Pulmonary Dysfunction Research Articles

Variation in thoracic inlet measurements and its correlation with pulmonary dysfunction in kyphoscoliotic deformities: a prospective case-control study.

Pulmonary dysfunction in thoracic kyphoscoliosis has been correlated with chest wall distortion, uneven trunk growth and restrictive pattern. The study aims to analyse the variation in thoracic inlet measurements on pulmonary dysfunction with varying curve magnitude and thoracic cage parameters. In a non-randomised, prospective case-control study, 80 consecutive patients with thoracic kyphoscoliosis were divided into 3 groups based on Cobb angle: Group 1 (31-50), Group 2 (51-80) and Group 3 (> 80). Thoracic inlet measurement was calculated by thoracic inlet index (TI) on MRI at the sternal level. Pulmonary function and thoracic cage parameters [hemi thorax height, rib-apex distance, AP chest diameter at sternal level and transverse thoracic diameter] were documented. TI values were compared with 20 age-matched asymptomatic controls. Multivariate correlation and regression analysis were performed to investigate the correlations. The mean age of the study cohort was 14.1 ± 4.4years, including Group 1 (6 patients), Group 2 (55 patients) and Group 3 (19 patients) versus 12.9 ± 2.2years in controls. The mean TI was 2.8 ± 0.56 in Group 1, 3.7 ± 0.9 in Group 2 and 4.0 ± 1.12 in Group 3 versus 2.6 ± 0.43 in controls. Pulmonary dysfunction was severe with TI > 7.1 (p < 0.001) in Group 3 patients with thoracic hypokyphosis. Multivariate regression for thoracic parameters and TI > 5.6 showed significant correlation of pulmonary dysfunction in Group 2 and 3 curves with apex between T1 and T4, whereas transverse thoracic diameter, rib-apex distance and hemi thorax height were weakly associated. Thoracic inlet index (TI), a neglected pre-operative variable associated with pulmonary dysfunction in thoracic kyphoscoliosis, can be evaluated on MRI without an additional cost and radiation.

Surgical management of omega deformity in a patient with neurofibromatosis type 1: a case report.

To describe the surgical treatment in a patient with a partial omega deformity in the thoracic spine with neurofibromatosis type 1. The patient was a 55-year-old man with an omega deformity, which is defined as a curvature in which the end vertebra is positioned at the level of, above, or below the apical vertebra (i.e., a horizontal line bisecting it). We performed halo gravity traction (HGT) for 7weeks, followed by posterior spinal instrumented nearly equal in situ fusion from T2-L5 with three femoral head allografts and a local bone autograft. We avoided reconstruction of the thoracic anterior spine because of his severe pulmonary dysfunction. HGT improved the % vital capacity from 32.5 to 43.5%, and improved the Cobb angle of the kyphosis from > 180° before traction to 144° after traction. The Cobb angle of kyphosis and scoliosis changed from > 180° preoperatively to 155° and 146°, respectively, postoperatively, and 167° and 156°, respectively, at final follow-up. His postoperative respiratory function deteriorated transiently due to bilateral pleural effusions and compressive atelectasis, which was successfully treated with a frequent change of position and nasal high flow for 1week. At final follow-up, his pulmonary function improved from 0.86 to 1.04L in VC, and from 32.5 to 37.9% in %VC. However, there was no overall improvement in preoperative distress following surgery, although his modified Borg scale improved from 3 preoperatively to 0.5 postoperatively. One month after discharge, he felt worsening respiratory distress (SpO2:75%) and was readmitted for pulmonary hypertension for 2months. He was improved by non-invasive positive pressure ventilation (biphasic positive airway pressure) for 1week, medication and daily lung physiotherapy. Thereafter, he has been receiving permanent daytime (0.5L/min) and nighttime (2L/min) oxygen therapy at home. A solid arthrodesis through the fusion area was confirmed on computed tomography. However, the kyphosis correction loss was 12° (i.e., 155°-167°), while the scoliosis correction loss was 10° (i.e., 146°-156°) at 2years of recovery. We suggest that nearly equal in situ fusion is a valid option for preventing further deformity deterioration and avoiding fatal complications.

