Hasil untuk "Diseases of the respiratory system"

Tariq Mahmood, Vimal Kumar

Susanna Esposito, Valentina Fainardi, Maria Elena Capra et al.

<i>Background</i>: Respiratory syncytial virus (RSV) bronchiolitis remains a leading cause of hospitalization in infants, particularly those with risk factors such as prematurity or chronic diseases. Nirsevimab, a long-acting monoclonal antibody, has recently been approved for RSV prevention. However, parental acceptance of this novel immunoprophylaxis is crucial for effective implementation. The aim of this study was to investigate parental acceptance of nirsevimab prophylaxis for RSV among eligible neonates in Emilia-Romagna, Italy, and to identify factors influencing decision making. <i>Methods</i>: A prospective, multicenter observational study enrolled 1042 parents of neonates eligible for nirsevimab prophylaxis according to regional criteria. Parents completed a semi-structured questionnaire during pre-immunization counseling, exploring knowledge, attitudes, perceived risks, information sources, and willingness to accept prophylaxis. Statistical analysis assessed associations between parental characteristics and acceptance rates. <i>Results</i>: Among the 1042 respondents, 87.0% (n = 907) expressed willingness to administer nirsevimab to their child, while 2.2% (n = 23) refused and 8.8% (n = 92) were undecided. Higher acceptance was significantly associated with awareness of RSV risks (72.1% vs. 41.7%, <i>p</i> < 0.01), belief in nirsevimab’s high efficacy (46.2% vs. 18.3%, <i>p</i> < 0.01), and lower concern over side effects (10.6% vs. 27.8%, <i>p</i> < 0.01). Trust in primary care pediatricians and the healthcare system was also notably higher among accepting parents (<i>p</i> < 0.001). Willingness to pay declined with a hypothetical EUR 250 cost but remained higher among the acceptance group (71.0% vs. 50.4%, <i>p</i> < 0.001). <i>Conclusions</i>: Parental acceptance of nirsevimab in Emilia-Romagna was high, though significant gaps in knowledge and concerns about safety persist. Targeted educational strategies that clarify the nature, efficacy, and safety of nirsevimab—alongside maintaining cost-free access—are essential to support the successful implementation of RSV prophylaxis programs.

Yi‐Xian Liang, Yan‐Ping Xie, Huan‐Ming Yu et al.

ABSTRACT Introduction Lung adenocarcinoma (LUAD) is one of the major histopathological types of non‐small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. Methods A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole‐exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA‐LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. Results The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA‐LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)‐ERK and p‐AKT (Ser473), and the reduced protein level of p‐ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. Conclusion Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.

Nai-Chien Huan, Larry Ellee Nyanti, Xin Ying Lee et al.

Brown-colored pleural effusion is rare and may result from high bilirubin levels such as bilothorax (often described as a pleural fluid-to-serum bilirubin ratio of > 1.0). We describe four patients with malignant pleural effusion that appeared macroscopically brown with a pleural fluid-to-serum bilirubin ratio between 3.7 and 16.2. All had metastatic adenocarcinomas; three were from lung and one from gastric origin. None demonstrated clear pleurobiliary fistulas on investigations. Postulates for the development of brown effusion include heme oxygenase 1 overexpression in malignant cells situated in the pleura, intrapleural hemolysis, passive movement of bile through microscopic diaphragmatic pores, and drainage of biliary fluid into the pleural lymphatics.

Carstens DD, Maselli DJ, Cook EE et al.

Donna D Carstens,1 Diego J Maselli,2 Erin E Cook,3 Fan Mu,3 Jingyi Chen,3 Danni Yang,3 Jessica Karacz DeMartino,1 Yen Chung1 1Respiratory & Immunology, AstraZeneca, Wilmington, DE, USA; 2Division of Pulmonary Diseases & Critical Care, University of Texas Health, San Antonio, TX, USA; 3Health Economic and Outcomes Research, Analysis Group, Boston, MA, USACorrespondence: Jessica Karacz DeMartino, AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE, 19897, USA, Tel +1 302-897-0843, Email jessica.demartino@astrazeneca.com

Katarzyna Walicka-Serzysko, Magdalena Postek, Urszula Borawska-Kowalczyk et al.

