced in Australian clinical guidelines and/or published ≤5years), except for cost-effectiveness analyses, where all known, relevant published analyses were included.

RESPIRATORY AND CIRCULATORY PROBLEMS OF COVID-19 IN THE CONTEXT OF ESTABLISHING INTENSIVE CARE UNIT NURSING DIAGNOSIS

Introduction: The novel coronavirus disease 2019 (COVID-19) is a virus that attacks the respiratory tract with rapid spread and high mortality. Initial reports that COVID-19 associated with critical care due to the severity of the disease requiring mechanical assistive devices in its treatment. The purpose to identify the nursing diagnosis related to respiratory and circulatory problems of COVID-19 in the critical care unit.
 Method: An integrative review highlights the issue that nursing problems related to respiratory and circulatory in COVID-19 patients admitted to the Intensive Care Unit (ICU). This study focuses on papers published from 2020 to 2021 using the keyword "clinical manifestation of COVID-19" which was accessed through the Pubmed database.
 Result: The results showed that findings in articles that were reviewed and integrated with the SDKI. Nursing diagnosis related to respiratory problems such as 1) Ineffective airway clearance; 2) Dysfunctional ventilatory weaning response; 3) Impaired gas exchange; 4) Impaired spontaneous ventilation. Nursing diagnosis related to circulatory problems such as 1) Risk / decreased cardiac output; 2) Risk for bleeding; 3) Risk for effective renal perfusion; 4) Risk for ineffective cerebral perfusion.
 Conclusion: Critical care nurses carry out a series of treatments based on the nursing process stages, one of which is the enforcement of a nursing diagnosis. The nursing diagnosis is needed to develop nursing plans and strategies for implementation so that the goals of nursing care are achieved.
 Keywords: covid-19, nursing diagnosis, intensive care unit

Multisystem Proteinopathies (MSP) and MSP-like Disorders: Clinical-Pathological-Molecular Spectrum and Long-term Follow Up (P5-8.004)