Relationship between commonly defined metabolic health phenotypes and obesity with lung function in a working population: A cross-sectional study

BackgroundFour phenotypes relate metabolism and obesity: metabolically healthy (MHO) and unhealthy (MUO) people with obesity and metabolically healthy (MHNO) and unhealthy (MUNO) people without obesity. No studies have addressed the association between these categories and lung function in the working population. ObjectivesThe aim was to determine the relationship of phenotypes to lung ageing as measured by lung age and its relationship to lung dysfunction. MethodsA descriptive cross-sectional study was conducted in a working population. The outcome variable was lung function assessed by lung age. The four phenotypes of obesity and metabolic health (MHNO, MHO, MUO and MUNO) were determined using NCEP-ATP III criteria. Lung dysfunctions were classified into restrictive, obstructive, and mixed patterns. ResultsThe mean age of the participants was 43.7 years, ranging from 18 to 67 years. Of the 1860 workers, 51.3 % were women. The prevalences found were 71.4 %, 12 %, 10.6 % and 6 % for MHNO, MUO, MHO, and MUNO, respectively. MHO (β = 0.66; p = 0.591) was not associated with increased lung ageing compared with MHNO, but MUO (β = 7.1; p < 0.001) and MUNO (β = 6.6; p < 0.001) were. Concerning pulmonary dysfunctions, MUNO (OR = 1.93; p < 0.001) and MUO (OR = 2.91; p < 0.001) were found to be related to the presence of a restrictive pattern, and MUNO (OR = 2.40; p = 0.028) to the mixed pattern. ConclusionThe results show that metabolic abnormalities, not obesity, are responsible for premature lung ageing and, therefore, lung function decline. In our study, having obesity without metabolic abnormality was not significantly associated with the presence of dysfunctional respiratory patterns.

Cardiopulmonary determinants of reduced exercise tolerance in Fabry disease.

Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A enzyme. This causes a progressive accumulation of glycosphingolipids in tissues and organs which represents the main pathogenetic mechanism of FD. The disease is progressive and multisystemic and is characterized by early symptoms and late complications (renal, cardiac and neurological dysfunction). Fatigue and exercise intolerance are early common symptoms in FD patients but the specific causes are still to be defined. In this narrative review, we deal with the contribution of cardiac and pulmonary dysfunctions in determining fatigue and exercise intolerance in FD patients.

Abstract PO5-19-03: 1st-in-human CAR T targets MUC1 transmembrane cleavage product

Abstract Background: huMNC2-CAR44 and huMNC2-CAR22 are autologous CAR T cell therapies under study in an ongoing 1st-in-human trial for metastatic breast cancers (NCT04020575), being performed at City of Hope. Both CARs are targeted to the tumor by an antibody, huMNC2, that recognizes a cryptic binding site on MUC1*, which is the transmembrane cleavage product of MUC1. The antibody binds to an epitope that is only unmasked when MUC1 is cleaved to MUC1* by enzymes in the tumor microenvironment. huMNC2 strongly reacts with over 90% of breast cancers. No therapeutic that targets MUC1* had ever been tested in humans before this trial. We note that neither 5E5 nor antibodies that bind to a MUC1 “heterodimer” recognize MUC1*. Eight patients have already been treated with huMNC2-CAR44. The next 8 patients will be treated with huMNC2-CAR22 to enable comparison and inform decision as to which CAR to bring forward for completion of Phase 1 and entry into Phase 2. huMNC2-CAR22 differs from huMNC2-CAR44 in that it is resistant to exhaustion. CAR22 achieves greater in vivo persistence due to Sadelain’s “1XX” mutations of Tyr to Phe in 2 of the 3 ITAMs, which prevent Tyr phosphorylation and signaling, leaving signaling through ITAM 1 alone. Trial Design: Dose escalation or de-escalation is tested in cohorts of 3 patients each using standard “3+3” dose-finding, with the starting dose of 3.3x105 CAR+ T cells/kg up to a maximum of 1.0x107 CAR+ T cells/kg. Patients receive cyclophosphamide (300 mg/m2/day) and fludarabine (30 mg/m2/day) for 3 days prior to CAR T cell infusion. Safety will be evaluated by CTCAE version 5.0 and Lee criteria. Anti-tumor activity will be assessed by imaging studies completed between 1 and 3 months after huMNC2-CAR T cell infusion for determination of response by RECIST 1.1 or by FDG PET modified PERCIST for patients with predominant bone disease. Inclusion Criteria: Patients with confirmed diagnosis of breast cancer, with documented ER, PR, and HER2 status per ASCO/CAP guidelines. Patients with MUC1* expression of at least 30% by IHC. Patients must have received standard metastatic systemic therapy per NCCN guidelines which are known to confer benefit. No maximum on number of prior treatments. Patients must have received at least 2 or 3 prior lines of chemotherapy in the metastatic setting. Exclusion Criteria: Patients requiring &amp;gt;15 mg of prednisone per day or immunosuppressives; patients with major organ dysfunction; Serum creatinine &amp;gt; 2 mg/dL; Bilirubin ≥ 1.5 mg/dL; AST/ALT ≥ 2.5 x upper limit normal; 3x upper limit for patients with known liver metastasis; significant pulmonary dysfunction; significant cardiovascular abnormalities; ANC &amp;lt; 1000/mm3. Primary Objectives: To determine the safety and maximally tolerated cell dose (MTD) and recommended phase 2 cell dose (RP2D) of ex vivo expanded autologous huMNC2-CAR T cells for patients with advanced MUC1* positive breast cancer using CTCAE version 5.0 and Lee criteria. Secondary: Determine duration of in vivo persistence and phenotype of adoptively transferred huMNC2-CAR T cells. Determine antitumor activity by RECIST 1.1. Determine MTD/RP2D. Contact: City of Hope Comprehensive Cancer Center Joanne Mortimer, MD 1-800-826-4673 Minerva18625@coh.org Citation Format: Cynthia Bamdad, Joanne Mortimer, Yuan Yuan, Jennifer M. Specht, Benoit Smagghe, Stephen Chi-Min Lin, Andrew Stewart, Danica Walkley, Mark Carter, Timothy Synold, Vishwas Parekh, Kevin Yi, Jac-Leen Nash, Michael Nash, Qing Liu-Michael, Stanley Hamilton, Stephen Forman. 1st-in-human CAR T targets MUC1 transmembrane cleavage product [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-03.