Abstract Background The long-term consequences of prematurity are often not sufficiently recognized. To address this gap, a prospective cohort study, which is a continuation of the multicenter Polish study PREMATURITAS, was conducted, utilizing unique clinical data from 20 years ago. Objective The main goal was to evaluate lung function, detect any structural abnormalities using lung ultrasound, and assess psychological well-being in young adults born between 24 and 34 weeks of gestational age (GA). Additionally, the study aimed to investigate potential associations between perinatal risk factors and abnormalities observed in pulmonary function tests (PFTs) during adulthood. Methods The young survivors underwent a comprehensive set of PFTs, a lung ultrasound, along with the quality of life assessment. Information regarding the neonatal period and respiratory complications was obtained from the baseline data collected in the PREMATURITAS study. Results A total of 52 young adults, with a mean age of 21.6 years, underwent PFTs. They were divided into two groups based on GA: 24–28 weeks (n = 12) and 29–34 weeks (n = 40). The subgroup born more prematurely had significantly higher lung clearance index (LCI), compared to the other subgroup (p = 0.013). LCI ≥ 6.99 was more frequently observed in the more premature group (50% vs. 12.5%, p = 0.005), those who did not receive prenatal steroids (p = 0.020), with a diagnosis of Respiratory Distress Syndrome (p = 0.034), those who received surfactant (p = 0.026), and mechanically ventilated ≥ 7 days (p = 0.005). Additionally, elevated LCI was associated with the diagnosis of asthma (p = 0.010). Conclusions The findings suggest pulmonary effects due to prematurity persist into adulthood and their insult on small airway function. Regular follow-up evaluations of young survivors born preterm should include assessments of PFTs. Specifically, the use of LCI can provide valuable insights into long-term pulmonary impairment.

Nicola Scichilone, Andrew Whittamore, Chris White et al.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common condition that causes irreversible airway obstruction. Fatigue and exertional dyspnoea, for example, have a detrimental impact on the patient’s daily life. Current research has revealed the need to empower the patient, which can result in not only educated and effective decision-making, but also a considerable improvement in patient satisfaction and treatment compliance. The current study aimed to investigate the perspectives and requirements of people living with COPD to possibly explore new ways to manage their disease. Methods Adults with COPD from 8 European countries were interviewed by human factor experts to evaluate their disease journey through the gathering of information on the age, performance, length, and impact of diagnosis, symptoms progression, and family and friends' reactions. The assessment of present symptoms, services, and challenges was performed through a 90-min semi-structured interview. To identify possible unmet needs of participants, a generic thematic method was used to explore patterns, themes, linkages, and sequences within the data collected. Flow charts and diagrams were created to communicate the primary findings. Following analysis, the data was consolidated into cohesive insights and conversation themes relevant to determining the patient's unmet needs. Results The 62, who voluntarily accepted to be interviewed, were patients (61% females, aged 32–70 years) with a COPD diagnosis for at least 6 months with stable symptoms of different severity. The main challenges expressed by the patients were the impact on their lifestyle, reduced physical activity, and issues with their mobility. About one-fourth had challenges with their symptoms or medication including difficulty in breathing. Beyond finding a cure for COPD was the primary goal for patients, their main needs were to receive adequate information on the disease and treatments, and to have adequate support to improve physical activity and mobility, helpful both for patients and their families. Conclusions These results could aid in the creation of new ideas and concepts to improve our patient’s quality of life, encouraging a holistic approach to people living with COPD and reinforcing the commitment to understanding their needs.

Jennifer H. Therkorn, Sean Hu, Anays M. Sotolongo et al.