<h3>Objective:</h3> To define phenotypic and genotypic spectrum of multisystem proteinopathies (MSP) and MSP-like disorders. <h3>Background:</h3> MSPs are genetically heterogenous disorders featured by neurodegeneration including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), inclusion body myopathy (IBM), and Paget disease of bone (PDB), sharing similar pathological findings of protein aggregation. Additional genes encoding RNA-binding proteins or proteins involved in quality-control pathways also lead to myopathy or neurodegeneration, although not necessarily within the same family, causing similar pathological abnormalities (MSP-like disorders). <h3>Design/Methods:</h3> We searched Mayo Clinic database (1/1/2010–6/30/2022) to identify patients with mutations in genes causative of MSP and MSP-like disorders. Clinical and laboratory data were reviewed. <h3>Results:</h3> Thirty-one individuals (11 female) from 27 unrelated families were identified. Pathogenic mutations were in: <i>VCP</i> (17 patients/14 families), <i>SQSTM1+TIA1</i> (5 patients/5 families), <i>TIA1</i> (5 patients/4 families), <i>MATR3, HNRNPA1</i>, <i>HSPB8</i>, and <i>TFG</i> (1 patient each). Myopathy occurred in all but 2 <i>VCP</i>-MSP patients and was the initial presentation at median age of 52. Patterns of weakness were limb-girdle in 12/15 <i>VCP</i>-MSP and distal-predominant in the remaining patients. Twenty/24 muscle biopsies showed myopathy with rimmed vacuoles. MND and FTD occurred in 5 (4 <i>VCP</i>, 1 <i>TFG</i>) and 4 (3 <i>VCP</i>, <i>1 SQSTM1+TIA1</i>) patients, respectively. PDB was present in 4 <i>VCP</i>-MSP. Twenty-one patients had last echocardiogram 8 years (median; range 3–22 years) after disease onset showing diastolic dysfunction in 2 <i>VCP</i>-MSP patients. Six patients demonstrated restrictive ventilatory impairment 15 years after disease-onset. At median follow-up of 11.5 years, 15 patients were ambulating without gait-aids; loss of ambulation (n=5) and death (n=3) were recorded only in <i>VCP</i>-MSP patients. <h3>Conclusions:</h3> Among MSP and MSP-related disorders, <i>VCP</i> was the most common causative gene, followed by <i>SQSTM1+TIA1</i> and <i>TIA1</i>; myopathy with rimmed vacuoles was the most frequent manifestation; distal-predominant weakness occurred frequently in non-<i>VCP</i>MSP; loss of ambulation was observed only in <i>VCP</i>-MSP at 11.5-year follow-up. <b>Disclosure:</b> Dr. Chompoopong has nothing to disclose. Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. The institution of Dr. Oskarsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AnnJi. The institution of Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Oskarsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Tsumura. The institution of Dr. Oskarsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MediciNova. The institution of Dr. Oskarsson has received research support from Biogen. The institution of Dr. Oskarsson has received research support from Medicinova. The institution of Dr. Oskarsson has received research support from Cytokinetics. The institution of Dr. Oskarsson has received research support from Calico. The institution of Dr. Oskarsson has received research support from Mitsubishi. The institution of Dr. Oskarsson has received research support from Tsumura. The institution of Dr. Oskarsson has received research support from Sanofi. The institution of Dr. Oskarsson has received research support from AZTherapeutics. The institution of Dr. Oskarsson has received research support from Orion. The institution of Dr. Oskarsson has received research support from Esaii. Dr. Madigan has nothing to disclose. Dr. Mirman has nothing to disclose. Dr. Martinez-Thompson has nothing to disclose. Dr. Liewluck has nothing to disclose. Dr. Milone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Milone has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics, AAN. The institution of Dr. Milone has received research support from Mayo Clinic, CCaTS-CBD. The institution of Dr. Milone has received research support from Mayo Clinic, SGP Award. The institution of Dr. Milone has received research support from MDA for Care Center grant. The institution of Dr. Milone has received research support from Regenerative medicine Minnesota.

Unilateral hearing loss: case report on the insidious consequence of nasopharyngeal tuberculosis

BackgroundNasopharyngeal tuberculosis constitutes 1% of the head and neck manifestation of extra-pulmonary tuberculosis. The rarity of the disease along with its non-specific presentation may pose a challenge in diagnosis.Case presentationWe present a case of a 33-year-old patient who presented with a gradual onset of unilateral hearing loss. Endoscopic examination revealed leukoplakic lesions over the bilateral torus tubarius with audiological assessment revealing a mixed hearing loss in the left ear. Patient completed a 6-month course of anti-tuberculous therapy with a complete resolution of nasopharyngeal lesions and hearing loss.ConclusionWe hypothesize that tuberculosis of the nasopharynx may not only lead to impaired middle ear ventilation but also damage to the ossicular chain and inner ear structures.

Post-COVID syndrome: clinical presentations and therapeutic approaches

The article presents a literature review on the pathogenesis, clinical and radiological manifestations and therapy options for post-COVID syndrome. The pathophysiological mechanisms underlying lung injury in severe COVID-19 and ARDS of any other aetiology include acute injury to the alveolar epithelium and pulmonary vascular endothelium with increased alveolar-capillary permeability, interstitial and alveolar oedema, formation of hyaluronic membranes, and accumulation of neutrophils in the lung tissue. The completion of the acute phase is followed by hyperplasia of type II alveolocytes, proliferation of fibroblasts and myofibroblasts as manifestations of the reparative processes. Post-COVID syndrome combines pathological conditions that are accompanied by the clinically meaningful decline in quality of life and risk of death and persist for a long time after the disappearance of the infectious symptoms of the disease. Post-COVID lung parenchymal consolidations are accompanied by impaired pulmonary ventilation, frequent development of chronic respiratory failure with exercise-induced hypoxemia, reduce the patients’ quality of life and require treatment. Currently, attempts are being made to use various drugs for the treatment of post-COVID interstitial changes in lungs, but the evidence base for providing guidelines is currently insufficient. Bovhyaluronidase azoximer is one of the promising drugs. A multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial to evaluate the efficacy of bovhyaluronidase azoximer in patients with post-covid interstitial changes in lungs is currently being conducted in the Russian Federation. The study results can provide reliable information about the place and role of this drug in the treatment of post-COVID interstitial changes in lungs.