REHABILITATION OF SPINAL DEFORMITIES IN ADOLESCENTS – THE FAMILY DOCTOR'S POINT OF VIEW

The spinal deformities that are commonly detected in the adolescent years has a significant impact on public health. In recent years, additional risk factors have been identified such as the modern lifestyle, sedentary lifestyle, online school during the Covid 19 pandemic. The spinal deformities that are commonly detected in the teenagers are scoliosis - with the special form adolescent idiopathic scoliosis and kyphosis – the special form Scheuermann kyphosis. The risk for spinal deformity among teenagers whose parents had a spinal deformity is higher in most situations. The family physician usually monitors both parents and children. Considering this, the family physician performs targeted screening on teenagers whose parents suffer from a spinal deformity, due to their genetic predisposition. Teenagers with spinal deformities without further limitations or pain have to be treated according to the indication guidelines. Kinetotherapy alone or in combination with medical massage, orthopaedic approaches, are approach to correct of posture, improve and maintain flexibility, to reduce the pain, the pulmonary dysfunction. Adolescents and adults with restrictive ventilation disorders can only be addressed in specialized centres for rehabilitation of breathing. The role of the family physician is to identify spinal deformities early, to intervene through physical therapy in order to correct the posture and reduce complications. Keywords: spinal deformities, rehabilitation, adolescent, family physician.

NKX2-1-conditioned disorder — «brain–lung–thyroid» syndrome: results of a multicenter study