Abstract Background Service member exposure to explosive blast overpressure waves is common with considerable attention to traumatic brain injury (TBI) and neuropsychological sequalae. Less is known about the impacts on the respiratory system, particularly long-term effects, despite vulnerability to overpressure. Using a national registry, we previously observed an independent relationship between self-reported blast exposure and respiratory symptoms; however, the impact on objective measures of pulmonary function is poorly understood. Methods 307 Veterans referred to our national specialty center for post-deployment health concerns underwent a comprehensive multi-day evaluation that included complete pulmonary function testing (PFT), occupational and environmental medicine history, neuropsychological or psychological evaluation. We developed an a priori chart abstraction process and template to classify Veterans into blast exposure groups: (1) none, (2) single-mild, or (3) multiple-mild. This template focused primarily on clinician documented notes of blast related TBI that were used as proxy for blast overpressure injury to thorax. PFT variables characterizing flow (FEV1%; %∆FEV1), volume (TLC%), diffusion (DLCO%) and respiratory mechanics (forced oscillometry) were selected for analysis. Results Veterans (40.5 ± 9.7 years; 16.3% female) were referred 8.6 ± 3.6 years after their last deployment and presented with considerable comorbid conditions and health problems (e.g., 62% post-traumatic stress, 55% dyspnea). After chart abstraction, Veterans were assigned to none (n = 208), single mild (n = 52) and multiple mild (n = 47) blast exposure groups. Among the blast exposed, clinicians documented 73.7% were < 50 m from the blast and 40.4% were physically moved by blast. PFT outcome measures were similar across all groups (p value range: 0.10–0.99). Conclusions In this referred sample of deployed Veterans, PFT measures of flow, volume, diffusion, and respiratory mechanics were not associated with clinician documented blast exposure per the retrospective chart abstraction methodology applied. Yet, these clinical findings suggest future research should determine and assess distinction between Veteran recollections of perceived blast experiences versus overpressure wave exposure to the respiratory system.

Noriaki Sunaga, Yasuhiko Koga, Yoshimasa Hachisu et al.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The diagnosis of sarcoidosis is based on clinicopathologic findings accompanied by the formation of granulomas in multiple organs, including the lung. Although angiotensin-converting enzyme (ACE) and soluble interleukin 2 receptor (sIL-2R) are traditionally used for the diagnosis of sarcoidosis, specific diagnostic markers remain to be determined. In the current study, we found that serum neuron-specific enolase (NSE) levels were elevated in patients with sarcoidosis. Serum NSE levels were positively correlated with serum ACE and sIL-2R levels. The sensitivity of NSE alone was modest, but its combination with sIL-2R and ACE had the highest sensitivity compared to those of each single marker. When comparing serum NSE and pro-gastrin-releasing peptide (ProGRP) levels in SCLC patients with those in patients with sarcoidosis and nonsarcoidotic benign diseases, serum NSE could be used to distinguish SCLC from sarcoidosis and nonsarcoidosis by setting at a cutoff value of 17.0 ng/ml with a sensitivity of 73.5% and a specificity of 90.2%, which were comparable to those of ProGRP. Serum NSE levels were associated with organ involvement and were higher in sarcoidosis patients who had been treated with oral corticosteroid (OCS) than in those who had never received OCS therapies; there was a positive association between elevated serum NSE levels and OCS use. Increased concentrations of serum NSE in patients at the nonremission phase decreased after spontaneous remission, whereas serum NSE levels fluctuated in accordance with serum ACE or sIL-2R levels during the follow-up period in patients with sarcoidosis. These findings suggest that NSE could be a marker for the diagnosis and monitoring of the clinical outcome of patients with sarcoidosis.

Lucélia Luna Melo-Diaz, George Alvicio Kieling

K P Suraj, Arjun Chandran

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. Even with advancement in understanding the pathophysiology and various monitoring tools and treatment measures, sepsis still remains a major cause of mortality and morbidity in critically ill patients. Over the last three decades, significant changes were seen regarding understanding the pathophysiology of sepsis. The management of sepsis has evolved over the last two decades by the advent of the Surviving Sepsis Campaign Guidelines which recommends early recognition and prompt treatment without delay.

Muluken Genetu Chanie, Mequannent Sharew Melaku, Melaku Yalew et al.