Effectiveness of Nonpharmacological Interventions in the Field of Ventilation: An Umbrella Review.

Systematic reviews of the literature published in English, Spanish, French, and Portuguese were used, which included studies in which nonpharmacological interventions were used as a response to impaired ventilation in adults in any given context of the clinical practice. The recommendations given by the Joanna Briggs Institute (JBI) for umbrella reviews were followed. This research took place in several databases such as MEDLINE, CINAHL Complete, CINHAL, MedicLatina, ERIC, Cochrane Reviews (Embase), and PubMed. The Joanna Briggs critical analysis verification list was used for the systematic review. The data extraction was performed independently by two investigators based on the data extraction tools of the Joanna Briggs Institute, and the data were presented in a summary table alongside the support text. Forty-four systematic reviews, thirty randomized clinical essays, and fourteen observational studies were included in this review. The number of participants varied between n = 103 and n = 13,370. Fifteen systematic revisions evaluated the effect of isolated respiratory muscular training; six systematic revisions evaluated, in isolation, breathing control (relaxed breathing, pursed-lip breathing, and diaphragmatic breathing exercises) and thoracic expansion exercises; and one systematic review evaluated, in isolation, the positions that optimize ventilation. Nineteen systematic reviews with combined interventions that reinforced the role of education and capacitation while also aiming for their success were considered. The articles analyzed isolated interventions and presented their efficacy. The interventions based on respiratory exercises and respiratory muscular training were the most common, and one article mentioned the efficacy of positioning in the compromisation of ventilation. Combined interventions in which the educational component was included were found to be effective in improving pulmonary function, diffusion, oxygenation, and functional capacity. The outcomes used in each study were variable, leading to a more difficult analysis of the data. The interventions that were the focus of the review were duly mapped. The results suggest that nonpharmacological interventions used to optimize ventilation are effective, with a moderate to high level of evidence. There is a strong foundation for the use of the chosen interventions. The lack of studies on the intervention of "positioning to optimize ventilation" points out the need for a deeper analysis of its effects and for studies with a clear focus. This study supports the decisions and recommendations for the prescription of these interventions to patients with impaired ventilation.

Impact of obstructive ventilatory impairment on intraoperative bleeding during laparoscopic hepatectomy.

An animal model of laparoscopic hepatectomy showed that bleeding from the hepatic vein is influenced by airway pressure. However, there are little research reports on how airway pressure leads to risks in clinical practice. The main objective of this study was to investigate the impact of preoperative forced expiratory volume % in 1s (FEV1.0%) on intraoperative blood loss in laparoscopic hepatectomy. All patients who underwent pure laparoscopic or open hepatectomy from April 2011 to July 2020 were classified into two groups by preoperative spirometry: those with obstructive ventilatory impairment (obstructive group; FEV1.0% < 70%) and those with normal respiratory function (ormal group; FEV1.0% ≥ 70%). Massive blood loss was defined as 400mL for laparoscopic hepatectomy. In total, 247 and 445 patients underwent pure laparoscopic and open hepatectomy, respectively. Regarding laparoscopic hepatectomy group, blood loss was significantly greater in the obstructive group (122 vs. 100mL, P = 0.042). Multivariate analysis revealed that high IWATE criteria which classify the surgical difficulty of laparoscopic hepatectomy (≥ 7, odds ratio (OR): 4.50, P = 0.004) and low preoperative FEV1.0% (< 70%, OR: 2.28, P = 0.043) were independent risk factors for blood loss during laparoscopic hepatectomy. In contrast, FEV1.0% did not affect the blood loss (522 vs. 605mL, P = 0.113) during open hepatectomy. Obstructive ventilatory impairment (low FEV1.0%) may affect the amount of bleeding during laparoscopic hepatectomy.