Introduction. Brain–lung–thyroid syndrome (BLTS, choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction) is an autosomal dominant disorder associated with mutations of the NKX2-1 gene. A triad of symptoms from three organs (brain, lungs, thyroid gland) is manifested in 50% of patients, in other cases there is an incomplete phenotype of the disease. The most common manifestations are neurological. The aim of the study was to provide genetic, clinical, laboratory, and instrumental characteristics in BLTS patients with a clinical and morphological assessment of the phenotype.&#x0D; Materials and methods. Ten children from 9 families with identified mutations in the NKX2-1 gene were observed. Methods used: genealogical, Sanger sequencing, clinical and morphological assessment of the phenotype, examination of thyroid hormone levels, CT, MRI of the brain, CT of the chest, lung biopsy.&#x0D; Results. The article presents the results of molecular genetic analysis, family history, age of manifestation and diagnosis. 9 out of 10 children had damage to the central nervous system, thyroid gland, lungs, and one child had a combination of neurological pathology and hypothyroidism. Neurological pathology was represented by benign hereditary chorea (2 children), delayed motor development (8), muscular hypotension (7), ataxia (5), choreoathetosis (1), clonuses (1), seizures (1), hyperkinesis (3); respiratory — respiratory distress syndrome (RDS) of newborns (6), chronic respiratory failure (5), interstitial lung disease (6), bronchial asthma (1), chronic pneumonitis of infants (1), bronchiectasis (1). There are presented changes in computed tomograms of the lungs and during preforming CT, MRI of the brain. Typical developmental microanomalia included a protruding forehead, a wide tip of the nose, elongated narrow palpebral fissure, deep-set eyes, hypertelorism of the eyes, large rotated low-lying auricles, conical fingers.&#x0D; Conclusion. A combination of congenital hypothyroidism, neonatal RDS, heart disease, neurological disorders (hypotension, ataxia, delayed motor development, chorea), craniofacial dysmorphia is the basis for a molecular genetic examination to exclude BLTS.

Refractory cor pulmonale under extracorporeal membrane oxygenation for acute respiratory distress syndrome: the role of conversion to veno-pulmonary arterial assist-a case series.

Pulmonary vascular dysfunction during severe acute respiratory distress syndrome (ARDS) may lead to right ventricle (RV) dysfunction and acute cor pulmonale (ACP). The occurrence/persistence of ACP despite conventional extracorporeal membrane oxygenation (ECMO) is a challenging situation. We explored the usefulness of a specific dual-lumen cannula that bypasses the RV, and on which a veno-pulmonary arterial assist (V-P ECMO) was mounted, in ARDS patients. We report a case-series of ARDS patients put on conventional veno-arterial or veno-venous ECMO and presented refractory ACP as an indication for a reconfiguration to V-P ECMO using the ProtekDuo cannula. The primary endpoint was the mitigation of RV and pulmonary vascular dysfunction as assessed by the change in end-diastolic RV/left ventricle (LV) surface ratio. Six patients had their conventional ECMO reconfigured to V-P ECMO to treat refractory ACP. There was a decrease in end-diastolic RV/LV surface ratio, as well as end-systolic LV eccentricity index, and lactatemia immediately after V-P ECMO initiation. The resolution of refractory ACP was immediately achieved in four of our six (66%) patients. The V-P ECMO was weaned after a median of 26 [8-93] days after implantation. All but one patient were discharged home. We detected one case of severe hemolysis with V-P ECMO and two suspected cases of right-sided infective endocarditis. V-P ECMO is useful to mitigate RV overload and to improve hemodynamics in case of refractory ACP despite conventional ECMO.

Mechanism of circRNA_SMG6 mediating lung macrophage ECM degradation via miR-570-3p in microplastics-induced emphysema

Microplastics (MPs) are plastic particles < 5 mm in diameter, of which polystyrene microplastics (PS-MPs) are representative type. The extracellular matrix (ECM) degradation of macrophages is associated with the development of emphysema. Additionally, circular RNAs (circRNAs) have a regulatory role in epigenetic mechanisms related to lung disease. However, the mechanisms of the ECM degradation and circRNAs in MPs-induced emphysema are still unclear. In our study, Sprague-Dawley (SD) rats were treated with 0, 0.5, 1.0 and 2.0 mg/m3 100 nm PS-MPs for 90 days in an inhalation experiment. PS-MPs-exposed rats showed elevated airway resistance and pulmonary dysfunction. Lung histopathology exhibited inflammatory cell infiltration, septal thickening and alveolar dilatation. Exposure to PS-MPs was able to induce elevated levels of ECM degradation-related markers MMP9 and MMP12, as well as reduced levels of elastin in rat lung tissues. CircRNA_SMG6 is a non-coding RNA (ncRNA) with a homologous circular structure in human, rat and mouse. The expression level of circRNA_SMG6 was decreased in both rat lung tissues exposed to PS-MPs and PS-MPs-treated THP-1 cells. The luciferase reporter gene demonstrated that circRNA_SMG6 combined with miR-570-3p and co-regulated PTEN, the target gene of miR-570-3p. Moreover, overexpression of circRNA_SMG6 or inhibition of miR-570-3p attenuated PS-MPs-induced ECM degradation in THP-1 cells. Taken together, circRNA_SMG6 may have a significant function in the deterioration of emphysema caused by PS-MPs-induced macrophage ECM degradation by regulating miR-570-3p. Our findings reveal a novel mechanism of emphysema caused by PS-MPs and provide valuable information for assessing the health risks of MPs.