Abstract Background Worldwide, pneumonia is the third leading cause of death in under 5 years children. Ethiopia is ranked 4th out of 15 countries having the highest burdens of the death rate among under-five children due to pneumonia. Regardless of this fact, efforts to identify determinants of pneumonia have been limited yet in Amhara region. This study was aimed to identify predictors of community-acquired childhood pneumonia among 2–59 months old children in the Amhara region, Ethiopia. Methods Facility-based case–control study was conducted in the Amhara region from June 4 to July 15, 2018, among 28 health centers distributed across the region. The total sample size used was 888 (296 cases and 592 controls) children whose age were 2–59 months. At first, multistage sampling technique was employed. Data were collected on a face-to-face interview. Epi data v. 4.6 for data entry and statistical packages for social sciences version 23 for data analysis were used. Multivariable logistic regression analyses were used to test the associations between the study variables at P-value < 0.05 with 95% CI. As a result, determinants were identified for CAP. Results Among 888 enrolled children (296 cases and 592 controls), who experienced a community-acquired pneumonia had an increased risk of maternal age of 18–24 years (AOR 0.03, at 95%CI (0.01, 0.14), Government employee (AOR 0.19, at 95% CI (0.07,0.54), lack of separate kitchen (AOR 5.37; at 95% CI (1.65, 17.43), history of diarrhea in the past two weeks (AOR 10.2; at 95% CI (5.13, 20.18), previous respiratory tract infections (AOR 8.3, at 95% CI (3.32, 20.55) and history of parental asthma (AOR 4.9, at 95% CI (2.42, 10.18). Conclusion Maternal age of 18–24 years and government employee, lack of separate kitchen, history of diarrhea in the past two weeks; previous respiratory tract infection and history of parental asthma were found statistically significant. Health personnel’s needs to focus on creating awareness to the community on the merit of the separate kitchen for reduction of Community-acquired childhood pneumonia, and focus on prevention and management of childhood diarrheal and acute respiratory tract infections.

Rong Zhang, Yonghao Xu, Ling Sang et al.

Abstract Background Intraoperative Extracorporeal membrane oxygenation (ECMO) is increasingly being applied as life-support for lung transplantation patients. However, factors associated with this procedure in lung transplantation patients have not yet been characterized. The aim of this study was to identify preoperative factors of intraoperative ECMO support during lung transplantation and to evaluated the outcome of lung transplantation patients supported with ECMO. Methods Patients underwent lung transplantation treated with and without ECMO in Guangzhou Institute of Respiratory Diseases between January 2015 to August 2018 were retrospectively reviewed. Patient demographics and clinical variables were collected and analyzed. Multivariate logistic regression was performed to identify factors independently associated with intraoperative extracorporeal membrane oxygenation support during lung transplantation. Results During the study period, 138 patients underwent lung transplantation at our institution, the mean LAS was (56.63 ± 18.39) (range, 32.79 to 88.70). Fourty four patients were treated with veno-venous/veno-arterial ECMO. Among the patients, 32 patients wean successfully ECMO after operation, 12 patients remain ECMO after operation, and 32 patients (62.74%) survived to hospital discharge. In multiple analysis, the following factors were associated with intraoperative ECMO support: advanced age, high PAP before operation, duration of mechanical ventilation before operation, a higher APACHE II and primary diagnosis for transplantation. The overall survival rates at 1, 3, and 12 months were 90.91, 72.73, and 56.81% in the ECMO group, and 95.40, 82.76, and 73.56% in the non-ECMO group, respectively (log-rank P = 0.081). Patients who underwent single lung transplant had a lower survival rates in ECMO group as compared with non-ECMO group at 1, 3, and 12 months (90.47% vs 98.25, 71.43% vs 84.21, and 52.38% vs 75.44%) (log-rank P = 0.048). Conclusions The preoperative factors of intraoperative ECMO support during lung transplantation included age, high PAP before operation, preoperative mechanical ventilation, a higher APACHE II and primary diagnosis for transplantation based on multivariate analysis.

Xin Yin, Jinghua Xia, Ying Sun et al.