Exercise intolerance in post-coronavirus disease 2019 survivors after hospitalisation.

Post-coronavirus disease 2019 (COVID-19) survivors frequently have dyspnoea that can lead to exercise intolerance and lower quality of life. Despite recent advances, the pathophysiological mechanisms of exercise intolerance in the post-COVID-19 patients remain incompletely characterised. The objectives of the present study were to clarify the mechanisms of exercise intolerance in post-COVID-19 survivors after hospitalisation. This prospective study evaluated consecutive patients previously hospitalised due to moderate-to-severe/critical COVID-19. Within mean±sd 90±10 days of onset of acute COVID-19 symptoms, patients underwent a comprehensive cardiopulmonary assessment, including cardiopulmonary exercise testing with earlobe arterialised capillary blood gas analysis. 87 patients were evaluated; mean±sd peak oxygen consumption was 19.5±5.0 mL·kg-1·min-1, and the tertiles were ≤17.0, 17.1-22.2 and ≥22.3 mL·kg-1·min-1. Hospitalisation severity was similar among the three groups; however, at the follow-up visit, patients with peak oxygen consumption ≤17.0 mL·kg-1·min-1 reported a greater sensation of dyspnoea, along with indices of impaired pulmonary function, and abnormal ventilatory, gas-exchange and metabolic responses during exercise compared to patients with peak oxygen consumption >17 mL·kg-1·min-1. By multivariate logistic regression analysis (receiver operating characteristic curve analysis) adjusted for age, sex and prior pulmonary embolism, a peak dead space fraction of tidal volume ≥29 and a resting forced vital capacity ≤80% predicted were independent predictors of reduced peak oxygen consumption. Exercise intolerance in the post-COVID-19 survivors was related to a high dead space fraction of tidal volume at peak exercise and a decreased resting forced vital capacity, suggesting that both pulmonary microcirculation injury and ventilatory impairment could influence aerobic capacity in this patient population.

Sleep-Disordered Breathing and Chronic Respiratory Infections: A Narrative Review in Adult and Pediatric Population

Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence and impact of SDB in chronic respiratory infections, including cystic fibrosis (CF), bronchiectasis and mycobacterial infections, and explore the possible pathophysiological mechanisms. Common pathophysiological mechanisms, underlying SDB onset in all chronic respiratory infections, include inflammation, which plays a central role, chronic nocturnal cough and pain, excessive production of mucous plugs, presence of obstructive and/or restrictive ventilatory impairment, upper airways involvement, and comorbidities, such as alteration of nutritional status. SDB may affect about 50% of patients with bronchiectasis. The severity of the disease, e.g., patients colonized with P. aeruginosa and frequent exacerbators, as well as comorbidities, such as chronic obstructive pulmonary disease and primary ciliary dyskinesia, may impact SDB onset. SDB may also frequently complicate the clinical course of both children and adults with CF, impacting the quality of life and disease prognosis, suggesting that their routine assessment should be incorporated into the clinical evaluation of patients from the first stages of the disease regardless of suggestive symptoms, in order to avoid late diagnosis. Finally, although the prevalence of SDB in patients with mycobacterial infections is uncertain, extrapulmonary manifestations, particularly nasopharyngeal locations, and concomitant symptoms, such as body pain and depression, may act as atypical predisposing factors for their development.

Sex-specific non-linear associations between body mass index and impaired pulmonary ventilation function in a community-based population: Longgang COPD study.