Pulmonary sequelae of COVID-19: An interpretive description study

The aim of this study was to explore the experiences of adults living with pulmonary sequelae of COVID-19 as a subtype of long-COVID to contribute to pandemic recovery efforts. A qualitative, Interpretive Description design was implemented using semi-structured interviews with 10 participants living with self-reported pulmonary sequelae of COVID-19. Three key findings illustrate the participant experience: (1) the illness burden of pulmonary dysfunction and symptoms, (2) emotional responses to lung damage and symptoms, and (3) navigating the healthcare system. Understanding the burdens associated with the pulmonary subtype of long-COVID such as respiratory symptoms, fatigue, activity intolerance, emotional responses, and inaccessible healthcare can lead to the development and implementation of strategies that support recovery. Further research is needed for a more precise understanding of the experiences of patients with specific pulmonary complications.

Ethical Considerations for Acutely Injured and Future Burn Patients Who Smoke While on Home Oxygen Therapy.

Home oxygen therapy (HOT) is prescribed to patients with pulmonary dysfunction to improve survival and quality of life. However, ignition of oxygen can lead to burns with significant morbidity and mortality. Providers who routinely treat this patient population face an ethical issue: balancing the obligation to provide beneficial treatment to a patient with the responsibility to protect that patient from suffering avoidable burn injuries. A thorough review was conducted to assess the literature regarding ethical considerations involved in managing patients who have been burned while smoking on HOT and who continue to smoke. Various aspects of this problem and potential approaches to address it were analyzed with respect to four core ethical principles of health care: beneficence, non-maleficence, autonomy and justice. For patients who repeatedly present with burns acquired secondary to smoking while on oxygen, the authors consider it ethically unacceptable to withhold standard of care intervention for acute burns because refusal to treat acute burns conflicts with all four ethical principles. A preventive strategy would encourage more judicious prescription of home oxygen therapy, supporting the principles of non-maleficence and beneficence. Additional preventive strategies include upstream solutions such as longitudinal patient education about smoking cessation and risks of smoking on home oxygen therapy. Physicians are tasked with the responsibility of both providing optimal care for this patient population and preventing future burn injuries. They may be able to address this challenging situation by thinking more critically about potential solutions while bearing in mind key ethical considerations and obligations.

Flexible and Rigid Bronchoscopy for Critically Ill Children on Extracorporeal Membrane Oxygenation.

We aim to describe our experience with bronchoscopy to diagnose and relieve tracheobronchial obstruction in anticipation of decannulation in children on extracorporeal membrane oxygenation (ECMO) support. A retrospective cohort study of children on ECMO between 1/2018 and 12/2022. A total of 107 children required ECMO support during the study period for cardiac (n = 48, 45%), pulmonary (n = 38, 36%), or cardiopulmonary dysfunction (n = 21, 20%). Thirty-seven (35%) patients underwent 99 bronchoscopies while on ECMO. Most (76%, n = 75) experienced no improvement or worsening of chest radiography 24 hours following bronchoscopy. Clinical improvement in tidal volumes 48 hours after the first bronchoscopy was noted in 13/25 patients with available data (p = 0.05). Adverse events were seen in 18 (49%) patients who underwent bronchoscopy, including pneumothorax (n = 8, 22%), pneumonia (n = 7, 19%), pulmonary hemorrhage (n = 6, 16%), and sepsis (n = 5, 14%). ECMO courses were longer (25.4 ± 37.2 vs 6.1 ± 8.8 days, p < 0.0001) and more likely to be complicated by pneumonia (p = 0.0004) and sepsis (p = 0.047) in patients who underwent bronchoscopy compared with those who did not. Adverse events following bronchoscopy were associated with the number of bronchoscopies (p = 0.0003) and the presence of obstructive materials but not with the type of bronchoscopy or indication for ECMO. Mortality rates were similar between patients who underwent bronchoscopy and those who did not. Children requiring bronchoscopy represent a subset of the sickest children on ECMO. Bronchoscopy may provide benefit in children with persistent cardiopulmonary failure who could not otherwise be decannulated. Adverse events are associated with the number of bronchoscopies and the presence of obstructive material. 4 Laryngoscope, 2024.