Abstract Background CHCHD2 was identified a novel cell migration-promoting gene, which could promote cell migration and altered cell adhesion when ectopically overexpressed in NIH3T3 fibroblasts, and it was identified as a protein necessary for OxPhos function as well. However, the clinic relevance of CHCHD2 expression in NSCLC remains unclear. Here we assumed that CHCHD2 expression would accompanies the expression of HIF-1α to response hypoxia in the occurrence of NSCLC. Methods In order to verify this hypothesis, correlations among the expression levels of CHCHD2 and HIF-1α were detected and analyzed in 209 pair cases of NSCLC. The expression and location of these molecules were assessed using Immunohistochemistry, immunohistofluorescence, qRT-PCR and western blotting. The differences and correlations of the expression of these two molecules with clinical pathological characteristics in NSCLC were statistically analyzed using Wilcoxon (W) text, Mann-Whitney U, Kruskal-Wallis H and cross-table tests. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of the expression of CHCHD2 and HIF-1α on the patients’ survival. Results Data showed that CHCHD2 and HIF-1α expression were higher in NSCLC than in normal tissues (all P = 0.000). CHCHD2 expression was significantly related with smoking, tumor size, differentiation degree, TNM Stage, lymph metastasis (all P<0.05). The HIF-1α expression was significantly associated with smoking, tumor category, differentiation degree, TNM Stage, Lymph metastasis (all P<0.05). There was a marked correlation of CHCHD2 and HIF-1α expression with histological type, differentiation and lymph metastasis of NSCLC (all P<0.05, rs >0.3). Immunohistofluorescence showed that there were co-localization phenomenon in cytoplasm and nucleus between CHCHD2 and HIF-1α expression. NSCLC patients with higher CHCHD2 and HIF-1α expression had a significantly worse prognosis than those with lower CHCHD2 and HIF-1α expression (all P = 0.0001; log-rank test). The multivariate analysis indicated that CHCHD2 expression was an independent prognostic factor in NSCLC (hazard ratio [HR], 0.492, P = 0.001). Conclusion Our results indicate that over-expression of CHCHD2 would promote the expression of HIF-1α to adapt the hypoxia microenviroment in NSCLC and CHCHD2 could serves as a prognostic biomarker in NSCLC.

Caroline Dahlqvist, Sebahat Ocak, Maximilien Gourdin et al.

Markus Glatzer, Olgun Elicin, Sara Ramella et al.

Definitive radiochemotherapy is the standard treatment for many patients with locally advanced nonsmall cell lung cancer (NSCLC). Treatment outcomes have improved over the last decades. Several treatment regimens have been shown effective and safe. This review summarises the results of significant studies between 1996 and 2015 on concomitant and sequential radiochemotherapy regimens and radiation dose per fraction. Beside therapy regimens, optimised radiotherapy planning is indispensable to improve outcome and minimise radiation-induced toxicity. An insight into the rationale of radiotherapy planning for stage III NSCLC is also provided.

Mohamed A. Saraya, Abd El-Azeem I. Amal

Background: The most common and most serious complication of varicella (chickenpox) in adults is pneumonia, which can lead to severe respiratory failure. Whether addition of corticosteroids to antiviral treatment benefits patients with varicella pneumonia is unclear. Objectives: To assess the effect of dexamethasone as adjunctive therapy for treatment of varicella pneumonia on the length of hospital stay, which might cause earlier resolution of varicella pneumonia. Patients and methods: Forty patients were diagnosed as varicella pneumonia and divided into two groups, the first one involved 20 patients who received dexamethasone and acyclovir, and the second one involved also 20 patients but they received placebo and acyclovir. We measured liver function test, kidney profile, complete blood count, blood glucose, C-reactive protein and the levels of interleukin-6 on the day of presentation, after 4 days of admission and on the day of discharge from the hospital. Result: The mean length of hospital stay in the dexamethasone group was 6.5 days compared with 7.1 days in the placebo group and was significantly different between two groups. The mean time of switching to oral administration of acyclovir was 3.4 days in the dexamethasone group and 4.2 days in the placebo group. The mean time of switching to oral was significantly lower in dexamethasone group than in placebo group. Conclusion: Adding of dexamethasone to acyclovir in patients with varicella pneumonia can reduce the length of hospital stay.

Darbari Anshuman, Tandon Shekhar, Singh G

Gastropleural fistula is a rare condition. We report a case where fistula developed iatrogenically during repeated intercostal drainage tube insertions for empyema.

Sindhwani G, Rawat J