Aim: To investigate the prevalence of pulmonary airflow limitation and its association with body mass index (BMI) in a community-based population in Shenzhen, China. Methods: Study participants were recruited from Nanlian Community in Shenzhen, China, and spirometry was performed to assess lung function including forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), FEV1/FVC ratio, and FEV1 divided by predicted value. Pulmonary airflow limitation was determined by the Chinese Guideline of Pulmonary Function Examination. Multivariable logistic regression models were used to examine the association between BMI and pulmonary airflow limitation. Age, sex, educational attainment, occupation, and current cigarette smoking were used as potential confounders. Results: Of the 1206 participants, 612 (50.7%) were men and 594 (49.3%) were women with the average age being 53.7years old. After adjusting for age, sex, educational attainment, occupation, and current cigarette smoking, higher BMI was associated with lower odds (odds ratio: 0.98, 95% confidence interval: 0.97, 0.99) of pulmonary airflow limitation by assuming a linear relationship. Further investigation of the interaction terms, we found that the magnitudes of the associations differed in men and women. A U-shaped relationship was observed in women, while the association was almost linear in men. Conclusion: The relationship between BMI and pulmonary airflow limitation was U-shaped in women and linear in men.

Immunothrombosis biomarkers as potential predictive factors of acute respiratory distress syndrome in moderate-to-critical COVID-19: A single-center, retrospective cohort study

BackgroundImmunothrombosis, a process of inflammation and coagulation, is involved in sepsis-induced acute respiratory distress syndrome formation (ARDS). However, the clinical correlation between immunothrombosis biomarkers (including tissue factor [TF] and von Willebrand factor [vWF]) and coronavirus disease 2019 (COVID-19)-related ARDS is unknown. This study investigated ARDS development following moderate-to-critical COVID-19 and examined immunothrombosis biomarkers as ARDS predictors. MethodsThis retrospective cohort study included patients with moderate-to-critical COVID-19 (n = 165) admitted to a northern teaching hospital during the 2021 pandemic in Taiwan, who had no COVID-19 vaccinations. Immunothrombosis biomarkers were compared between COVID-19 patients with and without ARDS (no-ARDS) and a control group consisting of 100 healthy individuals. ResultsThe study included 58 ARDS and 107 no-ARDS patients. In multivariable analysis, TF (aOR=1.031, 95% CI: 1.009–1.053, p = 0.006); and vWF (aOR=1.053, 95% CI: 1.002–1.105, p = 0.041) were significantly associated with ARDS episodes, after adjusting for other confounding factors. vWF and TF predicted ARDS with the area under the curve of 0.870 (95% CI: 0.796–0.945). Further mechanical ventilation analysis found TF to be correlated significantly with pCO2 and ventilatory ratio. ConclusionsTF and vWF levels potentially predicted ARDS development within 7 days of admission for COVID-19 after adjusting for traditional risk factors. TF correlated with ventilation impairment in COVID-19 ARDS but further prospective studies are needed.

Significance of Preoperative Pulmonary Function on Short- and Long-Term Outcomes Following Gastrectomy for Gastric Cancer

BackgroundPreoperative pulmonary function assessment is useful for selecting surgical candidates and operative methods and assessing the risk of postoperative pulmonary complications. However, few studies have investigated the relationship between preoperative pulmonary function and short- and long-term outcomes in patients who underwent gastrectomy for gastric cancer. MethodsOf the 1040 patients with gastric cancer (stages I–III) who had undergone R0 gastrectomy between 2009 and 2020, 750 who underwent preoperative spirometry were included. Restrictive ventilatory impairment was defined as a vital capacity of the predicted value (%VC) < 80%, while obstructive ventilatory impairment was defined as forced expiratory volume in one second (FEV1%) < 70%. Postoperative complications were assessed using the Clavien–Dindo (CD) classification. The relationship between clinical factors, including %VC, FEV1%, severe postoperative complications (CD ≥ 3b), overall survival (OS), and relapse-free survival, were assessed. ResultsThe mean age of the 750 patients was 68 ± 10.5 years. Severe postoperative complications were observed in 25 (3.3%) patients and were significantly associated with FEV1% < 70% in the univariate analysis. The 5-year OS was 72.5%. Multivariate analysis showed that the cancer stage, age > 75 years, preoperative comorbidities, %VC < 80%, total gastrectomy, severe postoperative complications, and postoperative adjuvant chemotherapy were the significant independent factors affecting OS. Pneumonia was significantly associated with %VC < 80%. ConclusionsFEV1% < 70%was associated with the development of severe postoperative complications, while %VC < 80% was associated with poor OS independent of the cancer stage because of death from pneumonia. Spirometry helps surgeons and patients discuss the risks and benefits of surgery.