The value of lung function assessment and Testin expression detection in clinicopathological features and prognosis of NSCLC patients.

The aim of this study is to investigate the clinical value and potential prognostic significance of lung function assessment and Testin expression in non-small cell lung cancer (NSCLC) patients. The NSCLC patients were classified into three groups according to lung function: group of normal lung function, group of PRISm (preserved ratio impaired spirometry) (FEV1, forced expiratory volume during the first second < 80% predicted and FEV1/FVC (forced vital capacity) ≥ 70%) and group of COPD (chronic obstructive pulmonary disease) (FEV1/FVC < 70%). The pre-operational clinicopathological characteristics of these patients were recorded and the markers of systemic inflammatory response, including neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and eosinophils (EOS), were compared between three groups. The expression of Testin in NSCLC samples was detected by IHC and we further explored the correlation between Testin expression and clinicopathological characteristics and prognosis of NSCLC patients. Finally, Cox regression analysis was conducted to study the prognostic factors of NSCLC patients. Of the 158 NSCLC patients, percentages of normal lung function, PRISm and COPD were 41.4%, 22.8% and 36.1%, respectively. Patients with tumor in the left lung were more likely to have pulmonary dysfunction (PRISm and COPD) than the right lung. The markers of systemic inflammatory response showed differences to various degree in the three groups and NSCLC patients with PRISm or COPD presented more unfavorable prognosis than patients with normal function. The expression of Testin correlated with lymph node metastasis, TNM stage and tumor invasion of NSCLC patients. Moreover, patients with low Testin expression exhibited poorer disease-free survival and overall survival than those with high Testin expression. In Cox regression analysis, we found that PRISm, COPD and Testin expression served as prognostic factors in NSCLC patients. The presence of COPD or PRISm influenced systemic inflammatory response and prognosis of NSCLC patients. Testin expression correlated with clinicopathological features and could be potentially used as a prognostic marker in NSCLC.

Risk factors predicting need for the pediatric intensive care unit (PICU) post-hematopoietic cell transplant, PICU utilization, and outcomes following HCT: a single center retrospective analysis.

Hematopoietic cell transplant (HCT) is a curative treatment for multiple malignant and non-malignant disorders. While morbidity and mortality have decreased significantly over the years, some patients still require management in the pediatric intensive care unit (PICU) during their HCT course for additional respiratory, cardiovascular, and/or renal support. We retrospectively reviewed pediatric patients (0-18 years) who underwent HCT from January 2015-December 2020 at our institution to determine risk factors for PICU care and evaluate PICU utilization and outcomes. We also assessed pulmonary function testing (PFT) data to determine if differences were noted between PICU and non-PICU patients as well as potential evolution of pulmonary dysfunction over time. Risk factors of needing PICU care were lower age, lower weight, having an underlying inborn error of metabolism, and receiving busulfan-based conditioning. Nearly half of PICU encounters involved use of each of respiratory support types including high-flow nasal cannula, non-invasive positive pressure ventilation, and mechanical ventilation. Approximately one-fifth of PICU encounters involved renal replacement therapy. Pulmonary function test results largely did not differ between PICU and non-PICU patients at any timepoint aside from individuals who required PICU care having lower DLCO scores at one-year post-HCT. Future directions include consideration of combining our data with other centers for a multi-center retrospective analysis with the goal of gathering and reporting additional multi-center data to work toward continuing to decrease morbidity and mortality for patients undergoing HCT.

Participant Selection from the General Japanese Population for Pulmonary Function Tests Using a Questionnaire on Symptoms and Smoking Habits during Annual Health Checkups: The Yamagata-Takahata Study.

Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.

Novel Method for Sealing Tracheostomies Immediately after Decannulation-An Acute Clinical Feasibility Study.