Carotid Body-Mediated Chemoreflex Function in Aging and the Role of Receptor-Interacting Protein Kinase.

Ventilatory impairment during aging has been linked to carotid body (CB) dysfunction. Anatomical/morphological studies evidenced CB degeneration and reductions in the number of CB chemoreceptor cells during aging. The mechanism(s) related to CB degeneration in aging remains elusive. Programmed cell death encompasses both apoptosis and necroptosis. Interestingly, necroptosis can be driven by molecular pathways related to low-grade inflammation, one hallmark of the aging process. Accordingly, we hypothesized that necrotic cell death dependent on receptor-interacting protein kinase-3 (RIPK3) may contribute, at least in part, to impair CB function during aging. Adult (3months) and aged (24months) wild type (WT) and RIPK3-/- mice were used to study chemoreflex function. Aging results in significant reductions in both the hypoxic (HVR) and hypercapnic ventilatory responses (HCVR). Adult RIPK3-/- mice showed normal HVR and HCVR compared to adult WT mice. Remarkable, aged RIPK3-/- mice displayed no reductions in HVR nor in HCVR. Indeed, chemoreflex responses obtained in aged RIPK3-/- KO mice were undistinguishable from the ones obtained in adult WT mice. Lastly, we found high prevalence of breathing disorders during aging and this was absent in aged RIPK3-/- mice. Together our results support a role for RIPK3-mediated necroptosis in CB dysfunction during aging.

Exosomal STIMATE derived from type II alveolar epithelial cells controls metabolic reprogramming of tissue-resident alveolar macrophages.

Background: Complete abolition of alveolar epithelial cells (AECs) is characteristic of end-stage lung disease. Transplantation therapy of type II AECs (AEC-IIs) or AEC-IIs-derived exosomes (ADEs) have been proposed as a means of repairing injury and preventing fibrosis. However, the mechanism by which ADEs balances airway immunity and alleviates damage and fibrosis remains unknown. Methods: We investigated STIM-activating enhancer-positive ADEs (STIMATE+ ADEs) in the lung of 112 ALI/ARDS and 44 IPF patients, and observed the correlation between STIMATE+ ADEs and subpopulation proportion and metabolic status of tissue-resident alveolar macrophages (TRAMs). We constructed the conditional knockout mice STIMATE sftpc , in which STIMATE was specifically knocked out in mouse AEC-IIs and observed the effects of STIMATE+ ADEs deficiency on disease progression, immune selection and metabolic switching of TRAMs. We constructed a BLM-induced AEC-IIs injury model to observe the salvage treatment of damage/fibrosis progression with STIMATE+ ADEs supplementation. Results: In clinical analysis, the distinct metabolic phenotypes of AMs in ALI/ARFS and IPF were significantly perturbed by STIMATE+ ADEs. The immune and metabolic status of TRAMs in the lungs of STIMATE sftpc mice was imbalanced, resulting in spontaneous inflammatory injury and respiratory disorders. STIMATE+ ADEs are taken up by tissue-resident alveolar macrophages TRAMs to regulate high Ca2+ responsiveness and long-term Ca2+ signal transduction, which maintains M2-like immunophenotype and metabolism selection. This involves calcineurin (CaN)-PGC-1α pathway mediated mitochondrial biogenesis and mtDNA coding. In a bleomycin-induced mouse fibrosis model, supplementation with inhaled STIMATE+ ADEs lessened early acute injury, prevented advanced fibrosis, alleviated ventilatory impairment and reduced mortality.