Tracheostomy decannulation leaves an iatrogenic passage in the upper airways. Inadequate sealing leads to pulmonary dysfunction and reduced voice quality. This study aimed to investigate the feasibility and impact of intratracheal tracheostomy sealing on laryngeal airflow and voice quality immediately after decannulation (ClinicalTrials.gov: NCT06138093). Fifteen adult, tracheostomized, intensive care unit patients were included from our hospital. A temporary, silicone-based sealing disc was inserted in the tracheostomy wound immediately after decannulation. Spirometry with measurement of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were performed as measures of airway flow. Voice recordings were assessed using an equal appearing interval scale from 1 to 5. Median FVC, FEV1, PEF, and voice quality score with interquartile range (IQR) was 883 (510-1910) vs. 1260 (1005-1723) mL (p < 0.001), 790 (465-1255) vs. 870 (617-1297) mL (p < 0.001), 103 (55-211) vs. 107 (62-173) mL (p = 0.720), and 2 (1-2.5) vs. 4 (3-5) points (p < 0.001), respectively, with open tracheostomy vs. after sealing the tracheostomy with the intratracheal sealing disc. This feasibility study showed that tracheostomy sealing with the intratracheal disc was safe and led to immediate improvements in FVC, FEV1, and voice quality.

Pulmonary blood volume measured by 82Rb-PET in patients with chronic obstructive pulmonary disease: a retrospective cohort study.

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 ([Formula: see text]) and mean 82Rb 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.

Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

Predicting delayed extubation and transfer to the intensive care unit in children undergoing posterior fusion surgery for scoliosis : Aretrospective observational study.

Delayed extubation and transfer to the intensive care unit (ICU) in children undergoing major scoliosis surgery may increase postoperative complications, prolong hospital stay, and increase medical expenses; however, whether achild will require delayed extubation or transfer to the ICU after scoliosis orthopedic surgery is not fully understood. In this study, we reviewed the risk factors for delayed extubation and transfer to the ICU after scoliosis orthopedic surgery in children. The electronic medical records of pediatric patients (≤ 18years) who underwent posterior spinal fusion surgery between January 2018 and November 2021 were reviewed and analyzed. Patient characteristics (age, sex, body mass index, American Society of Anesthesiologists, ASA, grade, preoperative lung function, and congenital heart disease), preoperative Cobb angle, scoliosis type, correction rate, vertebral fusion segments, pedicle screws, surgical osteotomy, intraoperative bleeding, intraoperative allogeneic transfusion, intraoperative hemoglobin changes, intraoperative mean arterial pressure changes, intraoperative tidal volume (ml/kg predicted body weight), surgical time, postoperative extubation, and transfer to the ICU were collected. The primary outcomes were delayed extubation and transfer to the ICU. Multivariate logistic regression models were used to determine the risk factors for delayed extubation and ICU transfer. Atotal of 246 children who satisfied the inclusion criteria were enrolled in this study, of whom 23(9.3%) had delayed extubation and 81(32.9%) were transferred to the ICU after surgery. High ASA grade (odds ratio [OR] 5.42; 95% confidence interval [CI] 1.49-19.78; p = 0.010), high Cobb angle (OR 1.04; 95% CI 1.02-1.07; p < 0.001), moderate to severe pulmonary dysfunction (OR 10.9; 95% CI 2.00-59.08; p = 0.006) and prolonged surgical time (OR 1.01; 95% CI 1.00-1.03; p = 0.040) were risk factors for delayed extubation. A high Cobb angle (OR 1.02; 95% CI 1.01-1.04; p = 0.004), high intraoperative bleeding volume (OR 1.06; 95% CI 1.03-1.10; p = 0.001), allogeneic transfusion (OR 3.30; 95% CI 1.24-8.83; p = 0.017) and neuromuscular scoliosis (OR 5.38; 95% CI 1.59-18.25; p = 0.007) were risk factors for transfer to the ICU. A high Cobb angle was arisk factor for both delayed extubation and ICU transfer. Age, sex, body mass index, number of vertebral fusion segments, correction rate, and intraoperative tidal volume were not associated with delayed postoperative extubation and ICU transfer. The most common risk factor for delayed extubation and ICU transfer in pediatric patients who underwent posterior spinal fusion was ahigh Cobb angle. Determining risk factors for apoor prognosis may help optimize perioperative respiratory management strategies and planning of postoperative care for children undergoing complicated spinal surgery.

Unravelling the Molecular Dimensions of Atmospheric Micro(nano)Plastics: Exploring Potential Impacts on Human Health and Strategies for Detection

Unravelling the Molecular Dimensions of Atmospheric Micro(nano)Plastics: Exploring Potential Impacts on Human Health and Strategies for Detection